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Novel immune checkpoint inhibitors hold promise for non-muscle-invasive bladder cancer. Cooperation between urologists and other multidisciplinary bladder cancer specialists can surmount the challenges involved in using these agents in bladder-sparing approaches. This strategy could deliver a new era of comprehensive evaluation and multimodal treatment for this patient population.

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.

Background Despite efforts aimed at preserving renal function, the functional decline after robot-assisted partial nephrectomy (RAPN) is not negligible. To address the risk of intraparenchymal vessel injuries during renorrhaphy, with consequent loss of functional renal parenchyma, we introduced a new surgical technique for RAPN. Objective To compare perioperative patient outcomes between selective-suturing or sutureless RAPN (suRAPN) and standard RAPN (stRAPN). Design, setting, and participants Ninety-two consecutive patients undergoing RAPN for a renal mass performed by a high-volume surgeon at a European tertiary center were included. Propensity-score matching was used to account for baseline differences between suRAPN and stRAPN patients. Intervention RAPN using a selective-suturing or sutureless technique versus standard RAPN. Outcome measurements and statistical analysis Perioperative outcomes included operative time, blood loss, length of stay, and intraoperative and 30-d postoperative complications. We also evaluated trifecta achievement (warm ischemia time ≤25 min, negative surgical margins, and no perioperative complications) and the incidence of postoperative acute kidney injury (AKI). We applied χ2 tests, t tests, and Kruskal-Wallis tests to assess differences in perioperative outcomes between suRAPN and stRAPN. Results and limitations Overall, 29 patients (31%) were treated with suRAPN. Only one suRAPN patient experienced intraoperative complications (p = 0.9). Two suRAPN patients (6.9%) and four stRAPN patients (13.8%) experienced 30-d postoperative complications (p = 0.3). Operative time (110 vs 150 min; p Conclusions A selective-suturing or sutureless technique in RAPN is feasible and safe. Moreover, suRAPN is a lower-impact surgical procedure. We obtained promising results for trifecta and functional outcomes, but prospective randomized trials are needed to validate the impact of selective suturing or a sutureless technique on long-term functional outcomes. Patient summary We assessed a new technique in robotic surgery to remove part of the kidney because of kidney cancer. Our new technique involves selective suturing or no suturing of the area from where the tumor is removed. We found that the rate of complications did not increase and the operating time and length of hospital stay were shorter using this new technique.

Background: For patients with nonmetastatic renal cell carcinoma (nmRCC) treated with nephrectomy, prediction of cancer-specific mortality (CSM) by T stage and substage has not been validated for the separate histological subtypes. Objective: To investigate the ability of pathological T stage and substage to predict CSM for patients with clear-cell, papillary, or chromophobe nmRCC treated with nephrectomy. Design, setting, and participants: Using the SEER database for 2004–2016, we identified 87 149 patients with T1–4 N0/X M0 nmRCC treated with nephrectomy for the clear-cell (65 715; 75.4%), papillary (14 587; 16.7%), or chromophobe (6847; 7.9%) histological subtype. Outcome measurements and statistical analysis: Kaplan-Meier plots and Cox regression models were used to estimate CSM. Results and limitations: For all three histological subtypes, patients with T1a–T3a disease exhibited more favorable CSM than patients with T3b–T4 RCC. For clear-cell RCC, there were clinically meaningful and statistically significant differences for virtually all intergroup comparisons among T1a–T3a stages. For papillary T1a–T3a RCC, clinically meaningful differences disappeared, although the statistical significance remained. For chromophobe T1a–T3a RCC, no clinically meaningful or statistically significant differences were observed. For all three histological subtypes, patients with T3b–T4 RCC exhibited virtually uniformly unfavorable CSM, with no clinically meaningful intergroup CSM differences. Conclusion: The use of T stage and substage for stratification of patients with nmRCC treated with nephrectomy revealed differences in CSM among T1a–T3a cases, but not T3b–T4. The magnitude of the CSM difference was greatest for clear-cell, intermediate for papillary, and marginal for chromophobe RCC. Patient summary: For patients with kidney cancer, the stage of their disease assessed after surgery on the affected kidney can predict how likely they are to die from their cancer. This prediction varies for different subtypes of kidney cancer. Stratification of surgically treated patients with nonmetastatic renal cell carcinoma (RCC) by T stage revealed mortality differences among T1a–T3a cases, but not T3b–T4 cases. The magnitude of the differences was greatest for the clear-cell subtype, intermediate for papillary histology, and marginal for chromophobe RCC.

Background Salvage treatment for local recurrence after prior partial nephrectomy (PN) or local tumor ablation (LTA) for kidney cancer is, as of yet, poorly investigated. Objective To classify the treatments and standardize the nomenclature of salvage robot-assisted renal surgery, to describe the surgical technique for each scenario, and to investigate complications, renal function, and oncologic outcomes. Design, setting, and participants Sixty-seven patients underwent salvage robot-assisted renal surgery from October 2010 to December 2020 at nine tertiary referral centers. Surgical procedure Salvage robot-assisted renal surgery classified according to treatment type as salvage robot-assisted partial or radical nephrectomy (sRAPN or sRARN) and according to previous primary treatment (PN or LTA). Measurements Postoperative complications, renal function, and oncologic outcomes were assessed. Results and limitations A total of 32 and 35 patients underwent salvage robotic surgery following PN and LTA, respectively. After prior PN, two patients underwent sRAPN, while ten underwent sRARN for a metachronous recurrence in the same kidney. No intra- or perioperative complication occurred. For local recurrence in the resection bed, six patients underwent sRAPN, while 14 underwent sRARN. For sRAPN, the intraoperative complication rate was 33%; there was no postoperative complication. For sRARN, there was no intraoperative complication and the postoperative complication rate was 7%. At 3 yr, the local recurrence-free rates were 64% and 82% for sRAPN and sRARN, respectively, while the 3-yr metastasis-free rates were 80% and 79%, respectively. At 33 mo, the median estimated glomerular filtration rates (eGFRs) were 57 and 45 ml/min/1.73 m2 for sRAPN and sRARN, respectively. After prior LTA, 35 patients underwent sRAPN and no patient underwent sRARN. There was no intraoperative complication; the overall postoperative complications rate was 20%. No local recurrence occurred. The 3-yr metastasis-free rate was 90%. At 43 mo, the median eGFR was 38 ml/min/1.73 m2. The main limitations are the relatively small population and the noncomparative design of the study. Conclusions Salvage robot-assisted surgery has a safe complication profile in the hands of experienced surgeons at high-volume institutions, but the risk of local recurrence in this setting is non-negligible. Patient summary Patients with local recurrence after partial nephrectomy or local tumor ablation should be aware that further treatment with robot-assisted surgery is not associated with a worrisome complication profile, but also that they are at risk of further recurrence.

