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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.

OBJECTIVE: To evaluate the relationship between pre-operative PSA value, 68Ga-prostate-specific-membrane-antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa). PATIENTS AND METHODS: The study included 164 patients diagnosed with ≤2 pelvic lymph-node recurrence(s) of PCa documented on 68Ga-PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high-volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (1.5 ng/ml). Clinical recurrence (CR)-free survival after sLND was calculated using multivariable analyses and plotted over pre-operative PSA value. RESULTS: Median [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre-operative PSA value, with highest rates for patients with pre-operative PSA > 1.5 ng/ml (pelvic-only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre-operative PSA was associated with PSA response (p

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.

Context: there is uncertainty regarding the most appropriate criteria for recruitment, monitoring, and reclassification in active surveillance (AS) protocols for localised prostate cancer (PCa). Objective: to perform a qualitative systematic review (SR) to issue recommendations regarding inclusion of intermediate-risk disease, biopsy characteristics at inclusion and monitoring, and repeat biopsy strategy. Evidence acquisition: a protocol-driven, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-adhering SR incorporating AS protocols published from January 1990 to October 2020 was performed. The main outcomes were criteria for inclusion of intermediate-risk disease, monitoring, reclassification, and repeat biopsy strategies (per protocol and/or triggered). Clinical effectiveness data were not assessed. Evidence synthesis: of the 17 011 articles identified, 333 studies incorporating 375 AS protocols, recruiting 264 852 patients, were included. Only a minority of protocols included the use of magnetic resonance imaging (MRI) for recruitment (n = 17), follow-up (n = 47), and reclassification (n = 26). More than 50% of protocols included patients with intermediate or high-risk disease, whilst 44.1% of protocols excluded low-risk patients with more than three positive cores, and 39% of protocols excluded patients with core involvement (CI) >50% per core. Of the protocols, ?80% mandated a confirmatory transrectal ultrasound biopsy; 72% (n = 189) of protocols mandated per-protocol repeat biopsies, with 20% performing this annually and 25% every 2 yr. Only 27 protocols (10.3%) mandated triggered biopsies, with 74% of these protocols defining progression or changes on MRI as triggers for repeat biopsy. Conclusions: for AS protocols in which the use of MRI is not mandatory or absent, we recommend the following: (1) AS can be considered in patients with low-volume International Society of Urological Pathology (ISUP) grade 2 (three or fewer positive cores and cancer involvement ?50% CI per core) or another single element of intermediate-risk disease, and patients with ISUP 3 should be excluded; (2) per-protocol confirmatory prostate biopsies should be performed within 2 yr, and per-protocol surveillance repeat biopsies should be performed at least once every 3 yr for the first 10 yr; and (3) for patients with low-volume, low-risk disease at recruitment, if repeat systematic biopsies reveal more than three positive cores or maximum CI >50% per core, they should be monitored closely for evidence of adverse features (eg, upgrading); patients with ISUP 2 disease with increased core positivity and/or CI to similar thresholds should be reclassified. Patient summary: We examined the literature to issue new recommendations on active surveillance (AS) for managing localised prostate cancer. The recommendations include setting criteria for including men with more aggressive disease (intermediate-risk disease), setting thresholds for close monitoring of men with low-risk but more extensive disease, and determining when to perform repeat biopsies (within 2 yr and 3 yearly thereafter)., NA

