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PURPOSE: Post-chemotherapy retroperitoneal lymph node dissection (pcRPLND) for residual nodal masses is a critical component of care in metastatic testicular germ cell tumour (GCT). However, the procedure is not of therapeutic value in up to 50% of individuals in whom histopathology demonstrates post-treatment necrosis or fibrosis alone. Improved diagnostic tools and clinicopathologic features are needed to separate individuals who benefit from pcRPLND and avoid surgery in those who do not. METHODS: A prospectively registered meta-analysis of studies reporting clinicopathologic features associated with teratoma, GCT and/or necrosis/fibrosis at pcRPLND for metastatic non-seminoma GCT (NSGCT) was undertaken. We examined the effect of various clinicopathologic factors on the finding of necrosis/fibrosis at pcRPLND. The log odds ratios (ORs) of each association were pooled using random-effects models. RESULTS: Using the initial search strategy, 4,178 potentially eligible abstracts were identified. We included studies providing OR relating to clinicopathologic factors predicting pcRPLND histopathology, or where individual patient-level data were available to permit the calculation of OR. A total of 31 studies evaluating pcRPLND histopathology in 3,390 patients were eligible for inclusion, including two identified through hand-searching the reference lists of eligible studies. The following were associated with the presence of necrosis/fibrosis at pcRPLND: absence of teratomatous elements in orchidectomy (OR 3.45, 95% confidence interval [CI] 2.94-4.17); presence of seminomatous elements at orchidectomy (OR 2.71, 95% CI 1.37-5.37); normal pre-chemotherapy serum bHCG (OR 1.96, 95% CI 1.62-2.36); normal AFP (OR 3.22, 95% CI 2.49-4.15); elevated LDH (OR 1.72, 95% CI 1.37-2.17); >50% change in mass during chemotherapy (OR 4.84, 95% CI 3.94-5.94); and smaller residual mass size (<2 cm versus >2 cm: OR 3.93, 95% CI 3.23-4.77; <5 cm versus >5 cm: OR 4.13, 95% CI 3.26-5.23). CONC

BACKGROUND: Survivors of testicular cancer may experience long-term morbidity following treatment. There is an unmet need to investigate techniques that can differentiate individuals who need additional therapy from those who do not. 2-18fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) with computerised tomography (CT) may be helpful in select settings and may be used outside of current evidence-based recommendations in real-world practice. METHODS: A institutional FDG-PET/CT database of scans performed between 2000 and 2020 for adults with testicular seminoma was interrogated. Endpoints of interest included the positive (PPV) and negative (NPV) predictive value of FDG-PET/CT for identifying active seminoma (defined by progressive radiology, response to treatment or biopsy); or no active seminoma within 24-months for patients with stage 1 and advanced seminoma. An exploratory analysis examining predictive role of SUVmax was also performed. RESULTS: 249 patients met eligibility criteria for the analysis, including 184 patients with stage 1 and 77 patients with advanced testicular seminoma. Of 193 FDG-PET/CT performed in stage 1 seminoma with available follow-up data, 79 were performed during active surveillance. 18 (23%) of these were positive, all of which had confirmed recurrent seminoma (PPV 100%). Of 45 negative FDG-PET/CT during active surveillance, 4 recurrences developed corresponding to a NPV 91%. When clinical suspicion precipitated FDG-PET/CT (n = 36): PPV 100%, NPV 86%. Of 145 FDG-PET/CT in advanced seminoma with available follow-up data, 25 (17%) were performed at baseline (within 2 months of diagnosis), 70 (48%) post-treatment for evaluation of treatment response and 50 (34%) during follow-up following prior curative treatment. 10 (14%) post-treatment FDG-PET/CT were positive corresponding to a PPV 60%. Of 46 negative FDG-PET/CT, 5 recurrences occurred (NPV 89%). During follow-up after prior curative treatment, 24 (50%) FDG-PET/CT were pos

BACKGROUND: Prostate-specific membrane antigen (PSMA) is overexpressed in the neovasculature of renal cell carcinoma (RCC). However, there remains limited evidence regarding the use of PSMA positron emission tomography/computed tomography (PET/CT) in RCC. OBJECTIVE: To assess the impact of PSMA PET/CT in the management of metastatic RCC. DESIGN SETTING AND PARTICIPANTS: This was a retrospective review of patients who underwent PSMA PET/CT from 2014 to 2020 for restaging or suspected metastatic RCC in a tertiary academic setting. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Management plans before and after PSMA PET/CT were recorded. Impact was classified as high (change of treatment intent, modality, or site), medium (change in treatment method), or low. Secondary outcomes included the patient-level detection rate, PSMA PET/CT parameters, sensitivity, and comparison to CT and, if available, fluorodeoxyglucose (FDG) PET/CT. RESULTS AND LIMITATIONS: Sixty-one patients met the inclusion criteria, of whom 54 (89%) had clear cell RCC. PSMA-positive disease was detected in 51 patients (84%). For 30 patients (49%) there was a change in management due to PSMA PET/CT (high impact, 29 patients, 48%). In 15 patients (25%), more metastases were detected on PSMA PET/CT than on CT. The sensitivity of combined PSMA PET/CT and diagnostic CT was 91% (95% confidence interval 77-98%). In a subcohort of 40 patients, the detection rate was 88% for PSMA and 75% for FDG PET/CT (p = 0.17). The maximum standardised uptake value (SUVmax) was higher for PSMA than for FDG PET/CT (15.2 vs 8.0; p = 0.02). Limitations include selection bias due to the retrospective design, and a lack of corresponding histopathology for all patients. CONCLUSIONS: PSMA PET/CT is a promising imaging modality in metastatic RCC and led to a change in management in 49% of patients. PSMA PET/CT detected additional metastases compared to CT in 25% of patients and registered a significantly higher SUVmax than FDG PET/CT

