Implementation of PSMA PET/CT and alignment of ordering to SNMMI appropriate use criteria in a large network system.

INTRODUCTION: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides appropriate use criteria (AUC) for prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) which include guidance on imaging in newly diagnosed prostate cancer and in patients with biochemically recurrent (BCR) disease. This study aims to examine trends in PSMA implementation and the prevalence and outcomes of scans ordered in scenarios deemed rarely appropriate or not meeting SNMMI AUC. METHODS: We retrospectively identified patients who were diagnosed with presumptive National Comprehensive Cancer Network unfavorable intermediate, high, or very high risk prostate cancer, patients who underwent staging for BCR, and all patients staged with PSMA between July 2021 and March 2023. Positivity was validated by adherence to a predetermined reference standard. RESULTS: The frequency of PSMA use increased in initial staging from 24% to 80% and work-up of BCR from 91% to 99% over our study period. In addition, 5% (17/340) of PSMA scans ordered for initial staging did not meet AUC and 3% (15/557) of posttreatment scans were deemed rarely appropriate. Initial staging orders not meeting SNMMI AUC resulted in no positivity (0/17), while rarely appropriate posttreatment scans were falsely positive in 75% (3/4) of cases. Urologists (53%, 17/32) comprised the largest ordering specialty in rarely appropriate use. CONCLUSION: The frequency of PSMA use rose across the study period. A significant minority of patients received PSMA PET/CT in rarely appropriate scenarios yielding no positivity in initial staging and significant false positivity post-therapy. Further education of providers and electronic medical record-based interventions could help limit the rarely appropriate use of PET imaging.

A prospective evaluation of the prostate microbiome in malignant and benign tissue using transperineal biopsy.

BACKGROUND: The link between the prostate microbiome and prostate cancer remains unclear. Few studies have analyzed the microbiota of prostate tissue, and these have been limited by potential contamination by transrectal biopsy. Transperineal prostate biopsy offers an alternative and avoids fecal cross-contamination. We aim to characterize the prostate microbiome using transperineal biopsy. METHODS: Patients with clinical suspicion for prostate cancer who were to undergo transperineal prostate biopsy with magnetic resonance imaging (MRI) fusion guidance were prospectively enrolled from 2022 to 2023. Patients were excluded if they had Prostate Imaging Reporting and Data System lesions with scores ≤ 3, a history of prostate biopsy within 1 year, a history of prostate cancer, or antibiotic use within 30 days of biopsy. Tissue was collected from the MRI target lesions and nonneoplastic transitional zone. Bacteria were identified using 16S ribosomal RNA gene sequencing. RESULTS: Across the 42 patients, 76% were found to have prostate cancer. Beta diversity indices differed significantly between the perineum, voided urine, and prostate tissue. There were no beta diversity differences between cancerous or benign tissue, or between pre- and postbiopsy urines. There appear to be unique genera more abundant in cancerous versus benign tissue. There were no differences in alpha diversity indices relative to clinical findings including cancer status, grade, and risk group. CONCLUSIONS: We demonstrate a rigorous method to better characterize the prostate microbiome using transperineal biopsy and to limit contamination. These findings provide a framework for future large-scale studies of the microbiome of prostate cancer.

Effectiveness of Liposomal Bupivacaine With Bupivacaine Hydrochloride vs Bupivacaine Hydrochloride Alone as a Local Anesthetic for Children Undergoing Ambulatory Urologic Surgery: The Baby ORIOLES Randomized Clinical Trial.

PURPOSE: We sought to determine if the addition of liposomal bupivacaine to bupivacaine hydrochloride improves opioid-free rate and postoperative pain scores among children undergoing ambulatory urologic surgery. MATERIALS AND METHODS: A prospective, phase 3, single-blinded, single-center randomized trial with superiority design was conducted in children 6 to 18 years undergoing ambulatory urologic procedures between October 2021 and April 2023. Patients were randomized 1:1 to receive dorsal penile nerve block (penile procedures) or incisional infiltration with spermatic cord block (inguinal/scrotal procedures) with weight-based liposomal bupivacaine plus bupivacaine hydrochloride or bupivacaine hydrochloride alone. The primary outcome was opioid-free rate at 48 hours. Secondary outcomes included parents' postoperative pain measure scores, numerical pain scale scores, and weight-based opioid utilization at 48 hours and 10 to 14 days. RESULTS: We randomized 104 participants, with > 98% (102/104) with complete follow-up data at 48 hours and 10 to 14 days. At interim analysis, there was no significant difference in opioid-free rate at 48 hours between arms (60% in the intervention vs 62% in the control group; estimated difference in proportion -1.9% [95% CI, -20%-16%]; P = .8). We observed no increased odds of patients being opioid-free at 48 hours with the intervention compared to the control group (OR 0.96 [95% CI 0.41-2.3]; P = .9). The trial met the predetermined futility threshold for early stopping. There was no difference in parents' postoperative pain measure scores, numerical pain scale scores, or opioid utilization at 48 hours or 10 to 14 days. No difference in adverse events was observed. CONCLUSIONS: The addition of liposomal bupivacaine to bupivacaine hydrochloride did not significantly improve opioid-sparing effect or postoperative pain compared with bupivacaine hydrochloride alone among children ≥ 6 years undergoing ambulatory urologic surgery.