Background: Prospective data collection for perioperative outcomes might increase awareness of surgical results obtained for patients with prostate cancer (PCa) undergoing robot-assisted radical prostatectomy (RARP). This would prompt the implementation of measures aimed at reducing the risk of adverse outcomes. Objective: To assess the efficacy of an audit and feedback process aimed at identifying the most common complications after RARP and at implementing measures to improve outcomes. Design, setting, and participants: Overall, 415 patients treated with RARP by a high-volume surgeon were included. Perioperative outcomes for 187 patients treated between September 2016 and December 2017 were prospectively collected at 30 d according to the European Association of Urology guideline recommendations (group 1). An audit and feedback process was implemented in January 2018 whereby the most common complication (anastomotic leak) was identified and measures aimed at improving outcomes (changes in the anastomotic technique) were implemented. The outcomes for group 1 were then compared to 228 patients treated after implementation of the modified surgical technique (group 2). Surgical procedure: A novel technique for posterior reconstruction and urethrovesical anastomosis was introduced. Measurements: Perioperative outcomes included blood loss, operative time, length of stay, and 30-d postoperative complications. Logistic regression models tested the effect of the novel surgical technique on anastomotic leaks. Results and limitations: Overall, 97 patients (23%) experienced postoperative complications at 30 d. The rate of anastomotic leaks was significantly lower in group 2 compared to group 1 (3.1% vs 9.6%; p < 0.01). Similarly, overall and Clavien-Dindo grade ≥2 complication rates were lower in group 2 versus group 1 (17% vs 31%, and 6% vs 20%; both p ≤ 0.001). In multivariable analyses, treatment after implementation of changes in the anastomotic technique independently predicted a lower risk of complications (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.38–0.89) and of anastomotic leaks (OR 0.43, 95% CI 0.17–0.97). The lack of randomization represents the main limitation. Conclusions: Implementation of changes in the urethrovesical anastomosis technique arising from increased awareness of surgical outcomes reduced the risk of anastomotic leaks. These findings highlight the importance of audit and feedback processes using a standardized method for reporting surgical morbidity. Patient summary: Increased awareness of surgical outcomes prompted us to change our technique for connecting the bladder to the urethra during robot-assisted surgery to remove the prostate in patients with prostate cancer. These changes resulted in significant improvements in surgical outcomes.

Contains fulltext : 291600.pdf (Publisher’s version ) (Open Access) BACKGROUND: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. OBJECTIVE: To present consensus voting results for select questions from APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members ("panellists") who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1-3. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. RESULTS AND LIMITATIONS: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. CONCLUSIONS: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.

In the PURE-01 study, patients with muscle-invasive bladder cancer (MIBC) who achieved a pathological complete response (CR; ypT0N0) had tumor features suggesting that pre-existing immunity may promote response. We focused on fibroblast growth factor receptor-3 (FGFR3) genomic alterations (GAs) as potential tumor resistance features. The primary endpoint of our study was CR. FGFR3 GAs were assessed via comprehensive genomic profiling of sequenced DNA (N = 112), a transcriptome-based FGFR3 activity signature, an FGFR3 subtyping model based on long noncoding RNA (lncRNA), and gene expression profiling (N = 84 for all three). We used Wilcoxon rank-sum tests, Fisher's exact test, and logistic regression analyses to analyze the associations between the various FGFR3 alterations and CR. High FGFR3 activity was defined as a signature score that was higher than the median value. Cases that were positive for lncRNA-FGFR3 subtype (lncRNA-FGFR3 active, N = 11) had consistent biology with published data: low epithelial-mesenchymal transition and immune-signature scores, high p53 activity, FGFR3 activity, and sonic hedgehog activity. In total, 17 (15.2%), 42 (50%), and 11 patients (13%) showed FGFR3 GAs or high FGFR3 signature scores, or had lncRNA-FGFR3–active tumors. Despite an association of high FGFR3 gene expression with a lower CR rate (p = 0.01), we did not find a correlation between FGFR3 activity or mutation/fusion and CR (p = 0.2 and p = 0.8). We conclude that the association of FGFR3 expression with pathological response is balanced by multiple factors. Overall, FGFR3-altered tumors should not be excluded from neoadjuvant immunotherapy studies at this time. Patient summary In patients with muscle-invasive bladder cancer treated within the PURE-01 trial, we analyzed the role of fibroblast growth factor receptor-3 (FGFR3) alterations, at the DNA and RNA levels, in association with the pathological response. We did not find any robust association, mainly when analyzing the landscape of alterations defining tumors with higher biological FGFR activity. Overall, FGFR3 activity and gene alterations did not provide sufficiently robust data to exclude patients whose tumors harbor these alterations from neoadjuvant immunotherapy trials.

