Impact of the extent of lymph node dissection on survival outcomes in clinically lymph node-positive bladder cancer.

OBJECTIVE: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). PATIENTS AND METHODS: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. RESULTS: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. CONCLUSION: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.

The optimal number of induction chemotherapy cycles in clinically lymph node-positive bladder cancer.

OBJECTIVE: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node-positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. PATIENTS AND METHODS: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose-dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1-3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni- and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer-specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. RESULTS: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2-year OS estimates were 63% (95% confidence interval [CI] 0.53-0.74) and 63% (95% CI 0.58-0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni- or multivariable Cox regression analyses. CONCLUSION: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.

An Empirical Survey on the Adaption of Neoadjuvant Chemotherapy in Bladder Cancer.

INTRODUCTION: The aim of the study was to determine the adaption of neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC) in Germany, Austria, and Switzerland and especially underlying reasons for potential low adherence to guidelines. METHODS: We conducted a non-validated survey among 336 urologic departments in Germany, Austria, and Switzerland. RedCap questionnaires were electronically distributed and included 23 items concerning the general NAC administration standards and guideline compliance in patient counseling regarding the actual treatment. RESULTS: The return rate of the questionnaire was 19.1% (63/336). Although 45 departments (71.4%) claim to perform NAC as the standard of care, only 49% of eligible patients actually receive NAC. An advanced disease stage (≥cT3) and a high tumor volume were mentioned to support the application of NAC, whereas 35% of responders worry about deterioration of patients' preoperative status due to NAC. Furthermore, 26.7% of respondents are concerned about the low extent of survival benefit. CONCLUSION: Application of NAC in eligible MIBC patients in Germany, Austria, and Switzerland remains low. Although the majority of urologic departments discuss NAC and acknowledge the need for intensified treatment in advanced disease stages, not all eligible patients will actually receive NAC before radical cystectomy.

Functional outcome after radical prostatectomy in 1313 patients: A single-center study.

OBJECTIVES: To assess the impact of urinary continence and erectile function on the quality of life in men undergoing radical prostatectomy (RP) for prostate cancer (PC), we analyzed the preoperative and 1-year postoperative outcomes of five functional domains and their influencing factors. PATIENTS AND METHODS: In this prospective study, all patients undergoing open or robot-assisted RP between Febuary 2017 and March 2020 in a single academic center were included. Patient-reported outcomes were assessed pre- and 12 months postoperatively using the Expanded Prostate Index Composite (EPIC-26) survey, evaluating continence, irritative/obstructive micturition, gastrointestinal symptoms, sexuality, and overall vitality. We examined the impact of RP on sexual function and urinary continence using multivariable logistic regression models, accounting for patient and tumor characteristics. RESULTS: Overall, 1313 consecutive patients gave consent for study participation and completed both surveys. The median age was 66 years (IQR: 60-70). The majority of patients (n = 601, 46%) had an intermediate risk PC. Robotic RP was performed in 71.6% and nerve-sparing technique in 81% of the cases. The median pre- versus postoperative scores were the following: urinary continence 100 (IQR: 91.8-100) versus 85.5 (64.8-100), irritative micturition 87.5 (IQR: 75-100) versus 93.8 (IQR: 87.5-100), gastrointestinal symptoms the same with 100 (IQR: 95.8-100), vitality 95 (IQR: 80-100) versus 90 (IQR: 75-100), and erectile function 65.3 (IQR: 38.8-87.5) versus 22.2 (IQR: 12.5-48.7), respectively. Age (p < 0.001), risk classification (p = 0.002), and nerve-sparing surgery (p = 0.016) were associated with good sexual function (EPIC-26 score ≥60), while only age (p = 0.001) was statistically significantly associated with good urinary continence (EPIC-26 score ≥80). CONCLUSION: Non-modifiable factors such as age and PC risk classification impact urinary continence and sexual function after RP. Nevertheless, urologic surgeons should further focus on improving nerve-sparing techniques, the only modifiable variable, to reduce the surgery's negative impact on urinary continence and sexual function.