Hypogonadism, frailty, and postoperative outcomes among men undergoing radical nephrectomy.

BACKGROUND AND OBJECTIVE: Hypogonadism and frailty may impact postoperative outcomes for men undergoing radical nephrectomy (RN). We aimed to determine the prevalence of hypogonadism in men undergoing RN and whether hypogonadism and frailty are associated with adverse postoperative outcomes. METHODS: We identified men undergoing RN between 2012 and 2021 using the IBM Marketscan database. Frailty was determined using the Hospital Frailty Risk Score (HFRS). Patients were considered to have hypogonadism if diagnosed <5 years before RN. Length of stay (LOS), complications, emergency department (ED) visits, and readmissions were evaluated between men with and without hypogonadism at the time of surgery. Subgroup analysis of men with hypogonadism was performed to determine the effect of testosterone replacement therapy (TRT) on clinical outcomes. RESULTS: Among 13 598 men who underwent RN, 972 (7.1%) had hypogonadism. Men with hypogonadism were more frail compared to men without hypogonadism (HFRS: median: 8.2, interquartile range [IQR]: 5.2-11.7 vs. median: 7.0, IQR: 4.3-10.7, p < 0.001) and had increased incidence of postoperative ileus (13.0% vs. 10.8%, p = 0.045), acute kidney injury (25.5% vs. 21.6% p = 0.005), and cardiac arrest (1.2% vs. 0.6%, p = 0.034). Hypogonadism was not associated with LOS, 90-day ED visit or readmission. However, high-risk frailty was associated with increased risk of 90-day ED visit (hazard ratio [HR]: 2.1, 95% confidence interval [95% CI]: 1.9-2.4, p < 0.001) and 90-day inpatient readmission (HR: 2.6, 95% CI: 2.2-3.1, p < 0.001), compared to low-risk frailty patients. Among men with hypogonadism, TRT was not associated with any postoperative outcomes. CONCLUSIONS: Hypogonadism and frailty should be considered in the preoperative evaluation for men undergoing RN as risk factors for adverse postoperative outcomes.

A prostate biopsy risk calculator based on MRI: development and comparison of the Prospective Loyola University multiparametric MRI (PLUM) and Prostate Biopsy Collaborative Group (PBCG) risk calculators.

OBJECTIVES: To develop and validate a prostate cancer (PCa) risk calculator (RC) incorporating multiparametric magnetic resonance imaging (mpMRI) and to compare its performance with that of the Prostate Biopsy Collaborative Group (PBCG) RC. PATIENTS AND METHODS: Men without a PCa diagnosis receiving mpMRI before biopsy in the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (2015-2020) were included. Data from a separate institution were used for external validation. The primary outcome was diagnosis of no cancer, grade group (GG)1 PCa, and clinically significant (cs)PCa (≥GG2). Binary logistic regression was used to explore standard clinical and mpMRI variables (prostate volume, Prostate Imaging-Reporting Data System [PI-RADS] version 2.0 lesions) with the final PLUM RC, based on a multinomial logistic regression model. Receiver-operating characteristic curve, calibration curves, and decision-curve analysis were evaluated in the training and validation cohorts. RESULTS: A total of 1010 patients were included for development (N = 674 training [47.8% PCa, 30.9% csPCa], N = 336 internal validation) and 371 for external validation. The PLUM RC outperformed the PBCG RC in the training (area under the curve [AUC] 85.9% vs 66.0%; P < 0.001), internal validation (AUC 88.2% vs 67.8%; P < 0.001) and external validation (AUC 83.9% vs 69.4%; P < 0.001) cohorts for csPCa detection. The PBCG RC was prone to overprediction while the PLUM RC was well calibrated. At a threshold probability of 15%, the PLUM RC vs the PBCG RC could avoid 13.8 vs 2.7 biopsies per 100 patients without missing any csPCa. At a cost level of missing 7.5% of csPCa, the PLUM RC could have avoided 41.0% (566/1381) of biopsies compared to 19.1% (264/1381) for the PBCG RC. The PLUM RC compared favourably with the Stanford Prostate Cancer Calculator (SPCC; AUC 84.1% vs 81.1%; P = 0.002) and the MRI-European Randomized Study of Screening for Prostate Cancer (ERSPC) RC (AUC 84.5% vs 82.6%; P = 0.05). CONCLUSIONS: The mpMRI-based PLUM RC significantly outperformed the PBCG RC and compared favourably with other mpMRI-based RCs. A large proportion of biopsies could be avoided using the PLUM RC in shared decision making while maintaining optimal detection of csPCa.