Context The variability of the positive predictive value (PPV) represents a significant factor affecting the diagnostic performance of multiparametric magnetic resonance imaging (mpMRI). Objective To analyze published studies reporting mpMRI PPV and the reasons behind the variability of clinically significant prostate cancer (csPCa) detection rates on targeted biopsies (TBx) according to Prostate Imaging Reporting and Data System (PI-RADS) version 2 categories. Evidence acquisition A search of PubMed, Cochrane library’s Central, EMBASE, MEDLINE, and Scopus databases, from January 2015 to June 2020, was conducted. The primary and secondary outcomes were to evaluate the PPV of PI-RADS version 2 in detecting csPCa and any prostate cancer (PCa), respectively. Individual authors’ definitions for csPCa and PI-RADS thresholds for positive mpMRI were accepted. Detection rates, used as a surrogate of PPV, were pooled using random-effect models. Preplanned subgroup analyses tested PPV after stratification for PI-RADS scores, previous biopsy status, TBx technique, and number of sampled cores. PPV variation over cancer prevalence was evaluated. Evidence synthesis Fifty-six studies, with a total of 16 537 participants, were included in the quantitative synthesis. The PPV of suspicious mpMRI for csPCa was 40% (95% confidence interval 36–43%), with large heterogeneity between studies (I2 94%, p Conclusions Our meta-analysis underlines that the PPV of mpMRI is strongly dependent on the disease prevalence, and that the main factors affecting PPV are PI-RADS version 2 scores and prior biopsy status. A substantially low PPV for PI-RADS 3 lesions was reported, while it was still suboptimal in PI-RADS 4 and 5 lesions. Lastly, even if the added value of a systematic biopsy for csPCa is relatively low, this rate can improve patient risk assessment and staging. Patient summary Targeted biopsy of Prostate Imaging Reporting and Data System 3 lesions should be considered carefully in light of additional individual risk assessment corroborating the presence of clinically significant prostate cancer. On the contrary, the positive predictive value of highly suspicious lesions is not high enough to omit systematic prostate sampling.

Data regarding the incidence and prognostic impact of immune-related imaging changes, assessed by 18[F] fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan, in patients receiving immune-checkpoint inhibitors (ICIs) are lacking. We relied on the population of patients enrolled in the PURE-01 study to evaluate such changes. Background: Data regarding the incidence and prognostic impact of immune-related imaging changes, assessed by 18[F] fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan, in patients receiving immune-checkpoint inhibitors (ICIs) are lacking. We relied on the population of patients enrolled in the PURE-01 study to evaluate such changes. Objective: To evaluate the role of PET/CT to visualize the immune-related adverse events (irAEs) following pembrolizumab. Design, setting, and participants: From February 2017 to August 2019, in 103 patients with nonmetastatic, clinical T2–4aN0M0 bladder cancer, PET/CT scan was performed before and after neoadjuvant pembrolizumab (N = 206 scans), before radical cystectomy. Intervention: PET/CT before and after neoadjuvant pembrolizumab, before radical cystectomy. Outcome measurements and statistical analysis: We analyzed the occurrence of irAEs, evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, against the development of inflammatory FDG uptake described at PET/CT (irAEs + PET/CT). Logistic regression analyses evaluated the association between irAEs + PET/CT and the pathological response to pembrolizumab. Kaplan-Meier curves tested their association with progression-free survival (PFS) after pembrolizumab and radical cystectomy. Results and limitations: Forty patients (39%) developed irAEs + PET/CT in several target organs. The most frequent target organs were the thyroid (N = 18), stomach (N = 14), mediastinal lymph nodes (N = 9), and lung (N = 5). These changes were clinically evident in 18 (45%) and were not associated with the pathological response, neither in terms of complete response (ypT0N0, p = 0.07) nor as downstaging to ypT≤1N0 disease (p = 0.1), although ypT0N0 responses were numerically more frequent in patients with irAEs+ PET/CT (47.5% vs 32%). Furthermore, irAE+ PET/CT events were associated with longer, not statistically significant, 24-mo PFS: 88.3% versus 76.5% (p = 0.5). Our results warrant further validation in larger datasets. Conclusions: We presented unique surrogate data of PET/CT that could help improve our understanding of nonclinically evident effects of ICI administration, especially in patients at the early disease stage. Patient summary: We evaluated the utility of PET/CT to visualize the occurrence of inflammatory changes after pembrolizumab in patients with localized bladder cancer without metastases. After immunotherapy, 39% of the patients developed 18[F] fluorodeoxyglucose uptake consistent of inflammatory changes. Overall, our data improve our knowledge on the effects induced by immunotherapy, which may have a clinical impact at longer follow-up. Take Home Message ● In the PURE-01 study, T2–4N0M0 muscle-invasive bladder cancer patients were staged with fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) before and after pembrolizumab. ● PET/CT after pembrolizumab revealed inflammatory FDG uptake in 39% of patients, but only 45% of these cases of uptake corresponded to clinically evident adverse events. ● The development of inflammatory uptake was associated with a higher pathological complete response rate and longer progression-free survival, although these differences were not statistically significant.