Comparison of prostate cancer detection rates in patients undergoing MRI/TRUS fusion prostate biopsy with two different software-based systems.

BACKGROUND: Magnetic resonance imaging (MRI)-targeted prostate biopsy is a routinely used diagnostic tool for prostate cancer (PCa) detection. However, a clear superiority of the optimal approach for software-based MRI processing during biopsy procedures is still unanswered. To investigate the impact of robotic approach and software-based image processing (rigid vs. elastic) during MRI/transrectal ultrasound (TRUS) fusion prostate biopsy (FBx) on overall and clinically significant (cs) PCa detection. METHODS: The study relied on the instructional retrospective biopsy data collected data between September 2013 and August 2017. Overall, 241 men with at least one suspicious lesion (PI-RADS ≥ 3) on multiparametric MRI underwent FBx. The study protocol contains a systematic 12-core sextant biopsy plus 2 cores per targeted lesion. One experienced urologist performed 1048 targeted biopsy cores; 467 (45%) cores were obtained using rigid processing, while the remaining 581 (55%) cores relied on elastic image processing. CsPCa was defined as International Society of Urological Pathology (ISUP) grade ≥ 2. The effect of rigid versus elastic FBx on overall and csPCa detection rates was determined. Propensity score weighting and multivariable regression models were used to account for potential biases inherent to the retrospective study design. RESULTS: In multivariable regression analyses, age, prostate-specific antigen (PSA), and PIRADS ≥ 3 lesion were related to higher odds of finding csPCa. Elastic software-based image processing was independently associated with a higher overall PCa (odds ratio [OR] = 3.6 [2.2-6.1], p < 0.001) and csPCa (OR = 4.8 [2.6-8.8], p < 0.001) detection, respectively. CONCLUSIONS: Contrary to existing literature, our results suggest that the robotic-driven software registration with elastic fusion might have a substantial effect on PCa detection.

Access denied: The relationship between patient insurance status and access to high-volume hospitals.

BACKGROUND: Underinsured patients face significant barriers in accessing high-quality care. Evidence of whether access to high-volume surgical care is mediated by disparities in health insurance coverage remains wanting. METHODS: The authors used the National Cancer Data Base to identify all adult patients who had a confirmed diagnosis of breast, prostate, lung, or colorectal cancer during 2004 through 2016. The odds of receiving surgical care at a high-volume hospital were estimated according to the type of insurance using multivariable logistic regression analyses for each malignancy. Then, the interactions between study period and insurance status were assessed. RESULTS: In total, 1,279,738 patients were included in the study. Of these, patients with breast cancer who were insured by Medicare (odds ratio [OR], 0.75; P < .001), Medicaid (OR, 0.55; P < .001), or uninsured (OR, 0.50; P < .001); patients with prostate cancer who were insured by Medicare (OR, 0.87; P = .003), Medicaid (OR, 0.58; P = .001), or uninsured (OR, 0.36; P < .001); and patients with lung cancer who were insured by Medicare (OR, 0.84; P = .020), Medicaid (OR, 0.74; P = .001), or uninsured (OR, 0.48; P < .001) were less likely to receive surgical care at high-volume hospitals compared with patients who had private insurance. For patients with colorectal cancer, the effect of insurance differed by study period, and improved since 2011. For those on Medicaid, the odds of receiving care at a high-volume hospital were 0.51 during 2004 through 2007 and 0.99 during 2014 through 2016 (P for interaction = .001); for uninsured patients, the odds were 0.45 during 2004 through 2007 and 1.19 during 2014 through 2016 (P for interaction < .001) compared with patients who had private insurance. CONCLUSIONS: Uninsured, Medicare-insured, and Medicaid-insured patients are less likely to receive surgical care at high-volume hospitals. For uninsured and Medicaid-insured patients with colorectal cancer, the odds of receiving care at high-volume hospitals have improved since implementation of the Patient Protection and Affordable Care Act of 2010.

