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Objective: Radical prostatectomy reduces mortality among patients with localized prostate cancer, however up to 35% of patients will experience biochemical recurrence, often treated with salvage radiotherapy. The objective of the study was to investigate long-term effects of salvage radiotherapy.Methods: A prospective, controlled, non-randomized trial at 14 Swedish center’s including 4,003 patients scheduled for radical prostatectomy 2008–2011. A target trial emulation approach was used to identify eligible patients that was treated with salvage radiotherapy. The control group received no salvage radiotherapy. Outcomes were assessed by patient questionnaires on ordinal scales and statistical group comparisons were made using ordered logit regression with adjustment for baseline outcome and confounding factors. The primary endpoints were bowel, urinary and sexual function and bothering due to dysfunction at 8 years.Results: Eleven percent (330/3,139) of the analyzed study population received salvage radiotherapy. Fecal leakage, leakage of mucus and hematochezia were more common after receiving salvage radiotherapy compared with the control group; 4.5% versus 2.6% odds ratio (95% confidence interval [CI]): (1.90 [1.38; 2.62]), 6.8% versus 1.5% 4.14 (2.98; 5.76) and 8.6% versus 1.2% 4.14 (2.98; 5.76), respectively. Urinary incontinence, erectile dysfunction and hematuria were more common after receiving salvage radiotherapy, 34% versus 23% 2.23 (2.65; 3.00), 65% versus 57% 1.65 (1.18; 2.29) and 16% versus 1.6% 11.17 (5.68; 21.99), respectively. Conclusion: Salvage radiotherapy was associated with increased risk for fecal leakage, hematochezia, urinary incontinence and hematuria. Our results emphasize the importance of selecting patients for salvage radiotherapy to avoid overtreatment and to give high quality pre-treatment information to ensure patients’ preparedness for late side-effects.

The aim of this study was to develop a model to predict high-genomic-risk prostate cancer (PCa) according to Decipher score, a validated 22 gene prognostic panel. By doing so, one might select the individuals who are likely to benefit from genomic testing and improve pre-op counseling about the need for adjuvant treatments.We retrospectively reviewed IRB-approved databases at two institutions. All patients had preoperative magnetic resonance imaging (MRI) and Decipher prostate radical prostatectomy (RP), a validated 22 gene prognostic panel. We used binary logistic regression to estimate high-risk Decipher (Decipher score 0.60) probability on RP specimen. Area under the curve (AUC) and calibration were used to assess the accuracy of the model in the development and validation cohort. Decision curve analysis (DCA) was performed to assess the clinical benefit of the model.The development and validation cohort included 622 and 185 patients with 283 (35%) and 80 (43%) of those with high-risk Decipher. The multivariable model included PSA density, biopsy Gleason Grade Group, percentage of positive cores and MRI extracapsular extension. AUC was 0.73 after leave-one-out cross-validation. DCA showed a clinical benefit in a range of probabilities between 15 and 60%. In the external validation cohort, AUC was 0.70 and calibration showed that the model underestimates the actual probability of the outcome.The proposed model to predict high-risk Decipher score at RP is helpful to improve risk stratification of patients with PCa and to assess the need for additional testing and treatments.

Although multiparametric magnetic resonance imaging (MRI) has high sensitivity, its lower specificity leads to a high prevalence of false-positive lesions requiring biopsy.To develop and externally validate a scoring system for MRI-detected Prostate Imaging Reporting and Data System (PIRADS)/Likert ≥3 lesions containing clinically significant prostate cancer (csPCa).The multicentre Rapid Access to Prostate Imaging and Diagnosis (RAPID) pathway included 1189 patients referred to urology due to elevated age-specific prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE); April 27, 2017 to October 25, 2019.Visual-registration or image-fusion targeted and systematic transperineal biopsies for an MRI score of ≥4 or 3 + PSA density ≥0.12 ng/ml/ml.Fourteen variables were used in multivariable logistic regression for Gleason ≥3 + 4 (primary) and Gleason ≥4 + 3, and PROMIS definition 1 (any ≥4 + 3 or ≥6 mm any grade; secondary). Nomograms were created and a decision curve analysis (DCA) was performed. Models with varying complexity were externally validated in 2374 patients from six international cohorts.The five-item Imperial RAPID risk score used age, PSA density, prior negative biopsy, prostate volume, and highest MRI score (corrected c-index for Gleason ≥3 + 4 of 0.82 and 0.80-0.86 externally). Incorporating family history, DRE, and Black ethnicity within the eight-item Imperial RAPID risk score provided similar outcomes. The DCA showed similar superiority of all models, with net benefit differences increasing in higher threshold probabilities. At 20%, 30%, and 40% of predicted Gleason ≥3 + 4 prostate cancer, the RAPID risk score was able to reduce, respectively, 11%, 21%, and 31% of biopsies against 1.8%, 6.2%, and 14% of missed csPCa (or 9.6%, 17%, and 26% of foregone biopsies, respectively).The Imperial RAPID risk score provides a standardised tool for the prediction of csPCa in patients with an MRI-detected PIRADS/Likert ≥3 lesion and can support the decision for prostate biopsy.In this multinational study, we developed a scoring system incorporating clinical and magnetic resonance imaging characteristics to predict which patients have prostate cancer requiring treatment and which patients can safely forego an invasive prostate biopsy. This model was validated in several other countries.

