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51. Patients with medical risk factors for chronic kidney disease are at increased risk of renal impairment despite the use of nephron-sparing surgery.

Author: Costello A., Appu S., Lawrentschuk N., Bolton D., Kearsley J., Frydenberg M., Satasivam P., Reeves F., Rao K., Ivey Z., Basto M., Yip M., Roth H., Grummet J., Goad J., Moon D., Murphy D., Costello A., Appu S., Lawrentschuk N., Bolton D., Kearsley J., Frydenberg M., Satasivam P., Reeves F., Rao K., Ivey Z., Basto M., Yip M., Roth H., Grummet J., Goad J., Moon D., and Murphy D.
Abstract: Objective To determine whether patients with normal preoperative renal function, but who possess medical risk factors for chronic kidney disease (CKD), experience poorer renal function after partial nephrectomy (PN) for renal cell carcinoma (RCC) compared with those without risk factors. Patients and Methods The effects of age, hypertension (HTN) and diabetes mellitus (DM) on estimated glomerular filtration rate (eGFR) were investigated in 488 consecutive operations for RCC performed during 2005-2012 at six Australian tertiary referral centres; 156 patients underwent PN and 332 patients underwent radical nephrectomy (RN). We used chi-squared test and binary logistic regression to analyse new-onset CKD, and multiple linear regression to investigate determinants of postoperative eGFR. Results The development of new-onset eGFR of <60 mL/min was related to undergoing RN rather than PN (risk ratio [RR] 2.7, P < 0.001), older age (RR 1.6, P < 0.001) and the presence of HTN (RR 1.6, P = 0.001) and DM (RR 1.5, P = 0.003). Patients undergoing PN were still at risk of new-onset CKD if medical risk factors were present. Whereas 7% of patients undergoing PN without CKD risk factors developed new-onset eGFR <60 mL/min, this figure increased to 24%, 30% and 42% for older age, HTN and DM, respectively. Patients with eGFR of 45-59 mL/min were more likely to progress to more severe forms of CKD and end-stage renal failure than those with eGFR of >=60 mL/min. On multivariate analysis, RN, rather than PN, age and the presence of DM (but not HTN), predicted both the development of new-onset eGFR of <60 mL/min (R2 = 0.37) and new-onset eGFR <45 mL/min (R2 = 0.42). Conclusion Patients with medical risk factors for CKD are at increased risk of progressive renal impairment despite the use of PN. Where feasible, nephron-sparing surgery should be considered for these patients.Copyright © 2015 The Authors © 2015 BJU International Published by John Wiley & Sons Ltd.
Published: 2015

52. Randomised phase 3 double-blind placebo-controlled trial of methoxyflurane with periprostatic local anaesthesia to reduce the discomfort of transrectal ultrasound-guided prostate biopsy (pain-free trus B): Anzup 1501.

Author: Woo H., Grummet J., Davis I., Martin A., Buchan N., Chalasani V., Chan H., Bishop C., Wong N., Coskinas X., Stockler M., Frydenberg M., Hayne D., Lalak A., Patel M., Williams A., Lawrence N., Woo H., Grummet J., Davis I., Martin A., Buchan N., Chalasani V., Chan H., Bishop C., Wong N., Coskinas X., Stockler M., Frydenberg M., Hayne D., Lalak A., Patel M., Williams A., and Lawrence N.
Abstract: Background: A transrectal ultrasound-guided prostate biopsy (TRUS) is the current gold standard for the diagnosis of prostate cancer. The standard analgesia for a TRUS biopsy is with periprostatic infiltration of local anaesthetic (PILA). However many men still experience significant pain. We hypothesise that the addition of methoxyflurane (Penthrox) to PILA will improve the pain, discomfort and experience of the TRUS biopsy, thereby increasing men's willingness to undergo repeat TRUS prostate biopsy. Method(s): This is a multi-centre, placebo-controlled, double-blinded, centrally randomised phase 3 trial. The target population is men scheduled to undergo their first TRUS biopsy of the prostate for a raised PSA or an abnormal digital rectal examination. Participants are randomised 1:1 to inhaled methoxyflurane or placebo and stratified by age and study site. All participants are treated with PILA (2% lignocaine), injected into and around the prostate prior to the biopsy. The primary objective is to determine the effects of inhaled methoxyflurane on pain rated by participants 15 minutes after biopsy. Secondary endpoints include other aspects of the biopsy experience rated by participants, willingness to undergo a biopsy in the future, Urologist's ratings of the participant's biopsy experience, biopsy completion, frequency of specified adverse events and frequency of hospitalisation. A sample size of 420 participants provides over 85% power at the two-sided 5% level of significance to detect a 0.80 point difference in mean pain scores (on scale from 0-10) assuming a standard deviation of 2.5 whilst allowing for missing data. Patients will complete a questionnaire to document their experience of the biopsy at 5-30 minutes following the procedure and at 7-35 days after the procedure. Urologists will also complete a questionnaire on the day of the procedure. Trial recruitment is scheduled to start by the last quarter of 2015.
Published: 2015

53. Risk factors for infection following prostate biopsy - a case control study

Author: Anderson, E, Leahy, O, Cheng, AC, Grummet, J, Anderson, E, Leahy, O, Cheng, AC, and Grummet, J
Abstract: BACKGROUND: Infection is a complication of TRUS prostate biopsy, despite the use of antimicrobial prophylaxis. Worryingly the rate of infectious complications following TRUS biopsy has been shown to be increasing. We aimed to determine the rate, severity, risk factors, standard patterns of care and microbiology resistance profiles associated with TRUS biopsy sepsis. METHODS: A retrospective case-control study was conducted. Using electronic coding all patients who presented to Cabrini Hospital with sepsis following a TRUS biopsy from 2009 to 2013 were identified. Validated cases were matched to controls in a ratio of 1:3. Eligible controls were required to have undergone a TRUS biopsy at the same surgical institution as the case and in the closest period of time. Demographic, procedural and patient related data-points were recorded for all patients using hospital and urologist records. Univariate logistic regression models were constructed and used to determine risk factors associated with infection. RESULTS: 71 cases developed sepsis following TRUS biopsy and were matched to 213 controls. The average rate of sepsis over the 5-year study period was 1.5 %. A SOFA score ≥ 2 was identified in 28 % of cases. We found a high prevalence of antimicrobial resistant E. coli, with 61 % of blood culture isolates classified as Multidrug resistant organisms. Eight different prophylactic antimicrobial regimens were identified with 33 % of cases receiving ineffective antimicrobial prophylaxis. Statistically significant risk factors included previous antimicrobial use and prior international travel within the six months prior to biopsy. CONCLUSIONS: TRUS biopsy is an elective procedure and as such needs to be associated with minimal morbidity. The patterns of care surrounding periprocedural variables for TRUS biopsies were non-uniform and diverse. A wide variety of different prophylaxis regimens and bowel preparation routines were recorded. Patients with risk factors for sepsis may
Published: 2015

54. 620 - Biparametric MRI: Could it reduce the cost of MRI while maintaining diagnostic accuracy for prostate cancer?

Author: Grummet, J., Pepdjonovic, L., Huang, S., Dat, A., Miller, R., Begashaw, K., Kalapara, A., Mann, S., Ryan, A., O’Sullivan, R., Moon, D., Landau, A., Snow, R., Hanegbi, U., and Frydenberg, M.
Published: 2018
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55. The effect of clinical stage and lesion complexity on the practice of surgery for renal cell carcinoma in the state of Victoria.

Author: Costello A., Goad J., Moon D., Murphy D., Appu S., Kearsley J., Lawrentschuk N., Bolton D., Frydenberg M., Satasivam P., Rao K., Reeves F., Ivey Z., Basto M., Yip M., Roth H., Grummet J., Costello A., Goad J., Moon D., Murphy D., Appu S., Kearsley J., Lawrentschuk N., Bolton D., Frydenberg M., Satasivam P., Rao K., Reeves F., Ivey Z., Basto M., Yip M., Roth H., and Grummet J.
Abstract: Introduction: Over the last decade partial nephrectomy (PN) has become the gold standard for the management of small renal masses (SRMs). Patients who have had PN may have a survival advantage over those treated with radical nephrectomy (RN) through decreased risk of chronic kidney disease (CKD). We sought to investigate the current practice of surgery for renal cell carcinoma (RCC) in the State of Victoria, in particular with regard to the effect of clinical stage and lesion complexity. Patients and Methods: We undertook a retrospective review of 738 consecutive surgeries for pathologically-confirmed RCC between 2005 and 2012 at six Victorian tertiary referral centres. The 488 RN and 250 PN operations were performed through both open and laparoscopic approaches. Statistical evaluation utilised chi square analysis. Result(s): There were 476 male and 262 female patients with a mean age of 60 years. Mean operative time was 206 minutes and median length of stay (LOS) was 5 days. The mean tumour size was 54 mm. Lower T-stage lesions were preferentially treated with PN (p < 0.001) and minimally-invasive (p < 0.001) approaches. Increasing T-stage was associated with a higher proportion of Clavien-Dindo Grade III-V complications (p < 0.001). RENAL nephrometry scores were available in 501 patients. There were 167 low-, 179 moderate- and 155 highcomplexity lesions. High-complexity lesions were more likely to undergo RN (p < 0.001) and have a longer operative time (p < 0.001). Lesion complexity was not associated with length of stay (p = 0.411) or the incidence of Clavien-Dindo Grade III-V complications (p = 0.220). For T1a lesions (n = 218) the use of RN increased with lesion complexity (p < 0.001), with 21% of low-complexity, 52% of moderate-complexity and 100% of high-complexity lesions undergoing radical surgery. Conclusion(s): The choice of radical versus partial nephrectomy for patients undergoing surgery for RCC in Victoria is largely determined by lesion complexity an
Published: 2014

56. Pathology of renal cell carcinoma in the state of Victoria.

Author: Bolton D., Satasivam P., Rao K., Reeves F., Frydenberg M., Basto M., Ivey Z., Yip M., Roth H., Grummet J., Goad J., Appu S., Kearsley J., Moon D., Murphy D., Lawrentschuk N., Costello A., Bolton D., Satasivam P., Rao K., Reeves F., Frydenberg M., Basto M., Ivey Z., Yip M., Roth H., Grummet J., Goad J., Appu S., Kearsley J., Moon D., Murphy D., Lawrentschuk N., and Costello A.
Abstract: Introduction: The utilisation of renal mass biopsy varies among institutions within the State of Victoria. Detractors oft en quote the risk of concurrent benign and malignant pathology as a reason for avoiding biopsy, preferring to base their management decisions on imaging and patient factors. We sought to determine the prevalence of multiple histologies in patients undergoing surgical extirpation for renal cell carcinoma, as well as the effect of lesion complexity on pathological outcomes. Patients and Methods: We performed a retrospective review of 488 radical (RN) and 250 partial nephrectomies (PN) performed for RCC at six Victorian tertiary referral centres. Patients with benign histopathology were excluded from analysis. The RENAL nephrometry score was calculated from the most contemporary pre-operative CT scan. Statistical evaluation utilised Student's T-tests and chi square analysis. Result(s): There were 476 male and 262 female patients with a mean age of 60 years. The distribution of pathological subtypes were 72% clear cell, 14% papillary, 8% chromophobe, 1% collecting duct, 1% multilocular cystic and 3% with other classifications. The mean tumour size was 54 mm. Twelve patients (2%) had multiple histologies. Oncocytoma coincided with RCC in five of these patients (0.67%). RENAL nephrometry scores were available in 501 patients. Higher-complexity lesions were more likely to have a higher pathological T-stage (p < 0.001), a higher Fuhrman grade (p = 0.023) and positive surgical margins (p = 0.012). Diabetic patients (n = 122) were also more likely to have positive margins (30% v 18%, p = 0.008). Conclusion(s): Increasing lesion complexity is associated with poorer pathological features, which supports a more aggressive approach in the management of these tumours. The low rate of multiple histologies reinforces the value of renal biopsy in small renal masses and complex PN cases.
Published: 2014

57. Comparison of two novel methods of TRUS biopsy analgesia: Methoxyflurane alone versus methoxyflurane plus local anaesthetic infiltration.