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.

There is a paucity of data describing the ability of margin, ischemia, complications, score (MIC) and trifecta in predicting long-term outcomes of robotic-assisted partial nephrectomy (RAPN).To compare a novel trifecta (negative margins, no significant complications, and perioperative estimated glomerular filtration rate [eGFR] decrease ≤30%) versus standard MIC as predictors of oncologic and functional results in a large series of RAPNs.Between 2009 and 2019, a multicenter dataset was queried for patients with nonmetastatic renal masses who underwent RAPN at eight participating institutions.RAPN.MIC and trifecta achievement were determined for the overall cohort and a subgroup undergoing off-clamp RAPN (ocRAPN), respectively. The overall survival (OS), recurrence-free survival (RFS), and new onset of end-stage renal disease (ESRD; defined as eGFR30 ml/min) probabilities were assessed by the Kaplan-Meier method. Cox regression analyses were used to identify predictors of OS, RFS, and ESRD. For all analyses, two-sided p0.05 was considered significant.Out of 1807 patients, MIC and trifecta were achieved in 71.1% (n = 1285) and 82.6% (n = 1492), respectively, and once restricted to the ocRAPN cohort, in 95.6% (n = 625) and 81.6% (n = 534), respectively. On Kaplan-Meier analysis, both MIC and trifecta achievement predicted higher OS and lower ESRD probabilities (all p0.014), while only trifecta achievement was a predictor of RFS probabilities (p = 0.009). On multivariable Cox regression, MIC did not predict any of the endpoints independently, while trifecta achievement was an independent predictor of higher OS (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.18-0.86; p = 0.019) and lower ESRD development probabilities (HR 0.32, 95% CI 0.15-0.72; p = 0.005).Trifecta, initially described as comprehensive measures of perioperative outcomes, needs to stand the test of time. Compared with MIC, the recent trifecta was an independent predictor of clinically significant endpoints, namely, survival and ESRD development probabilities.Our novel trifecta represents a reliable method for estimating survival and development of end-stage renal disease after robotic-assisted partial nephrectomy.

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.

Presently, major guidelines do not provide specific recommendations on oncologic surveillance for patients who harbor variant histology (VH) bladder cancer (BCa) at radical cystectomy. We aimed to create a personalized followup scheme that dynamically weighs other cause mortality (OCM) vs the risk of recurrence for VH BCa, and to compare it with a similar one for pure urothelial carcinoma (pUC).Within a multi-institutional registry, 528 and 1,894 patients with VH BCa and pUC, respectively, were identified. The Weibull regression was used to detect the time points after which the risk of OCM exceeded the risk of recurrence during followup. The risk of OCM over time was stratified based on age and comorbidities, and the risk of recurrence on pathological stage and recurrence site.Individuals with VH had a higher risk of recurrence (recurrence-free survival 30% vs 51% at 10 years, p0.001) and shorter median time to recurrence (88 vs 123 months, p0.01) relative to pUC. Among VH, micropapillary variant conferred the greatest risk of recurrence on the abdomen and lungs, and mixed variants carried the greatest risk of metastasizing to bones and other sites compared to pUC. Overall, surveillance should be continued for a longer time for individuals with VH BCa. Notably, patients younger than 60 years with VH and pT0/Ta/T1/N0 at radical cystectomy should continue oncologic surveillance after 10 years vs 6.5 years for pUC individuals.VH BCa is associated with greater recurrence risk than pUC. A followup scheme that is valid for pUC should not be applied to individuals with VH. Herein, we present a personalized approach for surveillance that may allow an improved shared decision.

Background: A severe male infertility factor has been associated with both lower health status and increased mortality in infertile men. Objectives: To investigate reproductive factors associated with health status impairment in infertile men over a 10-year time frame since the first clinical evaluation. Materials and methods: Data from 899 infertile men were analysed at baseline between 2003 and 2010. Health-significant comorbidities were scored with the Charlson Comorbidity Index. Patients were followed up yearly recording any worsening in their health status until 2019. Cox regression models were used to estimate hazard ratios and 95% confidence intervals of Charlson Comorbidity Index score increase. Results: At a median follow-up of 136 months (Interquartile range: 121, 156), 85 men (9.5%) depicted an increase of their baseline Charlson Comorbidity Index score of at least one point. The most frequent reason for Charlson Comorbidity Index upgrade was cancer (34%), cardiovascular diseases (29%) and diabetes mellitus (22%). Compared to patients without a Charlson Comorbidity Index increase, patients with a Charlson Comorbidity Index increase presented with higher body mass index and follicle-stimulating hormone values, a higher rate of baseline Charlson Comorbidity Index ≥ 1 (all p&nbsp

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.

Introduction The COVID-19 outbreak has become the dominant issue throughout the world whilst the governments, nations and health services are trying to deal with its impact. The aim of our study is to assess the impact of COVID-19 on patients treated with radical prostatectomy (RP) for prostate cancer (PCa) at European referral centers in terms of surgical volume (SV), waiting list meant as time from biopsy to surgery (WL) and risk of adverse pathologic findings at RP due to the selection of men with more adverse disease characteristics at final pathology. Material and methods Consecutive patients with a diagnosis of histologically proven PCa treated with RP between March 2020 (WHO declaration of pandemic) and December 2020 were identified. Patients with metastatic disease not eligible to local treatment and recurrent prostate cancer after RP or RT were excluded. Patients treated at the same institutions between March 2019 and December 2019 were considered as the control group. Multivariable logistic regression analysis tested the impact of the COVID-19 outbreak on the risk of adverse pathologic findings at RP after adjusting for confounders. The percentage change of SV and WL was assessed comparing the months of pandemic with the equivalent timespan of the previous year. Results A total of 2,574 patients treated with RP (927 cases and 1647 controls) were identified in 8 European tertiary referral centers. At multivariable analysis patients who were treated during the pandemic had higher risk of extra prostatic disease (OR:1.35, p = 0.038) and lymph node invasion (LNI) (OR:1.72, p = 0.048). An average 23% reduction of the SV with the equivalent timespan of the previous year allowed an illusory reduction of the WL after the peak gained during the first wave of COVID-19. Conclusions Our results showed that the COVID-19 outbreak resulted in a delay in the administration of curative-intent therapies in patients with localized PCa. This, in turn, resulted in a stage migration phenomenon with a potential impact on oncologic control. Weitere Verfasser:innen aus Einrichtungen außerhalb der Universität Duisburg-Essen sind nicht aufgeführt.