BACKGROUND: Differences in outcome after radical prostatectomy for prostate cancer can partly be explained by inter-surgeon differences, where degree of experience is one important aspect. OBJECTIVE: To define the learning curve of robot-assisted laparoscopic prostatectomy regarding oncological and functional outcomes. MATERIALS AND METHODS: Out of 4003 enrolled patients in the LAPPRO trial, 3583 met the inclusion criteria, of which 885 were operated by open technique. A total of 2672 patients with clinically localized prostate cancer from seven Swedish centers were operated by robot-assisted laparoscopic and followed for eight years (LAPPRO trial). Oncological outcomes were pathology reported surgical margin and biochemical recurrence at eight years. Functional outcomes included patient-reported urinary incontinence and erectile dysfunction at 3, 12 and 24 months. Experience was surgeon-reported experience prior to and within the study. The relationship between surgeon experience and functional outcomes and surgical margin status was analysed by mixed effect logistic regression. Biochemical recurrence was analysed by Cox regression with robust standard errors. RESULTS: The learning curve for positive surgical margin was relatively flat with a rate of 21% for surgeons between 0–74 cases and 24% for surgeons who had performed >300 cases. Biochemical recurrence at 4 years was 11% (0–74 cases) and 13% (>300 cases). Incontinence was stable over the learning curve but erectile function improved (at 2 years from 38% (0–74 cases) to 53% (>300 cases)). CONCLUSIONS: Analysis of the learning curve for surgeons performing robot assisted laparoscopic prostatectomy showed erectile function improved with increasing number of procedures which was not the case for the oncological outcomes.

Background Current European Association of Urology, American Urological Association, and National Comprehensive Cancer Network guidelines recommend active surveillance (AS) for selected intermediate-risk prostate cancer (PCa) patients. However, limited evidence exists regarding which men can be selected safely. Objective To externally validate the Gandaglia risk calculator (Gandaglia-RC), designed to predict adverse pathology (AP) at radical prostatectomy (RP) and thus able to improve selection of intermediate-risk PCa patients suitable for AS, and to assess whether addition of magnetic resonance imaging (MRI) findings (MAP model) improves the predictive ability of Gandaglia-RC. Design, setting, and participants This is a retrospective analysis of a single-center cohort of 1284 consecutive men with low- and intermediate-risk PCa treated with RP between 2013 and 2019. Outcome measurements and statistical analysis AP was defined as non–organ-confined disease and/or lymph node invasion and/or pathological grade group ≥ 3 at RP. Logistic regression was used to calculate the predictors of AP; calculated coefficients were used to develop a risk score. Receiver operating characteristic curve analysis and decision curve analysis were performed to evaluate the net benefit within models. Results and limitations At multivariable analysis, age at surgery, prostate-specific antigen, systematic and targeted biopsy Gleason grade group, MRI prostate volume, Prostate Imaging Reporting and Data System score, and MRI extraprostatic extension were significantly associated with AP. The model significantly improved the ability of Gandaglia-RC to predict AP (area under the curve 0.71 vs 0.63 [p Conclusions Compared with Gandaglia-RC, the MAP model significantly increased the number of patients eligible for AS without significantly increasing the risk of AP at RP. Patient summary In this report, we have developed a risk prediction tool to select men for conservative treatment of prostate cancer. Using the novel tool, more men could safely be allocated to conservative treatment rather than surgery or radiation.

Background A common side effect following radical prostatectomy is urinary incontinence. Here, we describe a novel surgical technique to reduce postoperative urinary incontinence and facilitate early return of continence. Objective To describe the novel “hood technique” for robotic-assisted radical prostatectomy (RARP). Design, setting, and participants This is an institutional review board–approved prospective study of 300 patients (median age 64 yr) with localized prostate cancer treated with the RARP hood technique at a major urban hospital between April 2018 and March 2019. The exclusion criteria were as follows: patients with anterior tumor location based on biopsy or multiparametric magnetic resonance imaging. All but one patient participated in follow-up over 12 mo after the procedure. Surgical procedure The RARP “hood technique” was performed to preserve the detrusor apron, puboprostatic ligament complex, arcus tendineus, endopelvic fascia, and pouch of Douglas. Measurements Clinical data collected included pre- and intraoperative variables, and postoperative functional and oncological outcomes and complications. Descriptive statistical analysis was performed. Results and limitations Continence rates at 1, 2, 4, 6 12, 24, and 48 wk after catheter removal were 21%, 36%, 83%, 88%, 91%, 94%, and 95%, respectively. Positive surgical margin rate was 6%. Thirty patients (9.7%) experienced complications after RARP: 17 (5.7%), 11 (3.6%), and one (0.4%) had Clavien-Dindo grade I, II, and III complications, respectively. This study was conducted within a single health system and may not be generalizable. The study lacked randomization and a comparative arm. Conclusions Results indicate that the hood technique spares musculofascial structures anterior to the urethral sphincter complex with early return of continence after surgery, without compromising positive surgical margin rates. Exclusion of anterior tumor location contributed to a reduction in positive surgical margins. Patient summary By better preservation of anatomical structures around the urethra, we were able to achieve early return of urinary continence without a negative impact on complications and cancer outcomes.