Identification of patients at risk for biochemical recurrence after radical prostatectomy with intra-operative frozen section.

OBJECTIVE: To identify patients at risk for biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy (RP) with intra-operative whole-mount frozen section (FS) of the prostate. MATERIAL AND METHODS: We examined differences in BCR between patients with initial negative surgical margins at FS, patients with final negative surgical margins with initial positive margins at FS without residual PCa after secondary tumour resection, and patients with final negative surgical margins with initially positive margins at FS with residual PCa in the secondary tumour resection specimen. Institutional data of 883 consecutive patients undergoing RP were collected. Intra-operative whole-mount FS was routinely used to check for margin status and, if necessary, to resect more periprostatic tissue in order to achieve negative margins. Patients with lymph node-positive disease or final positive surgical margins were excluded from the analysis. Kaplan-Meier curves and multivariable Cox proportional hazards regression analyses adjusting for clinical covariates were employed to examine differences in biochemical recurrence-free survival (BRFS) according to the resection status mentioned above. RESULTS: The median follow-up was 22.4 months. The 1- and 2-year BRFS rates in patients with (81.0% and 72.9%, respectively; P = 0.001) and without residual PCa (90.3% and 82.3%, respectively; P = 0.033) after secondary tumour resection were significantly lower compared to patients with initial R0 status (93.4% and 90.9%, respectively). On multivariable Cox regression only residual PCa in the secondary tumour resection was associated with a higher risk of BCR compared to initial R0 status (hazard ratio 1.99, 95% confidence interval 1.01-3.92; P = 0.046). CONCLUSION: Despite being classified as having a negative surgical margin, patients with residual PCa in the secondary tumour resection specimen face a high risk of BCR. These findings warrant closer post-RP surveillance of this particular subgroup. Further research of this high-risk subset of patients should focus on examining whether these patients benefit from early salvage therapy and how resection status impacts oncological outcomes in the changing landscape of PCa treatment.

Probability of Prostate Cancer Diagnosis following Negative Systematic and Targeted MRI: Transrectal Ultrasound Fusion Biopsy: A Real-Life Observational Study.

INTRODUCTION: The risk of occult prostate carcinoma (PCa) after negative multiparametric MRI (mpMRI)-transrectal fusion biopsy (F-Bx) is unknown. To determine the false-negative predictive value, we examined PCa detection after prior negative F-Bx. METHODS: Between December 2012 and November 2016, 491 patients with suspected PCa and suspicious mpMRI findings underwent transrectal F-Bx. Patients with benign pathology (n = 191) were eligible for our follow-up (FU) survey. Patient characteristics and clinical parameters were correlated to subsequent findings of newly detected PCa. RESULTS: Complete FU with a median of 31 (interquartile range: 17-39) months was available for 176/191 (92.2%) patients. Of those, 54 men had either surgical interventions on the prostate or re-Bxs. Newly detected PCa was evident in 14/176 (7.95%) patients stratified to ISUP ≤2 in 10 and ≥3 in 4 cases. The comparison of patients with newly detected PCa to those without cancerous findings in FU showed significant differences in prostate-specific antigen (PSA) density (0.16 vs. 0.13 ng/mL2) and prostate volume (45 vs. 67 mL, both p < 0.05). Both factors are significant predictors for newly detected cancer after initial negative F-Bx. CONCLUSION: Only PSA density (>0.13 ng/mL2) and small prostate volume are significant predictors for newly detected PCa after initial negative F-Bx. Despite negative mpMRI/TRUS F-Bx results, patients should be further monitored due to a risk of developing PCa over time. Notwithstanding the limitation of our study that not all patients underwent another Bx, we assume that the false-negative rate is low but existing. Our data represent a real-world scenario.

