Impact of Preoperative Plasma Potassium Levels on Oncological Outcomes, Major Complications, and 30-Day Mortality in Bladder Cancer Patients Undergoing Radical Cystectomy.

INTRODUCTION AND OBJECTIVES: We examined the impact of preoperative plasma potassium levels (PPLs) on outcomes in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB), hypothesizing that potassium imbalances might influence outcomes. PATIENTS AND METHODS: In this retrospective study, 501 UCB patients undergoing RC from 2009 to 2017 at a tertiary center were analyzed. Blood samples collected a week prior to surgery defined normal and abnormal PPL based on institutional standards. We assessed overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), postoperative complications, 30-day mortality, and non-organ confined disease. Kaplan-Meier estimates, Cox proportional hazards, logistic regression, and decision curve analyses (DCA) were employed. RESULTS: 63 (13%) patients had abnormal preoperative PPLs, with 50 (10%) elevated and 13 (2.5%) decreased. In a 59 months median follow-up, 152 (31%) had disease recurrence, 197 (39%) died from any cause, and 119 (24%) from UCB. Multivariable cox regression analyses adjusting for perioperative parameters demonstrated abnormal PPL was associated with worse OS (HR=1.9, P=0.009), CSS (HR=2.8, P<0.001) and RFS (HR=2.1; P=0.007). Elevated preoperative PPLs also demonstrated significant associations with adverse outcomes in OS, CSS, and RFS (all P<0.05). In multivariable logistic regression analyses, abnormal and elevated PPLs were not associated with 30-day mortality, major 30-day postoperative complications, positive nodal disease, pT3/4 stage, and non-organ confined disease (all P>0.05). CONCLUSION: Abnormal and elevated preoperative PPLs correlate with adverse oncologic outcomes in UCB patients treated with RC. Pending external validation, preoperative PPLs might be a cost-effective, easily obtainable supplemental biomarker for enriching accuracy of outcome prediction in this highly variable maladie.

The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer: A Multicenter Study.

CONTEXT: Despite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP. EVIDENCE SYNTHESIS: We retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis. EVIDENCE ACQUISITION: We included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P < .01). This held true at multivariable analysis: (HR 6.184, 95% CI: 3.386-11-295; P < .001) whilst no significant results were highlighted for Choline PET/CT. No significant associations for both PET types were found for local progression, BCR, and overall mortality (all P > .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P < .05). CONCLUSIONS: PSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging.

Oncological and safety profiles in patients undergoing simultaneous transurethral resection (TUR) of bladder tumour and TUR of the prostate.

OBJECTIVES: To determine the oncological impact and adverse events of performing simultaneous transurethral resection of bladder tumour (TURB) and transurethral resection of the prostate (TURP), as evidence on the outcomes of simultaneous TURB for bladder cancer and TURP for obstructive benign prostatic hyperplasia is limited and contradictory. PATIENTS AND METHODS: Patients from 12 European hospitals treated with either TURB alone or simultaneous TURB and TURP (TURB+TURP) were retrospectively analysed. A propensity score matching (PSM) 1:1 was performed with patients from the TURB+TURP group matched to TURB-alone patients. Associations between surgery approach with recurrence-free (RFS) and progression-free (PFS) survivals were assessed in Cox regression models before and after PSM. We performed a subgroup analysis in patients with risk factors for recurrence (multifocality and/or tumour size >3 cm). RESULTS: A total of 762 men were included, among whom, 76% (581) underwent a TURB alone and 24% (181) a TURB+TURP. There was no difference in terms of tumour characteristics between the groups. We observed comparable length of stay as well as complication rates including major complications (Clavien-Dindo Grade ≥III) for the TURB-alone vs TURB+TURP groups, while the latest led to longer operative time (P < 0.001). During a median follow-up of 44 months, there were more recurrences in the TURB-alone (47%) compared to the TURB+TURP group (28%; P < 0.001). Interestingly, there were more recurrences at the bladder neck/prostatic fossa in the TURB-alone group (55% vs 3%, P < 0.001). TURB+TURP procedures were associated with improved RFS (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.29-0.53; P < 0.001), but not PFS (HR 1.63, 95% CI 0.90-2.98; P = 0.11). Within the PSM cohort of 254 patients, the simultaneous TURB+TURP was still associated with improved RFS (HR 0.33, 95% CI 0.22-0.49; P < 0.001). This was also true in the subgroup of 380 patients with recurrence risk factors (HR 0.41, 95% CI 0.28-0.62; P < 0.001). CONCLUSION: In our contemporary cohort, simultaneous TURB and TURP seems to be an oncologically safe option that may, even, improve RFS by potentially preventing disease recurrence at the bladder neck and in the prostatic fossa.