Background Reports on possible benefits for continence with nerve-sparing (NS) radical prostatectomy have expanded the indications beyond preservation of erectile function. It is unclear whether NS surgery affects oncological outcomes. Objective To determine whether the degree of NS during radical prostatectomy influences oncological outcomes. Design, setting, and participants Of 4003 patients enrolled in a prospective, controlled trial comparing open and robotic radical prostatectomy during 2008–2011, we evaluated 2401 patients who received robotic radical prostatectomy at seven Swedish centres. Patients were followed for 8 yr. Outcome measurements and statistical analysis Data for recurrence and positive surgical margin status were assessed using validated patient questionnaires, patient interviews, and clinical record forms before and at 3, 12, and 24 mo and 6 and 8 yr after surgery. Cox and logistic regressions were used to model the effect on recurrence and positive surgical margins (PSM), respectively. Results and limitations A total of 481 men had PSM and 467 experienced recurrence during follow-up. Median follow-up for men without recurrence was 6.6 yr. There were no statistically significant differences in recurrence rate between degrees of NS. The PSM rate was significantly higher with a higher degree of NS: interfascial NS, odds ratio (OR) 2.32 (95% confidence interval [CI] 1.69–3.16); intrafascial NS, OR 3.23 (95% CI 2.17–4.80). Recurrence rates were higher for patients with pT2 disease and PSM (hazard ratio [HR] 3.32, 95% CI 2.43–4.53) than for patients with pT3 disease without PSM (HR 2.08, 95% CI 1.66–2.62). The lack of central review of pathological specimens is a limitation. Conclusions A higher degree of NS significantly increased the risk of PSM but did not significantly increase the risk of cancer recurrence. Combined with the known functional benefits of NS surgery, these results underscore the need to identify an individualised balance. Patient summary In this report we looked at the effect of a nerve-sparing approach during removal of the prostate on cancer outcomes for patients having robot-assisted surgery at seven Swedish hospitals. We found that a high degree of nerve-sparing increased the rate of cancer positivity at the margins of surgical specimens and that positive surgical margins increased the risk of recurrence of prostate cancer., Take Home Message Nerve-sparing radical prostatectomy increases the rate of positive surgical margins. Although no direct effect on recurrence is evident, this is important to address in mutual decision-making with the patient.

To evaluate urinary continence (UC) recovery and oncological outcomes in different risk-groups after robot-assisted radical prostatectomy (RALP) and open retropubic radical prostatectomy (RRP). We analysed 2650 men with prostate cancer from seven open (n = 805) and seven robotic (n = 1845) Swedish centres between 2008 and 2011 in a prospective non-randomised trial, LAPPRO. UC recovery was defined as change of pads less than once in 24 h. Information was collected through validated questionnaires. Rate of positive surgical margins (PSM) and biochemical recurrence (BCR), defined as prostate-specific antigen (PSA) > 0.25 mg/ml, were recorded. We stratified patients into two risk groups (low-intermediate and high risk) based on the D’Amico risk classification system. Among men with high-risk prostate cancer, we found significantly higher rates of UC recovery up to 24 months after RRP compared to RALP (66.1% vs 60.5%) RR 0.85 (CI 95% 0.73–0.99) while PSM was more frequent after RRP compared to RALP (46.8% vs 23.5%) RR 1.56 (CI 95% 1.10–2.21). In the same group no significant difference was seen in BCR. Overall, however, BCR was significantly more common after RRP compared to RALP at 24 months (9.8% vs 6.6%) RR 1.43 (Cl 95% 1.08–1.89). The limitations of this study are its non-randomized design and the relatively short time of follow-up. Our study indicates that men with high-risk tumour operated with open surgery had better urinary continence recovery but with a higher risk of PSM than after robotic-assisted laparoscopic surgery. No significant difference was seen in biochemical recurrence. ISRCTN06393679.

Following several attempts to achieve a molecular stratification of bladder cancer (BC) over the last decade, a “consensus” classification has been recently developed to provide a common base for the molecular classification of bladder cancer (BC), encompassing a six-cluster scheme with distinct prognostic and predictive characteristics. In order to implement molecular subtyping (MS) as a risk stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The second part of this review deals with the pathological and clinical features of the molecular clusters, both in conventional and divergent urothelial carcinoma, with a focus on the role of IHC-based subtyping.

