Time to progression is the main predictor of survival in patients with high-risk nonmuscle invasive bladder cancer: Results from a machine learning-based analysis of a large multi-institutional database.

BACKGROUND: In patients affected by high-risk nonmuscle invasive bladder cancer (HR-NMIBC) progression to muscle invasive status is considered as the main indicator of local treatment failure. We aimed to investigate the effect of progression and time to progression on overall survival (OS) and to investigate their validity as surrogate endpoints. METHODS: A total of 1,510 patients from 18 different institutions treated for T1 high grade NMIBC, followed by a secondary transurethral resection and BCG intravesical instillation. We relied on random survival forest (RSF) to rank covariates based on OS prediction. Cox's regression models were used to quantify the effect of covariates on mortality. RESULTS: During a median follow-up of 49.0 months, 485 (32.1%) patients progressed to MIBC, while 163 (10.8%) patients died. The median time to progression was 82 (95%CI: 78.0-93.0) months. In RSF time-to-progression and age were the most predictive covariates of OS. The survival tree defined 5 groups of risk. In multivariable Cox's regression models accounting for progression status as time-dependent covariate, shorter time to progression (as continuous covariate) was associated with longer OS (HR: 9.0, 95%CI: 3.0-6.7; P < 0.001). Virtually same results after time to progression stratification (time to progression ≥10.5 months as reference). CONCLUSION: Time to progression is the main predictor of OS in patients with high risk NMIBC treated with BCG and might be considered a coprimary endpoint. In addition, models including time to progression could be considered for patients' stratification in clinical practice and at the time of clinical trials design.

Clinical studies of bacillus of Calmette-Guerin polysaccharide nucleic acid adjunctive therapy in pulmonary tuberculosis / 中国医师进修杂志

Objective To evaluate the effectiveness, the influence on cellular immune function and the side-effect of bacillus of Calmette-Guerin polysaccharide nucleic acid(BCG-PSN)combined with antituberculous chemotherapy in the treatment of pulmonary tuberculosis. Methods A total of 60 pulmonary tuberculosis patients were divided into treatment group(30 patients)and control group(30 patients)by random digits table. All patients accepted the same standard antituberculous chemotherapy, meanwhile patients in treatment group were injected with BCG-PSN. Observed and compared the clinical symptom,the size of the focas nidus,the change of toxic response and immunity. Results The symptoms were significantly relieved in both groups after treatment(P＜0.05), but it was significantly better in treatment group(P＜0.05), the effective rate and control rate in treatment group[36.7%(11/30),96.7%(29/30)]were significantly higher than those in control group[23.3%(7/30), 86.7%(26/30)](P ＜ 0.05). After treatment,the levels of CD3,CD4 and IL-2 were higher, and the level of CD8 was lower, but the treatment group improved significantly better than control group(P ＜ 0.05). The rate of leukopenia was lower in treatment group than that in control group[10.0%(3/30)vs. 33.3%(10/30),P ＜0.05]. As to the safety,no other toxicities were observed in the treatment group. Conclusions BCG-PSN combined with antituberculous chemotherapy in the treatment of pulmonary tuberculosis contributes to relieve the symptom, reduce size of the nidus, decrease leukopenia incidence and enhance the cell immunity. It is safe.

Tubercular disease caused by bacillus of Calmette-Guerin administered as a local adjuvant treatment of relapsing bladder carcinoma: Pathogenetic, diagnostic and therapeutic issues, and literature review

Two exemplary case reports of respiratory granulomatous infection caused by bacillus of Calmette-Guérin (BCG) in patients who were repeatedly treated with local, intravesical adjuvant BCG therapy for a relapsing transitional bladder carcinoma, are outlined and discussed, on the ground of the cumbersome diagnostic and differential diagnostic process (especially when a prior tuberculosis and a concurrent chronic obstructive pulmonary disease are of concern), and an updated literature revision. Only four cases of respiratory BCG-itis (pulmonary tuberculosis-like forms), have been reported until now to the best of our knowledge (two of them following bladder instillation of BCG). One episode of ours represents the first described case with a dual, concomitant granulomatous localization of BCG-itis, also involving the genitourinary tract