Objectives Lymph node invasion (LNI) is related to long-term survival in patients with muscle-invasive bladder cancer. However, in the case of variant histology (VH), data on pelvic lymph node dissection (PLND) and LNI are sparse. We described the pattern of care of PLND in patients with VHs of bladder cancer, exploring predictors of LNI. Methods Using the 2001–2016 SEER registry, 20 767 bladder cancer patients who underwent PLND were identified. Included histological variants were pure urothelial carcinoma (UC), micropapillary UC, sarcomatoid UC, lymphoepithelioma-like UC, adenocarcinoma, sarcoma, giant and spindle cell carcinoma, squamous cell carcinoma (SCC), and neuroendocrine tumor. Uni- and multivariable logistic regression analyses tested for LNI predictors. Cox regression was used to test for predictors of overall mortality (OM) among both LNI positive and LNI negative patients. Results Overall, 2464 (11.9%) harbored a VH. On multivariate analysis, only micropapillary UC was associated with higher risk (OR = 3.39) of LNI. This association was maintained when only the subset of patients treated without perioperative chemotherapy were analyzed (OR = 3.30). Similarly, higher T stage (T2 stage OR = 2.24; T3–4 stage OR = 9.44) and the use of chemotherapy (OR = 2.29) were associated with a higher risk of LNI. Among patients with LNI (5299, 25.5%), SCC (HR = 1.87), T3–4 stage (HR = 1.94), age at diagnosis (HR = 1.01) and geographic region (south) (HR = 1.22) were predictors of higher risk of OM. Conversely, chemotherapy (HR = 0.69) and number of removed LN (HR = −0.99) were associated with lower risk of OM. Finally, in a subgroup of patients without LNI, sarcomatoid UC (HR = 1.58) and giant and spindle cell carcinoma (HR = 1.83) were the only VH predictors of OM. Conclusions We described different patterns of care in patients with VHs of bladder cancer. Micropapillary UC was an independent risk factor for LNI. Among patients harboring LNI, those with SCC VH had higher OM compared to pure UC. Conversely, sarcomatoid UC and giant and spindle cell carcinoma were predictors of OM in patients without nodal involvement.

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.

Despite bladder perforation (BP) is a frequent complication during transurethral resection of bladder (TURB) for bladder cancer (BCa), literature lacks systematic reviews focusing on this issue. We aimed to investigate incidence, diagnosis, therapy, and prognosis after BP during TURB for BCa; therapy was distinguished between conservative (without the need for bladder repair) and surgical management (requiring bladder wall closure).A systematic search was conducted up to April 2021 using PubMed, Scopus, Cochrane Database of Systematic Reviews, and Web of Science to identify articles focusing on incidence, detection, management, or survival outcomes after iatrogenic BP. The selection of articles followed the preferred reporting items for systematic review and meta-analyses process.We included 41 studies, involving 21,174 patients. Overall, 521 patients experienced BP during TURB for BCa, with a mean incidence of 2.4%, up to 58.3% when postoperative cystography is routinely performed after all TURB procedures. Risk factors were low body mass index (BMI) (P=0.01), resection depth (P=0.006 and P=0.03), and low surgical experience (P=0.006). Extraperitoneal BP (68.5%) were treated conservatively in 97.5% of patients; intraperitoneal BP were managed with surgical bladder closure in 56% of cases. Overall, three immediate BP-related deaths were recorded due to septic complications. Extravesical tumor seeding was observed after 6 intraperitoneal and 1 extraperitoneal BP (median time: 6.2 months). Intraperitoneal BP (P=0.0003) and bladder closure (P0.001) were found as independent predictors of extravesical tumor recurrence.BP is more frequent than expected when proper diagnosis is routinely performed after all TURB procedures. Risk factors include low BMI, resection depth, and unexperienced surgeon. The risk of sepsis after BP suggests empirical antibiotic prophylaxis after BP.

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: Ischemia time during partial nephrectomy (PN) is among the greatest determinants of acute kidney injury (AKI). Whether this association is affected by the preoperative risk of AKI has never been investigated.OBJECTIVE: To assess the effect of the interaction between the preoperative risk of AKI and ischemia time on the probability of AKI during PN.DESIGN, SETTING, AND PARTICIPANTS: Data of 944 patients treated with on-clamp PN for cT1 renal tumors were extracted from the Registry of Conservative and Radical Surgery for Cortical Renal Tumor Disease (RECORD2) database, a prospective multicenter project.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We estimated the preoperative risk of AKI (defined according to the risk/injury/failure/loss/end-stage [RIFLE] criteria) according to age, baseline renal function, clinical stage, preoperative aspects and dimensions used for an anatomical (PADUA) score, and surgical approach. Classification and regression tree (CART) analysis identified patients at "high" and "low" risk of AKI. Finally, we plotted the probability of AKI over ischemia time stratified by the preoperative risk of AKI.RESULTS AND LIMITATIONS: Overall, 235 (25%) patients experienced AKI after surgery. At multivariable analysis, older patients, those with more complex tumors, those with higher baseline function, and those treated with open surgery had an increased risk of AKI (all p ≤ 0.011). According to the first split at CART analysis, patients were categorized as those with "high" and "low" risk of AKI having a probability of >40% or 20 min of ischemia was 13% versus 28% (absolute risk increase 15%). The risk of AKI for high-risk patients who had 20 min of ischemia was 31% versus 77%. This corresponds to an absolute risk increase of 45%. Limitations include retrospective data analyses and lack of surgeons' prior experience.CONCLUSIONS: Ischemia time during PN has different implications for patients with different health status. Clamp time seems less clinically relevant for patients in good conditions who may endure prolonged ischemia with a mild increase in the risk of AKI, whereas frail patients seem to be more vulnerable to ischemic damage even for short clamp time. For individualized intra- and postoperative management, duration of ischemia needs to be questioned in the context of the individual health status.PATIENT SUMMARY: Functional sequelae related to ischemia time during partial nephrectomy depend on baseline health status. The correlation between the duration of ischemia and baseline health status should be taken into account toward individualized intra- and postoperative management.