Facility-Level Variation in Pelvic Lymphadenectomy During Radical Prostatectomy and Effect on Overall Survival in Men with High-Risk Prostate Cancer.

PURPOSE: This study was designed to examine facility-level variation in the extent of pelvic lymphadenectomy and to determine whether more extensive lymphadenectomy is associated with a survival benefit among men with localized high-risk prostate cancer. METHODS: Using data from the National Cancer Data Base, we identified 13,652 men with a high predicted probability of 10-year survival (≤ 65 years of age and Charlson Comorbidity Index score of 0) who underwent radical prostatectomy at 1023 facilities for biopsy-confirmed localized high-risk prostate cancer diagnosed between January 2004 and December 2011. Multilevel, multinomial logistic regression was fitted to predict facility-level probability of receiving different extents of lymphadenectomy. Inverse probability of treatment weighting-adjusted Cox regression model with Bonferroni correction was fitted to compare risk of overall mortality. RESULTS: Overall, 11,284 (82.7%), 1601 (11.7%), and 767 (5.6%) men who underwent radical prostatectomy underwent concomitant none/limited lymphadenectomy (0-9 lymph nodes), standard lymphadenectomy (10-16 lymph nodes), and extended lymphadenectomy (≥ 17 lymph nodes), respectively. Extended lymphadenectomy was not associated with a survival benefit relative to standard lymphadenectomy (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.48-1.23; p = 0.4) nor no/limited lymphadenectomy (HR 0.77, 95% CI 0.87-2.20; p = 0.29) at a median follow-up of 83.3 months. Risk-adjusted facility-level predicted probabilities of extended, standard, or no/limited lymphadenectomy ranged from 0.01 to 52.6%, 3.3-53.3%, and 17.8-96.3%, respectively. CONCLUSIONS: We found significant facility-level variation in the extent of pelvic lymphadenectomy during radical prostatectomy despite no apparent survival benefit associated with more extensive lymphadenectomy. Further prospective data are needed to reevaluate the role of lymphadenectomy in the management of clinically localized prostate cancer.

Differences in survival and impact of adjuvant chemotherapy in patients with variant histology of tumors of the renal pelvis.

BACKGROUND: The impact of variant histologies on overall survival (OS), as well as their influence on the response to neoadjuvant and adjuvant chemotherapy (AC) is well studied in patients diagnosed with bladder cancer. However, little is known about tumors with variant histologies of the upper urinary tract. The objective of this study was to assess the survival of the predominant variant histologies of tumors of the renal pelvis (RPT) after surgical intervention, and to examine the influence of AC on the OS of the different variant histologies. METHODS: We identified 21,318 patients with RPT undergoing surgical intervention using the National Cancer Database for the period 2004-2015. We employed multivariable Cox proportional hazards regression models and Kaplan-Meier curves to evaluate the OS according to variant histology. Separate multivariable Cox regression models were used to assess the specific effect of AC on OS of the histological subgroups. RESULTS: The majority of patients were diagnosed with pure urothelial carcinoma (PUC) (96.1%). Overall, 826 patients were diagnosed with variant histologies (adenocarcinoma N = 298, squamous cell carcinoma N = 291, sarcomatoid N = 137, others N = 100). Compared to PUC, adenocarcinomas showed longer OS (HR 0.76, 95% confidence interval (CI) 0.62-0.94, p = 0.01), while sarcomatoid tumors had shorter OS (HR 1.59, 95% CI 1.12-2.26, p = 0.011). A subgroup analysis of patients undergoing AC showed a survival benefit in patients with PUC (HR 0.81, 95% CI 0.73-0.9, p < 0.001). CONCLUSION: We found that variant histologies of upper urinary tract carcinomas exhibit different survival rates and that AC was only associated with an OS benefit in patients with PUC.

Minimally invasive cancer surgery is associated with a lower risk of venous thromboembolic events.