Disparities in access to robotic technology and perioperative outcomes among patients treated with radical prostatectomy.

BACKGROUND: Most radical prostatectomies are completed with robotic assistance. While studies have previously evaluated perioperative outcomes of robot-assisted radical prostatectomy (RARP), this study investigates disparities in access and clinical outcomes of RARP. STUDY DESIGN: The National Cancer Database (NCDB) was used to identify patients who received radical prostatectomy for cancer between 2010 and 2017 with outcomes through 2018. RARP was compared to open radical prostatectomy (ORP). Odds of receiving RARP were evaluated while adjusting for covariates. Overall survival was evaluated using a propensity-score matched cohort. RESULTS: Overall, 354 752 patients were included with 297 676 (83.9%) receiving RARP. Patients who were non-Hispanic Black (82.8%) or Hispanic (81.3%) had lower rates of RARP than non-Hispanic White (84.0%) or Asian patients (87.7%, p < 0.001). Medicaid or uninsured patients were less likely to receive RARP (75.5%) compared to patients with Medicare or private insurance (84.4%, p < 0.001). Medicaid or uninsured status was associated with decreased odds of RARP in adjusted multivariable analysis (OR 0.61, 95% CI 0.49-0.76). RARP was associated with decreased perioperative mortality and improved overall survival compared to ORP. CONCLUSION: Patients who were underinsured were less likely to receive RARP. Improved access to RARP may lead to decreased disparities in perioperative outcomes for prostate cancer.

Self-reported quality of life as a predictor of mortality in renal cell carcinoma.

BACKGROUND: This study evaluated the utility of self-reported quality of life (QOL) metrics in predicting mortality among all-comers with renal cell carcinoma (RCC) and externally tested the findings in a registry of patients with small renal masses. METHODS: The Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) captured QOL metrics composed of mental component summary (MCS) and physical component summary (PCS) scores. Regression models assessed associations of MCS and PCS with all-cause, RCC-specific, and non-RCC-specific mortality. Harrell's concordance statistic (the C-index) and the Akaike information criterion (AIC) determined predictive accuracy and parsimony, respectively. Findings were tested in the prospective Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry. RESULTS: In SEER-MHOS, 1494 patients had a median age of 73.4 years and a median follow-up time of 5.6 years. Each additional MCS and PCS point reduced the hazard of all-cause mortality by 1.3% (95% CI, 0.981-0.993; P < .001) and 2.3% (95% CI, 0.971-0.984; P < .001), respectively. Models with QOL metrics demonstrated higher predictive accuracy (C-index, 72.3% vs 70.1%) and parsimony (AIC, 9376.5 vs 9454.5) than models without QOL metrics. QOL metrics exerted a greater effect on non-RCC-specific mortality than RCC-specific mortality. External testing in the DISSRM registry confirmed these findings with similar results for all-cause mortality. CONCLUSIONS: Models with self-reported QOL metrics predicted all-cause mortality in patients with RCC with higher accuracy and parsimony than those without QOL metrics. Physical health was a stronger predictor of mortality than mental health. The findings support the incorporation of QOL metrics into prognostic models and patient counseling for RCC.

Risk of prostate cancer for men with prior negative biopsies undergoing magnetic resonance imaging compared with biopsy-naive men: A prospective evaluation of the PLUM cohort.

BACKGROUND: Men with prior negative prostate biopsies have a lower risk of being diagnosed with prostate cancer in comparison with biopsy-naive men. However, the relative clinical utility of identified lesions on multiparametric magnetic resonance imaging (mpMRI) is uncertain between the 2 settings. METHODS: Patients from the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (January 2015 to June 2020) were examined. The detection of any prostate cancer and clinically significant prostate cancer (Gleason score ≥ 3 + 4) was stratified by Prostate Imaging-Reporting and Data System (PI-RADS) scores in the prior negative and biopsy-naive settings. Multivariable logistic regression models (PLUM models) assessed predictors, and decision curve analyses were used to estimate the clinical utility of PI-RADS cutoffs relative to the models. RESULTS: Nine hundred men (420 prior negative patients and 480 biopsy-naive patients) were included. Prior negative patients had lower risks of any prostate cancer (27.9% vs 54.4%) and clinically significant prostate cancer (20.0% vs 38.3%) in comparison with biopsy-naive patients, and this persisted when they were stratified by PI-RADS (eg, PI-RADS 3: 13.6% vs 27.4% [any prostate cancer] and 5.2% vs 15.4% [clinically significant prostate cancer]). The rate of detection of clinically significant prostate cancer was 5.3% among men with prior negative biopsy and PI-RADS ≤ 3. Family history and Asian ancestry were significant predictors among biopsy-naive patients. PLUM models demonstrated a greater net benefit and reduction in biopsies (45.8%) without missing clinically significant cancer in comparison with PI-RADS cutoffs (PI-RADS 4: 34.0%). CONCLUSIONS: Patients with prior negative biopsies had lower prostate cancer detection by PI-RADS score category in comparison with biopsy-naive men. Decision curve analyses suggested that many biopsies could be avoided by the use of the PLUM models or a PI-RADS 4 cutoff without any clinically significant cancer being missed. LAY SUMMARY: Men with a prior negative prostate biopsy had a lower risk of harboring prostate cancer in comparison with those who never had a biopsy. This was true even when patients in each group had similar multiparametric magnetic resonance imaging (mpMRI) findings in terms of Prostate Imaging-Reporting and Data System (PI-RADS)-graded lesions. Decision curve analyses showed that many biopsies could be avoided by the use of the Prospective Loyola University mpMRI prediction models or a PI-RADS 4 cutoff for patients with prior negative biopsies.

