Summary We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival ‘neuronal’ subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, lncRNA, and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma-in-situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.

PURPOSE: Simple diversions are underutilized, mostly for unfit, bedridden, and very self-limited patients requiring palliative surgical management due to life-threatening conditions. Experience with cutaneous ureterostomy (CU) as palliative urinary diversion option for unfit bladder cancer patients is reported. METHODS: We retrospectively reviewed clinical and operative parameters of 41 patients who underwent CU following RC in three specialized Cancer Centers from July/2005 to July/2010. Muscle-invasive disease (clinical Stage T2/worse), multifocal high-grade tumor, and carcinoma in situ refractory to intravesical immunotherapy were the main indications for RC. Double-J ureteral stents were used in all patients and replaced every 6 months indefinitly. Peri-operative morbidity and mortality were evaluated. RESULTS: Median age was 69 years (interquartile range - IQR 62, 76); 30 (73%) patients were men. Surgery in urgency setting was performed in 25 (61%) of patients, most due to severe bleeding associated with hemodynamic instability; 14 patients (34%) showed an American Society of Anesthesiologists score 4. Median operative time was 180 minutes (IQR 120, 180). Peri-operative complications occurred in 30 (73%) patients, most Clavien grade I and II (66.6 %). There was no per-operative death. Re-intervention was necessary in 7 (17%) patients. Overall survival was 24% after 9.4 months follow-up. CONCLUSIONS: CU with definitive ureteral stenting represents a simplified alternative for urinary diversion after palliative cystectomy in unfit patients. It can be performed quickly, with few early and late postoperative complications allowing RC in a group of patients otherwise limited to suboptimal alternatives. Future studies regarding the quality of life are warranted.

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Patients with IH present higher IPSS. The role of IPSS as a marker to predict the development of clinical IH still to be determined.

E 6 5 3What ' s known on the subject? and What does the study add? In spite of its low specifi city, PSA is the most widely used screening test for prostate cancer (PCa), and is considered the main cause of the stage migration recently observed. The ratio of free to total PSA (%fPSA) has been shown to increase PSA accuracy in cancer detection; however, few screening studies have systematically evaluated its role in cancer detection rates in men with PSA levels < 4.0 ng/mL and normal DRE.The present study supports a possible role of %fPSA as an adjunct to screening in men with total PSA 2.5 -4.0 ng/mL and normal DRE, with a marked increase in cancer detection rates in a large Brazilian PCa screening study. We believe that %fPSA maybe a useful refi nement to biopsy indications in men with low PSA levels. OBJECTIVE• To evaluate the role of the free to total prostate-specifi c antigen ratio (%fPSA) in identifying prostate cancer (PCa) in men with a prostate-specifi c antigen (PSA) level of 2.5 -3.9 ng/mL and a normal digital rectal examination (DRE). PATIENTS AND METHODS• A prospective PCa screening study was conducted, which included 17 571 men aged ≥ 45 years, across six Brazilian states, where men were recalled for further evaluation in the case of either a suspicious DRE and/or PSA ≥ 4.0 ng/mL, or PSA 2.5 -3.9 ng/mL and %fPSA ≤ 15.• We evaluated the impact of a %fPSA ≤ 15 on cancer detection rates and the clinical and pathological stage of tumours in men with a normal DRE and PSA 2.5 -3.9 ng/mL. RESULTS• When suspicious DRE and/or PSA ≥ 4.0 ng/mL were considered as criteria to prompt further evaluation, the cancer detection rate was 3.1%. When %fPSA ≤ 15 in men with total PSA levels of 2.5 -3.9 ng/ mL were considered as criteria, the PCa detection rate increased to 3.7%. Considering %fPSA ≤ 15 in men with PSA 2.5 -3.9 ng/mL and normal DRE, the positive predictive value of biopsy was 31.1%.• Clinical stage was more favourable among men with PSA 2.5 -3.9 ng/mL, normal DRE, and %fPSA ≤ 15 compared with men with normal DRE and PSA ≥ 4.0 ng/mL ( P = 0.02).• Among those who underwent radical prostatectomy, pathological stage and the proportion of insignifi cant tumours were similar between men with PSA 2.5 -3.9 ng/mL, normal DRE fi ndings and %fPSA ≤ 15, and men with PSA ≥ 4.0 ng/mL. CONCLUSIONS• The use of %fPSA ≤ 15 as a biopsy indication in men with normal DRE and PSA 2.5 -4.0 ng/mL in a PCa screening programme, increased cancer detection rates. Tumours in this subset of patients had similar pathological characteristics.• Using %fPSA ≤ 15 to indicate biopsy in men with PSA 2.5 -3.9 ng/mL is a useful adjunct to PCa screening. Use of low free to total PSA ratio in prostate cancer screening: detection rates, clinical and pathological fi ndings in Brazilian men with serum PSA levels < 4.0 ng/mL