Author: Pepdjonovic L., Huang S., Konstantantos A., Grummet J., Frydenberg M., Ong W.L., Pepdjonovic L., Huang S., Konstantantos A., Grummet J., Frydenberg M., and Ong W.L.
Abstract: Introduction: Transrectal ultrasound guided (TRUS) biopsy of the prostate is well-recognized as a potential source of pain and distress for patients. * Currently, peri-prostatic infiltration of local anaesthetic (PILA) is described as the 'gold standard' of analgesia for TRUS biopsy * However, this technique is not widely practised in Australia and NZ. Our survey in 2012 showed that less than 27% of urologists in our region reported using PILA alone as analgesia for TRUS biopsies * As the resource-intensive transperineal biopsy approach continues to gain momentum, the search continues for an improved analgesic method for TRUS biopsy that does not require the use of the operating theatre. * Recently, we reported a safe and feasible novel methods of analgesia for TRUS using only the inhaled methoxyflurane (PenthroxTM) - the 'green whistle' * In this study we aimed to compare patient-reported analgesia of methoxyflurane alone versus methoxyflurane with PILA for TRUS biopsy Patients and Methods * Two consecutive series of patients who underwent TRUS biopsy at a Victorian regional hospital from August 2010 to August 2013 were included * All patients were provided with, and instructed on the use of, a Penthrox inhaler (3 ml methoxyflurane) immediately prior to TRUS biopsy * For patients in the combination analgesia group, 2.5 ml of 2% of lignocaine was also injected into the junction of prostate base and seminal vesicle bilaterally using a 23G needle (total 5 ml) * Immediately following the TRUS biopsy, the overall pain of the procedure was assessed using the verbal rating scale, with 0 being no pain and 10 being the worst pain imaginable * Student t-test (or Wilcoxon rank-sum test as appropriate) was used to compare characteristics and pain scores between the two groups Results * 72 patients underwent TRUS prostate biopsy during the study period, of which the first 42 had methoxyflurane alone (Group 1) while the following 30 had a combination of methoxyflurane plus PILA
Published: 2014

58. Choosing the best surgical approach for T1b renal cell carcinoma.

Author: Bolton D., Frydenberg M., Lawrentschuk N., Kearsley J., Costello A., Satasivam P., Reeves F., Rao K., Ivey Z., Basto M., Yip M., Roth H., Grummet J., Goad J., Moon D., Murphy D., Appu S., Bolton D., Frydenberg M., Lawrentschuk N., Kearsley J., Costello A., Satasivam P., Reeves F., Rao K., Ivey Z., Basto M., Yip M., Roth H., Grummet J., Goad J., Moon D., Murphy D., and Appu S.
Abstract: Introduction: Stage T1b renal cell carcinoma (RCC) is a contentious entity as both radical and nephron-sparing approaches may be justified in different circumstances. The excess morbidity of partial nephrectomy must oft en be weighed against the benefits of nephronsparing surgery. We sought to develop a conceptual framework for the management of these challenging lesions. Patients and Methods: We undertook a retrospective review of 110 radical (RN) and 36 partial nephrectomies (PN) performed for T1b RCC between 2005 and 2012 at six Victorian tertiary referral centres. Data was collected with regard to age, surgical approach, lesion complexity as assessed by RENAL nephrometry, postoperative renal function and the presence of CKD risk factors. Statistical analysis utilised two-sample Student's T-tests and chi square analysis. Result(s): There were 90 male and 56 female patients with a mean age of 58 years. 62% of patients underwent laparoscopic RN, 14% open RN, 12% open PN, 9% lap PN and 3% robotic PN. Age > 60 years (n = 73) was associated with increased postoperative complications (p = 0.027), longer LOS (p = 0.012) and higher risk of pre-existing CKD with eGFR < 60 mL/min (34% vs 15%, p = 0.012). RENAL nephrometry scores were available in 101 patients. The more complex the lesion, the less likely the patient would undergo PN (p < 0.001) or minimally invasive surgery (p < 0.001). Nephrometry score had no significant relationship with operative time, LOS, margin rate or complication rate. Whilst patients undergoing PN recovered renal function by the 6th postoperative month, those undergoing RN experienced a mean drop in eGFR of 29% (p = 0.012). Beyond the 6th postoperative month, patients undergoing RN experienced greater loss of renal function if they were hypertensive (p = 0.025) or both hypertensive and diabetic (p = 0.016). Minimally-invasive approaches were associated with a shorter LOS (4 vs 6 days, p < 0.001) but no benefit in terms of postoperative complicati
Published: 2014

59. The presence of risk factors for chronic kidney disease may diminish the benefit of partial nephrectomy for renal cell carcinoma.

Author: Rao K., Yip M., Roth H., Grummet J., Goad J., Appu S., Kearsley J., Moon D., Murphy D., Lawrentschuk N., Costello A., Bolton D., Frydenberg M., Satasivam P., Reeves F., Basto M., Ivey Z., Rao K., Yip M., Roth H., Grummet J., Goad J., Appu S., Kearsley J., Moon D., Murphy D., Lawrentschuk N., Costello A., Bolton D., Frydenberg M., Satasivam P., Reeves F., Basto M., and Ivey Z.
Abstract: INTRODUCTION & OBJECTIVES: There exists conflicting evidence in the literature regarding the benefit of nephron-sparing surgery for tumours larger than 4cm. We sought to determine whether renal function post partial nephrectomy (PN) for renal cell carcinoma (RCC) could be affected by the presence of risk factors for chronic kidney disease (CKD). MATERIAL & METHODS: We performed a retrospective review of 488 operations for pathologically-confirmed RCC performed between 2005 and 2012 at six Victorian tertiary referral centres. All patients had renal function data available beyond the sixth postoperative month. We investigated the effect of hypertension (HTN) and diabetes (DM), known risk factors for CKD, on the development of new-onset CKD (eGFR < 60mL/min) in patients with normal preoperative renal function. Data was analysed using two-sample Student's T-tests, chi square analysis, Pearson product-moment correlation and multivariate analysis of variance. RESULT(S): The mean patient age was 60 years (range 25 to 87), with 325 males and 163 females. Age correlated significantly with HTN (R = 0.327, p < 0.001), DM (R = 0.124, p = 0.006) and the presence of preoperative CKD (R = 0.215, p < 0.001). Mean tumour size was 53mm (range 6 to 240mm). Patients undergoing RN (n = 332) rather than PN (n = 156) experienced a greater mean percentage reduction in eGFR at 6 months (26% vs 7%, p < 0.001). On univariate analysis, the development of new-onset CKD in patients with preoperative eGFR > 60mL/min (n = 384) was related to RN (RR 2.74, p < 0.001), HTN (RR 1.62, p = 0.001) and DM (RR 1.47, p = 0.005). In patients undergoing PN, new-onset CKD increased with the number of risk factors present. The rate of new-onset CKD post PN was 7%, 25%, 60% and 35% for patients with no risk factors, HTN, DM or both risk factors, respectively. Likewise the rate of new-onset CKD post RN was 41%, 67%, 67% and 70% for patients with no risk factors, HTN, DM or both risk factors, respectively. The dif
Published: 2014

60. P007 Transperineal biopsy prostate cancer detection in first biopsy and post-negative TRUS biopsy settings: The Victorian transperineal biopsy collaboration experience

Author: Ong, W.L., primary, Weerakoon, M., additional, Huang, S., additional, Paul, E., additional, Lawrentschuk, N., additional, Frydenberg, M., additional, Moon, D., additional, Murphy, D., additional, and Grummet, J., additional
Published: 2014
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61. V42 - Robotic MRI/US fusion transperineal biopsy using the iSR’obot Mona Lisa: Technique, safety and accuracy

Author: Patel, A., Servian, P., Winkler, M., Tiong, L.C., Yuen, J., Ho, H., Chen, K., Kruck, S., and Grummet, J.
Published: 2017
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62. 652 The presence of risk factors for chronic kidney disease may diminish the benefit of partial nephrectomy for renal cell carcinoma

Author: Satasivam, P., primary, Rao, K., additional, Reeves, F., additional, Basto, M., additional, Ivey, Z., additional, Yip, M., additional, Roth, H., additional, Grummet, J., additional, Goad, J., additional, Appu, S., additional, Kearsley, J., additional, Moon, D., additional, Murphy, D., additional, Lawrentschuk, N., additional, Costello, A., additional, Bolton, D., additional, and Frydenberg, M., additional
Published: 2014
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63. Primary apocrine adenocarcinoma of scrotum suspected as urothelial carcinoma metastasis: A clinical and pathological dilemma.

Author: Frydenberg M., Pham A., Pedersen J., Grummet J., Huang S., Frydenberg M., Pham A., Pedersen J., Grummet J., and Huang S.
Abstract: A 78 year old man presented with an enlarging, tender mass in the scrotum separate to the testes. Th is was on the background of radical cystoprostatectomy, urethrectomy and ileal conduit formation for high-grade urothelial carcinoma of the bladder invading submucosa three years prior. Examination revealed a 4 cm x 5 cm lesion, which was hard, fixed to the overlying skin and nodular to palpation. Th is was confirmed by an ultrasound that clearly showed a solid mass in the scrotum extending into the perineum. Computerised tomography of the chest, abdomen and pelvis revealed enlargement of inguinal lymph nodes but no other metastases. Complete resection of the scrotal lesion and selective removal of regional lymph nodes was performed. Rather than a cutaneous scrotal metastasis from the bladder urothelial carcinoma, histopathological examination suggested a primary apocrine adenocarcinoma of the scrotum. Th is case report explores the clinical and pathological features associated with both of these unusual diff erential diagnoses. MeSH Terms : S crotum, Apocrine Glands, Adenocarcinoma, Case Reports, Urologic Neoplasms .
Published: 2013

64. The green whistle: A novel method of analgesia for transrectal prostate biopsy.

Author: Konstantatos A., Frydenberg M., Grummet J., Huang S., Konstantatos A., Frydenberg M., Grummet J., and Huang S.
Abstract: Introduction and objectives: The transrectal ultrasonography-guided (TRUS) biopsy of the prostate is well-known to be a significant source of discomfort as a result of both insertion of the ultrasound probe as well as penetration of the biopsy trocar through the prostate. The current standard methods of analgesia have significant drawbacks. Intravenous sedation is labour-intensive and costly; local anaesthetic infiltration has not received widespread uptake and does not address the pain of anal probe insertion. This pilot study was conducted to determine the feasibility of using a novel inhaled analgesic agent (PenthroxTM) in reducing the pain associated with TRUS biopsy of the prostate. Method(s): Patients undergoing TRUS biopsies were each given a Penthrox inhaler to self-administer during the procedure and instructed in its use. Immediately after the procedure, patients were asked to rate their pain using a verbal rating scale from 0 to 10. Result(s): 42 consecutive men underwent a TRUS biopsy. The median pain score was 3. Only 5 patients had more than 12 cores taken. Their mean pain score was 2.4, indicating no correlation between number of cores taken and degree of pain experienced. All 42 patients stated they would be happy to undergo the same procedure again. The only adverse effects reported by patients were brief light-headedness and a sickly sweet taste. Conclusion(s): This pilot study suggests that Penthrox may have a role as analgesia for TRUS biopsy. It may provide safe, adequate analgesia that is easy for urologists to use and avoids excessive resources. Further research into this novel inhaled analgesic agent is warranted.
Published: 2013

65. Painful scrotal swelling in adolescent boys and men.

Author: Grummet J., Frydenberg M., Grummet J., and Frydenberg M.
Abstract: Painful scrotal swellings are commonly caused by acute epididymitis. However, the possibility of torsion of the spermatic cord or testis cancer must be considered in the diagnosis.
Published: 2012

66. The Green Whistle: A novel method of analgesia for transrectal prostate biopsy.

Author: Konstantatos A., Frydenberg M., Grummet J., Huang S., Konstantatos A., Frydenberg M., Grummet J., and Huang S.
Abstract: Introduction and Objectives: The transrectal ultrasonography-guided (TRUS) biopsy of the prostate is well-known to be a significant source of discomfort as a result of both insertion of the ultrasound probe as well as penetration of the biopsy trocar through the prostate. The current standard methods of analgesia have significant drawbacks. Intravenous sedation is labour-intensive and costly; local anaesthetic infiltration has not received widespread uptake and does not address the pain of anal probe insertion. This pilot study was conducted to determine the feasibility of using a novel inhaled analgesic agent (PenthroxTM) in reducing the pain associated with TRUS biopsy of the prostate. Method(s): Patients undergoing TRUS biopsies were each given a Penthrox inhaler to self-administer during the procedure and instructed in its use. Immediately after the procedure, patients were asked to rate their pain using a verbal rating scale from 0 to 10. Result(s): 42 consecutive men underwent a TRUS biopsy. The median pain score was 3. Only 5 patients had more than 12 cores taken. Their mean pain score was 2.4, indicating no correlation between number of cores taken and degree of pain experienced. All 42 patients stated they would be happy to undergo the same procedure again. The only adverse effects reported by patients were brief light-headedness and a sickly sweet taste. Conclusion(s): This pilot study suggests that Penthrox may have a role as analgesia for TRUS biopsy. It may provide safe, adequate analgesia that is easy for urologists to use and avoids excessive resources. Further research into this novel inhaled analgesic agent is warranted.
Published: 2012

67. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer—2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent

Author: Thomas Van den Broeck, Philip Cornford, Michael Lardas, Nicola Fossati, Stefano Fanti, Ann Henry, Erik Briers, Thomas Wiegel, Marcus G. Cumberbatch, Nicolas Mottet, Olivier Rouvière, Roderick C.N. van den Bergh, Silke Gillessen, Ivo G. Schoots, Theodorus H. van der Kwast, Peter-Paul M. Willemse, Giorgio Gandaglia, Maria De Santis, Derya Tilki, N. Grivas, Lisa Moris, Matthew Liew, Malcolm David Mason, Henk G. van der Poel, Daniela E. Oprea-Lager, Jeremy Grummet, Thomas B. Lam, Mottet, N., van den Bergh, R. C. N., Briers, E., Van den Broeck, T., Cumberbatch, M. G., De Santis, M., Fanti, S., Fossati, N., Gandaglia, G., Gillessen, S., Grivas, N., Grummet, J., Henry, A. M., van der Kwast, T. H., Lam, T. B., Lardas, M., Liew, M., Mason, M. D., Moris, L., Oprea-Lager, D. E., van der Poel, H. G., Rouviere, O., Schoots, I. G., Tilki, D., Wiegel, T., Willemse, P. -P. M., Cornford, P., Pathology, Radiology & Nuclear Medicine, and Mottet N, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, Fanti S, Fossati N, Gandaglia G, Gillessen S, Grivas N, Grummet J, Henry AM, van der Kwast TH, Lam TB, Lardas M, Liew M, Mason MD, Moris L, Oprea-Lager DE, van der Poel HG, Rouvière O, Schoots IG, Tilki D, Wiegel T, Willemse PM, Cornford P.
Subjects: Male, Quality of life, medicine.medical_specialty, Staging, Urology, medicine.medical_treatment, 030232 urology & nephrology, Active surveillance, Scientific evidence, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, Biopsy, Diagnosis, medicine, Humans, Prostate cancer, EAU-EANM-ESTRO-ESUR-SIOG, EAU-EANM-ESTRO-ESUR-SIOG guidelines, Intensive care medicine, Early Detection of Cancer, medicine.diagnostic_test, business.industry, Prostatic Neoplasms, medicine.disease, Radical prostatectomy, Radiation therapy, Treatment, Localised, Geriatric oncology, 030220 oncology & carcinogenesis, Life expectancy, Screening, Androgen deprivation, business
Abstract: Objective: To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on screening, diagnosis, and local treatment of clinically localised prostate cancer (PCa). Evidence acquisition: The panel performed a literature review of new data, covering the time frame between 2016 and 2020. The guidelines were updated and a strength rating for each recommendation was added based on a systematic review of the evidence. Evidence synthesis: A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. Risk-adapted screening should be offered to men at increased risk from the age of 45 yr and to breast cancer susceptibility gene (BRCA) mutation carriers, who have been confirmed to be at risk of early and aggressive disease (mainly BRAC2), from around 40 yr of age. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is performed, a combination of targeted and systematic biopsies must be offered. There is currently no place for the routine use of tissue-based biomarkers. Whilst prostate-specific membrane antigen positron emission tomography computed tomography is the most sensitive staging procedure, the lack of outcome benefit remains a major limitation. Active surveillance (AS) should always be discussed with low-risk patients, as well as with selected intermediate-risk patients with favourable International Society of Urological Pathology (ISUP) 2 lesions. Local therapies are addressed, as well as the AS journey and the management of persistent prostate-specific antigen after surgery. A strong recommendation to consider moderate hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term hormonal treatment. Conclusions: The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for their use in clinical practice. These PCa guidelines reflect the multidisciplinary nature of PCa management. Patient summary: Updated prostate cancer guidelines are presented, addressing screening, diagnosis, and local treatment with curative intent. These guidelines rely on the available scientific evidence, and new insights will need to be considered and included on a regular basis. In some cases, the supporting evidence for new treatment options is not yet strong enough to provide a recommendation, which is why continuous updating is important. Patients must be fully informed of all relevant options and, together with their treating physicians, decide on the most optimal management for them. The 2020 European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on prostate cancer (PCa) summarise the most recent findings and provide recommendations for clinical practice, addressing screening, diagnosis, and local treatment with curative intent. Key stakeholders in PCa management were involved in their development, including a patient representative. A full version is available at the EAU office and online at http://uroweb.org/guideline/prostate-cancer/. A separate publication will address the management of relapsing-, metastatic-, and castration-resistant PCa.
Published: 2021

68. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II-2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer

Author: Nicolas Mottet, Lisa Moris, Maria De Santis, Thomas B. Lam, Matthew Liew, Giorgio Gandaglia, Theodorus H. van der Kwast, Nikolaos Grivas, Silke Gillessen, Thomas Van den Broeck, Ann Henry, Philip Cornford, Michael Lardas, Marcus G. Cumberbatch, Nicola Fossati, Erik Briers, Malcolm David Mason, Daniela E. Oprea-Lager, Jeremy Grummet, Thomas Wiegel, Henk G. van der Poel, Ivo G. Schoots, Stefano Fanti, Roderick C.N. van den Bergh, Peter-Paul M. Willemse, Derya Tilki, Olivier Rouvière, Cornford, P., van den Bergh, R. C. N., Briers, E., Van den Broeck, T., Cumberbatch, M. G., De Santis, M., Fanti, S., Fossati, N., Gandaglia, G., Gillessen, S., Grivas, N., Grummet, J., Henry, A. M., der Kwast, T. H. V., Lam, T. B., Lardas, M., Liew, M., Mason, M. D., Moris, L., Oprea-Lager, D. E., der Poel, H. G. V., Rouviere, O., Schoots, I. G., Tilki, D., Wiegel, T., Willemse, P. -P. M., Mottet, N., and Cornford P, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, Fanti S, Fossati N, Gandaglia G, Gillessen S, Grivas N, Grummet J, Henry AM, der Kwast THV, Lam TB, Lardas M, Liew M, Mason MD, Moris L, Oprea-Lager DE, der Poel HGV, Rouvière O, Schoots IG, Tilki D, Wiegel T, Willemse PM, Mottet N.
Subjects: Biochemical recurrence, Oncology, Quality of life, Male, medicine.medical_specialty, Castration resistant, Urology, medicine.medical_treatment, 030232 urology & nephrology, urologic and male genital diseases, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Palliative, Prostate cancer, Follow-up, Internal medicine, medicine, Chemotherapy, Humans, EAU-EANM-ESTRO-ESUR-SIOG guidelines, Relapse, Neoplasm Metastasis, Palliative, Prostatectomy, business.industry, Follow-up, Prostatic Neoplasms, Evidence-based medicine, Guideline, medicine.disease, Radiation therapy, Geriatric oncology, 030220 oncology & carcinogenesis, Hormonal therapy, Metastatic, Neoplasm Recurrence, Local, business
Abstract: Objective: To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy & Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (CRPC). Evidence acquisition: The working panel performed a literature review of the new data (2016–2019). The guidelines were updated, and the levels of evidence and/or grades of recommendation were added based on a systematic review of the literature. Evidence synthesis: Prostate-specific membrane antigen positron emission tomography computed tomography scanning has developed an increasingly important role in men with biochemical recurrence after local therapy. Early salvage radiotherapy after radical prostatectomy appears as effective as adjuvant radiotherapy and, in a subset of patients, should be combined with androgen deprivation. New treatments have become available for men with metastatic hormone-sensitive prostate cancer (PCa), nonmetastatic CRPC, and metastatic CRPC, along with a role for local radiotherapy in men with low-volume metastatic hormone-sensitive PCa. Also included is information on quality of life outcomes in men with PCa. Conclusions: The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are first endorsed by the EANM and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online (http://uroweb.org/guideline/prostate-cancer/). Patient summary: This article summarises the guidelines for the treatment of relapsing, metastatic, and castration-resistant prostate cancer. These guidelines are evidence based and guide the clinician in the discussion with the patient on the treatment decisions to be taken. These guidelines are updated every year; this summary spans the 2017–2020 period of new evidence. The knowledge in the field of advanced and metastatic prostate cancer (PCa) and castration-resistant prostate cancer is changing rapidly. The 2020 European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy & Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are first endorsed by the EANM and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online (http://uroweb.org/guideline/prostate-cancer/).
Published: 2020

69. A0669 - When does focal LDR brachytherapy fail? Early lessons from Australia's LIBERATE registry.

Author: Anderson, E., Smyth, L., Harkin, T., O'sullivan, R., Ryan, A., Lawrenthshuk, N., Katz, D., See, A., and Grummet, J.
Subjects: *LOW dose rate brachytherapy
Published: 2024
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70. Patient- and Tumour-related Prognostic Factors for Urinary Incontinence After Radical Prostatectomy for Nonmetastatic Prostate Cancer

Author: Thomas P. A. Debray, Christopher Berridge, Thomas Van den Broeck, Cathy Yuhong Yuan, Silke Gillessen, Nicola Fossati, Fabio Zattoni, Malcolm David Mason, Thomas B. Lam, Giorgio Gandaglia, Ann Henry, Olivier Rouvière, Marcus G. Cumberbatch, Guillaume Ploussard, Shane O'Hanlon, Thomas Wiegel, Philip Cornford, Henk G. van der Poel, Andrea Farolfi, Lisa Moris, Jeremy Grummet, Matthew Liew, N. Grivas, Daniela E. Oprea-Lager, Michael Lardas, Ivo G. Schoots, Erik Briers, Maria De Santis, Nicolas Mottet, Theodorus H. van der Kwast, Derya Tilki, Peter-Paul M. Willemse, Roderick C.N. van den Bergh, Lardas, M., Grivas, N., Debray, T. P. A., Zattoni, F., Berridge, C., Cumberbatch, M., Van den Broeck, T., Briers, E., De Santis, M., Farolfi, A., Fossati, N., Gandaglia, G., Gillessen, S., O'Hanlon, S., Henry, A., Liew, M., Mason, M., Moris, L., Oprea-Lager, D., Ploussard, G., Rouviere, O., Schoots, I. G., van der Kwast, T., van der Poel, H., Wiegel, T., Willemse, P. -P., Yuan, C. Y., Grummet, J. P., Tilki, D., van den Bergh, R. C. N., Lam, T. B., Cornford, P., and Mottet, N.
Subjects: Male, medicine.medical_specialty, Evidence synthesis, Patient-related factors, Prognostic factors, Prostate cancer, Systematic review, Tumour-related factors, Urinary incontinence, Urology, medicine.medical_treatment, 030232 urology & nephrology, Context (language use), 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, medicine, Humans, Prospective Studies, Randomized Controlled Trials as Topic, Retrospective Studies, Prostatectomy, business.industry, Confounding, Prostate, Prostatic Neoplasms, Odds ratio, Prognosis, medicine.disease, Urinary Incontinence, Urethra, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Meta-analysis, medicine.symptom, business
Abstract: Context While urinary incontinence (UI) commonly occurs after radical prostatectomy (RP), it is unclear what factors increase the risk of UI development. Objective To perform a systematic review of patient- and tumour-related prognostic factors for post-RP UI. The primary outcome was UI within 3 mo after RP. Secondary outcomes included UI at 3–12 mo and ≥12 mo after RP. Evidence acquisition Databases including Medline, EMBASE, and CENTRAL were searched between January 1990 and May 2020. All studies reporting patient- and tumour-related prognostic factors in univariable or multivariable analyses were included. Surgical factors were excluded. Risk of bias (RoB) and confounding assessments were performed using the Quality In Prognosis Studies (QUIPS) tool. Random-effects meta-analyses were performed for all prognostic factor, where possible. Evidence synthesis A total of 119 studies (5 randomised controlled trials, 24 prospective, 88 retrospective, and 2 case-control studies) with 131 379 patients were included. RoB was high for study participation and confounding; moderate to high for statistical analysis, study attrition, and prognostic factor measurement; and low for outcome measurements. Significant prognostic factors for postoperative UI within 3 mo after RP were age (odds ratio [OR] per yearly increase 1.04, 95% confidence interval [CI] 1.03–1.05), membranous urethral length (MUL; OR per 1-mm increase 0.81, 95% CI 0.74–0.88), prostate volume (PV; OR per 1-ml increase 1.005, 95% CI 1.000–1.011), and Charlson comorbidity index (CCI; OR 1.28, 95% CI 1.09–1.50). Conclusions Increasing age, shorter MUL, greater PV, and higher CCI are independent prognostic factors for UI within 3 mo after RP, with all except CCI remaining prognostic at 3–12 mo. Patient summary We reviewed the literature to identify patient and disease factors associated with urinary incontinence after surgery for prostate cancer. We found increasing age, larger prostate volume, shorter length of a section of the urethra (membranous urethra), and lower fitness were associated with worse urinary incontinence for the first 3 mo after surgery, with all except lower fitness remaining predictive at 3–12 mo.
Published: 2022

71. A0521 - Adding Mitomycin to BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive -bladder cancer: A randomised phase 3 trial: The BCG+MM Study (ANZUP1301).

Author: Hayne, D., Stockler, M., Martin, A.J., Mccombie, S., Zebic, D., Krieger, L., Anderson, P., Bastick, P., Beardsley, E., Blatt, A., Frydenberg, M., Green, W., Grummet, J., Hawks, C., Ischia, J., Mitterdorfer, A., Patel, M., Roberts, M., Sengupta, S., and Srivastav, R.
Subjects: *CLINICAL trials, *CANCER invasiveness
Published: 2023
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72. A0294 - Is there an impact of transperineal vs. transrectal MRI-targeted biopsy on the risk of upgrading and concordance with final pathology in prostate cancer patients undergoing radical prostatectomy? An EAU-YAU study.

Author: Zattoni, F., Marra, G., Martini, A., Kasivisvanathan, V., Grummet, J., Harkin, T., Ploussard, G., Olivier, J., Chiu, P.K., Valerio, M., Marquis, A., Gontero, P., Guo, H., Zhuang, J., Frydenberg, M., Moon, D., Kretschmer, A., Heidegger, I., Tilki, D., and Van Den Bergh, R.
Subjects: *ENDORECTAL ultrasonography, *PROSTATE cancer patients, *RADICAL prostatectomy, *PROSTATE cancer, *PATHOLOGY, *BIOPSY
Published: 2023
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73. A Systematic Review of the Impact of Surgeon and Hospital Caseload Volume on Oncological and Nononcological Outcomes After Radical Prostatectomy for Nonmetastatic Prostate Cancer

Author: N. Grivas, Guillaume Ploussard, Peter-Paul M. Willemse, Jakub Pecanka, Roderick C.N. van den Bergh, Maria De Santis, Thomas Van den Broeck, Nicolas Mottet, Thomas Wiegel, Olivier Rouvière, Jeremy Grummet, Silke Gillessen Sommer, Mithun Kailavasan, Daniela E. Oprea-Lager, Michael Lardas, Shane O'Hanlon, Cathy Yuhong Yuan, Henk G. van der Poel, Thomas B. Lam, Giorgio Gandaglia, Lisa Moris, Matthew Liew, Derya Tilki, Philip Cornford, Erik Briers, Ivo G. Schoots, Malcolm David Mason, Van den Broeck, T., Oprea-Lager, D., Moris, L., Kailavasan, M., Briers, E., Cornford, P., De Santis, M., Gandaglia, G., Gillessen Sommer, S., Grummet, J. P., Grivas, N., Lam, T. B. L., Lardas, M., Liew, M., Mason, M., O'Hanlon, S., Pecanka, J., Ploussard, G., Rouviere, O., Schoots, I. G., Tilki, D., van den Bergh, R. C. N., van der Poel, H., Wiegel, T., Willemse, P. -P., Yuan, C. Y., and Mottet, N.
Subjects: Male, Biochemical recurrence, medicine.medical_specialty, Blood transfusion, Urology, medicine.medical_treatment, 030232 urology & nephrology, MEDLINE, Context (language use), Workload, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Interquartile range, Outcome Assessment, Health Care, Oncological outcomes, Humans, Medicine, Prostatectomy, Surgeons, Surgeon volume, business.industry, General surgery, Prostate, Prostatic Neoplasms, Perioperative, medicine.disease, Functional outcomes, Hospitals, Hospital volume, Treatment Outcome, Evidence synthesis, 030220 oncology & carcinogenesis, Systematic review, Neoplasm Recurrence, Local, business, Delivery of Health Care, Hospitals, High-Volume
Abstract: Context The impact of surgeon and hospital volume on outcomes after radical prostatectomy (RP) for localised prostate cancer (PCa) remains unknown. Objective To perform a systematic review on the association between surgeon or hospital volume and oncological and nononcological outcomes following RP for PCa. Evidence acquisition Medline, Medline In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched. All comparative studies for nonmetastatic PCa patients treated with RP published between January 1990 and May 2020 were included. For inclusion, studies had to compare hospital or surgeon volume, defined as caseload per unit time. Main outcomes included oncological (including prostate-specific antigen persistence, positive surgical margin [PSM], biochemical recurrence, local and distant recurrence, and cancer-specific and overall survival) and nononcological (perioperative complications including need for blood transfusion, conversion to open procedure and within 90-d death, and continence and erectile function) outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Both a narrative and a quantitative synthesis were planned if the data allowed. Evidence synthesis Sixty retrospective comparative studies were included. Generally, increasing surgeon and hospital volumes were associated with lower rates of mortality, PSM, adjuvant or salvage therapies, and perioperative complications. Combining group size cut-offs as used in the included studies, the median threshold for hospital volume at which outcomes start to diverge is 86 (interquartile range [IQR] 35–100) cases per year. In addition, above this threshold, the higher the caseload, the better the outcomes, especially for PSM. RoB and confounding were high for most domains. Conclusions Higher surgeon and hospital volumes for RP are associated with lower rates of PSMs, adjuvant or salvage therapies, and perioperative complications. This association becomes apparent from a caseload of >86 (IQR 35–100) per year and may further improve hereafter. Both high- and low-volume centres should measure their outcomes, make them publicly available, and improve their quality of care if needed. Patient summary We reviewed the literature to determine whether the number of prostate cancer operations (radical prostatectomy) performed in a hospital affects the outcomes of surgery. We found that, overall, hospitals with a higher number of operations per year have better outcomes in terms of cancer recurrence and complications during or after hospitalisation. However, it must be noted that surgeons working in hospitals with lower annual operations can still achieve similar or even better outcomes. Therefore, making hospital’s outcome data publicly available should be promoted internationally, so that patients can make an informed decision where they want to be treated.
Published: 2021