Race/ethnicity may predispose to less favorable prostate cancer characteristics in intermediate risk prostate cancer (IR PCa) patients. We tested this hypothesis in a subgroup of IR PCa patients treated with radical prostatectomy (RP). We relied on the Surveillance, Epidemiology and End Results 2004–2016. The effect of race/ethnicity was tested in univariable and multivariable logistic regression analyses predicting upstaging (pT3+/pN1) and/or upgrading (Gleason Grade Group [GGG] 4–5) at RP. Of 20,391 IR PCa patients, 15,050 (73.8%) were Caucasian, 2857 (14.0%) African-American, 1632 (8.0%) Hispanic/Latino and 852 (4.2%) Asian. Asian patients exhibited highest age (64 year), highest PSA (6.8 ng/ml) and highest rate of GGG3 (31.9%). African-Americans exhibited the highest percentage of positive cores at biopsy (41.7%) and the highest proportion of NCCN unfavorable risk group membership (54.6%). Conversely, Caucasians exhibited the highest proportion of cT2 stage (35.6%). In univariable analyses, Hispanic/Latinos exhibited the highest rates of upstaging/upgrading among all race/ethnicities, in both favorable and unfavorable groups, followed by Asians, Caucasians and African-Americans in that order. In multivariable analyses, Hispanic/Latino race/ethnicity represented an independent predictor of higher upstaging and/or upgrading in favorable IR PCa (odds ratio [OR] 1.27, p

