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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.

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.

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 (

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.

Purpose:We compared the use of 11C-choline and 68Ga-prostate specific membrane antigen in men undergoing salvage lymph node dissection for nodal recurrent prostate cancer.Materials and Methods:The ...

BackgroundIn the PURE-01 study (NCT02736266), we aimed to evaluate the ability to predict the pathologic complete response (pT0N0) after pembrolizumab by using clinical and tumor biomarkers.MethodsIn an open-label, single-arm, phase 2 study, 3 courses of 200 mg pembrolizumab preceding radical cystectomy were administered in patients with T2-4aN0M0 muscle-invasive bladder cancer. The analyses included a comprehensive genomic profiling and programmed cell-death-ligand-1 (PD-L1)–combined positive score assessment (CPS; Dako 22C3 antibody) of pre- and posttherapy samples. Multivariable logistic regression analyses evaluated baseline clinical T stage and tumor biomarkers in association with pT0N0 response. Corresponding coefficients were used to develop a calculator of pT0N0 response based on the tumor mutational burden (TMB), CPS, and the clinical T stage. Decision-curve analysis was also performed. All statistical tests were 2-sided.ResultsFrom February 2017 to June 2019, 112 patients with biomarker data were enrolled (105 with complete TMB and CPS data). Increasing TMB and CPS values featured a linear association with logistic pT0N0 probabilities (P = .02 and P = .004, respectively). For low TMB values (≤11 mut/Mb, median value, n = 53), pT0N0 probability was not associated with increasing CPS. Conversely, for high TMB values (>11 mut/Mb, n = 52), pT0N0 was statistically significantly associated with higher CPS (P = .004). The C index of the pT0N0 probability calculator was 0.77. On decision-curve analysis, the net benefit of the model was higher than the “treat-all” option within the clinically meaningful threshold probabilities of 40%-50%.ConclusionsThe study presents a composite biomarker-based pT0N0 probability calculator that reveals the complex interplay between TMB and CPS, added to the clinical T stage.

Purpose: To test the effect of perioperative chemotherapy (CHT) on overall mortality (OM) and cancer-specific mortality (CSM) in patients with locally advanced or metastatic squamous cell carcinoma of the urinary bladder (SCC UB). Methods: Within the Surveillance, Epidemiology and End Results database (1988–2016), we identified 1,018 SCC UB patients (664 T3–4aN0M0, 197 TanyN1–3M0 and 156 T4bN0–3 or M1), who underwent radical cystectomy with or without perioperative chemotherapy administration. Inverse probability of treatment-weighting (IPTW), Kaplan–Meier plots and Cox-regression models (CRMs) were used. Results: CHT was administrated in 116 (17.5%) T3–4aN0M0, 77 (39.1%) TanyN1–3M0 and 47 (30.1%) T4bN0–3 or M1 patients. IPTW-adjusted 2-year cancer-specific survival (CSS) was 66.5 vs. 71.5% (p = 0.19), 60.9 vs. 29.5% (p < 0.001) and IPTW-adjusted 1-year CSS was 46.2 vs. 31.1% (p = 0.03) for CHT vs. no CHT administration in T3–4aN0M0, TanyN1–3M0 and T4bN0–3 or M1, respectively. In multivariable IPTW-adjusted CRMs, chemotherapy was an independent predictor of lower CSM in TanyN1–3M0 (HR 0.44) and in T4bN0–3 or M1 (HR 0.60), but not in T3–4aN0M0 (p = 0.6) patients. Virtually the same results were obtained on OM, as well as without IPTW-adjustment and after stratification according to age and gender. Conclusions: The use of perioperative CHT in patients with SCC UB confers survival benefit in the presence of T4b disease, lymph node or distant metastases. Conversely, patients with locally advanced disease but negative lymph node invasion do not benefit from its use. Pending higher quality data from prospective trials, these data should encourage the use of perioperative CHT in those high-risk patient groups.

Background: In the PURE-01 study, pembrolizumab was given preoperatively before radical cystectomy in clinical T2-4aN0M0 patients. An accurate clinical response assessment may be useful for developing new perioperative strategies in these patients. Objective: To evaluate the association between bladder multiparametric magnetic resonance imaging (mpMRI) findings after pembrolizumab and the pathological complete response (CR; pT0). Design, setting, and participants: Patients were staged using bladder mpMRI whereby radiologists were asked to characterize the following parameters: residual disease at T1- and T2-weighted images (step 1: yes/no), presence of hyperintense spots within the bladder wall on diffusion-weighted imaging (step 2: yes/no), and presence of pathological contrast enhancement (step 3: yes/no), before and after three cycles of pembrolizumab. Examinations were internally assessed by two senior radiologists and externally evaluated by a third senior radiologist. Intervention: To evaluate bladder tumor response after neoadjuvant pembrolizumab, mpMRI was used. Outcome measurements and statistical analysis: The primary objective was to predict the pT0 after neoadjuvant pembrolizumab by relying on the mpMRI findings. Cohen's kappa statistics was used to assess interobserver variability. Univariable analyses for pT0 were performed including internal and external post-therapy mpMRI steps. Results and limitations: From February 2017 to October 2018, 82 patients (164 total mpMRI assessments) were analyzed. The agreement between the internal and external mpMRI assessments after therapy was acceptable (κ values ranging from 0.5 to 0.76). Each mpMRI step was significantly associated with pT0 in both internal and external assessments. In patients with CR/no evidence of residual disease (NED) in all internally evaluated mpMRI steps (N = 37), the pT0 was seen in 23 (62%), compared with 19 of 26 externally evaluated NED patients (73%). Conclusions: In post-pembrolizumab muscle-invasive bladder cancer, mpMRI sequence assessment had acceptable interobserver variability and represented the basis for the proposal of a radiological CR/NED status definition predicting the pT0 response to pembrolizumab. After validation of these findings with external datasets, we propose this tool for developing bladder-sparing immunotherapy maintenance therapies. Patient summary: Assessment of the extent of disease in patients with muscle-invasive bladder cancer using conventional imaging yields serious limitations. In the PURE-01 study, we evaluated the potential of bladder multiparametric magnetic resonance imaging (MRI) to predict the pathological complete response to neoadjuvant pembrolizumab. After validation with larger datasets, the proposed stepwise assessment incorporating multiparametric MRI sequences will be used at our center to develop bladder-sparing approaches in future studies. • In the PURE-01 study, multiparametric magnetic resonance imaging (mpMRI) of the bladder was used to stage and evaluate the response to pembrolizumab, before radical cystectomy. • Assessments of mpMRI sequence were externally reviewed, showing preliminary but promising reproducibility. • We proposed an mpMRI-based definition of complete response predicting the pathological complete response to pembrolizumab that was externally replicated.

