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.

Lower urinary tract symptoms are associated with clinically relevant depression, anxiety, and stress symptoms.

OBJECTIVES: To investigate the correlation between lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and testosterone deficiency (TD) with depressive, stress, and anxiety symptoms. MATERIAL AND METHODS: From October 2019 to March 2020, 113 males were included. Inclusion criteria: age 40-75, no clinical suspicion of prostate cancer, no serious cardiovascular comorbidities. All patients completed a set of questionnaires: International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5), and Depression Anxiety Stress Scales (DASS-21). RESULTS: Median age was 62 years (range 40-74), mean IPSS score was 10.94 (SD 7.75), mean IIEF-5 score 13.12 (SD 7.08), and mean DASS-21 score 11.35 (SD 8.24). According to DASS-21 subscales, 28 (24.8%) patients had depressive symptoms, 25 (22.1%) anxiety symptoms, and 25 (22.1%) stress symptoms. Depression was associated with LUTS (14.5 vs. 8 score, p = .002). Similarly, stress symptoms were associated with LUTS (IPSS 15 vs. 7 score, p = .0001) and with ED (IIEF-5 5 vs. 15 score, p = .01). Positive Spearman's rho correlations between LUTS and all three, depression, anxiety, and stress symptoms were found (p values <.001). CONCLUSIONS: LUTS is associated with depression, anxiety, and stress symptoms. Screening for these symptoms could help with individual counseling and management.