Background There is a lack of evidence on the ability of magnetic resonance imaging (MRI) of the prostate to detect clinically significant prostate cancer (csPCa) in young patients. Objective We hypothesised that the diagnostic performance of MRI for csPCa varies according to patient's age. To address this, we assessed the variation in the csPCa detection rate of MRI targeted biopsy (MRI-TBx) versus systematic random biopsy (SBx) across different patient ages. Design, setting, and participants We retrospectively identified 930 patients who underwent prostate MRI and subsequent biopsy at two referral centres between 2013 and 2018. The Prostate Imaging Reporting and Data System (PI-RADS) was used for MRI reporting. Intervention A lesion with a PI-RADS score of ≥3 detected at MRI received an MRI-TBx in addition to an SBx during the same session. Outcome measurements and statistical analysis The outcome of our study was the relationship between age and csPCa detection rate at MRI-TBx and SBx, respectively. Clinically significant prostate cancer (PCa) was defined as the presence of PCa with Gleason score ≥3 + 4. Multivariable logistic regression analyses (MVAs) predicting csPCa detection were assessed for both MRI-TBx and SBx. Covariates were age, prostate-specific antigen density, PI-RADS score, previous biopsy status, digital rectal examination, and the number of targeted and systematic cores. The hypothesis that MRI accuracy in detecting csPCa differed by age was finally tested with a nonparametric loess analysis. Results and limitations The overall rate of csPCa was 54% (n = 506). Overall, 325 (35%) and 461 (50%) patients had csPCa at SBx and MRI-TBx, respectively. The median numbers of SBx and MRI-TBx cores were 12 (interquartile range [IQR]: 10–13) and 5 (IQR: 4–7), respectively. At MVA, age at biopsy was an independent predictor of csPCa at MRI-TBx only (odds ratio: 1.05), after accounting for confounders. In men aged less than roughly 50 yr, SBx had a higher probability of detecting csPCa relative to MRI-TBx (25% vs 16% at 40 yr). Conversely, in patients aged >50 yr, the probability of csPCa was higher in MRI-TBx than in SBx, reaching the highest difference for very elderly patients (48% vs 68% at 80 yr). The main limitations were the retrospective design and the small number of young patients. Conclusions In this study, we reported the performance of MRI and MRI-TBx in detecting csPCa changes according to patients’ age. Patient summary In young patients, the performance of a systematic random biopsy in detecting clinically significant prostate cancer (csPCa) is higher relative to magnetic resonance imaging targeted biopsy (MRI-TBx), reflecting the lower accuracy of MRI in younger men. Conversely, in older patients, MRI-TBx showed a clinical benefit with a higher csPCa detection rate compared with SBx, suggesting an increase of MRI accuracy with the increase of age.

The best surgical template for salvage pelvic lymph node dissection (sLND) in patients with nodal recurrence from prostate cancer (PCa) after radical prostatectomy (RP) is currently unknown. We analyzed data of 189 patients with a unilateral positive positron emission tomography (PET) scan of the pelvic lymph node areas, who were treated with bilateral pelvic sLND after RP at 11 high-volume centers. The primary endpoint was missed contralateral disease at final pathology, defined as lymph node positive for PCa in the side opposite to the positive spot(s) at the PET scan. Overall, 93 (49%) and 96 (51%) patients received a 11C-choline and a 68Ga prostate-specific membrane antigen (PSMA) PET scan, respectively, and 171 (90%) and 18 (10%) men had one and two positive spots, respectively. The rate of missed contralateral PCa was 18% (34/189), with the rates being 17% (29/171) and 28% (5/18) in men with one and two positive spots, respectively. While the rate of contralateral disease did not differ between 68Ga-PSMA and 11C-choline (29% and 27%, respectively) among men with two positive spots, the rate of contralateral PCa was only 6% with 68Ga-PSMA versus 28% with 11C-choline in patients with a single positive spot. This finding was confirmed at multivariable logistic regression analysis predicting missed disease at final pathology after accounting for confounders (odds ratio: 0.24; p = 0.001). However, in men with a single positive spot at 68Ga-PSMA PET/computed tomography, the rate of single confirmed lymph node metastasis at final pathology was only 33%, suggesting the need for extended template even if unilateral dissection is performed. Awaiting confirmatory studies, patients diagnosed with a single positive spot at the 68Ga-PSMA PET scan might be considered for unilateral extended pelvic sLND. Patient summary We assessed the risk of missing contralateral disease in patients with a positron emission tomography (PET) scan suggestive of unilateral nodal recurrence from prostate cancer (PCa) after radical prostatectomy and who were treated with bilateral salvage lymph node dissection (sLND). Variability exists according to the number of positive spots and PET tracer, with the lowest rate of missed PCa in men diagnosed with a single positive spot at a 68Ga prostate-specific membrane antigen PET scan (6%). If replicated, our data suggest that these patients might be considered for unilateral extended pelvic sLND.