Background Patients with predominant variant histology (VH) of bladder tumors, defined as involving >50 % of the tumor specimens, are typically excluded from clinical trials, and for these patients, the efficacy of standard chemotherapy is limited. Objective To evaluate the activity of preoperative pembrolizumab in patients with muscle-invasive bladder carcinoma (MIBC) and VH, enrolled in PURE-01 study (NCT02736266). Design, setting, and participants In the open-label, single-arm, phase 2 PURE-01 study, three courses of 200 mg pembrolizumab preceding radical cystectomy (RC) were administered in T2-4aN0M0 MIBC patients. The amended study design included patients with predominant VH. Intervention Neoadjuvant pembrolizumab and RC. Outcome measurements and statistical analysis Pathological complete response (pT0) in intention-to-treat population was the primary endpoint. Biomarker analyses included programmed cell-death ligand-1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 antibody) and comprehensive genomic profiling (FoundationOne assay). Multivariable logistic regression analyses (MVAs) evaluated the histological category (predominant VH vs nonpredominant VH vs pure urothelial carcinoma), tumor mutational burden (TMB) and CPS in association with the pathological response. Results and limitations From February 2017 to June 2019, 114 patients were enrolled; 34 (30%) of them presented with VH, including 19 (17%) with predominant VH. In total, the pT0 rate was 37% (95% confidence interval [CI]: 28–46) and the pT ≤ 1 rate was 55% (95% CI: 46–65). The majority of predominant VH patients presented with squamous-cell carcinoma (SCC; N = 7), and six of seven (86%) had downstaging to pT ≤ 1, with one pT0; two of three lymphoepithelioma-like (LEL) variants had a pT0 response. None of the remaining nine predominant VHs had a response. On MVA, TMB and CPS were associated with both the pT0 and the pT ≤ 1 response, regardless of tumor histology. Conclusions The updated PURE-01 results confirm the activity of neoadjuvant pembrolizumab in MIBC. Patients with SCC and LEL features may be suitable for neoadjuvant immunotherapy trials. CPS and TMB are the key response predictors irrespective of the histological subtypes. Patient summary In the PURE-01 study, we have preliminarily evaluated the activity of neoadjuvant pembrolizumab in patients with predominant variant histology (VH). Of these patients, those harboring squamous-cell carcinoma or a lymphoepithelioma-like variant feature had major, although preliminary, pathological responses compared with those with other predominant VHs. Expression of programmed cell-death ligand-1 and tumor mutational burden may predict the pathological response to pembrolizumab, and provide a rationale for selecting patients according to these features instead of the histological bladder cancer subtypes.

Background: To investigate the effect of frailty on short-term postoperative outcomes in patients with prostate cancer treated with radical prostatectomy (RP). Methods: Within the National Inpatient Sample database, we identified 91,618 RP patients treated between 2008 and 2015. The Johns Hopkins Adjusted Clinical Groups frailty-defining indicator was applied, and we examined the rates of frailty over time, as well as its effect on overall complications, major complications, nonhome-based discharge, length of stay (LOS), and total hospital charges (THCs). Time trends and multivariable logistic, Poisson and linear regression models were applied. Results: Overall, 12,185 (13.3%) patients were frail. Rates of frail patients increased over time (from 10.3 to 18.2%; p < 0.001). Frail patients had higher rates of overall complications (16.6 vs. 8.6%), major complications (4.9 vs. 2.6%), nonhome-based discharge (5.9 vs. 5%), longer LOS (2 vs. 1), and higher THCs ($37,186 vs. $35,241) (all p < 0.001). Moreover, frailty was an independent predictor of overall complications (OR: 1.95), major complications (OR: 1.76), nonhome-based discharge (OR: 1.20), longer LOS (RR: 1.19), and higher THCs (RR: $3160) (all p < 0.001). Of frail patients, 10,418 (85.5%) neither exhibited body mass index ≥ 30 nor Charlson comorbidity index ≥ 2. Conclusions: On average, every seventh RP patient is frail and that proportion is on the rise. Frail individuals are at higher risk of adverse short-term postoperative outcomes, that cannot be predicted by other risk factors, such as obesity or comorbidities.