BACKGROUND: Venous thromboembolism (VTE) is a significant source of postoperative morbidity and mortality in patients undergoing common oncologic procedures. We sought to estimate the effect of surgical approach on the risk of developing a VTE. METHODS: IBM Watson Health Marketscan Database was used to conduct this retrospective study. In total, 12 938 patients who underwent either a radical prostatectomy, partial colectomy, or hysterectomy via a minimally invasive or open approach. We used a propensity-weighted logistic regression analysis to assess the independent effect of surgical approach on VTE. The primary outcome of interest was the 90-day rate of VTE after surgery. RESULTS: Patients undergoing minimally invasive surgery across all three surgical procedures were noted to have a lower odds of developing a VTE: (radical prostatectomy, odds ratio [OR]: 0.667, 95% confidence interval [CI]: 0.500-0.891; P = .006 |partial colectomy: OR, 0.620, 95% CI: 0.477-0.805; P < .001| hysterectomy: OR, 0.549 95% CI: 0.353-0.854; P = .008). CONCLUSION: We found that a minimally invasive approach was associated with significantly lower odds of VTE compared with undergoing the same open procedure. This study highlights how surgical approach may be an independent risk factor for development of VTE and may elucidate potential risk mitigation strategy.

Side effects of drug-antibody conjugates enfortumab-vedotin and sacituzumab-govitecan in targeted therapy in cancer.

OBJECTIVE: Antibody-drug conjugates (ADC), enfortumab-vedotin (EV) and sacituzumab-govitecan are new drugs in the treatment of urologic tumors, whose safety profile has not been fully investigated. Therefore, the aim of our study was to evaluate adverse events related to both agents reported to VigiBase, the World Health Organization's global pharmacovigilance database. METHODS: We employed Bayesian disproportionality analysis based on the information component (IC) to explore the safety profile associated with both therapies. Additionally, we used the proportional reporting ratio approach to examine the safety profile further. RESULTS: We identified 41,752 reports connected to ADC therapy (EV: n=5359; SG: n=36,393). In the EV subgroup, most reports were associated with dermatologic (38.6%), neurologic adverse events (16.5%), or adverse laboratory assessments (19.4%). In contrast, reports in the SG subgroup were mainly associated with gastrointestinal adverse events (24.2%) and adverse laboratory assessments (39.0%). Adverse laboratory assessments in both cohorts were often based on haematotoxic adverse events. CONCLUSION: We could provide a comprehensive real-world safety profile of EV and SG using a global pharmacovigilance database. Based on the safety signals explored in this study, further research regarding the impact of these side effects on patient outcomes is justified.

Treating BCG-Induced Cystitis with Combined Chondroitin and Hyaluronic Acid Instillations in Bladder Cancer.

In non-muscle invasive bladder cancer, Bacillus Calmette-Guérin (BCG) responders benefit from strong Th1-type inflammatory and T cell responses mediating tumor rejection. However, the corresponding lack of anti-inflammatory Th2-type immunity impairs tissue repair in the bladder wall and facilitates the development of cystitis, causing urinary pain, urgency, incontinence, and frequency. Mechanistically, the leakage of the glycosaminoglycan (GAG) layer enables an influx of potassium ions, bacteria, and urine solutes towards the underlying bladder tissue, promoting chronic inflammation. Treatments directed towards re-establishing this mucopolysaccharide-based protective barrier are urgently needed. We discuss the pathomechanisms, as well as the therapeutic rationale of how chondroitin and hyaluronic acid instillations can reduce or prevent BCG-induced irritative bladder symptoms. Moreover, we present a case series of five patients with refractory BCG-induced cystitis successfully treated with combined chondroitin and hyaluronic acid instillations.

The Natural History of Renal-Cell Carcinoma with Sarcomatoid Differentiation, a Stage-by-Stage Analysis.