Background: The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown. Objective: To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy. Design, setting, and participants: The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016. Outcome measurements and statistical analysis: We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM. Results and limitations: We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p 10%. Conclusions: PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials. Patient summary: We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.

Objective: To assess the relationship between the volume of the index lesion (IL) measured at multiparametric magnetic resonance imaging (mpMRI; MRIvol) and at radical prostatectomy (RPvol), stratifying it according to Prostate Imaging-Reporting and Data System (PI-RADS) score. Patients and Methods: We identified 332 men with a positive mpMRI (single lesion with PI-RADS ≥3) who underwent systematic plus targeted biopsy and subsequent RP at two tertiary referral centres between 2013 and 2018. All mpMRIs were reviewed by experienced radiologists using PI-RADS scores. The study outcome was to assess the relationship between MRIvol (based on planimetry from MRI sequence best showing tumour) and RPvol (based on tumour involved area of each RP pathology slice). To achieve this endpoint, we performed a multivariable linear regression analysis (LRA) to predict RPvol using PI-RADS, prostate-specific antigen level, prostate volume, age, digital rectal examination, Gleason score at MRI-targeted biopsy, biopsy history and time from mpMRI to RP as covariates. Non-parametric locally estimated scatterplot smoothing (LOESS) function was used to graphically explore the relationship between MRIvol and RPvol, stratifying for PI-RADS score. Results: Overall, 24%, 49% and 27% of men had visible PI-RADS 3, 4 and 5 lesions at mpMRI. The median (interquartile range [IQR]) MRIvol and RPvol were 0.67(0.29–1.76)mL and 1.39(0.58–4.23)mL. At LRA, MRIvol was significantly correlated with a RPvol underestimation (slope: 2.4, 95% confidence interval [CI] 0.1–46.3). The non-parametric LOESS analysis showed a non-linear relationship between MRIvol and RPvol. Significant underestimation was reported across all volumes with the highest differences between MRIvol and RPvol in the low volume range (

Recent studies reported a potential benefit associated with adjuvant radiotherapy for patients with adverse pathology features of prostate cancer. We hypothesized that not all the patients with adverse features may benefit from adjuvant radiotherapy and, therefore, observation ± early salvage radiotherapy may still be considered in a subgroup of these patients.Among 8,362 patients treated with radical prostatectomy at a single center between 1987 and 2020, 926 eligible patients with adverse pathology features (ie, grade group 4-5 with ≥pT3a stage and/or lymph node invasion) were identified. Cox models were used to assign a score to each feature. Patients were then stratified in low-, intermediate-, and high-risk groups, and interaction term analyses tested the impact of adjuvant radiotherapy for each risk subgroup after adjusting for inverse probability of treatment weighting.Overall, 538 (58%) vs 89 (10%) vs 299 (32%) patients received adjuvant radiotherapy vs early salvage radiotherapy vs observation. The 10-year overall survival rate was 90%. A significant interaction between adjuvant radiotherapy and high-risk group was recorded (HR 0.21,Among patients with adverse pathology features, we identified 3 subclassifications of risk. When testing the effect of adjuvant radiotherapy vs observation with or without early salvage radiotherapy on survival, only patients included in the high-risk group seemed to benefit from adjuvant radiotherapy.