Background and objectives To examine the effect of conditional survival on 5-year cancer-specific survival (CSS) probability after radical nephroureterectomy (RNU) in a contemporary cohort of patients with non-metastatic urothelial carcinoma of the upper urinary tract (UTUC). Methods Within the Surveillance, Epidemiology and End Results database (2004-2015), 6826 patients were identified. Conditional 5-year CSS estimates were assessed after event-free follow-up duration. Multivariable Cox regression (MCR) models predicted cancer-specific mortality (CSM) according to event-free follow-up length. Results Overall, 956 (14.0%) were T1 low grade(LG)N0 , 1305 (19.1%) T1 high grade(HG)N0 , 1215 (17.8%) T2 N0 , 2249 (32.9%) T3 N0 and 1101 (16.1%) T4 N0 /Tany N1-3 . From baseline, 93.4% to 94.2% in T1 LGN0 provided 5-year CSS and, respectively, 86.2% to 95.3% in T1 HGN0 , 77.5% to 87.8% in T2 N0 , 63.0% to 91.1% in T3 N0 , and 38.8% to 88.2% in T4 N0 /Tany N1-3 . In MCR models, relative to T1 LGN0 , T1 HGN0 (Hazard ratio [HR] 1.7), T2 N0 (HR 3.0), T3 N0 (HR: 5.2), and T4 N0 /Tany N1-3 (HR 11.9) were independent predictors of higher CSM. Conditional HRs decreased to levels equivalent to T1 LGN0 at 3 years vs 5 years of event-free survival for T1 HGN0 and all other groups, respectively. Conclusions A direct relationship exists between event-free follow-up and survival probability after RNU. From a clinical perspective, such survival estimates may have particular importance during preoperative counseling.

Whether or not adding systematic biopsies (transrectal ultrasound-guided biopsy [TRUS-Bx]) to targeted cores in patients with a lesion detected at multiparametric magnetic resonance imaging (mpMRI) is still a debated topic.To identify patients who can avoid TRUS-Bx at the time of mpMRI targeted biopsy (MRI-TBx) relying on individual patient probability to harbour clinically significant prostate cancer (csPCa) outside the index lesion (IL).A total of 339 European and 441 North American patients underwent fusion MRI-TBx and concomitant TRUS-Bx at two tertiary care referral centres between 2013 and 2017.The study outcome was csPCa, defined as a Gleason score at biopsy of ≥7, outside the IL. Multivariable logistic regression analyses (MVAs) were performed to develop a predictive model for the study outcome. Multivariable-derived coefficients were used to develop a novel risk calculator in each cohort. The models were evaluated using the area under the curve (AUC), calibration plot, and decision-curve analyses.In the European cohort, csPCa detection rate was 55%. The csPCa detection rate for TRUS-Bx was 41%. At MVAs, prostate volume, previous negative biopsy, and Prostate Imaging Reporting and Data System versions 4 and 5 were independent predictors for the presence of csPCa outside the IL. The multivariable model had an AUC of 0.78. Omitting TRUS-Bx in patients with a calculated risk of15% would have spared 16% of TRUS-Bx at the cost of missing 7% of csPCa. Similar findings were obtained when the same analyses were performed in the North American cohort. No net benefit was observed for low-threshold probabilities (15%) of the each model relative to the standard of care (performing TRUS-Bx in addition to MRI-TBx to all patients) in both cohorts. The study is limited by its retrospective design.We failed to identify those patients who might safely benefit from MRI-TBx alone. The combination of MRI-TBx and TRUS-Bx should strongly be considered the best available approach.In the presence of positive multiparametric magnetic resonance imaging (mpMRI) of the prostate, physicians should always perform systematic sampling of the prostate in addition to mpMRI targeted biopsy.

Background: The PURE-01 study (NCT02736266) evaluated the use of pembrolizumab before radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC). Objective: To evaluate the ability of molecular signatures to predict the pathological complete response (CR: ypT0N0) and progression-free survival (PFS) after pembrolizumab and RC. Design, setting, and participants: We analyzed the expression data from patients with T2–4aN0M0 MIBC enrolled in the PURE-01 study (N = 84) and from patients of a retrospective multicenter cohort treated with cisplatin-based neoadjuvant chemotherapy (NAC; N = 140). Intervention: Neoadjuvant pembrolizumab or NAC and RC. Outcome measurements and statistical analysis: Immune signatures and molecular subtyping (The Cancer Genome Atlas, consensus model, and genomic subtyping classifier [GSC]) were evaluated in relation to CR and PFS. Multivariable logistic regression analyses for CR were used, adjusting for gender and clinical T stage. Results and limitations: The Immune190 signature was significant for CR on multivariable logistic regression analyses (p = 0.02) in PURE-01, but not in the NAC cohort (p = 0.7). Hallmark signatures for interferon gamma (IFNγ; p = 0.004) and IFNα response (p = 0.006) were also associated with CR for PURE-01, but not for NAC (IFNγ: p = 0.9 and IFNα: p = 0.8). In PURE-01, 93% of patients with the highest Immune190 scores (>1st quartile) had 2-yr PFS versus 79% of those with lower scores; no difference was observed in NAC patients, as well as for the other hallmarks in both groups. The neuroendocrine-like subtype had the worst 2-yr PFS in all three subtyping models (33%) and the GSC claudin-low subtype had the best, with no recurrences in 2 yr. Basal subtypes (across classifications) with higher Immune190 scores showed 100% 2-yr PFS after pembrolizumab therapy (p = 0.04, compared with basal-Immune190 low). Statistical analyses are limited by the small number of events and short follow-up. Conclusions: Higher RNA-based immune signature scores were significantly associated with CR and numerically improved PFS outcomes after pembrolizumab, but not after NAC. These data emphasize that RNA profiling is a potential tool for personalizing neoadjuvant therapy selection. Patient summary: We used gene expression profiling to evaluate the association between immune gene expression and response to neoadjuvant immunotherapy, compared with standard chemotherapy, in patients with muscle-invasive bladder cancer (MIBC). We found a significant association between immune gene expression and response to pembrolizumab, but not chemotherapy. We conclude that gene expression profiling has the potential to guide personalized neoadjuvant therapy in MIBC. By using gene expression profiling of transurethral bladder tumor resection samples from patients with muscle-invasive bladder cancer (MIBC), we reported a significant association between pre-existing immune gene expression and response to neoadjuvant pembrolizumab, but not to neoadjuvant chemotherapy. Different outcomes were also obtained according to the molecular subtype. Gene expression profiling has the potential to guide personalized neoadjuvant therapy in MIBC.

