An immediate, single intravesical instillation of mitomycin C is of benefit in patients with non-muscle-invasive bladder cancer irrespective of prognostic risk groups.

BACKGROUND: In a recent meta-analysis, subgroups of patients were defined that may not benefit from a single, immediate instillation with chemotherapy. This led to a change in the European Association of Urology bladder cancer guidelines. In a previous paper, our group confirmed the efficacy of an immediate instillation of mitomycin C (MMC). However, prognostic groups in that study differ from those in the meta-analysis. Therefore, we performed a reanalysis using contemporary risk groups. OBJECTIVES: To validate whether specific subgroups of patients with non-muscle-invasive bladder cancer (NMIBC) benefit from an immediate instillation with MMC. PATIENTS AND METHODS: All 2,243 NMIBC patients enrolled in our randomized controlled trial between 1998 and 2003 were analyzed. Treatment effect was investigated for all subgroups, including subgroups that did not benefit from an immediate instillation according to the meta-analysis. Time to recurrence was assessed using Kaplan-Meier curves and multivariable Cox regression. Differences in treatment effect between subgroups was tested using the variable treatment by covariate interactions in a Cox regression model. RESULTS: The difference in time to recurrence was statistically significant in favor of an immediate instillation with MMC (P < 0.001) which corresponds to a 25% risk reduction (hazard ratio: 0.75, 95% confidence interval, 0.64-0.88, P < 0.001). Treatment effect of an immediate instillation with MMC did not differ significantly between any of the subgroups. CONCLUSIONS: In contrast to the recommendations in the European Association of Urology guidelines, we could not identify any subgroup of patients with NMIBC who do not benefit from an immediate instillation with MMC after transurethral resection.

The effect of timing of an immediate instillation of mitomycin C after transurethral resection in 941 patients with non-muscle-invasive bladder cancer.

OBJECTIVE: To investigate whether the timing of an immediate instillation of mitomycin C (on the day of transurethral resection of bladder tumour [TURBT] or 1 day later) has an impact on time to recurrence of non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: All patients with NMIBC who were enrolled in a prospective trial between 1998 and 2003, and treated with an early mitomycin C instillation (on the day of TURBT or 1 day later), were selected. Statistical analysis was performed with Kaplan-Meier curves and multivariable Cox regression. RESULTS: Administering an instillation of mitomycin C on the day of TURBT or 1 day later did not show a statistically significant difference in time to recurrence in a univariable model (log-rank P = 0.99). After correcting for the number of scheduled adjuvant instillations, no statistically significant difference could be detected either: hazard ratio 1.05 (95% confidence interval 0.81-1.35, P = 0.74). CONCLUSION: These data do not support the hypothesis that a very early instillation (on the day of TURBT) of mitomycin C decreases the risk of recurrence as compared with an early instillation (1 day after TURBT).

Value of an Immediate Intravesical Instillation of Mitomycin C in Patients with Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Randomised Study in 2243 patients.

BACKGROUND: The efficacy of an immediate single chemotherapy instillation after transurethral resection of a bladder tumour (TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC) remains a topic of debate. Evidence is even more scarce when an immediate instillation is followed by adjuvant instillations. OBJECTIVE: To compare the effect of a mitomycin C (MMC) instillation within 24h to an instillation 2 wk after TURBT in patients with NMIBC with or without adjuvant instillations. DESIGN, SETTING, AND PARTICIPANTS: Between 1998 and 2003, 2844 NMIBC patients were randomised for immediate versus delayed MMC instillation after TURBT. Patients were categorised in low-risk (LOR), intermediate-risk (IMR), and high-risk (HIR) groups. Total numbers of instillations in these groups were 1, 9, and 15, respectively. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end point was 3-yr recurrence risk for the IMR and HIR groups and 5-yr risk for the LOR group. Secondary outcomes were time to recurrence and incidence of adverse events. Analyses were performed with the log-rank test, Cox-regression, and χ2 test in SPSS. RESULTS AND LIMITATIONS: A total of 2243 patients were eligible on an intention-to-treat basis. Recurrence risks were 43% and 46% in the LOR group (5-yr follow-up, p=0.11), 20% and 32% in the IMR group (3-yr follow-up, p=0.037), and 28% and 35% in the HIR group (3-yr follow-up, p=0.007), for an immediate and a delayed instillation, respectively. For all patients, the recurrence risk was 27% (95% confidence interval [CI], 24-30) in the immediate and 36% (95% CI, 33-39) in the delayed instillation group (p<0.001) with a 27% reduction in relative recurrence risk (hazard ratio: 0.73, 95% CI, 0.63-0.85, p<0.001). The incidence of adverse events did not differ significantly between treatment groups (immediate instillation 25%, delayed instillation 22%, p=0.08). The risk groups in our study differ slightly from the current guidelines, which is a limitation of our study. CONCLUSIONS: An immediate, single instillation after TURBT reduces the recurrence risk in NMIBC patients, independent of the number of adjuvant installations. PATIENT SUMMARY: A single instillation of chemotherapy after the resection of non-muscle-invasive bladder cancer reduces the recurrence risk, even if patients are treated with an adjuvant schedule of instillations.

Tuberculin skin testing in patients with HIV infection: limited benefit of reduced cutoff values.

BACKGROUND: When determining eligibility for isoniazid preventive therapy of human immunodeficiency virus (HIV)-infected patients, the cutoff value of the tuberculin skin test (TST) is often reduced from an induration of 10 mm in diameter to one of 5 mm in diameter to compensate for loss of sensitivity. The effectiveness of this reduction depends on the underlying mechanism: a gradual decrease in skin test responsiveness with decreasing immunocompetence or an all-or-nothing switch to complete anergy. No published studies have assessed this directly in patients with tuberculosis. METHODS: We performed a cross-sectional study of TST responses and HIV infection among patients with sputum smear-positive pulmonary tuberculosis in 6 hospitals in Tanzania. Skin test anergy was defined as a TST reaction < or =2 mm in diameter. RESULTS: Of 991 patients with complete results, 451 (45.5%) had HIV infection. Anergy was observed in 111 (24.6%) of 451 HIV-infected patients and 18 (3.3%) of 540 HIV-uninfected patients (P<.001). The reaction size distributions among nonanergic HIV-infected and uninfected patients showed a limited difference (mean diameter +/- standard deviation, 15.9 +/- 5.0 mm and 16.8 +/- 3.8 mm, respectively; P=.048). The sensitivity of the TST among HIV-uninfected patients was 91.1% at a cutoff value of 10 mm and 95.2% at a cutoff value of 5 mm. The sensitivity of the TST among HIV-infected patients was 64.3% at a cutoff value of 10 mm and 71.2% at a cutoff value of 5 mm; the sensitivity of the TST was 67.6% and 74.5%, respectively, after adjustment for tuberculosis-specific anergy. CONCLUSION: In subjects with tuberculosis disease and HIV infection, loss of TST sensitivity is predominantly attributable to anergy (i.e., an all-or-nothing phenomenon). The decrease in the proportion of false-negative TST results obtained by reducing the cutoff value from 10 mm to 5 mm is limited.