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 inspection of the urethra in patients with documented or suspected urethral stricture should be carried out with small caliber ureteroscope of 6/7.5Ch. Different from flexible cystoscope (16Ch) or resectoscope (26Ch), small caliber ureteroscope allows a comprehensive evaluation of the stricture, including its length and the status of the mucosa in its proximity, without injuring or overstretching the urethra. With a small caliber ureteroscope it is also possible to cross the stricture, allowing the evaluation of the proximal urethra, the external urethral sphincter, and the bladder. A 6/7.5Ch ureteroscope also allows estimation of the real caliber of the stricture, providing a useful landmark for further treatment decisions.

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 (

PURPOSE: Men with nonseminomatous germ cell tumors of the testicle without evidence of residual disease after radical orchiectomy (clinical stage I) are increasingly managed with active surveillance. The guideline-recommended cornerstones of surveillance are conventional serum tumor markers and computerized tomography. The reliability of serum tumor markers as a tool to diagnose early recurrence of clinical stage I nonseminomatous germ cell tumors is unclear. The study objective was to conduct a systematic review of the currently available evidence assessing the reliability of serum tumor markers as a test to diagnose recurrence in patients with clinical stage I nonseminomatous germ cell tumors under active surveillance. MATERIALS AND METHODS: A systematic review was conducted in accordance with PRISMA guidelines, with no language or date restrictions. Studies were included that readily identified the tumor marker status of patients with clinical stage I nonseminomatous germ cell tumors who had a recurrence on active surveillance. The primary outcome was marker positivity at the time of recurrence. Risk of bias assessment was undertaken. RESULTS: A total of 2,157 studies were identified and independently screened by 2 reviewers, with 37 studies ultimately being included. A relatively high risk of bias was identified among the studies, with the vast majority being retrospective series. The total population for the included studies was 8,545 patients with clinical stage I nonseminomatous germ cell tumors managed by active surveillance, and 2,254 ultimately relapsed. Serum tumor markers were elevated in 28% to 75% of patients at the time of recurrence and were the only indication of recurrence in 4% to 39%. The unavailability of patient-level data is the major limitation to the present findings. CONCLUSIONS: In patients with clinical stage I nonseminomatous germ cell tumors managed by active surveillance, the use of serum tumor markers cannot obviate the need for computerized tomography. More reliable serum markers are needed in order to limit radiation exposure for these patients.

Objective: Significant efforts are currently being made to identify novel biomarkers for the diagnosis and risk stratification of prostate cancer (PCa). Metabolomics can be a very useful approach in biomarker discovery because metabolites are an important read-out of the disease when characterized in biological samples. We aimed to determine a metabolomic signature which can accurately distinguish men with clinically significant PCa from those affected by benign prostatic hyperplasia (BPH). Methods: We first performed untargeted metabolomics using ultrahigh-performance liquid chromatography tandem mass spectrometry on expressed prostatic secretion urine (EPS-urine) from 25 patients affected by BPH and 25 men with clinically significant PCa (defined as Gleason score ≥ 3 + 4). Diagnosis was histologically confirmed after surgical treatment. The EPS-urine metabolomic approach was then applied to a larger, prospective cohort of 92 consecutive patients undergoing multiparametric magnetic resonance imaging for clinical suspicion of PCa prior to biopsy. Results: We established a novel metabolomic signature capable of accurately distinguishing PCa from benign tissue. A metabolomic signature was associated with clinically significant PCa in all subgroups of the Prostate Imaging Reporting and Data System (PI-RADS) classification (100% and 89.13% of accuracy when the PI-RADS was in range of 1–2 and 4–5, respectively, and 87.50% in the more critical cases when the PI-RADS was 3). Conclusions: A combination of metabolites and clinical variables can effectively help in identifying PCa patients that might be overlooked by current imaging technologies. Metabolites from EPS-urine should help in defining the diagnostic pathway of PCa, thus improving PCa detection and decreasing the number of unnecessary prostate biopsies.

CONTEXT Pelvic lymph node dissection (PLND) yields the most accurate staging in patients undergoing radical prostatectomy (RP) for prostate cancer (PCa), although it can be associated with morbidity. OBJECTIVE To systematically evaluate the impact of PLND extent on perioperative morbidity in patients undergoing RP. A new PLND-related complication assessment tool is proposed. EVIDENCE ACQUISITION A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) was conducted. MEDLINE/PubMed, Scopus, Embase and Web of Science databases were searched to yield studies discussing perioperative complications following RP and PLND. The extent of PLND was classified according to the European Association of Urology PCa guidelines. Studies were categorized according to the extent of PLND. Intra- and postoperative complications were classified as "strongly," "likely," or "unlikely" related to PLND. Anatomical site of perioperative complications was recorded. A cumulative meta-analysis of comparative studies was conducted using Review Manager 5.3 (Cochrane Collaboration, Oxford, UK). EVIDENCE SYNTHESIS Our search generated 3645 papers, with 176 studies meeting the inclusion criteria. Details of 77 303 patients were analyzed. Of these studies, 84 (47.7%), combining data on 28 428 patients, described intraoperative complications as an outcome of interest. Overall, 534 (1.8%) patients reported one or more intraoperative complications. Postoperative complications were reported in 151 (85.7%) studies, combining data on 73 629 patients. Overall, 10 401 (14.1%) patients reported one or more postoperative complication. The most reported postoperative complication strongly related to PLND was lymphocele (90.6%). The pooled meta-analysis revealed that RP���+���limited PLND/standard PLND had a significantly decreased risk of experiencing any intraoperative complication (risk ratio [RR]: 0.55; p���=��� 0.01) and postoperative complication strongly related to PLND (RR: 0.46; p���=���

Patient-reported outcome instruments for erectile function often ask respondents about their experience over the previous 4wk. This is problematic for baseline assessment of patients with prostate cancer (PC) before treatment, as the previous 4wk would probably have involved procedures such as biopsy and considerable anxiety related to their diagnosis. At San Raffaele Hospital, the International Index of Erectile Function (IIEF-6) was used to ask new PC patients about function in both the previous 4wk and 6mo. We compared responses to these two timeframes. IIEF-6 scores were lower for the 4-wk period (median 24 vs 26; p