74. A Systematic Review of Focal Ablative Therapy for Clinically Localised Prostate Cancer in Comparison with Standard Management Options: Limitations of the Available Evidence and Recommendations for Clinical Practice and Further Research

Author: Ann Henry, Stefano Fanti, Nicolas Mottet, Olivier Rouvière, Thomas Lumsden, Theodorus H. van der Kwast, Thomas Van den Broeck, Nicola Fossati, Nikolaos A. Kostakopoulos, Malcolm David Mason, Daniela E. Oprea-Lager, Thomas B. Lam, Philip Cornford, Erik Briers, Henk G. van der Poel, Thomas Wiegel, Guillaume Ploussard, Peter-Paul M. Willemse, Giorgio Gandaglia, Anthony Simon Bates, Marcus G. Cumberbatch, Silke Gillessen, Derya Tilki, Ivo G. Schoots, Jeremy Grummet, Michael Lardas, Roderick C.N. van den Bergh, Maria De Santis, Lisa Moris, Matthew Liew, Jennifer Ayers, James N'Dow, Yuhong Yuan, Bates, A. S., Ayers, J., Kostakopoulos, N., Lumsden, T., Schoots, I. G., Willemse, P. -P. M., Yuan, Y., van den Bergh, R. C. N., Grummet, J. P., van der Poel, H. G., Rouviere, O., Moris, L., Cumberbatch, M. G., Lardas, M., Liew, M., Van den Broeck, T., Gandaglia, G., Fossati, N., Briers, E., De Santis, M., Fanti, S., Gillessen, S., Oprea-Lager, D. E., Ploussard, G., Henry, A. M., Tilki, D., van der Kwast, T. H., Wiegel, T., N'Dow, J., Mason, M. D., Cornford, P., Mottet, N., Lam, T. B. L., and Bates AS, Ayers J, Kostakopoulos N, Lumsden T, Schoots IG, Willemse PM, Yuan Y, van den Bergh RCN, Grummet JP, van der Poel HG, Rouvière O, Moris L, Cumberbatch MG, Lardas M, Liew M, Van den Broeck T, Gandaglia G, Fossati N, Briers E, De Santis M, Fanti S, Gillessen S, Oprea-Lager DE, Ploussard G, Henry AM, Tilki D, van der Kwast TH, Wiegel T, N'Dow J, Mason MD, Cornford P, Mottet N, Lam TBL.
Subjects: Male, Radical treatment, medicine.medical_specialty, Localised prostate cancer, Urology, medicine.medical_treatment, 030232 urology & nephrology, Context (language use), law.invention, External validity, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Randomized controlled trial, law, Internal medicine, Clinical practice guidelines and recommendations, Humans, Medicine, Radiology, Nuclear Medicine and imaging, External beam radiotherapy, Limitations of evidence base, Prospective cohort study, Prostatectomy, Clinical practice, Systematic review, Localised prostate cancer, business.industry, Prostate, Prostatic Neoplasms, Retrospective cohort study, Clinical trial, Treatment Outcome, Oncology, Evidence synthesis, 030220 oncology & carcinogenesis, Systematic review, Quality of Life, Oncological and functional outcomes, Surgery, business, Focal ablative therapy
Abstract: Context The clinical effectiveness of focal therapy (FT) for localised prostate cancer (PCa) remains controversial. Objective To analyse the evidence base for primary FT for localised PCa via a systematic review (SR) to formulate clinical practice recommendations. Evidence acquisition A protocol-driven, PRISMA-adhering SR comparing primary FT (sub-total, focal, hemi-gland, or partial ablation) versus standard options (active surveillance [AS], radical prostatectomy [RP], or external beam radiotherapy [EBRT]) was undertaken. Only comparative studies with ≥50 patients per arm were included. Primary outcomes included oncological, functional, and quality-of-life outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Eligible SRs were reviewed and appraised (AMSTAR) and ongoing prospective comparative studies were summarised. Evidence synthesis Out of 1119 articles identified, four primary studies (1 randomised controlled trial [RCT] and 3 retrospective studies) recruiting 3961 patients and ten eligible SRs were identified. Only qualitative synthesis was possible owing to clinical heterogeneity. Overall, RoB and confounding were moderate to high. An RCT comparing vascular-targeted focal photodynamic therapy (PDT) with AS found a significantly lower rate of treatment failure at 2 yr with PDT. There were no differences in functional outcomes, although PDT was associated with worse transient adverse events. However, the external validity of the study was contentious. A retrospective study comparing focal HIFU with robotic RP found no significant differences in treatment failure at 3 yr, with focal HIFU having better continence and erectile function recovery. Two retrospective cohort studies using Surveillance, Epidemiology and End Results data compared focal laser ablation (FLA) against RP and EBRT, reporting significantly worse oncological outcomes for FLA. The overall data quality and applicability of the primary studies were limited because of clinical heterogeneity, RoB and confounding, lack of long-term data, inappropriate outcome measures, and poor external validity. Virtually all the SRs identified concluded that there was insufficient high-certainty evidence to make definitive conclusions regarding the clinical effectiveness of FT, with the majority of SRs judged to have a low or critically low confidence rating. Eight ongoing prospective comparative studies were identified. Ways of improving the evidence base are discussed. Conclusions The certainty of the evidence regarding the comparative effectiveness of FT as a primary treatment for localised PCa was low, with significant uncertainties. Until higher-certainty evidence emerges from robust prospective comparative studies measuring clinically meaningful outcomes at long-term time points, FT should ideally be performed within clinical trials or well-designed prospective cohort studies. Patient summary We examined the literature to determine the effectiveness of prostate-targeted treatment compared with standard treatments for untreated localised prostate cancer. There was no strong evidence showing that focal treatment compares favourably with standard treatments; consequently, focal treatment is not recommended for routine standard practice.
Published: 2021

75. Evaluation of Oncological Outcomes and Data Quality in Studies Assessing Nerve-sparing Versus Non–Nerve-sparing Radical Prostatectomy in Nonmetastatic Prostate Cancer: A Systematic Review

Author: Michael Lardas, Maria De Santis, Erik Briers, Giorgio Gandaglia, Thomas B. Lam, Shane O'Hanlon, Silke Gillessen, Peter-Paul M. Willemse, Nicolas Mottet, Cathy Yuhong Yuan, Thomas Van den Broeck, Guillaume Ploussard, Roderick C.N. van den Bergh, Olivier Rouvière, Ivo G. Schoots, Thomas Wiegel, Antoni Vilaseca, Malcolm David Mason, Henk G. van der Poel, Ann Henry, Derya Tilki, N. Grivas, Daniela E. Oprea-Lager, Jeremy Grummet, Philip Cornford, Lisa Moris, Moris, L., Gandaglia, G., Vilaseca, A., Van den Broeck, T., Briers, E., De Santis, M., Gillessen, S., Grivas, N., O'Hanlon, S., Henry, A., Lam, T. B., Lardas, M., Mason, M., Oprea-Lager, D., Ploussard, G., Rouviere, O., Schoots, I. G., van der Poel, H., Wiegel, T., Willemse, P. -P., Yuan, C. Y., Grummet, J. P., Tilki, D., van den Bergh, R. C. N., Cornford, P., and Mottet, N.
Subjects: Biochemical recurrence, Oncology, Male, medicine.medical_specialty, Urology, medicine.medical_treatment, 030232 urology & nephrology, Subgroup analysis, Context (language use), 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Internal medicine, Medicine, Humans, Prospective Studies, Prostatectomy, Positive surgical margins, business.industry, Prostate, Cancer, Margins of Excision, Prostatic Neoplasms, medicine.disease, Neurovascular bundle, Data Accuracy, Nerve-sparing radical prostatectomy, Evidence synthesis, 030220 oncology & carcinogenesis, Systematic review, business, Cohort study, Oncological outcome
Abstract: Context Surgical techniques aimed at preserving the neurovascular bundles during radical prostatectomy (RP) have been proposed to improve functional outcomes. However, it remains unclear if nerve-sparing (NS) surgery adversely affects oncological metrics. Objective To explore the oncological safety of NS versus non-NS (NNS) surgery and to identify factors affecting the oncological outcomes of NS surgery. Evidence acquisition Relevant databases were searched for English language articles published between January 1, 1990 and May 8, 2020. Comparative studies for patients with nonmetastatic prostate cancer (PCa) treated with primary RP were included. NS and NNS techniques were compared. The main outcomes were side-specific positive surgical margins (ssPSM) and biochemical recurrence (BCR). Risk of bias (RoB) and confounding assessments were performed. Evidence synthesis Out of 1573 articles identified, 18 studies recruiting a total of 21 654 patients were included. The overall RoB and confounding were high across all domains. The most common selection criteria for NS RP identified were characteristic of low-risk disease, including low core-biopsy involvement. Seven studies evaluated the link with ssPSM and showed an increase in ssPSM after adjustment for side-specific confounders, with the relative risk for NS RP ranging from 1.50 to 1.53. Thirteen papers assessing BCR showed no difference in outcomes with at least 12 mo of follow-up. Lack of data prevented any subgroup analysis for potentially important variables. The definitions of NS were heterogeneous and poorly described in most studies. Conclusions Current data revealed an association between NS surgery and an increase in the risk of ssPSM. This did not translate into a negative impact on BCR, although follow-up was short and many men harbored low-risk PCa. There are significant knowledge gaps in terms of how various patient, disease, and surgical factors affect outcomes. Adequately powered and well-designed prospective trials and cohort studies accounting for these issues with long-term follow-up are recommended. Patient summary Neurovascular bundles (NVBs) are structures containing nerves and blood vessels. The NVBs close to the prostate are responsible for erections. We reviewed the literature to determine if a technique to preserve the NVBs during removal of the prostate causes worse cancer outcomes. We found that NVB preservation was poorly defined but, if applied, was associated with a higher risk of cancer at the margins of the tissue removed, even in patients with low-risk prostate cancer. The long-term importance of this finding for patients is unclear. More data are needed to provide recommendations.
Published: 2021

76. Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review

Author: Maria De Santis, Suneil Jain, Nicolas Mottet, Philip Cornford, Henk G. van der Poel, Peter Paul M. Willemse, Olivier Rouvière, Theodorus H. van der Kwast, Malcolm David Mason, Muhammad Imran Omar, Raj P. Pal, Silke Gillessen, Nicola Fossati, Brian D. Kelly, Marcus G. Cumberbatch, Derya Tilki, Tanya B. Dorff, Stefano Fanti, Thomas Van den Broeck, Erik Briers, Ivo G. Schoots, Michael Lardas, Lisa Moris, Thomas Wiegel, Matthew Liew, Roderick C.N. van den Bergh, Badrinath R. Konety, Thomas B. Lam, Ann Henry, Jeremy Grummet, Cathy Yuhong Yuan, Giorgio Gandaglia, Moris L, Cumberbatch MG, Van den Broeck T, Gandaglia G, Fossati N, Kelly B, Pal R, Briers E, Cornford P, De Santis M, Fanti S, Gillessen S, Grummet JP, Henry AM, Lam TBL, Lardas M, Liew M, Mason MD, Omar MI, Rouvière O, Schoots IG, Tilki D, van den Bergh RCN, van Der Kwast TH, van Der Poel HG, Willemse PM, Yuan CY, Konety B, Dorff T, Jain S, Mottet N, Wiegel T., Moris, L., Cumberbatch, M. G., Van den Broeck, T., Gandaglia, G., Fossati, N., Kelly, B., Pal, R., Briers, E., Cornford, P., De Santis, M., Fanti, S., Gillessen, S., Grummet, J. P., Henry, A. M., Lam, T. B. L., Lardas, M., Liew, M., Mason, M. D., Omar, M. I., Rouviere, O., Schoots, I. G., Tilki, D., van den Bergh, R. C. N., van Der Kwast, T. H., van Der Poel, H. G., Willemse, P. -P. M., Yuan, C. Y., Konety, B., Dorff, T., Jain, S., Mottet, N., Wiegel, T., Radiology & Nuclear Medicine, and Pathology
Subjects: Oncology, Male, medicine.medical_specialty, Internationality, medicine.medical_treatment, Urology, Brachytherapy, 030232 urology & nephrology, Locally advanced, External beam radiotherapy, Systemic treatment, Review, Modality treatment, Risk Assessment, Primary therapy, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Multidisciplinary approach, Internal medicine, medicine, Journal Article, Humans, Neoplasm Metastasis, Intensive care medicine, Neoplasm Staging, business.industry, Prostatic Neoplasms, Androgen Antagonists, Localized, medicine.disease, Radical prostatectomy, 030220 oncology & carcinogenesis, Systematic review, business
Abstract: Context: The optimal treatment for men with high-risk localized or locally advanced prostate cancer (PCa) remains unknown. Objective: To perform a systematic review of the existing literature on the effectiveness of the different primary treatment modalities for high-risk localized and locally advanced PCa. The primary oncological outcome is the development of distant metastases at ≥5 yr of follow-up. Secondary oncological outcomes are PCa-specific mortality, overall mortality, biochemical recurrence, and need for salvage treatment with ≥5 yr of follow-up. Nononcological outcomes are quality of life (QoL), functional outcomes, and treatment-related side effects reported. Evidence acquisition: Medline, Medline In-Process, Embase, and the Cochrane Central Register of Randomized Controlled Trials were searched. All comparative (randomized and nonrandomized) studies published between January 2000 and May 2019 with at least 50 participants in each arm were included. Studies reporting on high-risk localized PCa (International Society of Urologic Pathologists [ISUP] grade 4-5 [Gleason score {GS} 8-10] or prostate-specific antigen [PSA] >20 ng/ml or ≥ cT2c) and/or locally advanced PCa (any PSA, cT3-4 or cN+, any ISUP grade/GS) or where subanalyses were performed on either group were included. The following primary local treatments were mandated: radical prostatectomy (RP), external beam radiotherapy (EBRT) (≥64 Gy), brachytherapy (BT), or multimodality treatment combining any of the local treatments above (±any systemic treatment). Risk of bias (RoB) and confounding factors were assessed for each study. A narrative synthesis was performed. Evidence synthesis: Overall, 90 studies met the inclusion criteria. RoB and confounding factors revealed high RoB for selection, performance, and detection bias, and low RoB for correction of initial PSA and biopsy GS. When comparing RP with EBRT, retrospective series suggested an advantage for RP, although with a low level of evidence. Both RT and RP should be seen as part of a multimodal treatment plan with possible addition of (postoperative) RT and/or androgen deprivation therapy (ADT), respectively. High levels of evidence exist for EBRT treatment, with several randomized clinical trials showing superior outcome for adding long-term ADT or BT to EBRT. No clear cutoff can be proposed for RT dose, but higher RT doses by means of dose escalation schemes result in an improved biochemical control. Twenty studies reported data on QoL, with RP resulting mainly in genitourinary toxicity and sexual dysfunction, and EBRT in bowel problems. Conclusions: Based on the results of this systematic review, both RP as part of multimodal treatment and EBRT + long-term ADT can be recommended as primary treatment in high-risk and locally advanced PCa. For high-risk PCa, EBRT + BT can also be offered despite more grade 3 toxicity. Interestingly, for selected patients, for example, those with higher comorbidity, a shorter duration of ADT might be an option. For locally advanced PCa, EBRT + BT shows promising result but still needs further validation. In this setting, it is important that patients are aware that the offered therapy will most likely be in the context a multimodality treatment plan. In particular, if radiation is used, the combination of local with systemic treatment provides the best outcome, provided the patient is fit enough to receive both. Until the results of the SPCG15 trial are known, the optimal local treatment remains a matter of debate. Patients should at all times be fully informed about all available options, and the likelihood of a multimodal approach including the potential side effects of both local and systemic treatment. Patient summary: We reviewed the literature to see whether the evidence from clinical studies would tell us the best way of curing men with aggressive prostate cancer that had not spread to other parts of the body such as lymph glands or bones. Based on the results of this systematic review, there is good evidence that both surgery and radiation therapy are good treatment options, in terms of prolonging life and preserving quality of life, provided they are combined with other treatments. In the case of surgery this means including radiotherapy (RT), and in the case of RT this means either hormonal therapy or combined RT and brachytherapy.
Published: 2020

77. EAU-EANM-ESTRO-ESUR-SIOG Prostate Cancer Guideline Panel Consensus Statements for Deferred Treatment with Curative Intent for Localised Prostate Cancer from an International Collaborative Study (DETECTIVE Study)

Author: Niall F. Davis, Muhammad Imran Omar, Alberto Briganti, Olivier Rouvière, James N'Dow, Ann Henry, Brett Cox, James W.F. Catto, Derya Tilki, Christopher J.D. Wallis, Maurizio Colecchia, Silke Gillessen, Steven MacLennan, Murali Varma, Thomas Van den Broeck, Philip Cornford, Susanne Vahr Lauridsen, J.P. Michiel Sedelaar, Nicola Fossati, Michael Lardas, Gemma Sancho Pardo, Paolo Dell'Oglio, André Deschamps, Nicolas Mottet, Lisa Moris, Marcus G. Cumberbatch, Thomas Wiegel, Raphaële Renard-Penna, Fabio Zattoni, James Donaldson, Phillip D. Stricker, Matthew Liew, Ivo G. Schoots, Stefano Fanti, Theodorus H. van der Kwast, Geert J.L.H. van Leenders, Nikolaos Grivas, Monique J. Roobol, Erik Briers, Hendrik Van Poppel, Karin Plass, Jeff Davies, Jonathan Richenberg, Maria De Santis, Jacques Irani, Daniel W. Lin, Shin Egawa, Tobias Gross, Peter Paul M. Willemse, Roderick C.N. van den Bergh, Alberto Bossi, Henk G. van der Poel, Chris H. Bangma, Maria J. Ribal, Giorgio Gandaglia, Alexandre Ingels, Karl H. Pang, Morgan Rouprêt, Robert Shepherd, Jeremy Grummet, Thomas B. Lam, Malcolm David Mason, Catherine Paterson, Karel Tim Buddingh, Christian D. Fankhauser, Ruud Baanders, Anders Bjartell, Philippe D. Violette, Karen Wilkinson, Lam, T. B. L., Maclennan, S., Willemse, P. -P. M., Mason, M. D., Plass, K., Shepherd, R., Baanders, R., Bangma, C. H., Bjartell, A., Bossi, A., Briers, E., Briganti, A., Buddingh, K. T., Catto, J. W. F., Colecchia, M., Cox, B. W., Cumberbatch, M. G., Davies, J., Davis, N. F., De Santis, M., Dell'Oglio, P., Deschamps, A., Donaldson, J. F., Egawa, S., Fankhauser, C. D., Fanti, S., Fossati, N., Gandaglia, G., Gillessen, S., Grivas, N., Gross, T., Grummet, J. P., Henry, A. M., Ingels, A., Irani, J., Lardas, M., Liew, M., Lin, D. W., Moris, L., Omar, M. I., Pang, K. H., Paterson, C. C., Renard-Penna, R., Ribal, M. J., Roobol, M. J., Roupret, M., Rouviere, O., Sancho Pardo, G., Richenberg, J., Schoots, I. G., Sedelaar, J. P. M., Stricker, P., Tilki, D., Vahr Lauridsen, S., van den Bergh, R. C. N., Van den Broeck, T., van der Kwast, T. H., van der Poel, H. G., van Leenders, G. J. L. H., Varma, M., Violette, P. D., Wallis, C. J. D., Wiegel, T., Wilkinson, K., Zattoni, F., N'Dow, J. M. O., Van Poppel, H., Cornford, P., Mottet, N., Urology, Radiology & Nuclear Medicine, Pathology, and Lam TBL, MacLennan S, Willemse PM, Mason MD, Plass K, Shepherd R, Baanders R, Bangma CH, Bjartell A, Bossi A, Briers E, Briganti A, Buddingh KT, Catto JWF, Colecchia M, Cox BW, Cumberbatch MG, Davies J, Davis NF, De Santis M, Dell'Oglio P, Deschamps A, Donaldson JF, Egawa S, Fankhauser CD, Fanti S, Fossati N, Gandaglia G, Gillessen S, Grivas N, Gross T, Grummet JP, Henry AM, Ingels A, Irani J, Lardas M, Liew M, Lin DW, Moris L, Omar MI, Pang KH, Paterson CC, Renard-Penna R, Ribal MJ, Roobol MJ, Rouprêt M, Rouvière O, Sancho Pardo G, Richenberg J, Schoots IG, Sedelaar JPM, Stricker P, Tilki D, Vahr Lauridsen S, van den Bergh RCN, Van den Broeck T, van der Kwast TH, van der Poel HG, van Leenders GJLH, Varma M, Violette PD, Wallis CJD, Wiegel T, Wilkinson K, Zattoni F, N'Dow JMO, Van Poppel H, Cornford P, Mottet N.
Subjects: Male, medicine.medical_specialty, Localised prostate cancer, Urology, education, 030232 urology & nephrology, Delphi method, Reclassification, Outcome measures, Time-to-Treatment, Outcome measure, 03 medical and health sciences, Prostate cancer, Active surveillance and monitoring, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Consensus group meeting, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], medicine, Humans, 610 Medicine & health, Clinical practice guideline, Curative intent, Clinical Oncology, Eligibility, business.industry, Follow-up, Prostatic Neoplasms, Consensus statements, Guideline, Deferred treatment with curative intent, medicine.disease, Clinical practice guidelines, Delphi survey, Deferred treatment, Consensus statement, 030220 oncology & carcinogenesis, Family medicine, business
Abstract: Background: There is uncertainty in deferred active treatment (DAT) programmes, regarding patient selection, follow-up and monitoring, reclassification, and which outcome measures should be prioritised. Objective: To develop consensus statements for all domains of DAT. Design, setting, and participants: A protocol-driven, three phase study was undertaken by the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Association of Urology Section of Urological Research (ESUR)-International Society of Geriatric Oncology (SIOG) Prostate Cancer Guideline Panel in conjunction with partner organisations, including the following: (1) a systematic review to describe heterogeneity across all domains; (2) a two-round Delphi survey involving a large, international panel of stakeholders, including healthcare practitioners (HCPs) and patients; and (3) a consensus group meeting attended by stakeholder group representatives. Robust methods regarding what constituted the consensus were strictly followed. Results and limitations: A total of 109 HCPs and 16 patients completed both survey rounds. Of 129 statements in the survey, consensus was achieved in 66 (51%); the rest of the statements were discussed and voted on in the consensus meeting by 32 HCPs and three patients, where consensus was achieved in additional 27 statements (43%). Overall, 93 statements (72%) achieved consensus in the project. Some uncertainties remained regarding clinically important thresholds for disease extent on biopsy in low-risk disease, and the role of multiparametric magnetic resonance imaging in determining disease stage and aggressiveness as a criterion for inclusion and exclusion. Conclusions: Consensus statements and the findings are expected to guide and inform routine clinical practice and research, until higher levels of evidence emerge through prospective comparative studies and clinical trials. Patient summary: We undertook a project aimed at standardising the elements of practice in active surveillance programmes for early localised prostate cancer because currently there is great variation and uncertainty regarding how best to conduct them. The project involved large numbers of healthcare practitioners and patients using a survey and face-to-face meeting, in order to achieve agreement (ie, consensus) regarding best practice, which will provide guidance to clinicians and researchers. (C) 2019 Published by Elsevier B.V. on behalf of European Association of Urology.
Published: 2019

78. Five-year outcomes of fractionated stereotactic body radiotherapy for oligometastatic prostate cancer from the TRANSFORM phase II trial.

Author: See AW, Conway P, Frydenberg M, Haxhimolla H, Costello AJ, Moon D, Ruljancich P, Grummet J, Pranavan G, Peters J, Smyth LML, Gwini SM, McKenzie DP, and Bowden P
Subjects: Humans, Male, Aged, Middle Aged, Prospective Studies, Neoplasm Metastasis, Aged, 80 and over, Treatment Outcome, Prostate-Specific Antigen blood, Dose Fractionation, Radiation, Prostatic Neoplasms pathology, Prostatic Neoplasms radiotherapy, Radiosurgery methods
Abstract: Metastasis-directed therapy (MDT) for oligometastatic prostate cancer (PCa), including stereotactic body radiotherapy (SBRT), has shown promise but is still considered investigational. This is the 5-year analysis of the TRANSFORM trial, the largest prospective cohort of men with oligometastatic PCa treated with SBRT-based MDT. The primary endpoint was 5-year treatment escalation-free survival (TE-FS), defined as freedom from any new cancer therapy other than further SBRT. In total, 199 men received SBRT; 76.4% were hormone-naïve at baseline. The rate of 5-year TE-FS was 21.7% (95% confidence interval [CI]: 15.7%-28.7%) overall and 25.4% (95% CI: 18.1%-33.9%) in the hormone-naïve subgroup. The subgroups with International Society of Urological Pathology Grade Groups 4-5 disease (hazard ratio [HR] = 1.48, 95% CI: 1.05-2.01, p = .026), a higher baseline prostate-specific antigen (PSA) (HR = 1.06, 95% CI: 1.03-1.09, p < .001) and those who received prior androgen deprivation therapy (ADT) (HR = 2.13, 95% CI: 1.40-3.26, p < .001), were at greater risk of treatment escalation. Outcomes for participants with four or five initial lesions were comparable to those with one to three lesions. At last follow-up, 18.9% (95% CI: 13.2%-25.7%) of participants were free from treatment escalation (median follow-up of 67.9 months) and two participants had an undetectable PSA level. No treatment-related grade three or higher adverse events were reported. The findings of this study demonstrate that SBRT-based MDT is an effective option for delaying systemic treatment escalation in the context of oligometastatic PCa. Future randomised trials comparing SBRT-based MDT to standard-of-care ADT-based approaches are required to evaluate the impact of delaying ADT on survival., (© 2024 UICC.)
Published: 2024
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79. Re: Biomarker vs MRI-Enhanced Strategies for Prostate Cancer Screening. The STHLM3-MRI Randomized Clinical Trial.

Author: Park H, Chen DC, Mazzone E, Grummet J, Perera ML, and Murphy DG
Published: 2024
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80. Primary Whole-gland Ablation for the Treatment of Clinically Localized Prostate Cancer: A Focal Therapy Society Best Practice Statement.

