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.

To compare biopsy performance of two approaches for multiparametric magnetic resonance (MR)-targeted biopsy (TB) with that of extended systematic biopsy (SB) in prostate cancer (PCa) detection. This institutional review board-approved multicenter prospective study (May 2009 to January 2011) included 95 patients with informed consent who were suspected of having PCa, with a suspicious abnormality (target) at prebiopsy MR. Patients underwent 12-core SB and four-core TB with transrectal ultrasonographic (US) guidance, with two cores aimed visually (cognitive TB [TB-COG]) and two cores aimed using transrectal US-MR fusion software (fusion-guided TB [TB-FUS]). SB and TB positivity for cancer and sampling quality (mean longest core cancer length, Gleason score) were compared. Clinically significant PCa was any 3 mm or greater core cancer length or any greater than 3 Gleason pattern for SB or any cancer length for TB. Statistical analysis included t test, paired χ(2) test, and κ statistic. Primary end point (core cancer length) was calculated (paired t test). Among 95 patients (median age, 65 years; mean prostate-specific antigen level, 10.05 ng/mL [10.05 μg/L]), positivity rate for PCa was 59% (n = 56) for SB and 69% (n = 66) for TB (P = .033); rate for clinically significant PCa was 52% (n = 49) for SB and 67% (n = 64) for TB (P = .0011). Cancer was diagnosed through TB in 16 patients (17%) with negative SB results. Mean longest core cancer lengths were 4.6 mm for SB and 7.3 mm for TB (P < .0001). In 12 of 51 (24%) MR imaging targets with positive SB and TB results, TB led to Gleason score upgrading. In 79 MR imaging targets, positivity for cancer was 47% (n = 37) with TB-COG and 53% (n = 42) with TB-FUS (P = .16). Neither technique was superior for Gleason score assessment. Prebiopsy MR imaging combined with transrectal US-guided TB increases biopsy performance in detecting PCa, especially clinically significant PCa. No significant difference was observed between TB-FUS and TB-COG for TB guidance.

Although the European Association of Urology, First International Consultation on Bladder Tumors, National Comprehensive Cancer Network and American Urological Association guidelines all provide an excellent evidence-based framework for the management of nonmuscle invasive bladder cancer, these guidelines vary with respect to important issues such as risk level definitions and management strategies for these risk categories. Therefore, we built on the existing framework provided by current guidelines, and provide consensus on the definitions of low, intermediate and high risk nonmuscle invasive bladder cancer, as well as practical recommendations for the treatment of patients in each of these risk categories. An international committee of experts on bladder cancer management identified and analyzed the European Association of Urology, First International Consultation on Bladder Tumors, National Comprehensive Cancer Network and American Urological Association guidelines as well as the published English language literature related to the treatment and management of nonmuscle invasive bladder cancer available as of April 2010. Based on review of the current guidelines and literature, the International Bladder Cancer Group developed practical recommendations for the management of nonmuscle invasive bladder cancer. Complete transurethral bladder tumor resection is recommended for all patients with nonmuscle invasive bladder cancer. For low risk disease a single, immediate chemotherapeutic instillation after transurethral bladder tumor resection is recommended. For intermediate or high risk disease there is no significant benefit from an immediate, postoperative chemotherapeutic instillation. For intermediate risk disease intravesical bacillus Calmette-Guérin with maintenance or intravesical chemotherapy is recommended. For high risk disease bacillus Calmette-Guérin induction plus maintenance is recommended. The appropriate management of recurrence depends on the patient level of risk as well as previous treatment, while the management of treatment failure depends on the type of failure as well as the level of risk for recurrence and disease progression.