Despite the advances in nerve sparing and minimally invasive radical prostatectomy, erectile dysfunction remains an important adverse event after radical prostatectomy. Penile rehabilitation strategies have been developed to expedite and improve erectile function recovery. However, the differential efficacy and the best penile rehabilitation strategy are unclear as yet. We conducted a systematic review and network meta-analysis to investigate and compare the efficacy of different penile rehabilitation strategies.A systematic search was performed in May 2020 using PubMed® and Web of Science™ databases according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) extension statement for network meta-analysis. Studies that compared the erectile function recovery rate and adverse events between penile rehabilitation treatment groups (eg medications, devices and actions) and control group were included. We used the Bayesian approach in the network meta-analysis.A total of 22 studies (2,711 patients) met our eligibility criteria. Out of 16 different penile rehabilitation strategies and schedules vs placebo, only pelvic floor muscle training (OR 5.21, 95% CrI 1.24-29.8) and 100 mg sildenafil regular doses, ie once daily or nightly (OR 4.00, 95% CrI 1.40-13.4) were associated with a significantly higher likelihood of erectile function recovery. The certainty of results for 100 mg sildenafil regular dose was moderate, while pelvic floor muscle training had low certainty. The sensitivity analysis confirmed that the regular high dose of phosphodiesterase-5 inhibitors regardless of type vs placebo (OR 2.09, 95% CrI 1.06-4.17) was associated with a significantly higher likelihood of erectile function recovery with a moderate certainty. The on-demand doses of phosphodiesterase-5 inhibitors were not proven to be more beneficial than placebo. Secondary outcomes such as adverse events were not analyzed due to incomplete data in the literature. However, no serious adverse events were reported in any of the studies.Sildenafil 100 mg regular dose is the best penile rehabilitation strategy to improve erectile function recovery rates after radical prostatectomy. Although pelvic floor muscle training has been shown to be effective in increasing the erectile function recovery rate, well designed randomized controlled trials with larger sample sizes are needed to confirm the presented early results. The on-demand dose of phosphodiesterase-5 inhibitors should not be considered as a penile rehabilitation strategy.

The use of pembrolizumab has been largely accepted in several advanced types of cancers. PURE 01 study (NCT02736266) enrolled consecutively 143 patients with muscle-invasive bladder cancer who received 3 cycles of pembrolizumab 200 mg every 3 weeks before planned radical cystectomy (RC). Clinical, pathological and laboratory data were collected to investigate the relationship between renal function, immunotherapy and cancer-related outcomes. Serum creatinine and estimated glomerular filtration rate (eGFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-equation 2009 were reported at baseline and after every cycle of pembrolizumab; the T stage from clinical classification TNM (cTNM) was stated before the treatment. Our analysis did not demonstrate a significant impairment of eGFR after any cycle of pembrolizumab, neither in the overall cohort nor in subgroups considering the T stages or the CKD G-categories according to K-DIGO 2012 classification. In conclusion, in neoadjuvant setting before RC our results suggest that pembrolizumab administration is safe for renal function preservation.

Testicular volume (TV) is considered a good clinical marker of hormonal and spermatogenic function. Accurate reference values for TV measures in infertile and fertile men are lacking. We aimed to assess references values for TV in white-European infertile men and fertile controls. We analyzed clinical and laboratory data from 1940 (95.0%) infertile men and 102 (5.0%) fertile controls. Groups were matched by age using propensity score weighting. TV was assessed using a Prader orchidometer (PO). Circulating hormones and semen parameters were investigated in every male. Descriptive statistics, Spearman's correlation, and logistic regression models tested potential associations between PO-estimated TV values and clinical variables. Receiver operating characteristic (ROC) curves were used to find TV value cutoffs for oligoasthenoteratozoospermia (OAT) and nonobstructive azoospermia (NOA) status in infertile men. The median testicular volume was smaller in infertile than that of fertile men (15.0 ml vs 22.5 ml; P < 0.001). TV positively correlated with total testosterone, sperm concentration, and progressive sperm motility (all P ≤ 0.001) in infertile men. At multivariable logistic regression analysis, infertile status (P < 0.001) and the presence of left varicocele (P < 0.001) were associated with TV < 15 ml. Testicular volume thresholds of 15 ml and 12 ml had a good predictive ability for detecting OAT and NOA status, respectively. In conclusion, infertile men have smaller testicular volume than fertile controls. TV positively correlated with total testosterone, sperm concentration, and progressive motility in infertile men, which was not the case in the age-matched fertile counterparts.

We performed a post hoc analysis of data from phase 3 and 4 studies to evaluate the efficacy of silodosin 8mg in patients with severe lower urinary tract symptoms (LUTS) related to benign prostatic obstruction (BPO). The presence of two or more of the following criteria was adopted to define severity: total International Prostate Symptom Score (IPSS) 20-35, quality of life (QoL) score 5-6, maximum urinary flow

Docetaxel is widely used in metastatic castration-resistant prostate cancer (mCRPC), however its optimal use remains unclear in the current treatment landscape. Biomarkers to predict Docetaxel toxicity may help optimize treatment selection. We aimed to create a predictive model for toxicity-related Docetaxel discontinuation (TRDD). Through Project Data Sphere, we accessed individual patient data from the control arms of three frontline mCRPC trials: ASCENT2, VENICE, and MAINSAIL. The inclusion criteria for these trials were all similar and included patients with chemotherapy-naive mCRPC. The primary outcome was occurrence of TRDD. A competing risks regression (CRR) was used to predict TRDD, after accounting for the occurrence of competing events (death or progression). The output of the model was used as the dependent variable on a classification and regression tree (CART) to identify risk groups for TRDD. Overall, 1568 patients were considered. Pooled CI of TRDD was 19% after accounting for competing events (death: 474; progression: 59) within 12 months of starting treatment. To build a risk calculator we relied on a CRR that ultimately included age, ECOG performance status, AST, bilirubin, use of analgesics, and presence of diabetes and chronic kidney disease. The CART analysis identified three risk groups that were named: low (model-derived TRDD risk ≤24%), intermediate (25–64%), and high (≥65%) risk group. In each risk group, probability of TRDD during treatment was 14%, 58%, and 79%, and median OS was 24 months, 20 months, and 13 months, respectively (p