Author: Deivasigamani S, Kotamarti S, Rastinehad AR, Salas RS, de la Rosette JJMCH, Lepor H, Pinto P, Ahmed HU, Gill I, Klotz L, Taneja SS, Emberton M, Lawrentschuk N, Wysock J, Feller JF, Crouzet S, Kumar M P, Seguier D, Adams ES, Michael Z, Abreu A, Jack Tay K, Ward JF, Shinohara K, Katz AE, Villers A, Chin JL, Stricker PD, Baco E, Macek P, Ahmad AE, Chiu PKF, Crawford ED, Rogers CG, Futterer JJ, Rais-Bahrami S, Robertson CN, Hadaschik B, Marra G, Valerio M, Chong KT, Kasivisvanathan V, Tan WP, Lomas D, Walz J, Guimaraes GC, Mertziotis NI, Becher E, Finelli A, Kasraeian A, Lebastchi AH, Vora A, Rosen MA, Bakir B, Arcot R, Yee S, Netsch C, Meng X, de Reijke TM, Tan YG, Regusci S, Benjamin TGR, Olivares R, Noureldin M, Bianco FJ, Sivaraman A, Kim FJ, Given RW, Dason S, Sheetz TJ, Shoji S, Schulman A, Royce P, Shah TT, Scionti S, Salomon G, Laguna P, Tourinho-Barbosa R, Aminsharifi A, Cathelineau X, Gontero P, Stabile A, Grummet J, Ledbetter L, Graton M, Stephen Jones J, and Polascik TJ
Subjects: Male, Humans, Prostate-Specific Antigen, Retrospective Studies, Treatment Outcome, Prostatic Neoplasms surgery, Cryosurgery adverse effects
Abstract: Context: Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up., Objective: To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings., Evidence Acquisition: We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed., Evidence Synthesis: Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively., Conclusions: The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values., Patient Summary: Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences., (Published by Elsevier B.V.)
Published: 2023
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81. Trends and variation in prostate cancer diagnosis via transperineal biopsy in Australia and New Zealand.

Author: O' Callaghan ME, Roberts M, Grummet J, Mark S, Gilbourd D, Frydenberg M, Millar J, and Papa N
Subjects: Male, Humans, Rectum pathology, New Zealand epidemiology, Biopsy methods, Image-Guided Biopsy methods, Perineum, Prostate pathology, Prostatic Neoplasms diagnosis, Prostatic Neoplasms pathology
Abstract: Background: To describe changes in the use of prostate biopsy techniques among men diagnosed with prostate cancer in Australia and New Zealand and examine factors associated with these changes., Methods: We extracted data between 2015 and 2019 from 7 jurisdictions of the Australia and New Zealand Prostate Cancer Outcomes Registry (PCOR-ANZ). Distribution and time trend of transrectal (TR) vs. transperineal (TP) biopsy type, differences in the proportion of biopsy type by geographic jurisdiction, diagnosing institute characteristics (public vs. private, metropolitan vs. regional, case volume) and patient characteristics such as socio-economic status (SES), and location of residence were analyzed., Results: We analyzed data from 37,638 patients. The overall proportion of prostate cancer diagnosed by TP increased from 26% to 57% between 2015 and 2019. Patients living in a major city, a more socioeconomically advantaged area or who were diagnosed in a metropolitan or private hospital were more likely to have TP than TR. While all subgroups were observed to increase their use of TP over the study period, uptake grew faster for men from low SES areas and those diagnosed at a regional or low-volume hospital but slower for men living in outer regional/remote areas or treated at a public hospital., Conclusions: In this binational registry, prostate cancer is now more commonly diagnosed by TP than the TR approach. While the gap between uptakes of TP has diminished for patients with low vs. high SES, disparity has widened for patients from outer regional areas vs major cities and public vs. private hospitals., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)
Published: 2023
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82. Is There an Impact of Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted Biopsy on the Risk of Upgrading in Final Pathology in Prostate Cancer Patients Undergoing Radical Prostatectomy? An European Association of Urology-Young Academic Urologists Prostate Cancer Working Group Multi-institutional Study.

Author: Zattoni F, Marra G, Martini A, Kasivisvanathan V, Grummet J, Harkin T, Ploussard G, Olivier J, Chiu PK, Valerio M, Marquis A, Gontero P, Guo H, Zhuang J, Frydenberg M, Moon D, Morlacco A, Kretschmer A, Barletta F, Heidegger I, Tilki D, van den Bergh R, Dal Moro F, Briganti A, Montorsi F, Novara G, and Gandaglia G
Subjects: Male, Humans, Prostate diagnostic imaging, Prostate surgery, Prostate pathology, Urologists, Biopsy methods, Prostatectomy methods, Magnetic Resonance Imaging methods, Urology, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms surgery
Abstract: Background: The concordance rates of transperineal (TP) versus transrectal (TR) prostate biopsies with radical prostatectomy (RP) specimen have been assessed poorly in men diagnosed with magnetic resonance imaging (MRI)-targeted biopsy (TBx)., Objective: To evaluate International Society of Urological Pathology (ISUP) concordance rates between the final pathology at RP and MRI-TBx or MRI-TBx + random biopsy (RB) according to the biopsy approach., Design, Setting, and Participants: A multi-institutional database included patients diagnosed with TP or TR treated with RP., Intervention: TP-TBx or TR-TBx of the prostate., Outcome Measurements and Statistical Analysis: The ISUP grade at biopsy was compared with the final pathology. A multivariable logistic regression analysis (MVA) was performed to assess the association between the biopsy approach (TP-TBx vs TR-TBx) and ISUP upgrading, downgrading, concordance, and clinically relevant increase (CRI)., Results and Limitations: Overall, 752 (59%) versus 530 (41%) patients underwent TR versus TP. At the MVA, TP-TBx was an independent predictor of upgrading (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.4-0.9, p < 0.01) and improved concordance relative to the final pathology (OR 1.7, 95% CI 1.2-2.5, p < 0.01) after adjusting for age, cT stage, Prostate Imaging Reporting and Data System, number of targeted cores, prostate-specific antigen, and prostate volume. Moreover, TP-TBx was associated with a lower risk of CRI than TR-TBx (OR 0.7, p < 0.01). This held true when considering patients who underwent MRI-TBx + RB (OR 0.6, p < 0.01). The inclusion of men who had RP represents a potential selection bias., Conclusions: The adoption of TP-TBx compared with TR-TBx may reduce the risk of upgrading and improve the concordance of biopsy grade with the final pathology. The TP approach decreases the odds of CRI with improved patient selection for the correct active treatment., Patient Summary: In this report, we evaluated whether transperineal (TP) targeted biopsy (TBx) may improve the concordance of clinically significant prostate cancer with the final pathology in comparison with transrectal (TR) TBx in a large worldwide population. We found that TP-TBx might increase concordance compared with TR-TBx. Adding random biopsies to target one increases accuracy; however, concordance with the final pathology is overall suboptimal even with the TP approach., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
Published: 2023
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83. Guidelines of guidelines: focal therapy for prostate cancer, is it time for consensus?

Author: Ong S, Chen K, Grummet J, Yaxley J, Scheltema MJ, Stricker P, Tay KJ, and Lawrentschuk N
Subjects: Male, Humans, United States, Aged, Prostatic Neoplasms therapy, Urology
Abstract: Objective: To provide a summary and discussion of international guidelines, position statements and consensus statements in relation to focal therapy (FT) for prostate cancer (PCa)., Methods: The European Association of Urology-European Association of Nuclear Medicine-European Society for Radiotherapy and Oncology-European Society of Urogential Radiology-International Society of Urological Pathology-International Society of Geriatric Oncology and American Urological Association-American Society for Radiation Oncology-Society of Urologic Oncology guidelines were interrogated for recommendations for FT. PubMed and Ovid Medline were searched for consensus statements. Only studies in English since 2015 were included. Reference lists of the included articles were also interrogated and a manual search for studies was also performed., Results: Our results showed a lack of long-term randomised data for FT. International Urological guidelines emphasised the need for more high-quality clinical trials with robust oncological and toxicity outcomes. Consensus and positions statements were heterogenous., Conclusion: A globally accepted guideline for FT planning, technique and follow-up are still yet to be determined. Well-designed studies with long-term follow-up and robust clinical and toxicity endpoints are needed to improve our understanding of FT and create uniform guidelines to streamline management and follow-up., (© 2022 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)
Published: 2023
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84. The Detection of Prostate Cancer with Magnetic Resonance Imaging-Targeted Prostate Biopsies is Superior with the Transperineal vs the Transrectal Approach. A European Association of Urology-Young Academic Urologists Prostate Cancer Working Group Multi-Institutional Study.

Author: Zattoni F, Marra G, Kasivisvanathan V, Grummet J, Nandurkar R, Ploussard G, Olivier J, Chiu PK, Valerio M, Gontero P, Guo H, Zhuang J, Barletta F, Leni R, Frydenberg M, Moon D, Hanegbi U, Landaumailto A, Snow R, Apfelbeck M, Kretschmer A, van den Bergh R, Novara G, Briganti A, Dal Moro F, and Gandaglia G
Subjects: Humans, Image-Guided Biopsy, Magnetic Resonance Imaging, Male, Prostate diagnostic imaging, Prostate pathology, Retrospective Studies, Urologists, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms pathology, Urology
Abstract: Purpose: Our aim was to evaluate whether transperineal (TP) MRI-targeted prostate biopsy (TBx) may improve the detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology ≥2, in comparison to transrectal (TR) TBx., Materials and Methods: A multicenter retrospective cohort study comprising patients who underwent MRI-guided prostate biopsy was conducted. To address possible benefits of TP-TBx in the detection of prostate cancer (PCa) and csPCa, a cohort of patients undergoing TP-TBx were compared to patients undergoing TR-TBx. Multivariable logistic regression analyses were performed to assess predictors of PCa and csPCa detection., Results: Overall, 1,936 and 3,305 patients who underwent TR-TBx vs TP-TBx at 10 referral centers were enrolled. The rate of PCa and csPCa diagnosed was higher for TP-TBx vs TR-TBx (64.0% vs 50%, p <0.01 and 49% vs 35%, p <0.01). At multivariable analysis adjusted for age, biopsy naïve/repeated biopsy, cT stage, Prostate Imaging-Reporting and Data System®, prostate volume, PSA, and number of biopsy cores targeted, TP-TBx was an independent predictor of PCa (odds ratio [OR] 1.37, 95% CI 1.08-1.72) and csPCa (1.19, 95% CI 1.12-1.50). When considering the approach according to the site of the index lesion, TP-TBx had a significantly higher likelihood than TR-TBx to detect csPCa in the apex (OR 4.81, 95% CI 1.03-6.27), transition/central zone (OR 2.67, 95% CI 1.42-5.00), and anterior zone (OR 5.62, 95% CI 1.74-8.13)., Conclusions: The use of TP-TBx allows a better cancer grade definition and PCa risk assessment. This has important implication in the decision-making process and in patient counseling for further therapies.
Published: 2022
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85. Left testicular venous infarction secondary to large spontaneous retroperitoneal haematoma compressing left testicular vein: a case report.

Author: Vu T, Lechmiannandan S, Birks S, and Grummet J
Subjects: Anticoagulants therapeutic use, Hematoma complications, Hematoma diagnostic imaging, Hematoma surgery, Humans, Infarction diagnostic imaging, Infarction drug therapy, Infarction etiology, Male, Scrotum, Spermatic Cord, Thrombosis complications
Abstract: A man in his early 50s presented with a spontaneous large left-sided retroperitoneal haematoma (RPH), on a background of therapeutic anticoagulation with warfarin for homozygous factor V Leiden. His international normalised ratio was found to be supra-therapeutic at 9.0 on presentation. He was treated non-operatively with prompt reversal of the coagulopathy and close monitoring. On day 4 of the admission, the patient reported scrotal pain and swelling. An urgent scrotal ultrasound revealed infarction of the left testis and the patient was taken to an emergency scrotal exploration. Intraoperatively, the left testis was found to be no longer viable with the left spermatic vein and venules completely thrombosed with extensive clots, while the left testicular artery remained intact. Consequently, a left orchidectomy was performed. Therapeutic anticoagulation was recommenced on day 3 postoperatively. It is thought that the large RPH caused extrinsic compression of the left testicular vein, in addition to the patient's pre-existing factor V Leiden, which resulted in thrombosis of the blood vessel., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2022
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86. 'Pain-free TRUS B': a phase 3 double-blind placebo-controlled randomized trial of methoxyflurane with periprostatic local anaesthesia to reduce the discomfort of transrectal ultrasonography-guided prostate biopsy (ANZUP 1501).

Author: Hayne D, Grummet J, Espinoza D, McCombie SP, Chalasani V, Ford KS, Frydenberg M, Gilling P, Gordon B, Hawks C, Konstantatos A, Martin AJ, Nixon A, O'Brien C, Patel MI, Sengupta S, Shahbaz S, Subramaniam S, Williams S, Woo HH, Stockler MR, Davis ID, and Buchan N
Subjects: Anesthesia, Local, Anesthetics, Local therapeutic use, Biopsy adverse effects, Biopsy methods, Humans, Lidocaine therapeutic use, Male, Methoxyflurane, Pain drug therapy, Pain etiology, Pain prevention & control, Pain Measurement, Ultrasonography, Prostate diagnostic imaging, Prostate pathology, Prostatic Neoplasms pathology
Abstract: Objective: To determine whether the addition of inhaled methoxyflurane to periprostatic infiltration of local anaesthetic (PILA) during transrectal ultrasonography-guided prostate biopsies (TRUSBs) improved pain and other aspects of the experience., Patients and Methods: We conducted a multicentre, placebo-controlled, double-blind, randomized phase 3 trial, involving 420 men undergoing their first TRUSB. The intervention was PILA plus a patient-controlled device containing either 3 mL methoxyflurane, or 3 mL 0.9% saline plus one drop of methoxyflurane to preserve blinding. The primary outcome was the pain score (0-10) reported by the participant after 15 min. Secondary outcomes included ratings of other aspects of the biopsy experience, willingness to undergo future biopsies, urologists' ratings, biopsy completion, and adverse events., Results: The mean (SE) pain scores 15 min after TRUSB were 2.51 (0.22) in those assigned methoxyflurane vs 2.82 (0.22) for placebo (difference 0.31, 95% confidence interval [CI] -0.75 to 0.14; P = 0.18). Methoxyflurane was associated with better scores for discomfort (difference -0.48, 95% CI -0.92 to -0.03; P = 0.035, adjusted [adj.] P = 0.076), whole experience (difference -0.50, 95% CI -0.92 to -0.08; P = 0.021, adj. P = 0.053), and willingness to undergo repeat biopsies (odds ratio 1.67, 95% CI 1.12-2.49; P = 0.01) than placebo. Methoxyflurane resulted in higher scores for drowsiness (difference +1.64, 95% CI 1.21-2.07; P < 0.001, adj. P < 0.001) and dizziness (difference +1.78, 95% CI 1.31-2.24; P < 0.001, adj. P < 0.001) than placebo. There was no significant difference in the number of ≥ grade 3 adverse events., Conclusions: We found no evidence that methoxyflurane improved pain scores at 15 min, however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies., (© 2021 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)
Published: 2022
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87. Re: NCCN Prostate Cancer Guidelines Version 1.2022 - September 10, 2021.