Multi-institutional analysis of clinical and imaging risk factors for detecting clinically significant prostate cancer in men with PI-RADS 3 lesions.

BACKGROUND: Most Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions do not contain clinically significant prostate cancer (CSPCa; grade group ≥2). This study was aimed at identifying clinical and magnetic resonance imaging (MRI)-derived risk fac- tors that predict CSPCa in men with PI-RADS 3 lesions. METHODS: This study analyzed the detection of CSPCa in men who underwent MRI-targeted biopsy for PI-RADS 3 lesions. Multivariable logistic regression models with goodness-of-fit testing were used to identify variables associated with CSPCa. Receiver operating curves and decision curve analyses were used to estimate the clinical utility of a predictive model. RESULTS: Of the 1784 men reviewed, 1537 were included in the training cohort, and 247 were included in the validation cohort. The 309 men with CSPCa (17.3%) were older, had a higher prostate-specific antigen (PSA) density, and had a greater likelihood of an anteriorly located lesion than men without CSPCa (p < .01). Multivariable analysis revealed that PSA density (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.05-1.85; p < .01), age (OR, 1.05; 95% CI, 1.02-1.07; p < .01), and a biopsy-naive status (OR, 1.83; 95% CI, 1.38-2.44) were independently associated with CSPCa. A prior negative biopsy was negatively associated (OR, 0.35; 95% CI, 0.24-0.50; p < .01). The application of the model to the validation cohort resulted in an area under the curve of 0.78. A predicted risk threshold of 12% could have prevented 25% of biopsies while detecting almost 95% of CSPCas with a sensitivity of 94% and a specificity of 34%. CONCLUSIONS: For PI-RADS 3 lesions, an elevated PSA density, older age, and a biopsy-naive status were associated with CSPCa, whereas a prior negative biopsy was negatively associated. A predictive model could prevent PI-RADS 3 biopsies while missing few CSPCas. LAY SUMMARY: Among men with an equivocal lesion (Prostate Imaging-Reporting and Data System 3) on multiparametric magnetic resonance imaging (mpMRI), those who are older, those who have a higher prostate-specific antigen density, and those who have never had a biopsy before are at higher risk for having clinically significant prostate cancer (CSPCa) on subsequent biopsy. However, men with at least one negative biopsy have a lower risk of CSPCa. A new predictive model can greatly reduce the need to biopsy equivocal lesions noted on mpMRI while missing only a few cases of CSPCa.

Active Surveillance versus Immediate Intervention for Small Renal Masses: A Cost-Effectiveness and Clinical Decision Analysis.

PURPOSE: Active surveillance (AS) with the possibility of delayed intervention (DI) is emerging as a safe alternative to immediate intervention for many patients with small renal masses (SRMs). However, limited comparative data exist to inform the most appropriate management strategy for SRMs. MATERIALS AND METHODS: Decision analytic Markov modeling was performed to estimate the health outcomes and costs of 4 management strategies for 65-year-old patients with an incidental SRM: AS (with possible DI), immediate partial nephrectomy, radical nephrectomy, and thermal ablation. Mortality, direct medical costs, quality-adjusted life-years, and incremental cost-effectiveness ratios were evaluated over 10 years. RESULTS: The 10-year all-cause mortality was 22.6% for AS, 21.9% for immediate partial nephrectomy, 22.4% for immediate radical nephrectomy, and 23.7% for immediate thermal ablation. At a willingness-to-pay threshold of $100,000/quality-adjusted life-year, AS was the most cost-effective management strategy. The results were robust in univariate, multivariate, and probabilistic sensitivity analyses. Clinical decision analysis demonstrated that the tumor's metastatic potential, patient age, individual preferences, and health status were important factors influencing the optimal management strategy. Notably, if the annual probability of metastatic progression from AS was sufficiently low (under 0.35%-0.45% for most ages at baseline), consistent with the typical metastatic potential of SRMs <2 cm, AS would achieve higher health utilities than the other strategies. CONCLUSIONS: Compared to immediate intervention, AS with timely DI offers a safe and cost-effective approach to managing patients with SRMs. For patients harboring tumors of very low metastatic potential, AS may lead to better patient outcomes than immediate intervention.