BACKGROUND: Sarcomatoid differentiation in patients diagnosed with renal cell carcinoma (sRCC) imply aggressive behavior and often metastatic disease at the time of diagnosis. We aim to examine the overall survival (OS) in patients with sRCC using the National Cancer Database (NCDB). MATERIALS AND METHODS: We identified patients diagnosed with sRCC between 2010-2015. We employed Kaplan-Meier curves and multivariable Cox proportional hazards regression models to examine the impact of several potential risk factors on OS in patients diagnosed with sRCC. RESULTS: In total, 8582 patients with renal cancer were found to have sarcomatoid differentiation, with 4105 patients (47.8%) being diagnosed with AJCC stage IV disease. The median OS was 17.2 months (IQR 5.4, 68.7 months). Compared to patients who did not undergo surgery, OS was significantly longer in patients undergoing partial or total nephrectomy across all stages. This result remained consistent on multivariable Cox proportional hazards regression adjusting for patient and tumor characteristics (Surgery: Hazard ratio 0.54, 95%Confidence interval 0.43 - 0.68, P < .001). CONCLUSION: In our cohort sRCC was found to have an unfavorable median OS, which was mainly caused by the high number of cases diagnosed with late-stage disease. Additionally, surgery was associated with favorable OS across all stages. This study supports the notion that surgical therapy, even in the setting of cytoreductive surgery, provides a survival benefit in patients with sRCC.

A Multivariable Approach Using Magnetic Resonance Imaging to Avoid a Protocol-based Prostate Biopsy in Men on Active Surveillance for Prostate Cancer-Data from the International Multicenter Prospective PRIAS Study.

BACKGROUND: There is ongoing discussion whether a multivariable approach including magnetic resonance imaging (MRI) can safely prevent unnecessary protocol-advised repeat biopsy during active surveillance (AS). OBJECTIVE: To determine predictors for grade group (GG) reclassification in patients undergoing an MRI-informed prostate biopsy (MRI-Bx) during AS and to evaluate whether a confirmatory biopsy can be omitted in patients diagnosed with upfront MRI. DESIGN, SETTING, AND PARTICIPANTS: The Prostate cancer Research International: Active Surveillance (PRIAS) study is a multicenter prospective study of patients on AS (www.prias-project.org). We selected all patients undergoing MRI-Bx (targeted ± systematic biopsy) during AS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A time-dependent Cox regression analysis was used to determine the predictors of GG progression/reclassification in patients undergoing MRI-Bx. A sensitivity analysis and a multivariable logistic regression analysis were also performed. RESULTS AND LIMITATIONS: A total of 1185 patients underwent 1488 MRI-Bx sessions. The time-dependent Cox regression analysis showed that age (per 10 yr, hazard ratio [HR] 0.84 [95% confidence interval {CI} 0.71-0.99]), MRI outcome (Prostate Imaging Reporting and Data System [PIRADS] 3 vs negative HR 2.46 [95% CI 1.56-3.88], PIRADS 4 vs negative HR 3.39 [95% CI 2.28-5.05], and PIRADS 5 vs negative HR 4.95 [95% CI 3.25-7.56]), prostate-specific antigen (PSA) density (per 0.1 ng/ml cm3, HR 1.20 [95% CI 1.12-1.30]), and percentage positive cores on the last systematic biopsy (per 10%, HR 1.16 [95% CI 1.10-1.23]) were significant predictors of GG reclassification. Of the patients with negative MRI and a PSA density of <0.15 ng/ml cm3 (n = 315), 3% were reclassified to GG ≥2 and 0.6% to GG ≥3. At the confirmatory biopsy, reclassification to GG ≥2 and ≥3 was observed in 23% and 7% of the patients diagnosed without upfront MRI and in 19% and 6% of the patients diagnosed with upfront MRI, respectively. The multivariable analysis showed no significant difference in upgrading at the confirmatory biopsy between patients diagnosed with or without upfront MRI. CONCLUSIONS: Age, MRI outcome, PSA density, and percentage positive cores are significant predictors of reclassification at an MRI-informed biopsy. Patients with negative MRI and a PSA density of <0.15 ng/ml cm3 can safely omit a protocol-based prostate biopsy, whereas in other patients, a multivariable approach is advised. Being diagnosed with upfront MRI appears not to significantly affect reclassification risk; hence, a confirmatory MRI-Bx cannot totally be omitted yet. PATIENT SUMMARY: A protocol-based prostate biopsy while on active surveillance can be omitted in patients with negative magnetic resonance imaging (MRI) and prostate-specific antigen density <0.15 ng/ml cm3. A confirmatory biopsy cannot simply be omitted in all patients diagnosed with upfront MRI.