Author: Grummet J and Eggener S
Subjects: Humans, Male, Prostatic Neoplasms diagnosis, Prostatic Neoplasms therapy
Published: 2022
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88. 68 Ga-PSMA-PET screening and transponder-guided salvage radiotherapy to the prostate bed alone for biochemical recurrence following prostatectomy: interim outcomes of a phase II trial.

Author: Bowden P, See AW, So K, Lawrentschuk N, Moon D, Murphy DG, Rao R, Crosthwaite A, King D, Haxhimolla H, Grummet J, Ruljancich P, Gyomber D, Landau A, Campbell N, Frydenberg M, Smyth LML, Nolan S, Gwini SM, and McKenzie DP
Subjects: Aged, Humans, Male, Middle Aged, Neoplasm Recurrence, Local blood, Prospective Studies, Prostate-Specific Antigen blood, Prostatectomy, Prostatic Neoplasms surgery, Treatment Outcome, Gallium Isotopes, Gallium Radioisotopes, Neoplasm Recurrence, Local radiotherapy, Positron-Emission Tomography methods, Prostatic Neoplasms radiotherapy, Radiopharmaceuticals, Salvage Therapy methods
Abstract: Purpose: To evaluate outcomes for men with biochemically recurrent prostate cancer who were selected for transponder-guided salvage radiotherapy (SRT) to the prostate bed alone by 68 Ga-labelled prostate-specific membrane antigen positron emission tomography ( 68 Ga-PSMA-PET)., Methods: This is a single-arm, prospective study of men with a prostate-specific antigen (PSA) level rising to 0.1-2.5 ng/mL following radical prostatectomy. Patients were staged with 68 Ga-PSMA-PET and those with a negative finding, or a positive finding localised to the prostate bed, continued to SRT only to the prostate bed alone with real-time target-tracking using electromagnetic transponders. The primary endpoint was freedom from biochemical relapse (FFBR, PSA > 0.2 ng/mL from the post-radiotherapy nadir). Secondary endpoints were time to biochemical relapse, toxicity and patient-reported quality of life (QoL)., Results: Ninety-two patients (median PSA of 0.18 ng/ml, IQR 0.12-0.36), were screened with 68 Ga-PSMA-PET and metastatic disease was found in 20 (21.7%) patients. Sixty-nine of 72 non-metastatic patients elected to proceed with SRT. At the interim (3-year) analysis, 32 (46.4%) patients (95% CI 34.3-58.8%) were FFBR. The median time to biochemical relapse was 16.1 months. The rate of FFBR was 82.4% for ISUP grade-group 2 patients. Rates of grade 2 or higher gastrointestinal and genitourinary toxicity were 0% and 15.2%, respectively. General health and disease-specific QoL remained stable., Conclusion: Pre-SRT 68 Ga-PSMA-PET scans detect metastatic disease in a proportion of patients at low PSA levels but fail to improve FFBR. Transponder-guided SRT to the prostate bed alone is associated with a favourable toxicity profile and preserved QoL., Trial Registration Number: ACTRN12615001183572, 03/11/2015, retrospectively registered., (© 2021. The Author(s).)
Published: 2021
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89. High-Throughput Imaging Assay for Drug Screening of 3D Prostate Cancer Organoids.

Author: Choo N, Ramm S, Luu J, Winter JM, Selth LA, Dwyer AR, Frydenberg M, Grummet J, Sandhu S, Hickey TE, Tilley WD, Taylor RA, Risbridger GP, Lawrence MG, and Simpson KJ
Subjects: Algorithms, Animals, Automation, Laboratory, Data Analysis, Disease Models, Animal, Drug Compounding, Heterografts, Humans, Male, Mice, Prostatic Neoplasms, Drug Discovery methods, Drug Screening Assays, Antitumor methods, High-Throughput Screening Assays, Molecular Imaging methods, Organoids, Tissue Culture Techniques
Abstract: New treatments are required for advanced prostate cancer; however, there are fewer preclinical models of prostate cancer than other common tumor types to test candidate therapeutics. One opportunity to increase the scope of preclinical studies is to grow tissue from patient-derived xenografts (PDXs) as organoid cultures. Here we report a scalable pipeline for automated seeding, treatment and an analysis of the drug responses of prostate cancer organoids. We established organoid cultures from 5 PDXs with diverse phenotypes of prostate cancer, including castrate-sensitive and castrate-resistant disease, as well as adenocarcinoma and neuroendocrine pathology. We robotically embedded organoids in Matrigel in 384-well plates and monitored growth via brightfield microscopy before treatment with poly ADP-ribose polymerase inhibitors or a compound library. Independent readouts including metabolic activity and live-cell imaging-based features provided robust measures of organoid growth and complementary ways of assessing drug efficacy. Single organoid analyses enabled in-depth assessment of morphological differences between patients and within organoid populations and revealed that larger organoids had more striking changes in morphology and composition after drug treatment. By increasing the scale and scope of organoid experiments, this automated assay complements other patient-derived models and will expedite preclinical testing of new treatments for prostate cancer.
Published: 2021
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90. Focal low dose-rate brachytherapy for low to intermediate risk prostate cancer: preliminary experience at an Australian institution.

Author: Anderson E, Smyth LML, O'Sullivan R, Ryan A, Lawrentschuk N, Grummet J, and See AW
Abstract: Background: Focal treatment for prostate cancer (PCa) is a hybrid approach combining ablative treatment of the involved prostate gland and continued active surveillance (AS) of the unaffected gland. Low dose-rate (LDR) brachytherapy can be used as a lesion-targeted focal therapy, however, further studies are required to support its use. The aim of this study is to evaluate the dosimetry, toxicity and oncological outcomes of men receiving lesion-targeted focal LDR brachytherapy for low to intermediate risk PCa., Methods: This is a retrospective cohort study of 26 men with unifocal, low to intermediate grade PCa diagnosed on a combination of multiparametric-magnetic resonance imaging (mp-MRI) and targeted plus template transperineal (TP) biopsy, who received focal LDR brachytherapy at a single institution. Brachytherapy involved a single monotherapy implant using iodine-125 seeds to deliver a prescribed dose of 145 Gy to the index lesion., Results: The mean focal planning target volume (F-PTV) as a percentage of the prostate volume was 24.5%. The percentage of the focal gross tumour volume (F-GTV) receiving 100% of the prescription dose was 100% for 12 patients and ≥98% for 18 patients. The median follow-up for toxicity and biochemical control outcomes was 23.1 [interquartile range (IQR) 19.1-31.3] and 24.2 (IQR 17.9-30.0) months, respectively. Grade 2 urinary and erectile toxicities were reported by 29.2% and 45.8% of patients, respectively, with resolution of urinary symptoms to baseline by last follow-up. There were no grade ≥3 urinary or erectile toxicities or grade ≥2 rectal toxicity. All 21 patients who underwent a repeat mp-MRI and TP biopsy at 12-24 months post-treatment were negative for clinically significant disease and 25 (96.2%) patients were free from biochemical failure (FFBF)., Conclusions: Focal LDR brachytherapy is associated with a favourable toxicity profile and a high rate of control of significant PCa at 12-18 months post-treatment. We have commenced the LIBERATE prospective registry in focal LDR brachytherapy based on the highly encouraging outcomes of this initial experience., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tau-21-508). The authors have no conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)
Published: 2021
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91. The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology.

Author: Risbridger GP, Clark AK, Porter LH, Toivanen R, Bakshi A, Lister NL, Pook D, Pezaro CJ, Sandhu S, Keerthikumar S, Quezada Urban R, Papargiris M, Kraska J, Madsen HB, Wang H, Richards MG, Niranjan B, O'Dea S, Teng L, Wheelahan W, Li Z, Choo N, Ouyang JF, Thorne H, Devereux L, Hicks RJ, Sengupta S, Harewood L, Iddawala M, Azad AA, Goad J, Grummet J, Kourambas J, Kwan EM, Moon D, Murphy DG, Pedersen J, Clouston D, Norden S, Ryan A, Furic L, Goode DL, Frydenberg M, Lawrence MG, and Taylor RA
Subjects: Animals, Disease Models, Animal, Genome, Humans, Male, Mice, Mice, Inbred NOD, Mice, SCID, Mutation, Neoplasm Metastasis, Organoids metabolism, Prospective Studies, Prostatic Neoplasms drug therapy, Prostatic Neoplasms genetics, Prostatic Neoplasms metabolism, Tissue Banks, Transcriptome, Xenograft Model Antitumor Assays, Drug Evaluation, Preclinical methods, Organoids pathology, Prostatic Neoplasms pathology
Abstract: Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012-2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naïve primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cultured from PDXs, providing further capabilities for preclinical studies. Using a 1 x 1 x 1 design, we rapidly identify tumors with exceptional responses to combination treatments. To govern the distribution of PDXs, we formed the Melbourne Urological Research Alliance (MURAL). This PDX collection is a substantial resource, expanding the capacity to test and prioritize effective treatments for prospective clinical trials in prostate cancer., (© 2021. The Author(s).)
Published: 2021
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92. Association Between Multiparametric Magnetic Resonance Imaging of the Prostate and Oncological Outcomes after Primary Treatment for Prostate Cancer: A Systematic Review and Meta-analysis.

Author: Stabile A, Mazzone E, Cirulli GO, De Cobelli F, Grummet J, Thoeny HC, Emberton M, Pokorny M, Pinto PA, and Taneja SS
Subjects: Humans, Magnetic Resonance Imaging, Male, Neoplasm Recurrence, Local diagnostic imaging, Prostate diagnostic imaging, Multiparametric Magnetic Resonance Imaging, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms surgery
Abstract: Context: The diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) for prostate cancer (PCa) diagnosis has been extensively explored. Little is known about the prognostic value of mpMRI suspicion scores and other quantitative mpMRI information., Objective: To systematically review the current literature assessing the relationship between pretreatment mpMRI and oncological outcomes after primary treatment for PCa to assess the role of mpMRI as a prognostic tool., Evidence Acquisition: A computerized bibliographic search of MEDLINE/PubMed, EMBASE, Scopus, and the Cochrane Library CENTRAL databases was performed for all studies assessing the relationship between mpMRI and oncological outcomes after primary treatment for PCa. The review protocol is registered in the PROSPERO database (CRD42020209899)., Evidence Synthesis: A total of six studies were included. Reliable evidence is still limited in this field. The Prostate Imaging-Reporting and Data System (PI-RADS) score was an independent predictor of biochemical recurrence (BCR) after radical prostatectomy (RP) in the majority of the studies included. The tumor volume at mpMRI was not significantly associated with BCR after RP for PCa. Data on disease progression and PCa-specific mortality are limited. Heterogeneity among the studies was substantial., Conclusions: The review shows that PI-RADS scores provide information on the future likelihood of cancer recurrence or progression, at least for men undergoing RP. We are of the view that this information should be taken into account to identify men at higher risk of unfavorable outcomes., Patient Summary: A higher Prostate Imaging-Reporting and Data System score for magnetic resonance imaging of the prostate seems to be positively associated with oncological failure in prostate cancer and should be incorporated into future risk models., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
Published: 2021
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93. Loss of SNAI2 in Prostate Cancer Correlates With Clinical Response to Androgen Deprivation Therapy.

Author: Cmero M, Kurganovs NJ, Stuchbery R, McCoy P, Grima C, Ngyuen A, Chow K, Mangiola S, Macintyre G, Howard N, Kerger M, Dundee P, Ruljancich P, Clarke D, Grummet J, Peters JS, Costello AJ, Norden S, Ryan A, Parente P, Hovens CM, and Corcoran NM
Subjects: Aged, Androgen Antagonists adverse effects, Androstenes, Anilides, Antineoplastic Agents, Hormonal adverse effects, Drug Resistance, Neoplasm genetics, Gene Expression Regulation, Neoplastic genetics, Humans, Male, Nitriles, Oligopeptides, Prostatic Neoplasms, Castration-Resistant genetics, Prostatic Neoplasms, Castration-Resistant pathology, Signal Transduction, Snail Family Transcription Factors deficiency, Tosyl Compounds, Androgen Antagonists administration & dosage, Antineoplastic Agents, Hormonal administration & dosage, Epithelial-Mesenchymal Transition genetics, Prostatic Neoplasms, Castration-Resistant drug therapy, Snail Family Transcription Factors genetics
Abstract: Purpose: Androgen receptor (AR) signaling is important in prostate cancer progression, and therapies that target this pathway have been the mainstay of treatment for advanced disease for over 70 years. Tumors eventually progress despite castration through a number of well-characterized mechanisms; however, little is known about what determines the magnitude of response to short-term pathway inhibition., Methods: We evaluated a novel combination of AR-targeting therapies (degarelix, abiraterone, and bicalutamide) and noted that the objective patient response to therapy was highly variable. To investigate what was driving treatment resistance in poorly responding patients, as a secondary outcome we comprehensively characterized pre- and post-treatment samples using both whole-genome and RNA sequencing., Results: We find that resistance following short-term treatment differs molecularly from typical progressive castration-resistant disease, associated with transcriptional reprogramming, to a transitional epithelial-to-mesenchymal transition (EMT) phenotype rather than an upregulation of AR signaling. Unexpectedly, tolerance to therapy appears to be the default state, with treatment response correlating with the prevalence of tumor cells deficient for SNAI2 , a key regulator of EMT reprogramming., Conclusion: We show that EMT characterizes acutely resistant prostate tumors and that deletion of SNAI2 , a key transcriptional regulator of EMT, correlates with clinical response., Competing Interests: Geoff Macintyre Stock and Other Ownership Interests: Tailor Bio Ltd Uncompensated Relationships: Tailor Bio Ltd Jeremy Grummet Stock and Other Ownership Interests: MRI PRO Pty Ltd Honoraria: BK Ultrasound, Biobot, Mundipharma Travel, Accommodations, Expenses: Astellas Pharma Christopher M. Hovens Patents, Royalties, Other Intellectual Property: past patents in unrelated field Niall M. Corcoran Research Funding: Janssen Oncology No other potential conflicts of interest were reported.Geoff Macintyre Stock and Other Ownership Interests: Tailor Bio Ltd Uncompensated Relationships: Tailor Bio Ltd Jeremy Grummet Stock and Other Ownership Interests: MRI PRO Pty Ltd Honoraria: BK Ultrasound, Biobot, Mundipharma Travel, Accommodations, Expenses: Astellas Pharma Christopher M. Hovens Patents, Royalties, Other Intellectual Property: past patents in unrelated field Niall M. Corcoran Research Funding: Janssen Oncology No other potential conflicts of interest were reported., (© 2021 by American Society of Clinical Oncology.)
Published: 2021
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94. Predictors of erectile dysfunction after transperineal template prostate biopsy.