Online Crowdfunding for Urologic Cancer Care.

Background: we aimed to characterize the financial needs expressed through online crowdfunding for urologic cancers. Methods: the data used in this study came from the online crowdfunding platform GoFundMe.com. Using an automated software method, we extracted data for campaigns related to urologic cancers. Subsequently, four independent investigators reviewed all extracted data on prostate, bladder, kidney and testicular cancer. We analyzed campaigns' basic characteristics, goals, fundraising, type of treatment and factors associated with successful campaigns. Results: in total, we identified 2126 individual campaigns, which were related to direct treatment costs (34%), living expenses (17%) or both (48%). Median fundraising amounts were greatest for testicular cancer. Campaigns for both complementary and alternative medicine (CAM) (median $11,000) or CAM alone (median $8527) achieved higher fundraising totals compared with those for conventional treatments alone (median $5362) (p < 0.01). The number of social media shares was independently associated with campaign success and highest quartile of fundraising. Conclusions: using an automated web-based approach, we identified and characterized online crowdfunding for urologic cancer care. These findings indicated a diverse range of patient needs related to urologic care and factors related to campaigns' success.

Rates of metastatic prostate cancer in newly diagnosed patients: Numbers needed to image according to risk level.

BACKGROUND: The numbers needed to image to identify pelvic lymph node and/or distant metastases in newly diagnosed prostate cancer (PCa) patients according to risk level are unknown. METHODS: Relying on Surveillance, Epidemiology, and End Results (2010-2016), we tabulated rates and proportions of patients with (a) lymph node or (b) distant metastases according to National Comprehensive Cancer Network (NCCN) risk level and calculated the number needed to image (NNI) for both endpoints. Multivariable logistic regression analyses were performed. RESULTS: Of 145,939 newly diagnosed PCa patients assessable for analyses of pelvic lymph node metastases (cN1), 4559 (3.1%) harbored cN1 stage: 13 (0.02%), 18 (0.08%), 63 (0.3%), 512 (2.8%), and 3954 (14.9%) in low, intermediate favorable, intermediate unfavorable, high, and very high-risk levels. These resulted in NNI of 4619, 1182, 319, 35, and 7, respectively. Of 181,109 newly diagnosed PCa patients assessable for analyses of distant metastases (M1a-c ), 8920 (4.9%) harbored M1a-c stage: 50 (0.07%), 45 (0.1%), 161 (0.5%), 1290 (5.1%), and 7374 (22.0%) in low, intermediate favorable, intermediate unfavorable, high, and very high-risk. These resulted in NNI of 1347, 602, 174, 20, and 5, respectively. CONCLUSIONS: Our observations perfectly validated the NCCN recommendations for imaging in newly diagnosed high and very high-risk PCa patients. However, in unfavorable intermediate-risk PCa patients, in whom bone and soft tissue imaging is recommended, the NNI might be somewhat elevated to support routine imaging in clinical practice.

Carboplatin-based adjuvant chemotherapy versus observation after radical cystectomy in patients with pN1-3 urothelial bladder cancer.

PURPOSE: To test the impact of carboplatin-based ACT on overall survival (OS) in patients with pN1-3 cM0 BCa. METHODS: A retrospective analysis was conducted on 1057 patients with pTany pN1-3 cM0 urothelial BCa treated with or without carboplatin-based ACT after radical cystectomy and bilateral lymph-node dissection between 2002 and 2018 at 12 European and North-American hospitals. No patient received neoadjuvant chemotherapy or radiation therapy. Only patients with negative surgical margins at surgery were included. A 3:1 propensity score matching (PSM) was performed using logistic regression to adjust for baseline characteristics. Univariable and multivariable Cox regression analyses were used to predict the effect of carboplatin-based ACT on OS. The Kaplan-Meier method was used to display OS in the matched cohort. RESULTS: Of the 1057 patients included in the study, 69 (6.5%) received carboplatin-based ACT. After PSM, 244 total patients were identified in two cohorts that did not differ for baseline characteristics. Death was recorded in 114 (46.7%) patients over a median follow-up of 19 months. In the multivariable Cox regression analyses, increasing age at surgery (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.01-1.06, p < 0.001) and increasing number of positive lymph nodes (HR 1.06, 95% CI 1.01-1.07, p = 0.02) were independent predictors of worse OS. The delivery of carboplatin-based ACT was not predictive of improved OS (HR 0.67, 95% CI 0.43-1.04, p = 0.08). The main limitations of this study are its retrospective design and the relatively low number of patients involved. CONCLUSIONS: Carboplatin-based might not improve OS in patients with pN1-3 cM0 BCa. Our results underline the need for alternative therapies for cisplatin-ineligible patients.

