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The use of androgen suppression ther- apy （AST） and radiotherapy for locallyadvanced prostate cancer has become the standard of care worldwide. At the same time, it has become clear that AST carries significant risk for side effects. Recently, Denham and colleagues have reported ini- tial quality of life （QoL） results from the TROG 03.04 RADAR trial. The authors identify clinically meaningful decrements in patient-reported QoL for those treated with 18 months of AST vs. 6 months but only marginal differences at 36 months. Once survival data becomes available, these data will help to frame any benefits seen for longer courses of AST.

Bladder-preserving trimodality therapy can be an effective alternative to radical cystectomy for treatment of muscle-invasive bladder cancer (MIBC), but biomarkers are needed to guide optimal patient selection. The DNA repair protein MRE11 is a candidate response biomarker that has not been validated in prospective cohorts using standardized measurement approaches. To evaluate MRE11 expression as a prognostic biomarker in MIBC patients receiving trimodality therapy using automated quantitative image analysis. This prognostic study analyzed patients with MIBC pooled from 6 prospective phase I/II, II, or III trials of trimodality therapy (Radiation Therapy Oncology Group [RTOG] 8802, 8903, 9506, 9706, 9906, and 0233) across 37 participating institutions in North America from 1988 to 2007. Eligible patients had nonmetastatic MIBC and were enrolled in 1 of the 6 trimodality therapy clinical trials. Analyses were completed August 2020. Trimodality therapy with transurethral bladder tumor resection and cisplatin-based chemoradiation therapy. MRE11 expression and association with disease-specific (bladder cancer) mortality (DSM), defined as death from bladder cancer. Pretreatment tumor tissues were processed for immunofluorescence with anti-MRE11 antibody and analyzed using automated quantitative image analysis to calculate a normalized score for MRE11 based on nuclear-to-cytoplasmic (NC) signal ratio. Of 465 patients from 6 trials, 168 patients had available tissue, of which 135 were analyzable for MRE11 expression (median age of 65 years [minimum-maximum, 34-90 years]; 111 [82.2%] men). Median (minimum-maximum) follow-up for alive patients was 5.0 (0.6-11.7) years. Median (Q1-Q3) MRE11 NC signal ratio was 2.41 (1.49-3.34). Patients with an MRE11 NC ratio above 1.49 (ie, above first quartile) had a significantly lower DSM (HR, 0.50; 95% CI, 0.26-0.93; P = .03). The 4-year DSM was 41.0% (95% CI, 23.2%-58.0%) for patients with an MRE11 NC signal ratio of 1.49 or lower vs 21.0% (95% CI, 13.4%-29.8%) for a ratio above 1.49. MRE11 NC signal ratio was not significantly associated with overall survival (HR, 0.84; 95% CI, 0.49-1.44). Higher MRE11 NC signal ratios were associated with better DSM after trimodality therapy. Lower MRE11 NC signal ratios identified a poor prognosis subgroup that may benefit from intensification of therapy.

Patients with T1 bladder tumors who experience a recurrence following transurethral resection (TUR) and adjuvant bacillus Calmette-Guérin (BCG) intravesical therapy represent a subset of patients with potentially aggressive disease. While alternative intravesical regimens exist for such patients, they are plagued by high failure rates and a lack of strong data to support their use.[l] These patients often require radical therapy that, in the view of many urologists, should consist only of radical cystectomy. While radical cystectomy is a highly effective treatment for this subgroup, many elderly or otherwise infirm patients are not considered candidates for this procedure. Furthermore, many patients refuse radical cystectomy, given its associated morbidity and effects on health-related quality of life. Might there exist an alternative but still potentially curative therapy to help fulfill the unmet need of these patients? The astute observer will note, and rightfully so, that these data pertain to an alternative primary therapy for T1 disease rather than to salvage therapy for the specific subpopulation who have a recurrence after BCG therapy. While there are currently no published reports investigating the role of chemoradiotherapy in a large cohort of patients with recurrent T1 disease, one series does address the use of chemoradiotherapy in patients who have failed to respond to BCG and progressed to clinical stage T2 (cT2).[4] Given that nearly half of patients undergoing radical cystectomy for T1 disease are found to have muscle invasion or positive lymph nodes, this report is highly relevant to the ongoing debate. [5] Of these cT2 patients treated with maximal TUR and chemoradiotherapy, 59% were free of any bladder recurrence at a median follow-up of 7 years, and disease-specific survival was 70%.

Bladder cancer can be thought of as a wide spectrum of diseases which can roughly be placed into three major categories: non‐muscle‐invasive; muscle‐invasive; and metastatic. This chapter describes the clinical behavior and standard treatment approach that varies significantly between these categories. Endoscopic evaluation and management forms the backbone of the initial treatment for bladder cancer. This should include a bimanual examination which fully characterizes the size and mobility of any palpable lesions in the bladder. Non‐muscle invasive bladder cancers (NMIBCs) of clinical stage Ta, T1 or Tis comprise 70‐80% of all newly diagnosed bladder cancer cases. These tumors are usually treated successfully by a variety of conservative techniques. The most common treatment offered for muscle‐invasive bladder cancer (MIBC) remains surgical in the form of radical cystoprostatectomy in men and an anterior exenteration in women. The ultimate goal of any therapy for MIBC should be to maximize post‐treatment quality of life while maintaining maximal disease control.