Bladder cancer (BC) is a heterogeneous disease with highly variable clinical and pathological features, and resulting in different outcomes. Such heterogeneity ensues from distinct pathogenetic mechanisms and may consistently affect treatment responses in single patients. Thus, over the last few years, several groups have developed molecular classification schemes for BC, mainly based on their mRNA expression profiles. A “consensus” classification has recently been proposed to combine the published systems, agreeing on a six-cluster scheme with distinct prognostic and predictive features. In order to implement molecular subtyping as a risk-stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The first part of this review deals with the steps resulting in the development of a molecular subtyping of BC, its prognostic and predictive implications, and the main features of immunohistochemical markers used as surrogates to stratify BC into pre-defined molecular clusters.

OBJECTIVES To evaluate if the blood biomarker, 4Kscore, in addition to multiparametric magnetic resonance imaging information could identify patients who would benefit from undergoing only a targeted biopsy. METHODS We retrospectively analyzed a population of 256 men with positive multiparametric magnetic resonance imaging who underwent standard + targeted biopsy at Mount Sinai Hospital, New York, NY, USA. 4Kscore (OPKO Health, Miami, FL, USA) was sampled from all patients before biopsy. Uni- and multivariable binary logistic regression analyses were carried out to predict clinically significant prostate cancer, defined as International Society of Urological Pathology grade group ≥2, in standard biopsy cores. The model with the best area under the curve was selected and internal validation was carried out using the leave-one-out cross-validation. RESULTS The developed model showed an area under the curve of 0.86. Carrying out only targeted biopsy in patients with a model-derived probability

Background Conclusive evidence of superiority in oncological outcome for robot-assisted laparoscopic prostatectomy (RALP) over retropubic radical prostatectomy (RRP) is lacking. Objective To compare RALP and RRP regarding recurrent disease and to report the mortality rate 6 yr after surgery. Design, setting, and participants A total of 4003 men with localized prostate cancer were enrolled between 2008 and 2011 in Laparoscopic Prostatectomy Robot Open (LAPPRO)— a prospective, controlled, nonrandomized trial performed at 14 Swedish centers. Outcome measurements and statistical analysis Data were collected at visits and by patient questionnaires at 3, 12, and 24 mo, and through a structured telephone interview at 6 yr. Cause of death was retrieved from the National Cause of Death Register in Sweden. The modified Poisson regression approach was used for analyses. Results and limitations After adjustment for patient-, tumor-, and surgeon-related confounders, no statistically significant difference was observed between RALP and RRP in biochemical recurrence rate (14 vs 16%, relative risk [RR] 0.77, 95% confidence interval [CI] 0.56–1.06) or in not cured endpoint (22% vs 23%, RR 0.82, 95% CI 0.6–1.11). Stratified by D’Amico risk group, a significant benefit for RALP existed for recurrent disease in high-risk patients (RR 0.47, 95% CI 0.26–0.86, p = 0.02). All-cause mortality was 3% (n = 96). Prostate cancer–specific mortality was 0.6% (n = 21) overall, 0.3% (n = 8) after RALP, and 1.5% (n = 13) after RRP. The nonrandomized design is a limitation. Conclusions No significant difference was observed for cancer recurrence rate between RALP and RRP 6 yr after surgery. However, in a subgroup analysis, we found a significant benefit for RALP regarding recurrence rate in the high-risk group. Larger studies with longer follow-up are needed to make a firm conclusion and to evaluate a possible survival benefit. Patient summary In general, the oncological outcome is comparable between robotic and open radical prostatectomy 6 yr after surgery. For high-risk patients, our findings indicate that there is an advantage for robotics, but further studies with longer follow-up time is needed to make a firm conclusion., Take Home Message Robot-assisted and open retropubic radical prostatectomy have comparable oncological outcome 6 yr after surgery. However, for high-risk patients, we observed a significant benefit for robotics regarding recurrence rate. Longer follow-up time is needed to make a firm conclusion and to evaluate a possible survival benefit for either of the surgical approaches.