Background: Infertile men are at greater risk for oncological and nononcological chronic disease than fertile individuals. Objective: To investigate prostate-specific antigen (PSA) values in men presenting for primary couple's infertility compared with a cohort of fertile individuals, according to the recommendation of the European Association of Urology guidelines that a first PSA assessment should be done at 40–45 yr of age. Design, setting, and participants: This is a cross-sectional study. Data from 956 (90%) infertile men and 102 (9.6%) fertile participants were analysed. Circulating hormones, total PSA, and semen parameters were investigated in every man. Outcome measurements and statistical analysis: Descriptive statistics, local polynomial smoothing, and linear regression models were used to test potential associations with PSA levels. Results and limitations: Overall, PSA >1 ng/ml was found in 318 (30%) men. Serum PSA was higher (p = 0.02), while serum testosterone (p < 0.01) was lower in infertile than in fertile men. In participants younger than 40 yr, 176 (27%) men had PSA >1 ng/ml; of them, a greater proportion were infertile (28% infertile vs 17% fertile, p = 0.03). At multivariable linear regression analysis, infertile status (coefficient 0.21; 95% confidence interval 0.02–0.39) was associated with higher PSA values, after adjusting for age and serum testosterone level. This was a single-centre study, raising the possibility of selection biases. Conclusions: Infertile men have higher PSA values than fertile individuals. Of all, almost one out of three primary infertile men younger than 40 yr has a first total PSA value of >1 ng/ml. Patient summary: In this study, we observed that (1) infertile men have higher prostate-specific antigen (PSA) values than fertile individuals and (2) a greater proportion of infertile men younger than 40 yr had total PSA >1 ng/ml at the first assessment. These data might be relevant to study the potential clinical impact of more rigorous screening in primary infertile men. Infertile men have higher prostate-specific antigen (PSA) values than fertile individuals. One out of three infertile men younger than 40 yr has a first total PSA value of >1 ng/ml. Serum PSA is related to worse semen quality in infertile men.

Current European Association of Urology guidelines suggest investigation of erectile dysfunction (ED) among patients with lower urinary tract symptoms (LUTS) whenever there is a clinical suspicion.To assess factors predictive of ED, which may drive the need for a clinical assessment in men only presenting for LUTS.Data from 914 men presenting for LUTS at a single-center outpatient clinic and without a previous diagnosis of ED were analyzed.All patients completed the International Prostatic Symptom Score (IPSS) and the International Index of Erectile Function-erectile function (IIEF-EF) questionnaires.Logistic regression analyses tested potential predictors of ED and severe ED. The accuracy of the predictive models was assessed, and decision curve analyses (DCAs) tested their clinical benefit.The median baseline IPSS score was 12 (7-19). IIEF-EF scores suggestive of unreported ED were observed in 503 (55%) patients; of all, 251 (27%) men showed severe ED. At logistic regression analysis, age (odds ratio [OR]: 1.04; p0.001), IPSS score (OR: 1.04; p0.001), diabetes mellitus (OR: 2.37; p=0.02), and smoking history (OR 1.36; p=0.03) were associated with unreported ED, after accounting for body mass index, hypertension, other cardiovascular diseases, and dyslipidemia. The same factors were associated with severe ED (all p≤0.03). The predictive model including these variables showed good accuracy for predicting ED (areas under the curve 0.69 and 0.72, respectively). However, DCAs showed no greater clinical benefit regarding identifying which patients should actually be screened for ED using these variables versus screening all patients with LUTS. Conversely, the net clinical benefit of the tested model was higher when predicting severe ED. As a limitation, we could not check prospectively the clinical impact of detecting ED in LUTS patients.Given the importance of ED in terms of overall men's health, segregating patients to be investigated or not for ED according to the traditional risk factors did not emerge more clinically useful than screening all patients presenting for LUTS.Lower urinary tract symptoms (LUTS) are frequently associated with erectile dysfunction (ED). Patients presenting for LUTS only in the everyday clinical practice should always be screened for ED and managed accordingly.

Objective: The treatment landscape for renal cell carcinoma (RCC) is rapidly evolving. The aim of this review is to summarize the randomized-controlled trials evaluating the role of immunotherapy in neoadjuvant or adjuvant setting. Materials and methods: We searched PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for studies including neoadjuvant or adjuvant immunotherapy, and provided a brief overview of the pharmacodynamics of immunotherapy for RCC. Results: Several drugs are currently under investigation. In the neoadjuvant setting, four studies are evaluating the role of single-agent immunotherapy, one of dual-agent immunotherapy, and four studies the role of immunotherapy in combination with tyrosine kinase inhibitors or anti-interleukin-1 beta. In the adjuvant setting, two studies are evaluating the role of single-agent immunotherapy and two of dual-agent immunotherapy. Conclusions: The approval of immune checkpoint inhibition as a front-line therapeutic strategy for advanced RCC has also ultimately led to the investigation of these agents first in the adjuvant and then in the neoadjuvant setting. Currently, there are nine studies aimed to evaluate the role of immunotherapy in the neoadjuvant setting and four studies in the adjuvant setting.

The objective of this study was to test Prostate Imaging Reporting and Data System (PI-RADS) classification on multiparametric magnetic resonance imaging (mpMRI) and MRI-derived prostate-specific antigen density (PSAD) in predicting the risk of reclassification in men in active surveillance (AS), who underwent confirmatory or per-protocol follow-up biopsy.Three hundred eighty-nine patients in AS underwent mpMRI before confirmatory or follow-up biopsy. Patients with negative (-) mpMRI underwent systematic random biopsy. Patients with positive (+) mpMRI underwent targeted fusion prostate biopsies + systematic random biopsies. Different PSAD cutoff values were tested (0.10, 0.10-0.20, ≥ 0.20). Multivariable analyses assessed the risk of reclassification, defined as clinically significant prostate cancer of grade group 2 or more, during follow-up according to PSAD, after adjusting for covariates.One hundred twenty-seven (32.6%) patients had mpMRI(-); 72 (18.5%) had PI-RADS 3, 150 (38.6%) PI-RADS 4, and 40 (10.3%) PI-RADS 5 lesions. The rate of reclassification to grade group 2 PCa was 16%, 22%, 31%, and 39% for mpMRI(-) and PI-RADS 3, 4, and 5, respectively, in case of PSAD 0.10 ng/mLPSAD ≥ 0.20 ng/mL

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.

