Boorjian, Stephen A.

The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non–muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non–muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody–drug conjugates for metastatic bladder cancer.

Abstract Context Urinary bladder paraganglioma (UBPGL) is rare. Objective We aimed to characterize the presentation and outcomes of patients diagnosed with UBPGL. Methods We conducted a multicenter study of consecutive patients with pathologically confirmed UBPGL evaluated between 1971 and 2021. Outcomes included repeat bladder surgery, metastases, and disease-specific mortality. Results Patients (n=110 total; n=56 [51%] women) were diagnosed with UBPGL at a median age of 50 years (interquartile range [IQR], 36-61 years). Median tumor size was 2 cm (IQR, 1-4 cm). UBPGL was diagnosed prior to biopsy in only 37 (34%), and only 69 (63%) patients had evaluation for catecholamine excess. In addition to the initial bladder surgery, 26 (25%) required multiple therapies, including repeat surgery in 10 (9%). Synchronous metastases were present in 9 (8%) patients, and 24 (22%) other patients with UBPGL developed metachronous metastases at a median of 4 years (IQR, 2-10 years) after the initial diagnosis. Development of metachronous metastases was associated with younger age (hazard ratio [HR] 0.97; 95% CI, 0.94-0.99), UBPGL size (HR 1.69; 95% CI, 1.31-2.17), and a higher degree of catecholamine excess (HR 5.48; 95% CI, 1.40-21.39). Disease-specific mortality was higher in patients with synchronous metastases (HR 20.80; 95% CI, 1.30-332.91). Choice of initial surgery, genetic association, sex, or presence of muscular involvement on pathology were not associated with development of metastases or mortality. Conclusions Only a minority of patients were diagnosed before biopsy/surgery, reflecting need for better diagnostic strategies. All patients with UBPGL should have lifelong monitoring for development of recurrence and metastases.

Abstract Background: Missing risk factors, whether random or not measured at all, across different hospitals and patients provide challenges, both for the developers of online clinical risk tools and the patients trying to use such tools. This paper provides a development and end-user solution to the commonly encountered limitations of clinical risk tool based decision making due to missing information.Methods: Six state-of-the-art logistic regression approaches accommodating missing data were compared using prostate cancer data from ten North American and European cohorts from the Prostate Biopsy Collaborative Group (PBCG). An additional large European PBCG cohort was withheld for external validation, where calibration-in-the-large (CIL), calibration curves, and area-underneath-the-receiver-operating characteristic curve (AUC) were evaluated. Ten-fold leave-one-cohort-internal validation further validated the optimal missing data approach.Results: Among 12,703 biopsies from 10 training cohorts, 3,597 (28%) had clinically significant prostate cancer, compared to 1,757 of 5,540 (32%) in the external validation cohort. In external validation, the available cases method that pooled individual patient data containing all risk factors input by an end-user had best CIL, under-predicting risks as percentages by 2.9% on average, and obtained an AUC of 75.7%. Imputation had the worst CIL (-13.3%). The available cases method was further validated as optimal in internal cross-validation and thus used for development of an online risk tool. For end-users of the risk tool, two risk factors were mandatory: serum prostate-specific antigen (PSA) and age, and ten were optional: digital rectal exam, prostate volume, prior negative biopsy, 5-alpha-reductase-inhibitor use, prior PSA screen, African ancestry, Hispanic ethnicity, first-degree prostate-, breast-, and second-degree prostate-cancer family history.Conclusion: Developers of clinical risk prediction tools should optimize use of available data and sources even in the presence of high amounts of missing data and offer options for users with missing risk factors.

Context.— In women, radical cystectomy includes removal of the bladder, uterus, fallopian tubes, ovaries, and anterior vaginal wall, yet contiguous extension of urothelial carcinoma to all pelvic organs is rare and routine removal may be unnecessary. Objective.— To study pelvic organ involvement in women at radical cystectomy and investigate oncologic outcomes. Design.— Women with bladder cancer who underwent radical cystectomy at the Mayo Clinic and University of Toronto (1980–2018) were evaluated. Cancer-specific survival (CSS) was estimated with the Kaplan-Meier method; comparisons were made with the log-rank test. Associations with CSS were evaluated with Cox proportional hazard modeling. Results.— A total of 70 women with pT4a and 83 with pT3b cancer were studied. Organs involved were vagina (n = 41 of 70; 58.6%), uterus (n = 26 of 54; 48.1%), cervix (n = 15 of 54; 27.8%), fallopian tubes (n = 10 of 58; 17.2%), and ovaries (n = 7 of 58; 12.1%); 22 of 58 patients (37.9%) had >1 organ involved. Of 70 with pT4a cancer, 64 were available for survival analysis by 3 pelvic organ groups: vaginal only, vaginal and/or cervical/uterine, and vaginal and/or cervical/uterine and/or fallopian tubes/ovarian involvement. Three-year CSS for vaginal involvement only was 39%; it was 14% if cervical/uterine involvement, and <1% if fallopian tube/ovarian involvement was included (P = .02). Among 20 women with pT4aN0/Nx and vaginal involvement only, 3-year CSS for vaginal involvement was 50%, whereas among 48 women with pT3bN0/Nx cancer, 3-year CSS was 58%, P = .70. Conclusions.— Isolated vaginal involvement should be separated from uterine and/or adnexal extension of urothelial carcinoma at pathologic staging. Direct ovarian extension is rare and routine removal may be unnecessary.

Background: Measuring quality of care indicators is important for clinicians and decision making in health care to improve patient outcomes. Objective: The primary objective was to identify quality of care indicators for patients with upper tract urothelial carcinoma (UTUC) and to validate these in an international cohort treated with radical nephroureterectomy (RNU). The secondary objective was to assess the factors associated with failure to validate the pentafecta. Design: We performed a retrospective multicenter study of patients treated with RNU for EAU high-risk (HR) UTUC. Outcome measurements and statistical analysis: Five quality indicators were consensually approved, including a negative surgical margin, a complete bladder-cuff resection, the absence of hematological complications, the absence of major complications, and the absence of a 12-month postoperative recurrence. After multiple imputations and propensity-score matching, log-rank tests and a Cox regression were used to assess the survival outcomes. Logistic regression analyses assessed predictors for pentafecta failure. Results: Among the 1718 included patients, 844 (49%) achieved the pentafecta. The median follow-up was 31 months. Patients who achieved the pentafecta had superior 5-year overall- (OS) and cancer-specific survival (CSS) compared to those who did not (68.7 vs. 50.1% and 79.8 vs. 62.7%, respectively, all p < 0.001). On multivariable analyses, achieving the pentafecta was associated with improved recurrence-free survival (RFS), CSS, and OS. No preoperative clinical factors predicted a failure to validate the pentafecta. Conclusions: Establishing quality indicators for UTUC may help define prognosis and improve patient care. We propose a pentafecta quality criteria in RNU patients. Approximately half of the patients evaluated herein reached this endpoint, which in turn was independently associated with survival outcomes. Extended validation is needed.