Context The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in a global health emergency, the like of which has never been seen before. Prostate cancer (PCa) services across the globe have been on hold due to changing medical and surgical priorities. There is also epidemiological evidence that PCa patients have increased incidence and mortality from SARS-CoV-2 infection due to gender differences, age, and higher propensity for risk factors (eg, respiratory disease, obesity, hypertension, and smoking status). Objective To contribute to the emerging body of knowledge on the risks of SARS-CoV-2 infection to PCa patients and, in the face of PCa treatment delays, provide evidence-based recommendations for ongoing management of specific PCa patient groups. Evidence acquisition A literature search was performed using all sources (MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science) as well as the media to harness emerging data on the SARS-CoV-2 pandemic and its influence on PCa. Eligibility criteria were originality of data and relevance to PCa management. The authors note that during these unprecedented times, retrospective data are constantly being updated from multiple sources globally. Evidence synthesis A total of 72 articles and data sources were found initially. Owing to repetition, lack of originality, or nonrelevance, six articles were rejected, leaving 23 retrospective studies, seven basic science research articles, 15 societal and journal guidelines, and 21 epidemiological data sources, from countries at different stages of SARS-CoV-2 pandemic. These were analyzed qualitatively to produce evidence-based guidelines for the management of PCa patients at different stages of the patient journey, with strategies to reduce the risk of viral spread. Conclusions PCa patients may have an increased risk of SARS-CoV-2 infection as well as morbidity and mortality if infected. Once appropriately triaged, and to reduce viral spread, PCa patients can have surveillance by telemedicine, and institute lifestyle changes and social quarantining measures. If risk stratification suggests that treatment should be planned, androgen deprivation therapy can be started, or potentially surgery or radiation therapy is possible on a case-by-case basis. Patient summary Prostate cancer patients can be followed up remotely until the severe acute respiratory syndrome coronavirus 2 pandemic resolves, but higher-risk cases may have treatment expedited to limit any negative impact on prostate cancer outcomes., Take Home Message Prostate cancer (PCa) patients may have an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mortality. Most can be followed up remotely until the pandemic resolves, but, once appropriately triaged, higher-risk cases can have treatment expedited to limit any negative impact on PCa outcomes.

Prostate biopsies are associated with infectious complications and approximately 80% are either benign or clinically insignificant prostate cancer. Our aim is to develop and independently validate prediction model to avoid unnecessary prostate biopsies by predicting clinically significant prostate cancer (csPCa) Materials and Methods: Retrospective analysis of single-center cohort (Mount Sinai Hospital, NY) of 1632 men who underwent systematic or combined systematic and Magnetic Resonance Imaging (MRI)/ultrasound fusion targeted prostate biopsy between 2014-2020. External cohort (University of Miami) included 622 men that underwent biopsy. Outcome for predicting csPCa was defined as International Society of Urologic Pathology (ISUP) Gleason grade ≥ 2 on biopsy. Multivariable logistic regression analysis was performed to build nomogram using coefficients of logit function. Nomogram validation was performed in external cohort by plotting receiver operating characteristics (ROC). We also plotted decision curve analysis (DCA) and compared nomogram-predicted probabilities with actual rates of csPCa probabilities in external cohort.Of 1632 men, 43% showed csPCa on biopsy. PSA density, prior negative biopsy, and Prostate Imaging and Reporting Data System (PI-RADS) scores 3, 4, and 5 were significant predictors for csPCa. ROC for prediction of csPCa was 0.88 in external cohort. There was agreement between predicted and actual rate of csPCa in external cohort. DCA demonstrated net benefit using the model. Using the prediction model at threshold of 30, 35% of biopsies and 46% of diagnosed indolent PCa could be avoided, while missing 5% of csPCa.Using our prediction model can help reduce unnecessary prostate biopsies with minimal impact on csPCa detection rates.

The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and β-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and β-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease. Video abstract Supplementary Information The online version contains supplementary material available at 10.1186/s12964-021-00755-6.

ImportanceThere is evidence that 5α-reductase inhibitors (5-ARIs), a standard treatment of benign prostate hyperplasia, are associated with a decrease in the incidence of prostate cancer (PCa). However, studies to date have had conflicting results regarding the association with prostate cancer mortality (PCM).ObjectiveTo evaluate the association of treatment with 5-ARIs with PCM in men without a prior diagnosis of PCa.Design, Setting, and ParticipantsThis population-based cohort study was conducted in Stockholm, Sweden, between January 1, 2007, and December 31, 2018, and included 429 977 men with a prostate-specific antigen (PSA) test within the study period. Study entry was set to 1 year after the first PSA test. Data were analyzed from September 2021 to December 2021.ExposuresAfter their initial PSA test, men with 2 or more newly dispensed prescriptions of 5-ARI, finasteride, or dutasteride were considered 5-ARI users (n = 26 190).Main Outcomes and MeasuresPrimary outcome was PCM. Cox proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% CIs for all-cause mortality and PCM.ResultsThe study cohort included 349 152 men. The median (IQR) age for those with 2 or more filled prescriptions of 5-ARI was 66 (61-73) years and 57 (50-64) years for those without. The median follow-up time was 8.2 (IQR, 4.9-10) years with 2 257 619 person-years for the unexposed group and 124 008 person-years for the exposed group. The median exposure to treatment with 5-ARI was 4.5 (IQR, 2.1-7.4) years. During follow-up, 35 767 men (8.3%) died, with 852 deaths associated with PCa. The adjusted multivariable survival analysis showed a lower risk of PCM in the 5-ARI group with longer exposure times (0.1-2.0 years: adjusted HR, 0.89; 95% CI, 0.64-1.25; >8 years: adjusted HR, 0.44; 95% CI, 0.27-0.74). No statistically significant differences were seen in all-cause mortality between the exposed and unexposed group. Men treated with 5-ARIs underwent more PSA tests and biopsies per year than the unexposed group (median of 0.63 vs 0.33 and 0.22 vs 0.12, respectively).Conclusions and RelevanceThe results of this cohort study suggest that there was no association between treatment with 5-ARI and increased PCM in a large population-based cohort of men without a previous PCa diagnosis. Additionally, a time-dependent association was seen with decreased risk of PCM with longer 5-ARI treatment. Further research is needed to determine whether the differences are because of intrinsic drug effects or PCa testing differences.