Background: Distress is common following a new testicular cancer (TC) diagnosis. Existing research and resources largely focus on long-term survivors. Nuts & Bolts has been designed by the Movember Foundation to address this unmet need. We conducted a prospective, randomised controlled trial evaluating the impact of Nuts & Bolts on distress. Method(s): Adults diagnosed with TC (within four weeks) were randomly assigned (1:1) to access to Nuts & Bolts at consent ('early intervention'), or 8 days later ('delayed intervention'). The primary endpoint was change in distress, measured by the National Comprehensive Cancer Network Distress Thermometer (DT; score range 0-10), from baseline to day 8. Secondary endpoints of distress, anxiety and depression were assessed using DT and Hospital Anxiety and Depression Scale (HADS) at defined intervals across four weeks. Semi-structured interviews conducted after four weeks were thematically analysed. Result(s): 39 patients diagnosed a median of 15 days earlier were randomised to 'early' (n=20) or 'delayed' (n=19) groups. Early intervention did not indicate significant decrease in mean DT score by day 8 (early: -1.9 versus delayed: -1.7, p=0.85). However, a reduction in distress was observed in both groups across one (early: p<0.0001; delayed: p<0.01) and four weeks (early: p<0.001; delayed: p=0.01) following intervention. Thematic analysis from semi-structured interviews revealed four key themes, including the helpfulness of the intervention across the TC journey. Nuts & Bolts was considered highly useful and early access was seen as key to maximising benefit. Conclusion(s): High levels of distress are common in men with newly diagnosed TC; however, this reduces over 1-4 weeks. While earlier introduction to Nuts & Bolts did not impact change in distress across oneweek, this may have been due to the timing of its implementation following diagnosis. Nuts & Bolts was considered highly useful, acceptable, and relevant by men diagnosed

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-naive 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.Copyright © 2021, The Author(s).

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.

Background: The intractability of castration-resistant prostate cancer (CRPC) is exacerbated by tumour heterogeneity, including diverse alterations to the androgen receptor (AR) axis and AR-independent phenotypes. The availability of additional models encompassing this heterogeneity would facilitate the identification of more effective therapies for CRPC. Objective(s): To discover therapeutic strategies by exploiting patient-derived models that exemplify the heterogeneity of CRPC. Design, setting, and participants: Four new patient-derived xenografts (PDXs) were established from independent metastases of two patients and characterised using integrative genomics. A panel of rationally selected drugs was tested using an innovative ex vivo PDX culture system. Intervention(s): The following drugs were evaluated: AR signalling inhibitors (enzalutamide and galeterone), a PARP inhibitor (talazoparib), a chemotherapeutic (cisplatin), a CDK4/6 inhibitor (ribociclib), bromodomain and extraterminal (BET) protein inhibitors (iBET151 and JQ1), and inhibitors of ribosome biogenesis/function (RNA polymerase I inhibitor CX-5461 and pan-PIM kinase inhibitor CX-6258). Outcome measurements and statistical analysis: Drug efficacy in ex vivo cultures of PDX tissues was evaluated using immunohistochemistry for Ki67 and cleaved caspase-3 levels. Candidate drugs were also tested for antitumour efficacy in vivo, with tumour volume being the primary endpoint. Two-tailed t tests were used to compare drug and control treatments. Results and limitations: Integrative genomics revealed that the new PDXs exhibited heterogeneous mechanisms of resistance, including known and novel AR mutations, genomic structural rearrangements of the AR gene, and a neuroendocrine-like AR-null phenotype. Despite their heterogeneity, all models were sensitive to the combination of ribosome-targeting agents CX-5461 and CX-6258. Conclusion(s): This study demonstrates that ribosome-targeting drugs may be effective again

PURPOSE: To determine the oncological implications of increased nodal dissection in node-negative bladder cancer during radical cystectomy in a contemporary Australian series. MATERIALS AND METHODS: We performed a multicenter retrospective study, including more than 40 surgeons across 5 sites over a 10-year period. We identified 353 patients with primary bladder cancer undergoing radical cystectomy. Extent of lymphadenectomy was defined as follows; limited pelvic lymph node dissection (PLND) (perivesical, pelvic, and obturator), standard PLND (internal and external iliac) and extended PLND (common iliac). Multivariable cox proportional hazards and logistic regression models were used to determine LNY effect on cancer-specific survival. RESULTS: Over the study period, the extent of dissection and lymph node yield increased considerably. In node-negative patients, lymph node yield (LNY) conferred a significantly improved cancer-specific survival. Compared to cases where LNY of 1 to 5 nodes were taken, the hazard ratio (HR) for 6 to 15 nodes harvested was 0.78 (95% confidence interval [CI], 0.43-1.39) and for greater than 15 nodes the HR was 0.31 (95% CI, 0.17-0.57), adjusted for age, sex, T stage, margin status, and year of surgery. The predicted probability of cancer-specific death within 2 years of cystectomy was 16% (95% CI, 13%-19%) with 10 nodes harvested, falling to 5.5% (95% CI, 0%-12%) with 30 nodes taken. Increasing harvest in all PLND templates conferred a survival benefit. CONCLUSIONS: The findings of the current study highlight the improved oncological outcomes with increased LNY, irrespective of the dissection template. Further prospective research is needed to aid LND data interpretation.

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.

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

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.

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

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