Systematic versus Targeted Magnetic Resonance Imaging/Ultrasound Fusion Prostate Biopsy among Men with Visible Lesions.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI)-ultrasound (US) fusion-guided biopsy may improve prostate cancer (PCa) detection and reduce grade misclassification. We compared PCa detection rates on systematic, magnetic resonance imaging-targeted, and combined biopsy with evaluation of important subgroups. MATERIALS AND METHODS: Men with clinical suspicion of harboring PCa from 2 institutions with visible Prostate Imaging-Reporting and Data System (PI-RADSTMv2) lesions receiving mpMRI-US fusion-guided prostate biopsy were included (2015-2020). Detection of PCa was categorized by grade group (GG). Clinically-significant PCa (csPCa) was defined as ≥GG2. Patients were stratified by biopsy setting and PI-RADS. RESULTS: Of 1,236 patients (647 biopsy-naïve) included, 626 (50.6%) harbored PCa and 412 (33.3%) had csPCa on combined biopsy. Detection of csPCa was 27.9% vs 23.3% (+4.6%) and GG1 PCa was 11.3% vs 17.8% (-6.5%) for targeted vs systematic cores. Benefit in csPCa detection was higher in the prior negative than biopsy-naïve setting (+7.8% [p <0.0001] vs +1.7% [p=0.3]) while reduction in GG1 PCa detection remained similar (-5.6% [p=0.0002] vs -7.3% [p=0.0001]). Targeted biopsy showed increased csPCa detection for PI-RADS 5, decrease in GG1 for PI-RADS 3, and both for PI-RADS 4 relative to systematic biopsy. Combined biopsy detected more csPCa (+10.0%) and slightly fewer GG1 PCa (-0.5%) compared to systematic alone. Upgrading to ≥GG2 by targeted biopsy occurred in 9.8% with no cancer and 23.6% with GG1 on systematic biopsy. CONCLUSIONS: Combined biopsy doubled the benefit of targeted biopsy alone in detection of csPCa without increasing GG1 PCa diagnoses relative to systematic biopsy. Utility of targeted biopsy was higher in the prior negative biopsy cohort, but advantages of combined biopsy were maintained regardless of biopsy history.

Association of Lymph Node Count and Survival after Primary Retroperitoneal Lymphadenectomy for Nonseminomatous Testicular Cancer.

PURPOSE: Retroperitoneal lymph node dissection (RPLND) for men with clinical stage (CS) I or II testicular nonseminomatous germ cell tumor (NSGCT) has both staging and therapeutic implications. We aimed to investigate the impact of lymph node count (LNC) on outcome after primary RPLND for men with CS I or II NSGCT using a nationally representative data set. MATERIALS AND METHODS: A retrospective analysis of men who received a primary RPLND for CS I or II NSGCT was performed using the National Cancer Database. The Kaplan-Meier method was used to determine overall survival (OS) according to LNC. Logistic regression analyses were used to identify factors associated with LNC >20 and factors predictive of lymph node-positive (pN+) disease after primary RPLND. RESULTS: Of 1,376 men who comprised our analytical cohort, 50.1% and 49.9% had 1-20 lymph nodes (LNs) and >20 LNs removed, respectively. Five-year OS rates were 96.4% and 99.1% for men with 1-20 and >20 LNs resected, respectively (p=0.004). A higher proportion of men with >20 LNs removed were treated at academic centers, had private insurance, presented with higher AJCC (American Joint Committee on Cancer) CS and were more likely to have pN+ disease, compared to those with 1-20 LNs removed. Factors significantly associated with pN+ disease after RPLND include higher AJCC CS and LNC (per 10-count increase). CONCLUSIONS: Higher LNC after primary RPLND significantly increases the likelihood of identifying pN+ disease and is associated with improved OS. Our data support the therapeutic implications of a thoroughly performed RPLND in the primary setting.

Perioperative Aspirin Use Is Associated with Bleeding Complications during Robotic Partial Nephrectomy.