Background The detection of prostate cancer requires histological confirmation in biopsy core. Currently, number of unnecessary prostate biopsies are being performed in the United States. This is due to the absence of appropriate biopsy decision‐making protocol. Aim To develop and validate a 4K score/multiparametric magnetic resonance imaging (mpMRI)‐based nomogram to predict prostate cancer (PCa), clinically significant prostate cancer (csPCa), and unfavorable prostate cancer (uPCa). Methods and Results Retrospective, single‐center study evaluating a cohort of 574 men with 4K score test >7% or suspicious digital rectal examination (DRE) or Prostate Imaging Reporting and Data System (PI‐RADS) scores 3, 4, or 5 on mpMRI that underwent systematic and/or mpMRI/ultrasound fusion–targeted prostate biopsy between 2016 and 2020. External cohort included 622 men. csPCa and uPCa were defined as Gleason score ≥3 + 4 and ≥4 + 3 on biopsy, respectively. Multivariable logistic regression analysis was performed to build nomogram for predicting PCa, csPCa, and uPCa. Validation was performed by plotting the area under the curve (AUC) and comparing nomogram‐predicted probabilities with actual rates of PCa, csPCa, and uPCa probabilities in the external cohort. 4K score, a PI‐RADS ≥4, prostate volume and prior negative biopsy were significant predictors of PCa, csPCa, and uPCa. AUCs were 0.84, 0.88, and 0.86 for the prediction of PCa, csPCa, and uPCa, respectively. The predicted and actual rates of PCa, csPCa, and uPCa showed agreement across all percentage probability ranges in the validation cohort. Using the prediction model at threshold of 30, 30% of overall biopsies, 41% of benign biopsies, and 19% of diagnosed indolent PCa could be avoided, while missing 9% of csPCa. Conclusion This novel nomogram would reduce unnecessary prostate biopsies and decrease detection of clinically insignificant PCa.

Background Radical prostatectomy reduces mortality among patients with localised prostate cancer. Evidence on whether different surgical techniques can affect mortality rates is lacking. Objective To evaluate functional and oncological outcomes 8 yr after robot-assisted laparoscopic prostatectomy (RALP) and open retropubic radical prostatectomy (RRP). Design, setting, and participants We enrolled 4003 patients in a prospective, controlled, nonrandomised trial comparing RALP and RRP in 14 Swedish centres between 2008 and 2011. Data for functional outcomes were assessed via validated patient questionnaires administered preoperatively and at 12 and 24 mo and 8 yr after surgery. Outcome measurements and statistical analysis The primary endpoint was urinary incontinence. Functional outcomes at 8 yr were analysed using the modified Poisson regression approach. Results and limitations Urinary incontinence was not significantly different at 8 yr after surgery between RALP and RRP (27% vs 29%; adjusted risk ratio [aRR] 1.05, 95% confidence interval [CI] 0.90–1.23). Erectile dysfunction was significantly lower in the RALP group (66% vs 70%; aRR 0.93, 95% CI 0.87–0.99). Prostate cancer–specific mortality (PCSM) was significantly lower in the RALP group at 8 yr after surgery (40/2699 vs 25/885; aRR 0.56, 95% CI 0.34–0.93). Differences in oncological outcomes were mainly seen in the group with high D'Amico risk, with a lower risk of positive surgical margins (21% vs 34%), biochemical recurrence (51% vs 69%), and PCSM (14/220 vs 11/77) for RALP versus RRP. The main limitation is the nonrandomised design. Conclusions In this prospective multicentre controlled trial, PCSM at 8 yr after surgery was lower for RALP in comparison to RRP. A causal relationship between surgical technique and mortality cannot be inferred, but the result confirms that RALP is oncologically safe. Taken together with better short-term results reported elsewhere, our findings confirm that implementation of RALP may continue. Patient summary Our study comparing two surgical techniques for removal of the prostate for localised prostate cancer shows that a robot-assisted minimally invasive technique is safe in the long term. Together with previous results showing some better short-term effects with this approach, our findings support continued use of robot-assisted surgery.

