Non-muscle-invasive bladder cancer molecular subtypes predict differential response to intravesical Bacillus Calmette-Guérin.

The recommended treatment for patients with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) is tumor resection followed by adjuvant Bacillus Calmette-Guérin (BCG) bladder instillations. However, only 50% of patients benefit from this therapy. If progression to advanced disease occurs, then patients must undergo a radical cystectomy with risks of substantial morbidity and poor clinical outcome. Identifying tumors unlikely to respond to BCG can translate into alternative treatments, such as early radical cystectomy, targeted therapies, or immunotherapies. Here, we conducted molecular profiling of 132 patients with BCG-naive HR-NMIBC and 44 patients with recurrences after BCG (34 matched), which uncovered three distinct BCG response subtypes (BRS1, 2 and BRS3). Patients with BRS3 tumors had a reduced recurrence-free and progression-free survival compared with BRS1/2. BRS3 tumors expressed high epithelial-to-mesenchymal transition and basal markers and had an immunosuppressive profile, which was confirmed with spatial proteomics. Tumors that recurred after BCG were enriched for BRS3. BRS stratification was validated in a second cohort of 151 BCG-naive patients with HR-NMIBC, and the molecular subtypes outperformed guideline-recommended risk stratification based on clinicopathological variables. For clinical application, we confirmed that a commercially approved assay was able to predict BRS3 tumors with an area under the curve of 0.87. These BCG response subtypes will allow for improved identification of patients with HR-NMIBC at the highest risk of progression and have the potential to be used to select more appropriate treatments for patients unlikely to respond to BCG.

Female sexual function and activity following cystectomy and continent urinary tract diversion for benign indications: a clinical pilot study and review of literature.

INTRODUCTION: There are limited data on female sexual function after cystectomy for benign indications. AIMS: To evaluate postoperative sexual items following cystectomy and continent urinary diversion for benign indications (e.g., severe incontinence, interstitial cystitis) in female patients. Furthermore, to review the studies investigating changes in women's sexual function after cystectomy. METHODS: In a retrospective study, 21 out of 23 patients (91%) who underwent a cystectomy for a benign indication completed a questionnaire. These women had a median age at the date of operation of 47.3 years (range 25-66 years) and a mean follow-up of 11.9 years. Questions on preoperative and postoperative sexuality, postoperative sexual activity, sexual appreciation, and the Female Sexual Function Index (FSFI) in patients at present were evaluated. Electronic databases were searched for the published studies investigating female sexual function after cystectomy. MAIN OUTCOME MEASURES: Female sexual function was evaluated by the FSFI domain scores and postoperative sexual appreciation questions. RESULTS: Sexual complaints before operation were present in 48% of the patients. The most common complaints reported were incontinence during intercourse, pain, and loss of libido. Seventeen out of 21 patients (81%) were sexually active preoperatively, 14 were still active postoperatively, and two preoperative inactive patients became active. Sexual inactivity postoperatively is mainly due to patient-related or combination of patient- and partner-related issues (70%), such as with pain during intercourse, loss of libido, and impaired body image. In the sexually active group, the majority (62.5%) showed improved or unchanged intercourse postoperatively. In the FSFI in 11 sexually active patients (52%) at present, domains of desire, arousal, lubrication, orgasm, and pain scored above average. The domain of satisfaction scored below average. CONCLUSIONS: Despite extensive surgery, female sexuality may remain unchanged or even improve, following cystectomy and continent diversion for benign indication. Sexual inactivity postoperatively needs more attention in respect to sexual counseling. Overall, the results are reassuring.