Changing the Prostate Cancer Detection Paradigm: Clinical Application of European Association of Urology Guideline-recommended Magnetic Resonance Imaging-based Risk Stratification in Men with Suspected Prostate Cancer.

BACKGROUND: Multiparametric magnetic resonance imaging using the Prostate Imaging Reporting and Data System version 2.1 allows for a personalized, risk-stratified approach to indicating prostate biopsies (PBx) in order to reduce PBx and concomitant complications in men with suspected prostate cancer (PCa). One way to achieve this goal is to implement the risk-stratified pathway (RSP) using the Rotterdam Prostate Cancer Risk Calculator. OBJECTIVE: To describe the clinical implementation of the RSP and to examine its impact on the number of PBx and the resulting changes in the PCa detection pattern compared with men undergoing PBx in a detection-focused pathway (DFP) without prior risk assessment. DESIGN, SETTING, AND PARTICIPANTS: An institutional dataset of 505 consecutive patients with suspected PCa between July 2019 and February 2020 was used. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Chi-square test and Mann-Whitney U test were employed to examine differences in the number of PBx and the PCa detection pattern between the DFP (n = 195, 38.6%) and the RSP (n = 310, 61.4%). To minimize differences in risk stratification, inverse probability of treatment weighting was used. RESULTS AND LIMITATIONS: After implementing the RSP, the overall biopsy rate could be reduced by 11.2% (100% vs 88.8%, p < 0.001. Additionally, compared with the DFP, the number of biopsy cores per patient was reduced in the RSP (14 [interquartile range {IQR} 14-15] vs 14 [IQR 6-14], p < 0.001) and the detection of clinically significant PCa was increased (44.3% vs 57.7%, p = 0.038). Overdiagnosis of clinically insignificant disease was decreased in the RSP (22.8% vs 12.6%, p = 0.039). CONCLUSIONS: Implementation of the RSP in clinical practice reduced the number of PBx and brought forth a shift in the PCa detection pattern toward clinically significant disease, while reducing overdiagnosis of clinically insignificant disease. PATIENT SUMMARY: In this study, we examined the impact of risk stratification on the number of prostate biopsies (PBx) and the consecutive detection pattern in men with suspected prostate cancer (PCa). We found that the risk-stratified pathway reduced the number of PBx while simultaneously shifting the PCa detection pattern toward clinically significant PCa.

Temporal Trends in the Incidence of Testicular Cancer in the United States over the Past Four Decades.

Testicular cancer is the most commonly diagnosed solid-organ neoplasm among young men, with variable incidence across racial groups. Testicular cancer incidence has increased since the 1970s, most notably among white men. Such trends in testicular cancer remain poorly understood. We investigated age-adjusted incidence rates of testicular cancer from 1975 to 2015 using Surveillance, Epidemiology and End Results data to further understand the nature of the temporal trends and potential drivers of disease. Across this time period, white men had the highest incidence and the largest increase in rate; however, we also note more recent increases in the incidence of testicular cancer across all racial groups being examined. PATIENT SUMMARY: We analyzed the rate of testicular cancer in the United States between 1975 and 2015. In that time, white patients had the highest rate and increase in rate of testicular cancer, but non-white patients also had increasing rates of disease.