Background Despite the key importance of magnetic resonance imaging (MRI) parameters, risk classification systems for biochemical recurrence (BCR) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) are still based on clinical variables alone. Objective We aimed at developing and validating a novel classification integrating clinical and radiological parameters. Design, setting, and participants A retrospective multicenter cohort study was conducted between 2014 and 2020 across seven academic international referral centers. A total of 2565 patients treated with RP for PCa were identified. Outcome measurements and statistical analysis Early BCR was defined as two prostate-specific antigen (PSA) values of ≥0.2 ng/ml within 3 yr after RP. Kaplan-Meier and Cox regressions tested time and predictors of BCR. Development and validation cohorts were generated from the overall patient sample. A model predicting early BCR based on Cox-derived coefficients represented the basis for a nomogram that was validated externally. Predictors consisted of PSA, biopsy grade group, MRI stage, and the maximum diameter of lesion at MRI. Novel risk categories were then identified. The Harrel’s concordance index (c-index) compared the accuracy of our risk stratification with the European Association of Urology (EAU), Cancer of the Prostate Risk Assessment (CAPRA), and International Staging Collaboration for Cancer of the Prostate (STAR-CAP) risk groups in predicting early BCR. Results and limitations Overall, 200 (8%), 1834 (71%), and 531 (21%) had low-, intermediate-, and high-risk disease according to the EAU risk groups. The 3-yr overall BCR-free survival rate was 84%. No differences were observed in the 3-yr BCR-free survival between EAU low- and intermediate-risk groups (88% vs 87%; p = 0.1). The novel nomogram depicted optimal discrimination at external validation (c-index 78%). Four new risk categories were identified based on the predictors included in the Cox-based nomogram. This new risk classification had higher accuracy in predicting early BCR (c-index 70%) than the EAU, CAPRA, and STAR-CAP risk classifications (c-index 64%, 63%, and 67%, respectively). Conclusions We developed and externally validated four novel categories based on clinical and radiological parameters to predict early BCR. This novel classification exhibited higher accuracy than the available tools. Patient summary Our novel and straightforward risk classification outperformed currently available preoperative risk tools and should, therefore, assist physicians in preoperative counseling of men candidate to radical treatment for prostate cancer.

INTRODUCTION AND OBJECTIVE:Previous studies on genitourinary malignancies have demonstrated a survival advantage for patients affected by high BMI, attributed to an inverse correlation between onco...

INTRODUCTIONAND OBJECTIVE: Docetaxel is widely used in metastatic castration-resistant prostate cancer (mCRPC), however its optimal use remains unclear. Biomarkers and prediction models assessing e...

INTRODUCTION AND OBJECTIVE:Existing evidence supporting a specific number of targeted biopsy (TBx) cores in case of a positive multi-parametric magnetic resonance imaging (mpMRI) of the prostate is...

INTRODUCTION AND OBJECTIVE:The impact of open or minimally invasive surgery (either laparoscopic or robotic approach) on survival and disease recurrence in the management of non-metastatic renal ce...

INTRODUCTION AND OBJECTIVE:Race/ethnicity may predispose to less favorable prostate cancer characteristics in intermediate risk prostate cancer (IR PCa) patients. We tested this hypothesis in a sub...

INTRODUCTION AND OBJECTIVE:Cytoreductive radical prostatectomy (cRP) might be an option in oligometastatic prostate cancer (PCa). However, no preoperative risk tool is available to select candidate...