Rectal preparation significantly improves prostate imaging quality: Assessment of the PI-QUAL score with visual grading characteristics.

PURPOSE: To investigate the effects of a rectal preparation regimen, that consisted of a rectal cleansing enema and an endorectal gel filling protocol, on prostate imaging quality (PI-QUAL). METHODS: Multiparametric MRI (mpMRI) was performed in 150 consecutive patients divided into two groups of 75 patients. One group received a rectal preparation with a cleansing enema and endorectal gel filling (median age 65.3 years, median PSA level 6 ng/ml). The other patient group did not receive such a preparation (median age 64 years, median PSA level 6 ng/ml). Two uroradiologists independently rated general image quality and lesion visibility on diffusion-weighted imaging (DWI), T2-weighted (T2w), and dynamic contrast-enhanced (DCE) images using a five-point ordinal scale. In addition, two uroradiologists assigned PI-QUAL scores, using the dedicated scoring sheet. Data sets were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/ area under the curve (AUC) analysis. RESULTS: VGC revealed significantly better general image quality for DWI (AUC R1 0.708 (0.628-0.779 CI, p < 0.001; AUC R2 0.687 (0.606-0.760 CI, p < 0.001) and lesion visibility for both readers (AUC R1 0.729 (0.607-0.831 CI, p < 0.001); AUC R2 0.714 (0.590-0.818CI, p < 0.001) in the preparation group. For T2w imaging, rectal preparation resulted in significantly better lesion visibility for both readers (R1 0.663 (0.537-0.774 CI, p = 0.014; R2 0.663 (0.537-0.774 CI, p = 0.014)). Averaged PI-QUAL scores were significantly improved with rectal preparation (AUC R3/R4 0.667, CI 0.581-0.754, p < 0.001). CONCLUSION: Rectal preparation significantly improved prostate imaging quality (PI-QUAL) and lesion visibility. Hence, a rectal preparation regimen consisting of a rectal cleansing enema and an endorectal gel filling could be considered.

Pembrolizumab outperforms tyrosine kinase inhibitors as adjuvant treatment in patients with high-risk renal cell carcinoma after nephrectomy.

We determined the oncologic outcomes and safety profiles of adjuvant immune checkpoint inhibitors (ICIs) compared to adjuvant tyrosine kinase inhibitors (TKIs) in patients at high risk after nephrectomy for clinically nonmetastatic renal cell carcinoma (RCC). Network meta-analyses were conducted for disease-free survival (DFS), overall survival (OS), and adverse events (AEs) with placebo as the common comparator arm. Six trials (KEYNOTE-564, S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our analysis. Compared to placebo, both pembrolizumab (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.51-0.92) and pazopanib 800 mg (HR 0.69, 95% CI 0.49-0.97) were significantly associated with better DFS. Adjuvant pembrolizumab (HR 0.54, 95% CI 0.30-0.97) was significantly associated with better OS compared to TKIs (HR 0.93, 95% CI 0.83-1.04). Analysis of treatment ranking revealed that pembrolizumab was the best treatment with regard to both DFS and OS and had the lowest likelihood of any-grade and high-grade AEs in comparison to TKIs. The superior oncologic benefit of pembrolizumab and its better toxicity profile support it as the new standard of care in the adjuvant setting for nephrectomy patients at high risk of RCC relapse. PATIENT SUMMARY: For patients with kidney cancer at high risk of relapse after surgical removal of their kidney, postoperative therapy with the immune checkpoint inhibitor pembrolizumab offers the best risk/benefit ratio.

Differences in rates of pelvic lymph node dissection in National Comprehensive Cancer Network favorable, unfavorable intermediate- and high-risk prostate cancer across United States SEER registries.