Whether early ligation of the dorsal venous complex (DVC) might improve recovery of urinary continence (UC) after robot-assisted radical prostatectomy (RARP) has never been investigated in a prospective randomized study.To assess whether early DVC ligation might affect UC recovery after RARP.DVC ligation (early vs standard).A total of 312 patients with prostate cancer underwent primary RARP at a tertiary care institution.The primary outcome was UC recovery at 1 and 4 mo after RARP. UC was defined as 0 pads/1 safety pad per day. All patients completed the International Prostate Symptom Score (IPSS) and International Consultation of Incontinence Questionnaire (ICIQ)-Short Form questionnaires. Secondary outcomes were early (≤4 mo) erectile function recovery, the positive surgical margin (PSM) rate, 30-d Clavien-Dindo complications, and biochemical recurrence rates. Quality of life was assessed using the EQ-5D-5L questionnaire. The association between treatment arm and UC recovery was also tested using multivariable regression models.After surgery, 23 patients withdrew their consent and 29 were lost to follow-up, leaving 261 patients available for per-protocol analyses. Of these, 32 patients (24%) in the experimental group and 37 (29%) in the control group used no pad/one safety pad at 1 mo after RARP, whereas 96 (72%) in the control group versus 83 (65%) in the control group were continent at 4-mo follow-up (both p = 0.3). Median ICIQ and IPSS scores did not differ between the groups at both time points. The results were confirmed on multivariable regression analyses. PSMs were observed for 32 patients (25%) in the experimental group versus 30 (22%) in the control group (p = 0.6). The incidence of postoperative complications (17% experimental vs 13% control) and the 1-yr biochemical recurrence-free survival did not differ between the groups.In this randomized clinical trial, we did not find evidence that early ligation of the DVC during RARP was associated with better UC recovery after surgery in comparison to the standard technique. Given its safety in terms of surgical margins and complications, this technique may be considered as an option for surgical dissection according to the physician's preference.Our trial showed that for patients undergoing robot-assisted surgical removal of the prostate, the timing of a specific step to control bleeding from a network of veins draining the prostate did not affect recovery of urinary continence after surgery. The results indicate that earlier control of these veins may be considered as an option according to the surgeon's preference.

Background The prognostic role of multiparametric magnetic resonance imaging (mpMRI) and systematic biopsy in predicting biochemical recurrence (BCR) after radical prostatectomy (RP) in prostate cancer (PCa) patients has not been addressed yet. Objective To develop a risk tool predicting BCR after RP in patients diagnosed with magnetic resonance imaging (MRI)-targeted biopsy. Design, setting, and participants A total of 804 patients with a clinical suspicion of PCa and positive mpMRI diagnosed with MRI-targeted plus concomitant systematic biopsy treated with RP were identified. Outcome measurements and statistical analyses The outcome was represented by BCR defined as two prostate-specific antigen (PSA) values ≥0.2 ng/ml after surgery. Multivariable Cox regression analyses assessed the predictors of BCR. A risk tool model based on imaging and biopsy parameters was developed and validated internally. The c-index, calibration plot, and decision curve analyses were used to assess discrimination, calibration, and the net benefit associated with its use in predicting BCR at 36 mo. Results and limitations Median (interquartile range) follow-up was 28 (25–29) mo, and 89 patients experienced BCR. The 36-mo BCR-free survival rate was 89%. The maximum diameter of the index lesion and seminal vesicle invasion (SVI) at mpMRI as well as the presence of clinically significant PCa at systematic biopsy (defined as a grade group of >2) were associated with BCR (all p ≤ 0.03). A model based on PSA, Prostate Imaging Reporting and Data System score, SVI at mpMRI, diameter of the index lesion, grade group at MRI-targeted biopsy, and clinically significant PCa at systematic biopsy achieved the highest discrimination (77%) among all clinical models, as well as the European Association of Urology risk groups (62%) and the Cancer of the Prostate Risk Assessment (CAPRA) score (60%). This tool was characterized by excellent calibration at internal validation and the highest net benefit when predicting BCR for the threshold risk between 0% and 30%. Conclusions The adoption of predictive models accounting for mpMRI and MRI-targeted biopsy-derived variables and concomitant systematic biopsy would improve clinicians’ ability to identify patients at a higher risk of early recurrence after surgery. Patient summary The use of information obtained at multiparametric magnetic resonance imaging (mpMRI), and MRI-targeted and concomitant systematic biopsy would improve clinicians’ ability to identify prostate cancer patients at a higher risk of experiencing early biochemical recurrence after surgery.