Background: Salvage lymph node dissection (sLND) for nodal recurrence in prostate cancer (PCa) patients with biochemical recurrence (BCR) is still not recommended in current guidelines, because of the diagnostic inaccuracy of current conventional imaging. To assess the performance of [68Ga] Ga-prostate-specific membrane antigen conjugate 11 positron emission tomography (PSMA-PET) in detecting PCa lymph node metastasis using pathologic confirmation through sLND. Methods: Literature search was conducted using the MEDLINE, SCOPUS, Web of Science, and Cochrane Library on November 11th, 2018 to identify the eligible studies. Studies were eligible if they investigated the diagnostic performance of PSMA-PET before sLND in PCa patients with BCR and reported the number of true positive, false positive, false negative, and true negative on a lesion-based and/or field-based analyses to compare with histopathologic findings in sLND specimens. Results: Fourteen studies published between 2015 and 2018 comprising 462 patients were selected in this systematic review and meta-analysis. The positive predictive value of PSMA-PET before sLND on a patient-based analysis ranged between 0.70 and 0.93. The pooled sensitivity using lesion-based and field-based analyses were 0.84 (95%CI: 0.61–0.95) and 0.82 (95%CI: 0.72–0.89), respectively. The pooled specificity using lesion-based and field-based analyses were 0.97 (95%CI: 0.95–0.99) and 0.95 (95%CI: 0.70–0.99), respectively. The diagnostic odds ratio using lesion-based and field-based analyses were 189 (95%CI: 39–920) and 82 (95%CI: 8–832), respectively. Conclusions: PSMA-PET before sLND provided highly accurate performance with clinically relevant high positive and negative predictive values for detecting lymph node disease in patients with BCR after local treatment with curative intent for PCa. PSMA-PET can identify the patients who are likely to benefit from sLND and possibly direct to lesion or region-based dissection.

Background Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies. Objective To assess the accuracy of available tools to predict LNI and to develop a novel model for men diagnosed via MRI-targeted biopsies. Design, setting, and participants A total of 497 patients diagnosed via MRI-targeted biopsies and treated with RP and extended pelvic lymph node dissection (ePLND) at five institutions were retrospectively identified. Outcome measurements and statistical analyses Three available models predicting LNI were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses. A nomogram predicting LNI was developed and internally validated. Results and limitations Overall, 62 patients (12.5%) had LNI. The median number of nodes removed was 15. The AUC for the Briganti 2012, Briganti 2017, and MSKCC nomograms was 82%, 82%, and 81%, respectively, and their calibration characteristics were suboptimal. A model including PSA, clinical stage and maximum diameter of the index lesion on multiparametric MRI (mpMRI), grade group on targeted biopsy, and the presence of clinically significant PCa on concomitant systematic biopsy had an AUC of 86% and represented the basis for a coefficient-based nomogram. This tool exhibited a higher AUC and higher net benefit compared to available models developed using standard biopsies. Using a cutoff of 7%, 244 ePLNDs (57%) would be spared and a lower number of LNIs would be missed compared to available nomograms (1.6% vs 4.6% vs 4.5% vs 4.2% for the new nomogram vs Briganti 2012 vs Briganti 2017 vs MSKCC). Conclusions Available models predicting LNI are characterized by suboptimal accuracy and clinical net benefit for patients diagnosed via MRI-targeted biopsies. A novel nomogram including mpMRI and MRI-targeted biopsy data should be used to identify candidates for ePLND in this setting. Patient summary We developed the first nomogram to predict lymph node invasion (LNI) in prostate cancer patients diagnosed via magnetic resonance imaging-targeted biopsy undergoing radical prostatectomy. Adoption of this model to identify candidates for extended pelvic lymph node dissection could avoid up to 60% of these procedures at the cost of missing only 1.6% patients with LNI.

Prostate cancer (PCa) patients with lymph node invasion at radical prostatectomy are at higher risk of tumor recurrence and receive immediate androgen deprivation therapy (ADT). While approximately 30% of these patients do not experience recurrence, others experience disease recurrence despite ADT, and currently no biomarkers can accurately identify them. We analyzed tumors from 51 patients with node-positive prostate cancer using immunohistochemistry to investigate whether expression of the immune checkpoint ligand PD-L1 by tumor cells or the density of CD8+ or CD20+ cells are associated with clinical progression. Patients with at least 1% PD-L1+ tumor cells had shorter metastasis-free survival than those with PD-L1- tumors (p =0.008, log-rank test). Univariate Cox regression showed that patients with PD-L1+ tumors had almost four times the risk of experiencing distant metastases than those with PD-L1- tumors (hazard ratio 3.90). In addition, we found that PD-L1 expression was significantly associated with CD8+ T-cell density, but not with CD20+ B-cell density. While these results need to be confirmed in larger studies, they show that PD-L1 and CD8 may be used as biomarkers for node-positive patients at high risk of progression. The study also provides a rationale for selecting patients with node-positive PCa who might benefit the most from adjuvant immunotherapies. Patient summary: None of the available biomarkers can identify node-positive prostate cancer that will recur after surgery. We found that expression of PD-L1 by tumor cells and a high density of CD8+ T cells in tumor are associated with a higher risk of clinical progression in men with node-positive prostate cancer. Biological markers predicting tumor recurrence in node-positive prostate cancer (PCa) are currently lacking. By investigating formalin-fixed paraffin-embedded tissue sections from 51 patients with node-positive PCa, we found that patients with tumors expressing PD-L1 and/or with a higher frequency of intratumor CD8+ T cells were at the highest risk of developing PCa metastasis after surgery. These results may open new frontiers for the use of adjuvant immunotherapy in this subset of node-positive patients.