Background: The National Comprehensive Cancer Network (NCCN) guidelines recommend pelvic lymph node dissection (PLND) in NCCN high- and intermediate-risk prostate cancer patients. We tested for PLND nonadherence (no-PLND) rates within the Surveillance Epidemiology and End Results (2010-2015). Materials and methods: We identified all radical prostatectomy patients who fulfilled the NCCN PLND guideline criteria (n = 23,495). Nonadherence rates to PLND were tabulated and further stratified according to NCCN risk subgroups, race/ethnicity, geographic distribution, and year of diagnosis. Results: Overall, the no-PLND rate was 26%; it was 41%, 25%, and 11% in the NCCN intermediate favorable, intermediate unfavorable, and high-risk prostate cancer patients, respectively (p < 0.001). Over time, the no-PLND rates declined in the overall cohort and within each NCCN risk subgroup. Georgia exhibited the highest no-PLND rate (49%), whereas New Jersey exhibited the lowest (15%). Finally, no-PLND race/ethnicity differences were recorded only in the NCCN intermediate unfavorable subgroup, where Asians exhibited the lowest no-PLND rate (20%) versus African Americans (27%) versus Whites (26%) versus Hispanic-Latinos (25%). Conclusions: The lowest no-PLND rates were recorded in the NCCN high-risk patients followed by NCCN intermediate unfavorable and favorable risk in that order. Our findings suggest that unexpectedly elevated differences in no-PLND rates warrant further examination. In all the NCCN risk subgroups, the no-PLND rates decreased over time.

Cancer-specific survival after radical prostatectomy versus external beam radiotherapy in high-risk and very high-risk African American prostate cancer patients.

BACKGROUND: To test for differences in cancer-specific mortality (CSM) rates between radical prostatectomy (RP) vs external beam radiotherapy (EBRT) in National Comprehensive Cancer Network (NCCN) high-risk African American patients, as well as Johns Hopkins University (JHU) high-risk and very high-risk patients. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 4165 NCCN high-risk patients, of whom 1944 (46.7%) and 2221 (53.3%) patients qualified for JHU high-risk or very high-risk definitions. Of all 4165 patients, 1390 (33.5%) were treated with RP versus 2775 (66.6%) with EBRT. Cumulative incidence plots and competing risks regression models addressed CSM before and after 1:1 propensity score matching between RP and EBRT NCCN high-risk patients. Subsequently, analyses were repeated separately in JHU high-risk and very high-risk subgroups. Finally, all analyses were repeated after landmark analyses were applied. RESULTS: In the NCCN high-risk cohort, 5-year CSM rates for RP versus EBRT were 2.4 versus 5.2%, yielding a multivariable hazard ratio of 0.50 (95% confidence interval [CI] 0.30-0.84, p = 0.009) favoring RP. In JHU very high-risk patients 5-year CSM rates for RP versus EBRT were 3.7 versus 8.4%, respectively, yielding a multivariable hazard ratio of 0.51 (95% CI: 0.28-0.95, p = 0.03) favoring RP. Conversely, in JHU high-risk patients, no significant CSM difference was recorded between RP vs EBRT (5-year CSM rates: 1.3 vs 1.3%; multivariable hazard ratio: 0.55, 95% CI: 0.16-1.90, p = 0.3). Observations were confirmed in propensity score-matched and landmark analyses adjusted cohorts. CONCLUSIONS: In JHU very high-risk African American patients, RP may hold a CSM advantage over EBRT, but not in JHU high-risk African American patients.

Accuracy and Clinical Utility of a Tumor Grade- and Stage-based Predictive Model in Localized Upper Tract Urothelial Carcinoma.

BACKGROUND: Among various clinicopathologic factors used to identify low-risk upper tract urothelial carcinoma (UTUC), tumor grade and stage are of utmost importance. The clinical value added by inclusion of other risk factors remains unproven. OBJECTIVE: To assess the performance of a tumor grade- and stage-based (GS) model to identify patients with UTUC for whom kidney-sparing surgery (KSS) could be attempted. DESIGN, SETTING, AND PARTICIPANTS: In this international study, we reviewed the medical records of 1240 patients with UTUC who underwent radical nephroureterectomy. Complete data needed for risk stratification according to the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) guidelines were available for 560 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable logistic regression analyses were performed to determine if risk factors were associated with the presence of localized UTUC. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the GS, EAU, and NCCN models in predicting pathologic stage were calculated. RESULTS AND LIMITATIONS: Overall, 198 patients (35%) had clinically low-grade, noninvasive tumors, and 283 (51%) had ≤pT1disease. On multivariable analyses, none of the EAU and NCCN risk factors were associated with the presence of non-muscle-invasive UTUC among patients with low-grade and low-stage UTUC. The GS model exhibited the highest accuracy, sensitivity, and negative predictive value among all three models. According to the GS, EAU, and NCCN models, the proportion of patients eligible for KSS was 35%, 6%, and 4%, respectively. Decision curve analysis revealed that the net benefit of the three models was similar within the clinically reasonable range of probability thresholds. CONCLUSIONS: The GS model showed favorable predictive accuracy and identified a greater number of KSS-eligible patients than the EAU and NCCN models. A decision-making algorithm that weighs the benefits of avoiding unnecessary kidney loss against the risk of undertreatment in case of advanced carcinoma is necessary for individualized treatment for UTUC patients. PATIENT SUMMARY: We assessed the ability of three models to predict low-grade, low-stage disease in patients with cancer of the upper urinary tract. No risk factors other than grade assessed on biopsy and stage assessed from scans were associated with better prediction of localized cancer. A model based on grade and stage may help to identify patients who could benefit from kidney-sparing treatment of their cancer.