PURPOSE: Daily aspirin use following cardiovascular intervention is commonplace and creates concern regarding bleeding risk in patients undergoing surgery. Despite its cardio-protective role, aspirin is often discontinued 5-7 days prior to major surgery due to bleeding concerns. Single institution studies have investigated perioperative outcomes of aspirin use in robotic partial nephrectomy (RPN). We sought to evaluate the outcomes of perioperative aspirin (pASA) use during RPN in a multicenter setting. MATERIALS AND METHODS: We performed a retrospective evaluation of patients undergoing RPN at 5 high volume RPN institutions. We compared perioperative outcomes of patients taking pASA (81 mg) to those not on aspirin. We analyzed the association between pASA use and perioperative transfusion. RESULTS: Of 1,565 patients undergoing RPN, 228 (14.5%) patients continued pASA and were older (62.8 vs 56.8 years, p <0.001) with higher Charlson scores (mean 3 vs 2, p <0.001). pASA was associated with increased perioperative blood transfusions (11% vs 4%, p <0.001) and major complications (10% vs 3%, p <0.001). On multivariable analysis, pASA was associated with increased transfusion risk (OR 1.94, 1.10-3.45, 95% CI). CONCLUSIONS: In experienced hands, perioperative aspirin 81 mg use during RPN is reasonable and safe; however, there is a higher risk of blood transfusions and major complications. Future studies are needed to clarify the role of antiplatelet therapy in RPN patients requiring pASA for primary or secondary prevention of cardiovascular events.

Four versus 3 Cycles of Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Implications for Pathological Response and Survival.

PURPOSE: The ideal number of neoadjuvant chemotherapy (NAC) cycles for muscle-invasive bladder cancer is uncertain with 3 to 4 representing the standard of care (SOC). We compared ypT0 rates and survival between patients receiving 4 versus 3 cycles of NAC with evaluation of chemotherapy-related toxicity for correlation with tumor chemosensitivity and pathological response. MATERIALS AND METHODS: Patients receiving NAC followed by radical cystectomy for cT2-4N0M0 urothelial carcinoma from 2 institutions were included. Primary study groups included 4 cisplatin-based NAC cycles, 3 cisplatin-based NAC cycles, and nonSOC NAC (1-2 cycles or noncisplatin-based) to compare ypT0/≤ypT1 rates and survival. A cohort of patients not receiving NAC was included for pathological reference. RESULTS: Of 693 total patients, 318 (45.9%) received NAC. ypT0 and ≤ypT1 rates were 42/157 (26.8%) and 86/157 (54.8%) for 4 cycles, 38/114 (33.3%) and 71/114 (62.3%) for 3 cycles, and 6/47 (12.8%) and 13/47 (27.7%) for nonSOC (p=0.03 and p <0.01, respectively). Pathological response appeared higher among patients receiving 3 cycles due to toxicity (ypT0: 29/77 [37.7%]; ≤ypT1: 51/77 [66.2%]) but did not reach statistical significance. Toxicities leading to treatment modifications were thrombocytopenia (32.1%), neutropenia (27.2%), renal insufficiency (22.2%), and constitutional symptoms (18.5%). NonSOC patients had lower Kaplan-Meier survival (cT2-cT4N0M0: log-rank p=0.07; cT2N0M0: log-rank p=0.02). There were no statistically significant differences in survival between 4 and 3 cycles (HR 1.00 [95% CI 0.57-1.74], p=0.99). CONCLUSIONS: Patients completing 3 cycles of cisplatin-based NAC have similar pathologic response and short-term survival compared to 4 cycles. Further evaluation of patients experiencing toxicity as a potential marker of tumor chemosensitivity is needed.

Imaging Features of Renal Masses to Select Optimal Candidates for Tumor Enucleation Partial Nephrectomy.

PURPOSE OF REVIEW: The goal of this paper was to critically evaluate preoperative findings that optimally select candidates for renal tumor enucleation partial nephrectomy. RECENT FINDINGS: Tumor enucleation has been widely accepted as a management option for patients with chronic kidney disease, hereditary renal cell carcinoma, or multifocal disease. Recent evidence suggests safety and efficacy in the management of routine small renal masses. With recent advances in imaging, the literature for ruling out aggressive renal cell carcinoma and selection for tumor enucleation is robust. As the incidence of renal cell carcinoma rises, partial nephrectomy continues to be the mainstay of treatment for localized renal cell carcinoma. Tumor enucleation maximizes preservation of renal parenchyma without hindering oncologic outcomes. It is important to recognize key tumor radiologic findings which urologists may use to optimize patient selection for tumor enucleation.

Effect of Erythropoietin on Erectile Function after Radical Prostatectomy: The ERECT Randomized Clinical Trial.