Background Intermediate risk prostate cancer (IR PCa) may exhibit a wide array of phenotypes, from favorable to unfavorable. NCCN criteria help distinguishing between favorable versus unfavorable subgroups. We studied and attempted to improve this classification. Methods Within the SEER database 2010-2016, we identified 19,193 IR PCa patients treated with radical prostatectomy. A multivariable logistic regression model predicting unfavorable IR PCa was developed and externally validated, in addition to a head-to-head comparison with NCCN IR PCa stratification. Results Model development (development cohort n=13,436: 3,585 unfavorable versus 9,851 favorable) rested on age, PSA, clinical T stage, biopsy Gleason Grade Group (GGG) and percentage of positive cores. All were independent predictors of unfavorable IR PCa. In external validation cohort (n=5,757: 1,652 unfavorable versus 4,105 favorable), NCCN stratification was 61.8% accurate in discriminating between favorable versus unfavorable, compared to 67.6% for nomogram, which exhibited excellent calibration, less pronounced departures from ideal prediction and greater net-benefit in decision curve analyses (DCA) than NCCN stratification. The optimal nomogram cutoff misclassified 312 of 1976 patients (15.8%) versus 598 of 2877 (20.8%) for NCCN stratification. Of NCCN misclassified patients, 90.0% harbored pT3-4 stages versus 84.6% of nomogram. Conclusions The newly developed, externally validated nomogram discriminates better between favorable versus unfavorable IR PCa, according to overall accuracy, calibration, DCA, and actual numbers and stage distribution of misclassified patients.

1021 Objectives: To investigate the anatomical and 68Ga-DOTATATE uptake features of bone metastases on 68Ga-DOTATATE PET/CT and its clinical value for neuroendocrine neoplasms (NENs). Methods: Enrolled in this retrospective analysis were 32 patients with NENs bone metastases, all of whom underwent 68Ga-DOTATATE PET/CT (17 men, 15 women; range 31-82 years). The patients9 age, sex, primary tumor location, and pathological grade were collected. The imaging features of the bone metastases were evaluated. The bone metastases of different primary locations and different grades of NENs were compared. In addition, the sensitivity and accuracy of 68Ga-DOTATATE PET/CT,68Ga-DOTATATE PET and CT alone in the diagnosis of bone metastases in NENs were compared. Results: Among the 32 patients, 68Ga-DOTATATE PET/CT found a total of 268 lesions, of which 234 were malignant lesions and 34 were benign lesions.There were 234 bone metastases, including 140 vertebrae (74 lumbar, 51 thoracic, 15 cervical), 54 pelvis, 23 ribs, 14 limbs, and 3 skulls. PET detected 208 bone metastases lesions, SUVmax was 3.1 ± 2.5, 26 lesions had no tracer uptake, no lesion tracer uptake was level 1, 164 lesions tracer were level 2, and 18s lesion tracer uptake was level 3; CT detected 192 bone metastases lesions with a diameter of about 1.0 ± 0.4cm; both PET and CT could measure 166 bone metastases lesions with an average size of (1.1 ± 0.5) cm, SUVmax of 2.9 ± 2.3, and there was a correlation between size and SUVmax (r = 0.34, P

Introduction Several studies have invariably shown that the risk of Grade Group (GG) upgrading between biopsy and radical prostatectomy (RP) is higher in elderly men. Whether this is due to a real biological effect or to a diagnostic bias is still unknown. We hypothesized that the introduction of multiparametric magnetic resonance imaging (MRI) has improved the diagnostic accuracy of PCa detection in older men thus reducing the risk of GG upgrading at RP reported in the pre-MRI era. Materials and Methods We selected 424 men who received a systematic plus targeted biopsy for a positive MRI and subsequent RP at two referral centers between 2013 and 2019. Upgrading was defined as an increase in GG at final pathology as compared to biopsy. Multivariable logistic regressions tested the risk of upgrading over increasing age according to any upgrading definition and after stratifying definitions according to GG group and biopsy type. Non-parametric functions explored the relationship between age and upgrading rate. Results Median rate of upgrading was 17%. In multivariable models, while age was not associated with increased risk of GG upgrading (p=0.4). At non-parametric analyses, probability of upgrading slightly decreased with age, without reaching statistical significance. In subgroup analyses according to different upgrading definition and to biopsy type, age did not predict higher risk of upgrading regardless of outcome definitions (GG 1 to 2 P = 0.1; GG 2 to 3 P = 0.2; GG 3 to 4-5 P = 0.2) and in GG detected at TBx (OR 0.998, P = 0.8). Conclusions We showed that use of MRI has obliterated the association between older age and increased risk of upgrading mainly due to improved diagnostic approaches in this group of men. Therefore, it is likely that the effect of age and GG upgrading reported in previous studies in elderly men was due to misdiagnosis and lead-time bias in the pre-MRI era.

Background The impact of positive surgical margins (PSMs) on the risk of metastases in prostate cancer (PCa) patients treated with radical prostatectomy (RP) is still debated. Objective To identify PSM features associated with recurrence in a stage-by-stage analysis. Design, setting, and participants A total of 1757 PCa patients treated with RP without neoadjuvant or adjuvant treatments between 2011 and 2017 were identified. Patients were stratified according to the presence of PSM and to margins characteristics in three groups: no versus favourable (single margin Outcome measurements and statistical analysis Predictors of biochemical recurrence (BCR) and clinical recurrence (CR) were assessed using semiparametric Cox proportional hazard models. Results and limitations Overall, 285 (16%) patients had PSMs; 146 (51%) had a unifocal PSM, while 139 (49%) had a multifocal PSM. The median length of a PSM was 1 mm. Overall, 120 (42%) versus 165 (58%) patients had favourable versus unfavourable PSMs. In patients with ≤pT3a and pathologic grade group ≤3 disease (n = 1351), favourable (hazard ratio [HR]: 2.24; 95% confidence interval [CI]: 1.19–4.22) and unfavourable (HR: 2.68; 95% CI: 1.49–4.84) PSMs significantly increased the risk of BCR (p 0.05). Conversely, in patients with pT3b/4 and/or pathologic grade group 4–5 and/or pN1 (n = 406), only an unfavourable PSM was associated with both BCR (HR: 2.96; 95% CI: 1.19–4.22) and CR (HR: 2.60; 95% CI: 1.07–6.30; all p ≤ 0.04). Conclusions Although the presence of PSMs was associated with an increased risk of BCR in all stages, only men with adverse pathologic characteristics and an unfavourable PSM were at an increased risk of experiencing metastases as compared with their counterparts with no or a single margin shorter than 3 mm. Patient summary In this study, we defined a new category of unfavourable positive surgical margins (namely, ≥3 mm and/or multifocal), which confers a higher risk of developing metastasis in men with more aggressive pathologic features.