Cancer-specific mortality after radical prostatectomy vs external beam radiotherapy in high-risk Hispanic/Latino prostate cancer patients.

PURPOSE: To test for differences in cancer-specific mortality (CSM) rates in Hispanic/Latino prostate cancer patients according to treatment type, radical prostatectomy (RP) vs external beam radiotherapy (EBRT). METHODS: Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 2290 NCCN (National Comprehensive Cancer Network) high-risk (HR) Hispanic/Latino prostate cancer patients. Of those, 893 (39.0%) were treated with RP vs 1397 (61.0%) with EBRT. First, cumulative incidence plots and competing risks regression models tested for CSM differences after adjustment for other cause mortality (OCM). Second, cumulative incidence plots and competing risks regression models were refitted after 1:1 propensity score matching (according to age, PSA, biopsy Gleason score, cT-stage, cN-stage). RESULTS: In NCCN HR patients, 5-year CSM rates for RP vs EBRT were 2.4 vs 4.7%, yielding a multivariable hazard ratio of 0.37 (95% CI 0.19-0.73, p = 0.004) favoring RP. However, after propensity score matching, the hazard ratio of 0.54 was no longer statistically significant (95% CI 0.21-1.39, p = 0.2). CONCLUSION: Without the use of strictest adjustment for population differences, NCCN high-risk Hispanic/Latino prostate cancer patients appear to benefit more of RP than EBRT. However, after strictest adjustment for baseline patient and tumor characteristics between RP and EBRT cohorts, the apparent CSM benefit of RP is no longer statistically significant. In consequence, in Hispanic/Latino NCCN high-risk patients, either treatment modality results in similar CSM outcome.

Survival after Radical Prostatectomy versus Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer.

PURPOSE: Our goal was to compare cancer-specific mortality (CSM) rates between radical prostatectomy (RP) vs external beam radiotherapy (EBRT) in National Comprehensive Cancer Network© (NCCN©) high risk (HR) patients, as well as in Johns Hopkins University (JH) HR and very high risk (VHR) subgroups. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 24,407 NCCN HR patients, of whom 10,300 (42%) vs 14,107 (58%) patients qualified for JH HR vs VHR, respectively. Overall, 9,823 (40%) underwent RP vs 14,584 (60%) EBRT. Cumulative incidence plots and competing-risks regression addressed CSM after 1:1 propensity score matching (according to age, prostate specific antigen, clinical T and N stages, and biopsy Gleason score) between RP and EBRT patients. All analyses addressed the combined NCCN HR cohort, as well as in JH HR and JH VHR subgroups. RESULTS: In the combined NCCN HR cohort 5-year CSM rates were 2.3% for RP vs 4.1% for EBRT and yielded a multivariate hazard ratio of 0.68 (95% CI 0.54-0.86, p <0.001) favoring RP. In VHR patients 5-year CSM rates were 3.5% for RP vs 6.0% for EBRT, yielding a multivariate hazard ratio of 0.58 (95% CI 0.44-0.77, p <0.001) favoring RP. Conversely, in HR patients no significant difference was recorded between RP vs EBRT (HR 0.7, 95% CI 0.39-1.25, p=0.2). CONCLUSIONS: Our data suggest that RP holds a CSM advantage over EBRT in the combined NCCN HR cohort, and in its subgroup of JH VHR patients.

Nomogram Predicting Downgrading in National Comprehensive Cancer Network High-risk Prostate Cancer Patients Treated with Radical Prostatectomy.