PURPOSE: Erectile dysfunction significantly impacts quality of life for men undergoing radical prostatectomy for prostate cancer. Erythropoietin is a promising neurotrophic factor for neurogenic erectile dysfunction based on preclinical and retrospective data. MATERIALS AND METHODS: ERECT (NCT00737893) is a phase 2, double-blinded, randomized, placebo-controlled trial (July 2017-December 2019) evaluating the impact of perioperative erythropoietin on recovery of erectile function and other patient-reported, health-related quality of life outcomes after bilateral nerve-sparing radical prostatectomy (3, 6, 9, and 12 months). Erythropoietin (20,000 units) or saline placebo was injected subcutaneously the day before, day of, and day after surgery for 3 total doses. RESULTS: Of 63 patients assessed for eligibility, 56 patients were randomized. Arms (29 erythropoietin, 27 placebo) were well balanced (89.3% robotic, median age 55.5 years). International Index of Erectile Function-Erectile Function Domain (IIEF-EF) scores increased from median 12.5 at 3 months to 24.5 at 12 months. Median 2-week serum hemoglobin was higher for the erythropoietin arm compared to placebo (14.7 vs 13.6, p=0.02). There was no statistically significant difference in IIEF-EF scores at 6 months comparing erythropoietin to placebo (p=0.50) or at other time points (mixed model regression coefficient: -1.7, 95% CI -6.1-2.7, p=0.45). Excellent nerve-sparing rating (10/10) was associated with improved IIEF-EF recovery (+5.2, p=0.022). Other patient-reported, health-related quality of life domains as well as oncologic outcome and complications were similar between arms during followup. CONCLUSIONS: In the context of brief perioperative dosing, erythropoietin did not improve recovery of erectile function for men undergoing radical prostatectomy for prostate cancer compared to placebo. Further research to identify effective adjuncts to improve health-related quality of life for these men is needed.

Comparative Effectiveness of Surveillance, Primary Chemotherapy, Radiotherapy and Retroperitoneal Lymph Node Dissection for the Management of Early Stage Testicular Germ Cell Tumors: A Systematic Review.

PURPOSE: Cancer specific survival for men with early stage (I to IIB) testicular germ cell tumors is greater than 90% with any management strategy. The data regarding the comparative effectiveness of surveillance, primary chemotherapy, radiotherapy and retroperitoneal lymph node dissection were synthesized with a focus on oncologic outcomes, patient reported outcomes, and short and long-term toxicities. MATERIALS AND METHODS: PubMed®, Embase® and the Cochrane Central Register of Controlled Trials were searched from 1980 to 2018 for studies addressing the effectiveness of surveillance, chemotherapy, radiotherapy and retroperitoneal lymph node dissection, according to pathology and clinical stage, for men with an early stage testicular germ cell tumor. RESULTS: Cancer specific survival ranged from 94% to 100% for patients with early stage testicular germ cell tumors regardless of tumor histology and initial management strategy. For men with seminoma the median cancer specific survival was 99.7% (range 97% to 100%), 99.5% (96.8% to 100%) and 100% (100% to 100%) among those managed by surveillance, radiotherapy and chemotherapy, respectively. Median cancer specific survival for men with nonseminomatous testicular germ cell tumors was 100% (range 98.6% to 100%), 100% (96.9% to 100%) and 100% (94% to 100%) when managed by surveillance, retroperitoneal lymph node dissection and chemotherapy, respectively. Recurrence rates and toxicities varied by management strategy. For men with seminoma surveillance, chemotherapy and radiotherapy were associated with median recurrence rates of 15%, 2% and 3.7%, respectively. For men with nonseminomatous testicular germ cell tumors the median recurrence rates were 20.5%, 3.3% and 11.1% for surveillance, chemotherapy and retroperitoneal lymph node dissection, respectively. Surveillance was associated with minimal toxicities compared to other approaches. Primary chemotherapy had the highest rate of short-term toxicities and was associated with long-term risks of metabolic syndrome, hypogonadism, renal impairment, neuropathy, infertility and secondary malignancies. Toxicities with radiotherapy included acute dermatitis and long-term gastrointestinal complications, infertility and high rates of secondary malignancies (2% to 3%). Patients undergoing retroperitoneal lymph node dissection had significant risk of toxicity perioperatively and long-term infertility in men with anejaculation. Transient detriments in patient reported outcomes and quality of life were noted with all management options. CONCLUSIONS: Men with early stage testicular germ cell tumors experience excellent cancer specific survival regardless of management strategy. Management options, however, differ in terms of associated recurrence rates, short and long-term toxicities, and patient reported outcomes. The profile for each approach should be clearly communicated to patients and matched with patient preferences to offer the best individual outcome.

Outcomes of Active Surveillance for Young Patients with Small Renal Masses: Prospective Data from the DISSRM Registry.