Background: To assess the diagnostic added value of sampling secondary lesions at prostate mpMRI (SL) in addition to index lesion (IL) in detecting significant prostate cancer (csPCa) when also systematic biopsy (SBx) is performed. Methods: We relied on a cohort of 312 men with two suspicious lesions at prostate mpMRI who underwent subsequent targeted biopsy of each lesion (TBx) and concomitant SBx at two tertiary-referral centers between 2013 and 2019. The study outcome was the added value of targeting SL (i.e., the one with a lower PI-RADS score and/or the smaller size compared to IL) in the detection of csPCa. To this aim, we compared different biopsy strategies (SBx + overall TBx vs SBx + IL-targeted biopsy vs SBx + SL-targeted biopsy) and assessed whether SL features could be correlated with detection of csPCa at overall TBx in a multivariable logistic regression model (MVA). Results: Overall, 44% of men had csPCa at TBx of all lesions while 39% and 23% of men had csPCa found in IL and SL, respectively. The rate of csPCa found at SBx, IL-TBx, and SL-TBx only was 5%, 6%, and 2%, respectively. The detection rate of csPCa for SBx + IL-TBx was 47%. The addition of SL-TBx increased csPCa detection by only 2% (p = 0.12). At MVA, neither PI-RADS of SL nor the number of cores targeting SL was associated with an increased detection of csPCa (all p > 0.3). Conversely, age (OR: 1.07), PSA (OR: 1.07), prostate volume (OR: 0.98), and PI-RADS of the IL (OR: 2.36) were independently associated with csPCa detection at TBx (all p < 0.01). Conclusions: There is no significant benefit in terms of csPCa detection when an adequate SBx is performed in combination with IL-TBx in patients with multiple mpMRI lesions. In these men target biopsy of secondary lesions can be safely omitted.

Objective: To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on screening, diagnosis, and local treatment of clinically localised prostate cancer (PCa). Evidence acquisition: The panel performed a literature review of new data, covering the time frame between 2016 and 2020. The guidelines were updated and a strength rating for each recommendation was added based on a systematic review of the evidence. Evidence synthesis: A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. Risk-adapted screening should be offered to men at increased risk from the age of 45 yr and to breast cancer susceptibility gene (BRCA) mutation carriers, who have been confirmed to be at risk of early and aggressive disease (mainly BRAC2), from around 40 yr of age. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is performed, a combination of targeted and systematic biopsies must be offered. There is currently no place for the routine use of tissue-based biomarkers. Whilst prostate-specific membrane antigen positron emission tomography computed tomography is the most sensitive staging procedure, the lack of outcome benefit remains a major limitation. Active surveillance (AS) should always be discussed with low-risk patients, as well as with selected intermediate-risk patients with favourable International Society of Urological Pathology (ISUP) 2 lesions. Local therapies are addressed, as well as the AS journey and the management of persistent prostate-specific antigen after surgery. A strong recommendation to consider moderate hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term hormonal treatment. Conclusions: The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for their use in clinical practice. These PCa guidelines reflect the multidisciplinary nature of PCa management. Patient summary: Updated prostate cancer guidelines are presented, addressing screening, diagnosis, and local treatment with curative intent. These guidelines rely on the available scientific evidence, and new insights will need to be considered and included on a regular basis. In some cases, the supporting evidence for new treatment options is not yet strong enough to provide a recommendation, which is why continuous updating is important. Patients must be fully informed of all relevant options and, together with their treating physicians, decide on the most optimal management for them. The 2020 European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on prostate cancer (PCa) summarise the most recent findings and provide recommendations for clinical practice, addressing screening, diagnosis, and local treatment with curative intent. Key stakeholders in PCa management were involved in their development, including a patient representative. A full version is available at the EAU office and online at http://uroweb.org/guideline/prostate-cancer/. A separate publication will address the management of relapsing-, metastatic-, and castration-resistant PCa.

Prostate-specific membrane antigen (PSMA) imaging is characterized by superior accuracy compared to conventional imaging for identification of nodal and distant metastases in prostate cancer. The majority of international clinical guidelines recommend PSMA positron emission tomography/computed tomography for patients experiencing biochemical recurrence, even at low prostate-specific antigen values, to identify candidates for salvage therapies. However, its use in for primary staging is still not recommended.

INTRODUCTION AND OBJECTIVE:Biochemical recurrence (BCR) after radical prostatectomy (RP) for non-metastatic prostate cancer (PCa) leads to clinical progression only in a subpopulation. The aim of t...