BACKGROUND: Some high-risk prostate cancer (PCa) patients may show more favorable Gleason pattern at radical prostatectomy (RP) than at biopsy. OBJECTIVE: To test whether downgrading could be predicted accurately. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology and End Results database (2010-2016), 6690 National Comprehensive Cancer Network (NCCN) high-risk PCa patients were identified. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: We randomly split the overall cohort between development and validation cohorts (both n = 3345, 50%). Multivariable logistic regression models used biopsy Gleason, prostate-specific antigen, number of positive prostate biopsy cores, and cT stage to predict downgrading. Accuracy, calibration, and decision curve analysis (DCA) tested the model in the external validation cohort. RESULTS AND LIMITATIONS: Of 6690 patients, 50.3% were downgraded at RP, and of 2315 patients with any biopsy pattern 5, 44.1% were downgraded to RP Gleason pattern ≤4 + 4. Downgrading rates were highest in biopsy Gleason pattern 5 + 5 (84.1%) and lowest in 3 + 4 (4.0%). In the validation cohort, the logistic regression model-derived nomogram predicted downgrading with 71.0% accuracy, with marginal departures (±3.3%) from ideal predictions in calibration. In DCA, a net benefit throughout all threshold probabilities was recorded, relative to treat-all or treat-none strategies and an algorithm based on an average downgrading rate of 50.3%. All steps were repeated in the subgroup with any biopsy Gleason pattern 5, to predict RP Gleason pattern ≤4 + 4. Here, a second nomogram (n = 2315) yielded 68.0% accuracy, maximal departures from ideal prediction of ±5.7%, and virtually the same DCA pattern as the main nomogram. CONCLUSIONS: Downgrading affects half of all high-risk PCa patients. Its presence may be predicted accurately and may help with better treatment planning. PATIENT SUMMARY: Downgrading occurs in every second high-risk prostate cancer patients. The nomograms developed by us can predict these probabilities accurately.

Adjuvant therapy with tyrosine kinase inhibitors for localized and locally advanced renal cell carcinoma: an updated systematic review and meta-analysis.

PURPOSE: Tyrosine kinase inhibitors (TKIs) have been widely used in the management of patients with metastatic renal cell carcinoma (RCC). However, the use of systemic therapies in the adjuvant setting of localized and locally advanced RCC has shown conflicting results across the literature. Therefore, we aimed to conduct an updated systematic review and meta-analysis comparing the efficacy and safety of TKIs in the adjuvant setting for patients with localized and locally advanced RCC. MATERIALS AND METHODS: The MEDLINE and EMBASE databases were searched in December 2020 to identify phase III randomized controlled trials of patients receiving adjuvant therapies with TKI for RCC. Disease-free survival (DFS) and overall survival (OS) were the primary endpoints. The secondary endpoints included treatment-related adverse events (TRAEs) of high and any grade. RESULTS: Five trials (S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our meta-analysis comprising 6,531 patients. The forest plot revealed that TKI therapy was associated with a significantly longer DFS compared to placebo (pooled HR: 0.88, 95% CI: 0.81-0.96, P= 0.004). The Cochrane's Q test (P = 0.51) and I2 test (I2 = 0%) revealed no significant heterogeneity. Adjuvant TKI was not associated with improved OS compared to placebo (pooled HR: 0.93, 95% CI: 0.83-1.04, P= 0.23). The Cochrane's Q test (P = 0.74) and I2 test (I2 = 0%) revealed no significant heterogeneity. The forest plot revealed that TKI therapy, compared to placebo, was associated with higher rates of high grade TRAEs (OR: 5.20, 95% CI: 4.10-6.59, P< 0.00001) as well as any grade TRAEs (OR: 3.85, 95% CI: 1.22-12.17, P= 0.02). The Cochrane's Q tests (P < 0.0001 and P < 0.00001, respectively) and I2 tests (I2 = 79% and I2 = 90%, respectively) revealed significant heterogeneity. CONCLUSIONS: The findings of our analyses suggest an improved DFS in patients with localized and locally advanced RCC receiving adjuvant TKI as compared to placebo; however, this did not translate into any significant OS benefit. Additionally, TKI therapy led to significant toxicity. Adjuvant TKI does not seem to offer a satisfactory risk and/orbenefit balance for all patients. Select patients with very poor prognosis may be considered in a shared decision-making process with the patient. With the successful arrival of immune-based therapies in RCC, these may allow a more favorable risk/benefit profile.

Trimodal therapy with high-dose-rate brachytherapy and hypofractionated external beam radiation combined with long-term androgen deprivation for unfavorable-risk prostate cancer.