Introduction To assess the feasibility of vacuum physiotherapy meant to decrease graft contraction and recurrent penile curvature (PC), hence successful tubularization and a straight penis in patients underwent two-stage buccal mucosa graft (BMG) urethroplasty, in proximal hypospadias repair. Material and methods Between January 2014 and July 2018, 59 two-stage BMG urethroplasties performed at our referral center, were included in the study. The parents were counseled to use the vacuum device between the two stages. An internal, self-administered, semiquantitative, non-validated questionnaire was designed to record parent and patient adherence to the vacuum physiotherapy and parent satisfaction. Success rate of graft tubularization, curvature correction rates, and status of early (4 months) postoperative urinary stream were evaluated. Results Of 45/59 (76.3%) who returned the questionnaire, 77.8% followed the recommended physiotherapy protocol using the vacuum device. 93.3% of parents replied that the use of the vacuum was easy or moderately easy. None of the parents interrupted the physiotherapy because of perceived difficulty or intolerability. 100% of parents would have repeated the physiotherapy, if they had to. Overall, success rate of tubularization was 98.3% (58/59), complete curvature correction was achieved in 88.2% (52/59) of patients, and 79.7% (47/59) of patients showed a straight and powerful early post-operative urinary stream. Conclusions Physiotherapy with the vacuum device is safe, easy and practically feasible. Our vacuum physiotherapy protocol had high compliance rate. Vacuum physiotherapy should be considered for further assessment in patients undergoing two stage hypospadias repair using buccal mucosa.

Background Prostate cancer (PCa) staging is crucial in clinical decision making and treatment assignment. Objective To develop a predictive tool that is capable of predicting the probability of metastases at initial PCa diagnosis. Design, setting, and participants Within the Surveillance, Epidemiology, and End Results database (2010–2014), we identified patients with newly diagnosed PCa and available clinical tumor stage, prostatic-specific antigen value (PSA), and Gleason grade group (GGG), and with or without metastases. Outcome measurements and statistical analysis We relied on PSA, clinical tumor stages, and GGG to discriminate between M1 and M0 patients. Patients were randomly divided according to the registry of origin between development (n = 102 469) and validation (n = 98 755) cohorts. Logistic regression modeling coefficients were used to devise a lookup table to discriminate between M0 and M1 stages. Receiver operating characteristic-derived area under the curve was tested for model accuracy, within the validation cohort. A total of 2000 bootstrap resamples were applied to 95% confidence intervals (CIs). Decision curve analysis (DCA) and calibration plots were used to test the performance of the lookup table. Results and limitations Of 201 224 patients, 3.5% harbored metastatic PCa (mPCa). PSA >40 ng/ml, GGG5, and GGG4, in that order, represented the strongest predictors of mPCa. Overall, PSA, clinical tumor stage, and GGG were 94.3% (95% CI: 94.2–94.3%) accurate in predicting the probability of mPCa, in the external validation cohort. Up to 39.4% probability of mPCa, the model demonstrated accurate predictions in the calibration plot. In DCA, a net benefit was recorded up to a threshold probability of approximately 54%. Conclusions The proposed lookup table for the prediction of the probability of mPCa may represent a useful clinical tool based on its high accuracy, excellent calibration, and robust nature of predictions. Patient summary Our study provides a highly accurate lookup table for the prediction of the probability of metastatic prostate cancer patients. This clinical tool can be useful in staging decisions.

Introduction Previous studies have shown a strong association between diabetes mellitus (DM) and the frequency and severity of some aspects of male sexual dysfunction (SD). The same relationship with prediabetes (preDM) has been less well investigated. Aim To systematically review the current literature on the association between preDM and SD, focusing on erectile dysfunction (ED), sex steroid hormone alterations, and premature ejaculation (PE). Methods The present review was conducted in accordance with the PRISMA declaration standards for systematic reviews. A systematic search for the terms “male sexual dysfunction,” “prediabetes,” “IFG or IGT,” “glycemia,” “ED,” “ejaculation,” and “hypoactive sexual desire disorder” was carried out in the PubMed and Embase databases. Main Outcome Measure Prevalence of SD in men with preDM and severity of ED, PE, and hormone alterations in men with preDM compared with controls. Results 12 studies reporting data on the association between SD and preDM were found in the literature. According to these studies, ED is more prevalent in men with preDM compared with controls, the severity of ED increases progressively as a function of impaired glucose metabolism, testosterone values and preDM are strongly correlated, men with preDM are at increased risk of testosterone deficiency and hypogonadism, men with hypogonadism have a higher prevalence of preDM, and the association between PE and preDM is controversial. Conclusion PreDM is a common and underdiagnosed clinical condition that is strongly associated with male SD. A detailed glucose metabolism investigation should be performed in every patient with SD to screen for glucose abnormalities and eventually to implement prevention program to decrease their chances of developing life-changing chronic illnesses. Boeri L, Capogrosso P, Ventimiglia E, et al. Sexual Dysfunction in Men with Prediabetes. Sex Med Rev 2019;8:622–634.

Background Over the years, several techniques for performing robot-assisted prostatectomy have been implemented in an effort to achieve optimal oncological and functional outcomes. Objective To provide an evidence-based description and video-based illustration of currently available dissection techniques for robotic prostatectomy. Design, setting, and participants A literature search was performed to retrieve articles describing different surgical approaches and techniques for robot-assisted radical prostatectomy (RARP) and to analyze data supporting their use. Video material was provided by experts in the field to illustrate these approaches and techniques. Surgical procedure Multiple surgical approaches are available: extraperitoneal, transvesical, transperitoneal posterior, transperitoneal anterior, Retzius sparing, and transperineal. Surgical techniques for prostatic dissection sensu strictu are the following: omission of the endopelvic fascia dissection, bladder neck preservation, incremental nerve sparing by means of an antegrade or retrograde approach, and preservation of the puboprostatic ligaments and dorsal venous complex. Recently, techniques for total or partial prostatectomy have been described. Measurements Different surgical approaches and techniques for robotic prostatectomy have been analyzed. Results and limitations Two randomized controlled trials evaluating the extraperitoneal versus the transperitoneal approach have demonstrated similar results. Level I evidence on the Retzius-sparing approach demonstrated earlier return to continence than the traditional anterior approach. The question whether Retzius-sparing RARP is associated with a higher rate of positive surgical margins is still open due to the intrinsic bias in terms of surgical expertise in the available comparative studies. This technique also offers an advantage in patients who have received kidney transplantation. Retrospective evidence suggests that the more the anatomical dissection (eg., more periprostatic tissue is preserved), the better the functional outcome in terms of continence. Yet, two randomized controlled trials evaluating the different techniques of dissection have so far been produced. Partial prostatectomies should not be offered outside clinical trials. Conclusions Several techniques and approaches are available for prostate dissection during RARP. While the Retzius-sparing approach seems to provide earlier return to continence than the traditional anterior transperitoneal approach, no technique has been proved to be superior to other(s) in terms of long-term outcomes in randomized studies. Patient summary We have summarized available approaches for the surgical treatment of prostate cancer. Specifically, we described the different techniques that can be adopted for the surgical removal of the prostate using robotic technology.