Context The prognosis and optimal management of pN0/pN1 patients with persistently elevated prostate-specific antigen (PSA) 6–8 wk after radical prostatectomy (RP) remain unclear. Objective To perform a systematic review of oncologic outcomes and effectiveness of salvage therapies in men with a detectable PSA level after RP. Evidence acquisition A systematic review was performed in May 2020. A total of 2374 articles were screened, and 25 studies including 5217 men were selected and included in the systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Evidence synthesis PSA persistence was most commonly defined as PSA >0.1 ng/ml. PSA persistence was significantly correlated with disease aggressiveness and associated with worse oncologic outcomes than in men with undetectable PSA levels. The 5-yr recurrence-free survival rates varied from 21.5% to 67.0%. The ≥10-yr cancer-specific survival was 75–88%. Salvage radiotherapy ± androgen deprivation therapy was associated with improved survival outcomes. Risk stratification according to pathologic features, PSA levels/kinetics, and genomic classifier may aid in personalization of treatment. The usefulness of molecular imaging in this setting remains underevaluated. Main limitations of this systematic review are the retrospective design of the included studies and the lack of randomized controlled trials (RCTs) focusing on this specific population. Conclusions PSA persistence after RP is strongly correlated with poor oncologic outcomes. Our review suggests a benefit from immediate radiotherapy; however, current evidence is still low. Indication of subsequent therapies should be based on individual discussions, taking into account all the prognostic factors and the efficacy/toxicity imbalance of proposed treatment. Results from ongoing RCTs are awaited to state on the role of more intensified systemic therapy in this population. Patient summary Patients with a detectable prostate-specific antigen level after surgery are at high risk of subsequent progression. Immediate radiotherapy might improve survival outcomes. Further research into the role of molecular imaging and genomic classifier is needed in this patient population.

Objective: To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy & Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (CRPC). Evidence acquisition: The working panel performed a literature review of the new data (2016–2019). The guidelines were updated, and the levels of evidence and/or grades of recommendation were added based on a systematic review of the literature. Evidence synthesis: Prostate-specific membrane antigen positron emission tomography computed tomography scanning has developed an increasingly important role in men with biochemical recurrence after local therapy. Early salvage radiotherapy after radical prostatectomy appears as effective as adjuvant radiotherapy and, in a subset of patients, should be combined with androgen deprivation. New treatments have become available for men with metastatic hormone-sensitive prostate cancer (PCa), nonmetastatic CRPC, and metastatic CRPC, along with a role for local radiotherapy in men with low-volume metastatic hormone-sensitive PCa. Also included is information on quality of life outcomes in men with PCa. Conclusions: The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are first endorsed by the EANM and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online (http://uroweb.org/guideline/prostate-cancer/). Patient summary: This article summarises the guidelines for the treatment of relapsing, metastatic, and castration-resistant prostate cancer. These guidelines are evidence based and guide the clinician in the discussion with the patient on the treatment decisions to be taken. These guidelines are updated every year; this summary spans the 2017–2020 period of new evidence. The knowledge in the field of advanced and metastatic prostate cancer (PCa) and castration-resistant prostate cancer is changing rapidly. The 2020 European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy & Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are first endorsed by the EANM and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online (http://uroweb.org/guideline/prostate-cancer/).

To design a dedicated risk calculator for patients with penile urethra stricture who are scheduled to urethroplasty that might be used to counsel patients according to their pre-operative risk of failure. Patients treated with penile urethroplasty at our center (1994–2018) were included in the study. Patients received 1-stage or staged penile urethroplasty. Patients with failed hypospadias repair, lichen sclerosus or incomplete clinical records were excluded. Treatment failure was defined as any required postoperative instrumentation, including dilation. Univariable Cox regression identified predictors of post-operative treatment failure and Kaplan–Meier analysis plotted the failure-free survival rates according to such predictors. Multivariable Cox regression-based risk calculator was generated to predict the risk of treatment failure at 10 years after surgery. 261 patients met the inclusion criteria. Median follow-up was 113 months. Out of 216 patients, 201 (77%) were classified as success and 60 (23%) failures. Former smoker (hazard ratio [HR] 2.12, p = 0.025), instrumentation-derived stricture (HR 2.55, p = 0.006), and use of grafts (HR 1.83, p = 0.037) were predictors of treatment failure. Model-derived probabilities showed that the 10-year risk of treatment failure varied from 5.8 to 41.1% according to patient’s characteristics. Long-term prognosis in patients who underwent penile urethroplasty is uncertain. To date, our risk-calculator represents the first tool that might help physicians to predict the risk of treatment failure at 10 years. According to our model, such risk is largely influenced by the etiology of the stricture, the use of graft, and patient’s smoking habits.

INTRODUCTION AND OBJECTIVE:Docetaxel is a widely used treatment option in metastatic castration-resistant prostate cancer (mCRPC). However, its optimal use remains unclear in the current treatment ...

INTRODUCTION AND OBJECTIVE:Previous studies have shown a survival advantage for patients with high body mass index (BMI) and metastatic renal cancer. In prostate cancer patients, findings regarding...

INTRODUCTION AND OBJECTIVE:Single-nucleotide polymorphisms (SNPs) are the most common genetic alterations and SNPs in DNA repair genes, such as BRCA1/2, have a relationship with a variety of cancer...

INTRODUCTION AND OBJECTIVE:Curative intent therapies such as radical prostatectomy (RP) might represent an option in prostate cancer (PCa) patients with enlarged lymph nodes at imaging (cN1), no da...