PURPOSE: A paradigm shift in the management of small renal masses has increased utilization of active surveillance. However, questions remain regarding safety and durability in younger patients. MATERIALS AND METHODS: Patients aged 60 or younger at diagnosis were identified from the Delayed Intervention and Surveillance for Small Renal Masses registry. The active surveillance, primary intervention, and delayed intervention groups were evaluated using ANOVA with Bonferroni correction, χ2 and Fisher's exact tests, and Kruskal-Wallis and Wilcoxon signed-rank tests. Survival outcomes were calculated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: Of 224 patients with median followup of 4.9 years 30.4% chose surveillance. There were 20 (29.4%) surveillance progression events, including 4 elective crossovers, and 13 (19.1%) patients underwent delayed intervention. Among patients with initial tumor size ≤2 cm, 15.1% crossed over, compared to 33.3% with initial tumor size 2-4 cm. Overall survival was similar in primary intervention and surveillance at 7 years (94.0% vs 90.8%, log-rank p=0.2). Cancer-specific survival remained at 100% for both groups. There were no significant differences between primary and delayed intervention with respect to minimally invasive or nephron-sparing interventions. Recurrence-free survival at 5 years was 96.0% and 100% for primary and delayed intervention, respectively (log-rank p=0.6). CONCLUSIONS: Active surveillance is a safe initial strategy in younger patients and can avoid unnecessary intervention in a subset for whom it is durable. Crucially, no patient developed metastatic disease on surveillance or recurrence after delayed intervention. This study confirms active surveillance principles can effectively be applied to younger patients.

Complications after open and robot-assisted radical prostatectomy and association with postoperative opioid use: an analysis of data from the PREVENTER trial.

OBJECTIVE: To evaluate perioperative complications for open radical prostatectomy (ORP) and robot-assisted RP (RARP) for patients enrolled in the PREvention of VENous ThromboEmbolism Following Radical Prostatectomy (PREVENTER; ClinicalTrials.gov Identifier: NCT03006562) trial, to determine predictors and impact on opioid consumption. PATIENTS AND METHODS: A prospective cohort of 500 patients undergoing ORP and RARP was followed to determine rates of complications and opioid use. Complications were classified 30 days after RP using the Clavien-Dindo system. Patient characteristics and outcomes were compared using appropriate statistical tests. Logistic and linear regressions were performed to identify predictors of complications and evaluate the relationship between complications and postoperative opioid use. RESULTS: A total of 124 (24.8%) men underwent ORP and 376 (75.2%) RARP, with 418 (83.6%) receiving pelvic lymph node dissection (PLND). While 83 patients (16.6%) had complications, only 19 (3.8%) were major (Clavien-Dindo Grade ≥III), with no differences by surgical approach. PLND (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.25-8.71; P = 0.03) and Stage pT3b (OR 2.76, 95% CI 1.23-6.00;P = 0.01) were the only predictors of complications after controlling for potential confounders. Patients who had complications had greater inpatient (P = 0.02) and outpatient (P = 0.005) opioid use, which persisted after controlling for patient-reported pain, attending surgeon variation, surgical approach, and undergoing PLND (inpatient ß:77.2, 95% CI 17.9-136.5,P = 0.03; and outpatient ß:21.9, 95% CI 4.7-39.1,P = 0.01). CONCLUSION: In an analysis of prospectively collected data, overall and major complications rates did not differ by surgical approach. Patients receiving PLND and with Stage pT3b disease had more complications. Complications were independently associated with higher inpatient and outpatient postoperative opioid use.

A prospective comparative study of routine versus deferred pelvic drain placement after radical prostatectomy: impact on complications and opioid use.

PURPOSE: To evaluate the association of post-RP drain placement with post-operative complications and opioid use at a high-volume institution. METHODS: A prospective, comparative cohort study of patients undergoing robot-assisted or open RP was conducted. Patients for two surgeons did not routinely receive pelvic drains ("No Drain" arm), while the remainder routinely placed drains ("Drain" arm). Outcomes were evaluated at 30 days including Clavien-Dindo complications and opioid use. Intention-to-treat primary analysis and additional secondary analyses were performed using appropriate statistical tests and logistic regression. RESULTS: Of 498 total patients, 144 (28.9%) were in the No Drain arm (all robot-assisted) and 354 (71.1%) in the Drain arm. In the No Drain arm, 19 (13.2%) intraoperatively were chosen to receive drains. There was no difference in overall or major (Clavien ≥ 3) complications between groups (p = 0.2 and 0.4, respectively). Drain deferral did not predict complications on multivariable analysis adjusted for age, BMI, comorbidities, clinical risk, surgical approach, operating time, lymphadenectomy, and number of nodes removed [OR 0.61, 95% CI 0.34-1.11, p = 0.10]; nor did it predict symptomatic fluid collection, adjusting for lymphadenectomy and nodes removed [OR 1.14, 95% CI 0.43-3.60, p = 0.8]. Drain deferral did not decrease opioid use (p = 0.5). Per protocol analysis and restriction to robot-assisted cases demonstrated similar results. CONCLUSION: There was no difference in adverse events, complications, symptomatic collections, or opioid use with deferral of routine drain placement after RP. Experienced surgeons may safely defer drain placement in the majority of robot-assisted RP cases.