To evaluate urinary continence (UC) recovery and oncological outcomes in different risk-groups after robot-assisted radical prostatectomy (RALP) and open retropubic radical prostatectomy (RRP).We analysed 2650 men with prostate cancer from seven open (n = 805) and seven robotic (n = 1845) Swedish centres between 2008 and 2011 in a prospective non-randomised trial, LAPPRO. UC recovery was defined as change of pads less than once in 24 h. Information was collected through validated questionnaires. Rate of positive surgical margins (PSM) and biochemical recurrence (BCR), defined as prostate-specific antigen (PSA) 0.25 mg/ml, were recorded. We stratified patients into two risk groups (low-intermediate and high risk) based on the D'Amico risk classification system.Among men with high-risk prostate cancer, we found significantly higher rates of UC recovery up to 24 months after RRP compared to RALP (66.1% vs 60.5%) RR 0.85 (CI 95% 0.73-0.99) while PSM was more frequent after RRP compared to RALP (46.8% vs 23.5%) RR 1.56 (CI 95% 1.10-2.21). In the same group no significant difference was seen in BCR. Overall, however, BCR was significantly more common after RRP compared to RALP at 24 months (9.8% vs 6.6%) RR 1.43 (Cl 95% 1.08-1.89). The limitations of this study are its non-randomized design and the relatively short time of follow-up.Our study indicates that men with high-risk tumour operated with open surgery had better urinary continence recovery but with a higher risk of PSM than after robotic-assisted laparoscopic surgery. No significant difference was seen in biochemical recurrence. TRIAL REGISTRATION: ISRCTN06393679.

Purpose To describe the predictive value of information on previous benign biopsy for the outcome of MRI-targeted biopsies. Methods An exploratory analysis was conducted using data from a prospective, multicenter, paired diagnostic study of 532 men undergoing diagnostics for prostate cancer during 2016–2017. All men underwent 1.5 T MRI; systematic prostate biopsies; and MRI-targeted biopsies to MRI lesions with Prostate Imaging Reporting and Data System version 2, PI-RADS ≥ 3. The main outcome was numbers of detected prostate cancer characterized by grade group (GG) where GG ≥ 2 defined clinically significant cancer (csPCa). Results Men with previous biopsies had significantly more often negative MRI (26% vs. 17%, p p p p p p = 0.05). In multivariate regression analysis, a previous benign prostate biopsy was associated with less than half the odds of csPCa (OR 0.38; 95% CI 0.20–0.71). Conclusion In this large prospective multicenter trial, we showed that men with a previous prostate biopsy had higher proportions of MRIs without lesions and lower proportion of highly suspicious lesions than biopsy-naïve men. Further, biopsy-naïve men showed higher detection of clinically significant cancer when using MRI-targeted biopsies. Also, in the era of MRI-targeted biopsy strategies, biopsy history should be carefully considered in biopsy decisions. Trial registration NCT02788825 (ClinicalTrials.gov). Date of registration June 2, 2016.

Background Prediction of extra-prostatic extension (EPE) in men undergoing radical prostatectomy (RP) is of utmost importance. Great variability in the performance of multiparametric magnetic resonance imaging (mpMRI) has been reported for prediction of EPE. The present study aimed to determine the diagnostic performance of mpMRI for predicting EPE in different National Comprehensive Cancer Network (NCCN) risk categories. Methods Overall 664 patients who underwent radical prostatectomy with a staging mpMRI were enrolled in this single-center, retrospective study. Patients with mpMRI report non-compliant with PI-RADSv2.0, were excluded. Patients were stratified according to NCCN criteria: very low/low (VLR-LR) to High Risk (HR) in order to assess final pathology EPE rates (focal and established). Sensitivity, specificity, positive and negative predictive values of staging mpMRI were computed in each group. Univariable and multivariable analysis were used to evaluate predictors of positive surgical margins. Results Pathological evaluation demonstrated established and focal EPE in 60 (9%) and 106 (16%) patients, respectively, while mpMRI suspicion for EPE was present in 180 (27%) patients. Age, preoperative PSA, PSA density, number of positive cores, NCCN groups, prostate volume, mpMRI suspicion for EPE, PIRADSv2.0 and lesion size differed significantly between the patients with any EPE and without EPE (all P≤0.05). The sensitivity of mpMRI in detecting any EPE varied from 12% (95% CI: 0.6-53%) in VLR-LR to 83% (66-93%) in HR while the corresponding values for the specificity were 92% (85-96%) and 63% (45-78%), respectively. Patients with false-negative mpMRI EPE prediction were more likely to have positive surgical margins in univariable (OR: 2.14; CI: 1.18, 3.87) as well as multivariable analysis adjusting for NCCN risk categories (OR: 1.97; CI: 1.08, 3.60). Conclusions The performance of mpMRI for prediction of EPE varies greatly between different NCCN risk categories with a low positive predicting value in patients at low to favorable intermediate risk and a low negative predictive value in patients at Unfavorable intermediate to high risk PCa. Given that mpMRI EPE misdiagnosis could have a negative impact on oncological and functional outcomes, NCCN risk categories should be considered when interpreting mpMRI findings in PCa patients.