Risk of Immune-related Adverse Events in Melanoma Patients With Preexisting Autoimmune Disease Treated With Immune Checkpoint Inhibitors: A Population-based Study Using SEER-Medicare Data.

OBJECTIVE: The objective of this study was to examine the risk of immune-related adverse events (irAEs) in patients with a preexisting autoimmune disease (pAID) presenting with a cutaneous melanoma receiving an immune checkpoint inhibitor (ICI) therapy. METHODS: Data from the Surveillance, Epidemiology, and End Results cancer registries and linked Medicare claims between January 2010 and December 2015 was used to identify patients diagnosed with cutaneous melanoma who had pAID or received ICI or both. Patients were then stratified into 3 groups: ICI+pAID, non-ICI+pAID, and ICI+non-pAID. Inverse probability of treatment weighted Cox proportional hazards regression models were fitted to assess the risk of cardiac, pulmonary, endocrine, and neurological irAE. RESULTS: In total, 3704 individuals were included in the analysis. The majority of patients consisted of non-ICI+pAID patients (N=2706/73.1%), while 106 (2.9%) patients and 892 (24.1%) were classified as ICI+pAID and ICI+non-pAID, respectively. The risk of irAE was higher in the ICI+pAID group compared with the non-ICI+pAID and ICI+non-pAID, respectively (non-ICI: cardiac: hazard ratio [HR]=3.59, 95% confidence interval [CI]: 2.83-4.55; pulmonary: HR=3.94, 95% CI: 3.23-4.81; endocrine: HR=1.72, 95% CI: 1.53-1.93; neurological: HR=3.88, 95% CI: 2.30-6.57/non-pAID: cardiac: HR=3.83, 95% CI: 3.39-4.32; pulmonary: HR=2.08, 95% CI: 1.87-2.32; endocrine: HR=1.23, 95% CI: 1.14-1.32; neurological: HR=3.77, 95% CI: 2.75-5.18). CONCLUSIONS: Patients with a pAID face a significantly higher risk of irAEs. Further research examining the clinical impact of these events on the patients' oncological outcome and quality of life is urgently needed given our findings of significantly worse rates of adverse events.

Risk of Dementia and Depression in Young and Middle-aged Men Presenting with Nonmetastatic Prostate Cancer Treated with Androgen Deprivation Therapy.

BACKGROUND: Previous studies have found an association between androgen deprivation therapy (ADT) and an increased risk of dementia and depression in elderly men. This association remains controversial, and little is known about the effects of ADT in younger men. OBJECTIVE: To examine the association between the receipt of ADT and these outcomes in young men aged 40-64 yr presenting with nonmetastatic prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: For this observational study, we identified 9117 men aged 40-64 yr diagnosed with localized PCa between 2007 and 2014, without a pre-existing neurocognitive diagnosis, using the TRICARE military database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier curves were fitted to compare ADT versus no ADT. We also performed a subgroup analysis in patients undergoing ADT for ≥12 mo. The association between ADT and new-onset dementia or depression was evaluated using inverse-probability-of treatment-weight-adjusted Cox proportional hazards regression analysis. RESULTS AND LIMITATIONS: Patients receiving ADT had a significantly higher incidence of depression (30.2 vs 15.8 per 1000 person years) and dementia (17.9 vs 7.5 per 1000 person years). The risk of developing either outcome was higher in the ADT cohort (depression: hazard ratio [HR] 2.07, p < 0.001; dementia: HR 1.70, p = 0.052). Additionally, there was a dose-response relationship between the duration of ADT and either outcome. CONCLUSIONS: In our cohort of young men with PCa, the receipt of ADT was associated with an increased risk of developing dementia and depression. Long-term use of ADT was associated with the highest risk of neurocognitive outcomes. PATIENT SUMMARY: In this study, we looked at the risk of dementia and depression in patients <65 yr of age undergoing androgen deprivation therapy (ADT) for prostate cancer. We found that these patients had a higher risk of dementia and depression than those who did not undergo ADT.