Author: Tan JL, Papa N, Hanegbi U, Snow R, Grummet J, Mann S, Cuthbertson A, Frydenberg M, and Moon D
Subjects: Aged, Biopsy adverse effects, Biopsy methods, Humans, Incidence, Male, Middle Aged, Perineum, Prognosis, Prospective Studies, Self Report, Erectile Dysfunction epidemiology, Erectile Dysfunction etiology, Postoperative Complications epidemiology, Postoperative Complications etiology, Prostate pathology
Abstract: Purpose: To investigate the incidence and possible contributing factors of erectile dysfunction (ED) after transperineal template prostate biopsy (TTPB)., Materials and Methods: Males undergoing TTPB were prospectively administered a Sexual Health Inventory for Men (SHIM) questionnaire before biopsy and one month after. SHIM questionnaires were repeated at 3- and 9-months for males not receiving interventional treatment. Sexually inactive males were excluded. Interval change in SHIM categories based upon baseline characteristics were evaluated. Multivariable logistic regression models were used to evaluate predictors of change in SHIM score category., Results: A total of 576 males were included in our sample. Of these, 450 (78%) males underwent their first biopsy. A decline in SHIM category within the immediate 4-weeks post-biopsy was reported by 167 males (31% of total eligible sample). Age was the strongest predictor of decline in SHIM category, the predicted probability of a decline in SHIM at age 50 was 10% (95% confidence interval [CI], 1%-19%), 32% at age 60 (95% CI, 25%-40%) and 36% at age 70 (95% CI, 29%-44%). For new onset ED, the predicted probability of ED within 4-weeks post-TTPB were 6.7% at age 50 (95% CI, 0%-15%), 26% at age 60 (95% CI, 17%-34%) and 31% at age 70 (95% CI, 21%-40%)., Conclusions: Older age at biopsy is an independent predictor of immediate ED after TTPB in sexually active males. This association was observed in the subgroup with no pre-existing ED. These findings provide useful information when counselling males undergoing TTPB., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)
Published: 2021
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95. Role of multiparametric prostate MRI in the management of prostate cancer.

Author: O'Connor LP, Lebastchi AH, Horuz R, Rastinehad AR, Siddiqui MM, Grummet J, Kastner C, Ahmed HU, Pinto PA, and Turkbey B
Subjects: Humans, Male, Prostatic Neoplasms therapy, Multiparametric Magnetic Resonance Imaging, Prostatic Neoplasms diagnostic imaging
Abstract: Introduction: Prostate cancer has traditionally been diagnosed by an elevation in PSA or abnormal exam leading to a systematic transrectal ultrasound (TRUS)-guided biopsy. This diagnostic pathway underdiagnoses clinically significant disease while over diagnosing clinically insignificant disease. In this review, we aim to provide an overview of the recent literature regarding the role of multiparametric MRI (mpMRI) in the management of prostate cancer., Materials and Methods: A thorough literature review was performed using PubMed to identify articles discussing use of mpMRI of the prostate in management of prostate cancer., Conclusion: The incorporation of mpMRI of the prostate addresses the shortcomings of the prostate biopsy while providing several other advantages. mpMRI allows some men to avoid an immediate biopsy and permits visualization of areas likely to harbor clinically significant cancer prior to biopsy to facilitate use of MR-targeted prostate biopsies. This allows for reduction in diagnosis of clinically insignificant disease as well as improved detection and better characterization of higher risk cancers, as well as the improved selection of patients for active surveillance. In addition, mpMRI can be used for selection and monitoring of patients for active surveillance and treatment planning during surgery and focal therapy.
Published: 2021
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96. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II-2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer.

Author: Cornford P, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, Fanti S, Fossati N, Gandaglia G, Gillessen S, Grivas N, Grummet J, Henry AM, der Kwast THV, Lam TB, Lardas M, Liew M, Mason MD, Moris L, Oprea-Lager DE, der Poel HGV, Rouvière O, Schoots IG, Tilki D, Wiegel T, Willemse PM, and Mottet N
Subjects: Humans, Male, Neoplasm Metastasis therapy, Prostatic Neoplasms pathology, Neoplasm Recurrence, Local therapy, Prostatic Neoplasms therapy
Abstract: Objective: To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy & Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (CRPC)., Evidence Acquisition: The working panel performed a literature review of the new data (2016-2019). The guidelines were updated, and the levels of evidence and/or grades of recommendation were added based on a systematic review of the literature., Evidence Synthesis: Prostate-specific membrane antigen positron emission tomography computed tomography scanning has developed an increasingly important role in men with biochemical recurrence after local therapy. Early salvage radiotherapy after radical prostatectomy appears as effective as adjuvant radiotherapy and, in a subset of patients, should be combined with androgen deprivation. New treatments have become available for men with metastatic hormone-sensitive prostate cancer (PCa), nonmetastatic CRPC, and metastatic CRPC, along with a role for local radiotherapy in men with low-volume metastatic hormone-sensitive PCa. Also included is information on quality of life outcomes in men with PCa., Conclusions: The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are first endorsed by the EANM and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online (http://uroweb.org/guideline/prostate-cancer/)., Patient Summary: This article summarises the guidelines for the treatment of relapsing, metastatic, and castration-resistant prostate cancer. These guidelines are evidence based and guide the clinician in the discussion with the patient on the treatment decisions to be taken. These guidelines are updated every year; this summary spans the 2017-2020 period of new evidence., (Copyright © 2020. Published by Elsevier B.V.)
Published: 2021
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97. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent.

Author: Mottet N, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, Fanti S, Fossati N, Gandaglia G, Gillessen S, Grivas N, Grummet J, Henry AM, van der Kwast TH, Lam TB, Lardas M, Liew M, Mason MD, Moris L, Oprea-Lager DE, van der Poel HG, Rouvière O, Schoots IG, Tilki D, Wiegel T, Willemse PM, and Cornford P
Subjects: Humans, Male, Early Detection of Cancer, Prostatic Neoplasms diagnosis, Prostatic Neoplasms therapy
Abstract: Objective: To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on screening, diagnosis, and local treatment of clinically localised prostate cancer (PCa)., Evidence Acquisition: The panel performed a literature review of new data, covering the time frame between 2016 and 2020. The guidelines were updated and a strength rating for each recommendation was added based on a systematic review of the evidence., Evidence Synthesis: A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. Risk-adapted screening should be offered to men at increased risk from the age of 45 yr and to breast cancer susceptibility gene (BRCA) mutation carriers, who have been confirmed to be at risk of early and aggressive disease (mainly BRAC2), from around 40 yr of age. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is performed, a combination of targeted and systematic biopsies must be offered. There is currently no place for the routine use of tissue-based biomarkers. Whilst prostate-specific membrane antigen positron emission tomography computed tomography is the most sensitive staging procedure, the lack of outcome benefit remains a major limitation. Active surveillance (AS) should always be discussed with low-risk patients, as well as with selected intermediate-risk patients with favourable International Society of Urological Pathology (ISUP) 2 lesions. Local therapies are addressed, as well as the AS journey and the management of persistent prostate-specific antigen after surgery. A strong recommendation to consider moderate hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term hormonal treatment., Conclusions: The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for their use in clinical practice. These PCa guidelines reflect the multidisciplinary nature of PCa management., Patient Summary: Updated prostate cancer guidelines are presented, addressing screening, diagnosis, and local treatment with curative intent. These guidelines rely on the available scientific evidence, and new insights will need to be considered and included on a regular basis. In some cases, the supporting evidence for new treatment options is not yet strong enough to provide a recommendation, which is why continuous updating is important. Patients must be fully informed of all relevant options and, together with their treating physicians, decide on the most optimal management for them., (Copyright © 2020. Published by Elsevier B.V.)
Published: 2021
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98. Augmented deep learning model for improved quantitative accuracy of MR-based PET attenuation correction in PSMA PET-MRI prostate imaging.

Author: Pozaruk A, Pawar K, Li S, Carey A, Cheng J, Sudarshan VP, Cholewa M, Grummet J, Chen Z, and Egan G
Subjects: Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Positron-Emission Tomography, Prostate, Tomography, X-Ray Computed, Deep Learning
Abstract: Purpose: Estimation of accurate attenuation maps for whole-body positron emission tomography (PET) imaging in simultaneous PET-MRI systems is a challenging problem as it affects the quantitative nature of the modality. In this study, we aimed to improve the accuracy of estimated attenuation maps from MRI Dixon contrast images by training an augmented generative adversarial network (GANs) in a supervised manner. We augmented the GANs by perturbing the non-linear deformation field during image registration between MRI and the ground truth CT images., Methods: We acquired the CT and the corresponding PET-MR images for a cohort of 28 prostate cancer patients. Data from 18 patients (2160 slices and later augmented to 270,000 slices) was used for training the GANs and others for validation. We calculated the error in bone and soft tissue regions for the AC μ-maps and the reconstructed PET images., Results: For quantitative analysis, we use the average relative absolute errors and validate the proposed technique on 10 patients. The DL-based MR methods generated the pseudo-CT AC μ-maps with an accuracy of 4.5% more than standard MR-based techniques. Particularly, the proposed method demonstrates improved accuracy in the pelvic regions without affecting the uptake values. The lowest error of the AC μ-map in the pelvic region was 1.9% for μ-map GAN + aug compared with 6.4% for μ-map dixon , 5.9% for μ-map dixon + bone , 2.1% for μ-map U-Net and 2.0% for μ-map U-Net + aug . For the reconstructed PET images, the lowest error was 2.2% for PET GAN + aug compared with 10.3% for PET dixon , 8.7% for PET dixon + bone , 2.6% for PET U-Net and 2.4% for PET U-Net + aug . . CONCLUSION: The proposed technique to augment the training datasets for training of the GAN results in improved accuracy of the estimated μ-map and consequently the PET quantification compared to the state of the art.
Published: 2021
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99. European Association of Urology Position Paper on the Prevention of Infectious Complications Following Prostate Biopsy.

Author: Pilatz A, Veeratterapillay R, Dimitropoulos K, Omar MI, Pradere B, Yuan Y, Cai T, Mezei T, Devlies W, Bruyère F, Bartoletti R, Köves B, Geerlings S, Schubert S, Grummet J, Mottet N, Wagenlehner F, and Bonkat G
Subjects: Bacterial Infections etiology, Biopsy adverse effects, Humans, Male, Postoperative Complications etiology, Antibiotic Prophylaxis, Bacterial Infections prevention & control, Postoperative Complications microbiology, Postoperative Complications prevention & control, Prostate pathology
Abstract: The transperineal approach is preferred to reduce prostate biopsy (PB)-related infections. Fluoroquinolones are suspended for prophylaxis of PB in the European Union; therefore, alternative antibiotics based on local resistance, or targeted prophylaxis, in conjunction with povidone-iodine rectal preparation are recommended for transrectal PB., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
Published: 2021
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100. Transperineal prostate biopsy: a review of technique.

Author: Thomson A, Li M, Grummet J, and Sengupta S
Abstract: As the second most diagnosed cancer worldwide, prostate cancer is confirmed via tissue biopsy. Given the large number of prostate biopsies performed each year, the technique should be as accurate and safe as possible for the patient's well-being. Transrectal ultrasound guided prostate biopsy (TRUS-biopsy) is most offered worldwide. Transperineal biopsy (TPP-biopsy), on the other hand, has been gaining popularity due to its superior sensitivity and lower rate of sepsis. This article offers a review of the brachytherapy grid technique used to perform a TPP-biopsy, as well as a discussion of possible variations in the procedure. TPP-biopsy is typically performed under general anaesthesia with patient in lithotomy. Through the perineum, cores of tissue are taken systematically, with or without targeting, under US guidance. Different fusion techniques (cognition, MRI-US fusion software, MRI in-bore) can be used to target pre-identified lesions on MRI. The sampling can be done either by free hand or using a brachytherapy grid. Robotic assisted prostate biopsy is also available on the market as an alternative. In recent years, there has been accumulating evidence showing that it is safe and feasible to perform TPPB under local anaesthesia. This may improve the uptake of TPPB as the preferred biopsy technique for prostate cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/doi: 10.21037/tau.2019.12.40). The series “Muscle-Invasive Bladder Cancer” was commissioned by the editorial office without any funding or sponsorship. SS served as the unpaid Guest Editor of the series and serves as an unpaid editorial board member of Translational Andrology and Urology from Jul 2018 to Jun 2020. The authors have no other conflicts of interest to declare., (2020 Translational Andrology and Urology. All rights reserved.)
Published: 2020
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