PURPOSE: To assess the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiation therapy (EBRT) combined with long-term androgen deprivation therapy (ADT) in very-high-risk (VHR) versus high-risk (HR) prostate cancer (PCa), as defined in the National Comprehensive Cancer Network (NCCN) criteria. METHODS: Data from 338 consecutive HR or VHR PCa patients who had undergone this tri-modal therapy between 2005 and 2018 were retrospectively analyzed. Biochemical recurrence (BCR)-free, progression-free, overall, and cancer-specific survival (BCRFS/PFS/OS/CSS) rates were analyzed using the Kaplan-Meier method and Wilcoxon test. Cox regression models were used to evaluate candidate prognostic factors for survival. C­indexes were used to assess model discrimination. RESULTS: Within a median follow-up of 84 months, 68 patients experienced BCR, 58 had disease progression including only 3 with local progression, 27 died of any cause, and 2 died from PCa. The 5­year BCRFS, PFS, OS, and CSS rates were 82.2% (HR 86.5%; VHR 70.0%), 90.0% (HR 94.3%; VHR 77.6%), 95.7% (HR, 97.1%; VHR, 91.8%), and 99.6% (HR, 100%; VHR, 98.0%), respectively. In multivariable analyses that adjusted for standard clinicopathologic features, the risk subclassification was associated both PFS and OS (p = 0.0003 and 0.001, respectively). Adding the risk subclassification improved the accuracy of models in predicting BCRFS, PFS, and OS. CONCLUSION: While the outcome of this trimodal approach appears favorable, VHR PCa patients had significantly worse oncological outcomes than those with HR PCa. The NCCN risk subclassification should be integrated into prognostic tools to guide risk stratification, treatment, and follow-up for unfavorable PCa patients receiving this trimodal therapy.

The recurrence and progression risk after simultaneous endoscopic surgery of urothelial bladder tumour and benign prostatic hyperplasia: a systematic review and meta-analysis.

OBJECTIVES: To evaluate recurrence and progression risk after simultaneous endoscopic surgery of bladder cancer and benign prostatic hyperplasia (BPH), as simultaneous surgery is not an unusual scenario and theoretically simultaneous transurethral resection of bladder tumour (TURBT) and transurethral resection of the prostate (TURP) can lead to an increased risk of recurrence in the bladder neck and prostatic urethra (BN/PU). METHODS: We conducted a systematic review and meta-analysis to assess the risk of recurrence (i.e. whole bladder and/or BN/PU) and tumour progression as outcomes after a simultaneous endoscopic surgery of bladder tumour and BPH, as compared to TURBT alone. We queried PubMed and Web of Science database on 1 January 2020. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to the I2 statistic, respectively. RESULTS: Nine retrospective and three clinical trial studies were selected after considering inclusion and exclusion criteria. We conducted the meta-analysis on retrospective and randomised controlled trials (RCTs) separately. Eight retrospective and three RCT studies were included to assess the BN/PU recurrence risk and the summarised risk ratio (RR) was 1.02 (95% confidence interval [CI] 0.74-1.41) and 0.93 (95% CI 0.47-1.84), respectively. Five retrospective and two RCT studies were included to assess the progression risk and the summarised RR was 0.91 (95% CI 0.56-1.48) and 1.16 (95% CI 0.30-4.51), respectively. Eight retrospective and three RCT studies were included to assess the whole bladder recurrence risk and the summarised RR was 0.87 (95% CI 0.78-0.97) and 0.89 (95% CI 0.65-1.21), respectively. CONCLUSION: We did not observe any increased risk of total bladder recurrence, BN/PU recurrence, or progression after a simultaneous endoscopic surgery of bladder tumour and BPH, as compared to TURBT alone.

Impact of tumor size on the oncological outcome of high-grade nonmuscle invasive bladder cancer - examining the utility of classifying Ta bladder cancer based on size.