Objective: To investigate the oncologic safety of neurovascular bundles (NVB) preservation at radical prostatectomy (RP) in patients with high-risk and/or locally advanced prostate cancer (PCa). Material and methods: Within a two-institutional high-volume center database we identified patients who harbored high-risk PCa at RP (2000–2017). Only patients with D’Amico high-risk PCa were included. Kaplan–Meier and multivariable Cox regression models tested the effect of NVB preservation on biochemical recurrence (BCR), metastasis and overall survival (OS). Subgroup analyses focused on patients with clinical stage T3 and/or biopsy ISUP grade 5 and pathologic stage T3. Results: Of 4351 patients with D’Amico high-risk, 35.7% vs. 38.0% vs. 26.3% underwent bilateral vs. unilateral vs. no NVB preservation, respectively. At 120 months after RP BCR-free, metastasis-free survival and OS rates were 62.2% vs. 44.3% vs. 27.1% (p < 0.001), 83.7% vs. 66.7% vs. 60.3% (p < 0.001), and 91.8% vs. 87.5% vs. 72.3% (p < 0.001) for bilateral vs. unilateral vs. no NVB preservation, respectively. In multivariable Cox regression models, bilateral and unilateral compared to no NVB preservation did not increase the risk for BCR, metastasis or death in the entire cohort and in subgroups with clinical stage T3 and/or biopsy ISUP grade 5, as well as pathologic stage T3. Conclusions: NVB preservation was not associated with worse oncological outcome in patients with high-risk and/or locally advanced PCa and may be offered to well-selected patients who are at risk of harboring nonorgan-confined PCa.

Objectives To develop and externally validate a risk calculator for prediction of any cancer recurrence in patients with penile squamous cell carcinoma (pSCC) and inguinal lymph node metastases (ILNM), as to date no validated prognostic tool is available for patients with pSCC and ILNM. Patients and methods The development cohort included 234 patients from seven referral centres. The external validation cohort included 273 patients from two additional referral centres. Cox regression identified predictors of any recurrence, which were used to develop a risk calculator. The risk-calculator grouped the development and the validation cohorts according to the individual risk of any recurrence at 24 months (24m-R). Adjuvant treatment effects were tested on overall survival (OS) according to the derived tertiles, within the development and validation cohorts. Results Positive surgical margins, pN3 , and ILNM ratio were associated with higher recurrence rate. The 2-year OS rates were lower for patients with high (>37%) and intermediate (19-37%) compared to low ( 0.1). Conclusion Adjuvant treatment planning is crucial in patients with pSCC with ILNM, where only weak evidence is available. The current tool proved to successfully stratify patients according to their individual risk, potentially allowing better tailoring of adjuvant treatments.

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 ...

Focal therapy (FT) for prostate cancer (PCa) is emerging as a novel therapeutic approach for patients with low- to intermediate-risk disease, in order to provide acceptable oncological control, whilst avoiding the side effects of radical treatment. Evidence regarding the ideal follow-up strategy and the significance of prostate-specific antigen (PSA) kinetics after treatment is needed. In this study, we aimed to assess the value of the percentage of PSA reduction (%PSA reduction) after FT in predicting the likelihood of any additional treatment or any radical treatment. We retrospectively analysed a multicentre cohort of 703 men receiving FT for low- and intermediate-risk PCa. Overall, the rates of any additional treatment and any radical treatment were 30% and 13%, respectively. The median follow-up period was 41 mo. The median %PSA reduction after FT was 73%. At Cox multivariable analysis, %PSA reduction was an independent predictor of any additional treatment (hazard ratio [HR]: 0.96; p 90%, the probability of any additional treatment within 5 yr was 20%. Conversely, for %PSA reduction of

Objective: We aimed to test the association between age, BMI and sex-hormone–binding globulin (SHBG) in a homogenous cohort of white-European men presenting for primary couple’s infertility. Design: Retrospective study. Methods: Data from 1547 infertile men were analysed. Health-significant comorbidities were scored with the Charlson comorbidity index (CCI). Fasting serum hormones were measured in every patient. Age was considered according to quartile groups (41 years) and BMI as normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2) and obesity (>30 kg/m2). Descriptive statistics and linear regression analysis tested the associations between age, BMI and SHBG. Results: Median SHBG levels increased across quartiles of age and decreased along with BMI increases (all P P P Conclusions: We found a wide distribution of SHBG concentrations across age and BMI values in primary infertile men. The association between BMI and lowered SHBG levels seems to be greater than the association of ageing with increased SHBG.

To compare functional outcomes of partial nephrectomy (PN) and active surveillance (AS) in oncocytoma. Multicenter retrospective analysis of patients with oncocytoma managed with PN or AS (biopsy-confirmed). Primary outcome development of de novo chronic kidney disease (CKD) (eGFR

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.

Introduction & objectives: We tested the role of multiparametric magnetic resonance imaging (mpMRI) in disease reclassification and whether the combination of mpMRI and clinicopathological variables could represent the most accurate approach to predict the risk of reclassification during active surveillance. Materials & methods: Three-hundred eighty-nine patients (pts) underwent mpMRI and subsequent confirmatory or follow-up biopsy according to the Prostate Cancer Research International Active Surveillance (PRIAS) protocol. Pts with negative (−) mpMRI underwent systematic random biopsy. Pts with positive (+) mpMRI [Prostate Imaging Reporting and Data System, version 2 (PI-RADS-V2) score ≥3] underwent targeted + systematic random biopsies. Multivariate analyses were used to create three models predicting the probability of reclassification [International Society of Urological Pathology ≥ Grade Group 2 (GG2)]: a basic model including only clinical variables (age, prostate-specific antigen density, and number of positive cores at baseline), an Magnetic resonance imaging (MRI) model including only the PI-RADS score, and a full model including both the previous ones. The predictive accuracy (PA) of each model was quantified using the area under the curve. Results: mpMRI negative (−) was recorded in 127 (32.6%) pts; mpMRI positive (+) was recorded in 262 pts: 72 (18.5%) had PI-RADS 3, 150 (38.6%) PI-RADS 4, and 40 (10.3%) PI-RADS 5 lesions. At a median follow-up of 12 months, 125 pts (32%) were reclassified to GG2 prostate cancer. The rate of reclassification to GG2 prostate cancer was 17%, 35%, 38%, and 52% for mpMRI (−), PI-RADS 3, 4, and 5, respectively (P