Bladder cancer (BC) is a significant health problem, and understanding the risk factors for this disease could improve prevention and early detection. To provide a systematic review and summary of novel developments in epidemiology and risk factors for BC. A systematic review of original articles was performed by two pairs of reviewers (M.G.C., I.J., F.E., and K.P.) using PubMed/Medline in December 2017, updated in April 2018. To address our primary objective of reporting contemporary studies, we restricted our search to include studies from the last 5yr. We subdivided our review according to specific risk factors (PICO [Population Intervention Comparator Outcome]). Our search found 2191 articles, of which 279 full-text manuscripts were included. We separated our manuscripts by the specific risk factor they addressed (PICO). According to GLOBOCAN estimates, there were 430000 new BC cases and 165000 deaths worldwide in 2012. Tobacco smoking and occupational exposure to carcinogens remain the factors with the highest attributable risk. The literature was limited by heterogeneity of data. Evidence is emerging regarding gene-environment interactions, particularly for tobacco and occupational exposures. In some populations, incidence rates are declining, which may reflect a decrease in smoking. Standardisation of reporting may help improve epidemiologic evaluation of risk. Bladder cancer is common worldwide, and the main risk factors are tobacco smoking and exposure to certain chemicals in the working and general environments. There is ongoing research to identify and reduce risk factors, as well as to understand the impact of genetics on bladder cancer risk.

Purpose: To provide recommendations on appropriate clinical trial designs in non–muscle-invasive bladder cancer (NMIBC) based on current literature and expert consensus of the International Bladder Cancer Group. Methods: We reviewed published trials, guidelines, meta-analyses, and reviews and provided recommendations on eligibility criteria, baseline evaluations, end points, study designs, comparators, clinically meaningful magnitude of effect, and sample size. Results: NMIBC trials must be designed to provide the most clinically relevant data for the specific risk category of interest (low, intermediate, or high). Specific eligibility criteria and baseline evaluations depend on the risk category being studied. For the population of patients for whom bacillus Calmette-Guérin (BCG) has failed, the type of failure (BCG unresponsive, refractory, relapsing, or intolerant) should be clearly defined to make comparisons across trials feasible. Single-arm designs may be relevant for the BCG-unresponsive population. Here, a clinically meaningful initial complete response rate (for carcinoma in situ) or recurrence-free rate (for papillary tumors) of at least 50% at 6 months, 30% at 12 months, and 25% at 18 months is recommended. For other risk levels, randomized superiority trial designs are recommended; noninferiority trials are to be used sparingly given the large sample size required. Placebo control is considered unethical for all intermediate- and high-risk strata; therefore, control arms should comprise the current guideline-recommended standard of care for the respective risk level. In general, trials should use time to recurrence or recurrence-free survival as the primary end point and time to progression, toxicity, disease-specific survival, and overall survival as potential secondary end points. Realistic efficacy thresholds should be set to ensure that novel therapies receive due review by regulatory bodies. Conclusion: The International Bladder Cancer Group has developed formal recommendations regarding definitions, end points, and clinical trial designs for NMIBC to encourage uniformity among studies in this disease.

BACKGROUND: Micropapillary bladder carcinoma is a rare variant of urothelial carcinoma. To improve understanding of this disease, the authors performed a retrospective review of their experience.METHODS: The authors reviewed the records of 100 consecutive patients with micropapillary bladder cancer who were evaluated at The University of Texas M. D. Anderson Cancer Center.RESULTS: The mean age of the patients was 64.7 years, with a male:female ratio of 10:1. The TNM stage of disease at the time of presentation was Ta in 5 patients, carcinoma in situ (CIS) in 4 patients, T1 in 35 patients, T2 in 26 patients, T3 in 7 patients, T4 in 6 patients; N+ in 9 patients, and M+ in 8 patients. Kaplan‒Meier estimates of 5‒year and 10‒year overall survival (OS) rates were 51% and 24%, respectively. Bladder‒sparing therapy with intravesical bacillus Calmette–Guerin therapy was attempted in 27 of 44 patients with nonmuscle‒invasive disease; 67% (18 patients) developed disease progression (≥cT2), including 22% who developed metastatic disease. Of 55 patients undergoing radical cystectomy for surgically resectable disease (≤cT4a), 23 received neoadjuvant chemotherapy and 32 were treated with initial cystectomy, with no significant difference noted in stage distribution between the 2 groups. For the 23 patients treated with neoadjuvant chemotherapy, the median OS was 43.2 months with 32% of patients still alive at 5 years. For the 32 patients treated with initial cystectomy, the median survival had not been reached at the time of last follow‒up, with 71% still alive at 5 years.CONCLUSIONS: Micropapillary bladder cancer is associated with a poor prognosis. Intravesical therapy appears to be ineffective in this disease and patients with surgically resectable disease should be offered early radical cystectomy. Cancer 2007. © 2007 American Cancer Society.