PURPOSE: To examine survival rates and to calculate the risk of disease recurrence, progression, overall, and cancer-specific mortality in patients diagnosed with high-risk NMIBC using a multi-institutional dataset to evaluate differences between the guidelines of the European Association of Urology and the guidelines of the National Comprehensive Cancer Network (NCCN) with regard to tumor size in risk stratification. METHODS AND MATERIAL: In total 1,116 individuals diagnosed with high-risk NMIBC between 2001 and 2013 were included in the analysis. Patients were stratified to NCCN guideline recommendations (high-grade T1, high-grade Ta ≤ 3 cm, and high-grade Ta > 3 cm). Recurrence and progression rates were calculated. Kaplan-Meier curves were fitted to examine differences in recurrence-free (RFS) and progression-free survival (PFS). Multivariable Cox proportional hazards regression models were employed to calculate differences in the RFS, PFS, overall, and cancer-specific survival (CSS). RESULTS: The majority of patients were diagnosed with high-grade T1 disease (N = 576, 51.6%), while 34.2% and 14.2% of patients were diagnosed with high-grade Ta ≤ 3 cm and Ta > 3 cm NMIBC, respectively. The 1- and 5-year RFS (1-year: 80.5% vs. 64.9%; 5-year: 58.6% vs. 48.3%, P = 0.048) and PFS (1-year: 99.1% vs. 98.6%; 5-year: 97.7% vs. 92.4%, P = 0.054) rates were higher in patients with Ta ≤ 3 cm. Patients diagnosed with high-grade Ta > 3 cm experienced unfavorable progression-free, and cancer-specific survival compared to high-grade Ta ≤ 3 cm, respectively (PFS: 2.41, 95% confidence interval [CI] 1.05-5.56, P = 0.038; CSS: hazard ratios [HR] 2.22, 95% CI 1.02-4.89, P = 0.048). CONCLUSION: Patients diagnosed with high-grade Ta NMIBC ≤3 cm demonstrated a favorable progression-free, and cancer-specific survival compared to patients diagnosed with high-grade Ta > 3 cm and high-grade T1 NMIBC.

Aristolochic acid and its effect on different cancers in uro-oncology.

PURPOSE OF REVIEW: To acquaint urologists with aristolochic acid nephropathy, an iatrogenic disease that poses a distinct threat to global public health. In China alone, 100 million people may currently be at risk. We illustrate the power of molecular epidemiology in establishing the cause of this disease. RECENT FINDINGS: Molecular epidemiologic approaches and novel mechanistic information established a causative linkage between exposure to aristolochic acid and urothelial carcinomas of the bladder and upper urinary tract. Noninvasive tests are available that detect urothelial cancers through the genetic analysis of urinary DNA. Combined with cytology, some of these tests can detect 95% of patients at risk of developing bladder and/or upper urothelial tract cancer. Robust biomarkers, including DNA-adduct and mutational signature analysis, unequivocally identify aristolochic acid-induced tumours. The high mutational load associated with aristolochic acid-induced tumours renders them candidates for immune-checkpoint therapy. SUMMARY: Guided by recent developments that facilitate early detection of urothelial cancers, the morbidity and mortality associated with aristolochic acid-induced bladder and upper tract urothelial carcinomas may be substantially reduced. The molecular epidemiology tools that define aristolochic acid-induced tumours may be applicable to other studies assessing potential environmental carcinogens.

The impact of cytoreductive nephrectomy on survival outcomes in patients treated with tyrosine kinase inhibitors for metastatic renal cell carcinoma in a real-world cohort.

BACKGROUND: Tyrosine kinase inhibitor therapy (TKI) has changed the treatment paradigm of metastatic renal cell carcinoma (mRCC). The recent CARMENA and SURTIME trials challenged the role of the cytoreductive nephrectomy (CN). OBJECTIVE: To assess the impact of CN prior to TKI therapy in patients with mRCC in a real-world setting. METHODS: Overall, 262 consecutive patients with mRCC were treated with CN plus TKI or TKI only at our institution between 2000 and 2016. Patients with prior immunotherapy or metastasectomy were excluded. Multiple imputation and inverse probability of treatment weighting (IPTW) were performed to account for missing values and imbalances between the treatment groups, respectively. Unadjusted and adjusted Kaplan-Meier estimates were used to determine differences in progression-free (PFS), overall (OS), and cancer-specific survival (CSS). RESULTS: Overall, 104 (40%) patients received CN before TKI treatment. Most frequent first line therapy was Sunitinib (66%), followed by Sorafenib (20%) and Pazopanib (10%). After adjustment with IPTW, there was no difference in PFS, CSS, and OS (all P > 0.05) between the treatment groups. In subgroup analyses, CSS was improved when CN was performed in patients with sarcomatoid features and clear cell histology (P = 0.04 and P = 0.03) and PFS was improved in patients with clear cell histology when CN was performed [0.04]). CN did not improve OS in any subgroup analysis. CONCLUSION: The role of CN remains controversial. We found no difference in survival outcomes between patients treated with and without CN before TKI therapy. However, CN was associated with improved survival in specific patient subgroups. Tailored, individualized treatment is key to further improve oncological outcomes for mRCC.