We compared the performance of multiparametric magnetic resonance imaging for the prediction of extraprostatic extension in African American and Caucasian American men and evaluated racial disparities in pathological outcomes after radical prostatectomy.We identified 975 patients who underwent radical prostatectomy with preoperative multiparametric magnetic resonance imaging between January 2013 and April 2019 at our institution. Multivariable logistic regression analysis was performed predicting pathological extraprostatic extension, high grade prostate cancer (final pathology GGG [Gleason Grade Group] 3 or greater) in the overall population and pathological upgrading (final pathology GGG 3 or greater) in patients with a diagnosis of GGG 1-2 prostate cancer. Adverse pathology was defined as pT3 and/or GGG 3 or greater.A total of 221 (23%) patients were African American. Preoperatively 594 (60.9%) were GGG 1-2 (low risk group) and 381 (39.1%) GGG 3 or greater (high risk group). In the low risk group rates of pathological extraprostatic extension (18% vs 12.8%, p=0.14), adverse pathology (18% vs 13.4%, p=0.2) or upgrading (9.4% vs 12.1%, p=0.4) were similar between races. Similarly, in the high risk group there was no difference in rates of pathological extraprostatic extension. On multivariable analysis multiparametric magnetic resonance imaging predicted the presence of extraprostatic extension (OR 1.80, 95% CI 1.29-2.50) and high grade prostate cancer (OR 1.82, 95% CI 1.25-2.67) on final pathology. Conversely, race did not predict the outcomes of interest (all values p0.05). Multiparametric magnetic resonance imaging showed comparable sensitivity (22.22% vs 27.84%), specificity (89.2% vs 79.2%), positive predictive value (89.2% vs 83.4%) and negative predictive value (89.2% vs 83.4%) between African American and Caucasian America men, respectively.The accuracy of multiparametric magnetic resonance imaging in staging prostate cancer was similar in African American and Caucasian American patients and no difference was found between races in pathological outcomes after radical prostatectomy. These findings suggest that access to and use of advanced diagnostic tests may help mitigate prostate cancer racial disparities.

Publisher's version (útgefin grein), Objective: To evaluate the effect of intrusive thoughts at diagnosis on quality of life, depressed mood and waking up with anxiety up to two years after radical prostatectomy. Method: The Laparoscopic Prostatectomy Robot Open (LAPPRO) trial was a prospective, longitudinal multicenter study of 4003 patients undergoing radical prostatectomy. Questionnaire data were collected preoperatively, at 3, 12 and 24 months after surgery. Results: The group of patients with intrusive thoughts at diagnosis had a statistically significant higher postoperative prevalence of impaired quality of life, depressed mood and waking up with anxiety as compared with the group of patients with no or minor intrusive thoughts. The highest risk increase for impaired QoL, depressed mood and waking up with anxiety ≥1/week was at 12, 3 and 3 months, respectively, where the three outcomes increased by 38% (RR: 1.38; 95%CI: 1.27–1.49)), 136% (RR: 2.36; 95%CI: 1.74–3.19)) and 165% (RR: 2.65; 95%CI: 2.22–3.17)), respectively. Conclusions: The demonstrated link between intrusive thoughts and quality of life, depressed mood and waking up with anxiety deliver is further evidence to the idea that intrusive thoughts has potential as an endpoint for assessing and predicting psychological distress among men with prostate cancer diagnosis. Trial registration number: ISRCTN06393679 (www.isrctn.com). Date of registration: 07/02/2008. Retrospectively registered., This study was supported by research grants from the Swedish Cancer Society [2008/922, 2010/593, 2016/362], The Swedish Research Council [2012?1770, 2015?02483], ALF grants [138751, 146201 and 4307771, HTA?VGR 6011], the Mrs. Mary von Sydow Foundation, the Anna and Edvin Berger Foundation and the Assar Gabrielsson?s Foundation [FB 18-19]. The authors gratefully acknowledge the participants in the LAPPRO trial.

Background Patient-related factors such as concern about cancer are believed to influence both men’s decisions to undergo prostate specific antigen (PSA) testing and to have definitive treatment if diagnosed with low risk prostate cancer (PCa). The potential link between screening frequency and choice of active surveillance (AS) for low risk disease has not been studied previously. Our aim was to investigate whether there is any association between PCa screening frequency or previous negative prostate biopsy and uptake of AS among men with low risk PCa. Methods This register-based study included all men ≤75 years from Stockholm who were diagnosed with low risk PCa from 2008 to 2014 (n = 4336). Pre-diagnostic PSA testing and biopsy histories were obtained from the Stockholm PSA and Biopsy Register, a population-based register for the Stockholm country. The association between previous screening/biopsy history and AS uptake (based on primary treatment recorded in the National Prostate Cancer Register) was examined using multivariable logistic regression. Results Forty seven percent of men with low risk PCa underwent AS. Uptake was associated with older age, very low risk disease, more recent diagnosis and absence of family history. None of the screening/biopsy measures (testing frequency, mean interval, PSA velocity, highest pre-diagnostic PSA or prior negative biopsy) were associated with uptake of AS among men with low risk PCa. Generalisability to settings with different policies and practices may be limited. Conclusion We found no evidence that screening frequency and negative biopsy influence uptake of AS among Swedish men with low risk PCa. Further research is required to determine factors that still present barriers for men taking up AS. Electronic supplementary material The online version of this article (10.1186/s12894-019-0502-4) contains supplementary material, which is available to authorized users.