Urothelial carcinoma of the bladder (UCB) is genomically heterogeneous, with frequent alterations in genes regulating chromatin state, cell cycle control, and receptor kinase signaling. To identify prognostic genomic markers in high-grade UCB, we utilized capture-based massively-parallel sequencing to analyze 109 tumors. Mutations were detected in 240 genes, with 23 genes mutated in ≥5% of cases. The presence of a recurrent PIK3CA mutation was associated with improved recurrence-free survival (RFS; HR=0.35, p=0.014) and cancer-specific survival (CSS; HR=0.35, p=0.040) in patients treated with radical cystectomy. In multivariable analyses controlling for pT and pN stages, PIK3CA mutation remained associated with RFS (HR=0.39, p=0.032). The most frequent alteration, TP53 mutation (57%), was more common in extravesical (69% vs. 32%, p=0.005) and lymph node-positive (77% vs. 56%, p=0.025) disease. Patients with CDKN2A altered tumors experienced worse RFS (HR=5.76, p<0.001) and CSS (HR=2.94, p=0.029) in multivariable analyses. Mutations in chromatin modifying genes were highly prevalent but not associated with outcomes. In UCB patients treated with radical cystectomy, PIK3CA mutations are associated with favorable outcomes whereas TP53 and CDKN2A alterations are associated with poor outcomes. Genomic profiling may aid in the identification of UCB patients at highest risk following radical cystectomy.

Purpose Parastomal hernia (PH) is a frequent complication from stoma formation after radical cystectomy (RC). We sought to determine the prevalence and risk factors for developing PH following RC. Material and Methods Retrospective study of 433 consecutive patients who underwent open RC and ileal conduit between 2006-2010. Postoperative cross-sectional imaging studies performed for routine oncologic follow-up (n=1736) were evaluated for PH, defined as radiographic evidence of protrusion of abdominal contents through the abdominal wall defect created by forming the stoma. Univariable and multivariable Cox regression analyses were used to determine clinical and surgical factors associated with PH. Results Complete data were available for 386 patients with radiographic PH occurring in 136. The risk of developing a PH was 27% (95% CI 22-33%) and 48% (95% CI 42-55%) at 1 and 2 years. Clinical diagnosis of PH was documented in 93 patients and 37 were symptomatic. Of 16 patients with clinical PH referred for repair, 8 had surgery. On multivariable analysis, female gender (HR=2.25, 95%CI 1.58-3.21; p<0.0001), higher BMI (HR=1.08 per unit increase 95%CI 1.05-1.12; p<0.0001), and lower preoperative albumin (HR=0.43 per g/dl, 95%CI 0.25-0.75; p=0.003) were significantly associated with PH. Conclusions The overall risk of radiographic evidence of PH approached 50% at 2 years. Female gender, higher BMI, and lower preoperative albumin were most associated with developing PH. Identifying those at greatest risk may allow for prospective surgical maneuvers at the time of initial surgery, such as placement of prophylactic mesh in selected patients, to prevent the occurrence of PH.

Objective To compare the oncologic outcomes of patients with upper tract urothelial carcinoma (UTUC) undergoing nephroureterectomy (NU) with and without prior ureteroscopy (URS). Methods We reviewed records of all patients with no prior history of bladder cancer that underwent NU at our institution (n = 201). We compared patients who underwent URS prior to NU to patients who proceeded directly to NU based on imaging alone. After excluding patients undergoing URS with therapeutic intent, we used multivariable Cox proportional hazards models, adjusting for tumor characteristics with cancer specific survival (CSS), intravesical recurrence free survival (IRFS), metastasis free survival (MFS), and overall survival (OS) as endpoints. Results 144 (72%) patients underwent URS prior to NU and 57 (28%) patients proceeded directly to NU. The median follow up time for survivors was 5.4 years from diagnosis. The performance of diagnostic URS prior to NU was significantly associated with IR (HR 2.58; 95% CI 1.47, 4.54; p = 0.001), although it was not associated with CSS, MFS, or OS. The adjusted IRFS probability 3 years after diagnosis is 71% and 42% for patients who did not and did receive URS prior to NU, respectively (adjusted risk difference 30%; 95% CI 13%, 47%). Conclusions We did not find evidence that URS adversely impacts disease progression and survival in patients with UTUC. Although patients are at higher risk for IR after NU when they have undergone prior diagnostic URS, their CSS, MFS, and OS are not significantly affected.

LN-positive patients previously treated with NAC have a poor prognosis, significantly worse than LN-positive patients subsequently treated with AC, and should be considered for protocols using sandwich chemotherapy approaches or novel agents. These results should be considered in the interpretation of and stratification for clinical trials.

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