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.

Advanced Age Impacts Survival After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

INTRODUCTION: Upper tract urothelial carcinoma is rare but has a poor prognosis. Prognostic factors have been extensively studied in order to provide the best possible management for patients. We have aimed to investigate commonly available factors predictive of recurrence and survival in this patient population at high risk of death and recurrence, with an emphasis on the effects of age (using a cutoff of 70 years) on survival outcomes. PATIENTS AND METHODS: From 1387 patients with clinically nonmetastatic upper tract urothelial carcinoma treated with radical nephroureterectomy at 21 academic hospital centers between 2005 and 2021, 776 patients were eligible and included in the study. Univariable and multivariable Cox regression models were built to evaluate the independent prognosticators for intravesical and extravesical recurrence, overall survival, and cancer-specific survival according to age groups. A P value of <.05 was considered statistically significant. RESULTS: We did not find an association between groups aged <70 and >70 years old and preoperatively clinical or histopathological characteristics. Kaplan-Meier analysis was found no statistical significance between the 2 age groups in terms of intravesical or extravesical recurrence (P = .09 and P = .57). Overall survival (P = .0001) and cancer-specific survival (P = .0001) have been found to be statistically significantly associated with age as independent predictors (confounding factors: gender, tumor size, tumor side, clinical T stage, localization, preoperative hydronephrosis, tumor localization, type of surgery, multifocality of the tumor, pathological grade, lymphovascular invasion, concomitant CIS, lymph node status, necrosis, or history of previous bladder cancer). CONCLUSION: This research confirms that patients aged 70 and above who undergo radical nephroureterectomy may have worse outcomes compared to younger patients, older patients needing an improved care and management of UTUC to improve their outcomes in the setting of an increase in this aged population group.

Conditional survival of patients with low-risk prostate cancer: Temporal changes in active surveillance permanence over time.

PURPOSE: To determine risk categories for patients with prostate cancer (PCa) in active surveillance (AS) and to test the conditional survival (CS) that examined the effect of event-free survival since AS-entrance. MATERIALS AND METHODS: From January 2012 to December 2020 we analyzed 606 patients with PCa enrolled in our AS program. Kaplan-Meier (KM) plots depicted AS-exit rate. Multivariable Cox regression models (MCRMs) tested for AS-exit rate independent predictors to determine risk categories. CS estimates were used to calculate overall AS-exit rate after event-free survival intervals of 1, 2, 3, and 5 years, and after stratification according to risk categories. RESULTS: At MCRMs PSAd ≥ 0.15 (HR: 1.43; P-value 0.04), PI-RADS 4-5 (HR: 2.56; P-value <0.001) and number of biopsy positive cores ≥ 2 (HR: 1.75; P-value <0.001) were independent predictors of AS-exit. These variables were used to determine risk categories: low-, intermediate- and high-risk. Overall, according to CS-analyses, 5-year AS-exit free rate increased from 59.7% at baseline, to 67.3%, 74.7%, and 89.4% in patients who remained in AS respectively ≥1, ≥2, ≥3 and ≥5 years. After stratification according to risk categories, in those patients who remained in AS ≥ 5 years, 5-year AS-exit free rates increased from 76.3% to 100% in patients with a low-risk, from 62.7% to 83.7% in patients with an intermediate-risk and from 42.3% to 87.5% in patients with a high-risk. CONCLUSIONS: CS models showed a direct relationship between event-free survival duration and subsequent AS permanence in overall PCa patients and after stratification according to risk categories.

Role of Rezum in the treatment of benign prostate hyperplasia: A review of the literature.

The aim of this study was to review the available literature on the efficacy and safety of the Rezum system for the treatment of symptomatic benign prostatic hyperplasia (BPH). A revision of literature up to January 2021 was carried out. Medline, Scopus, Web of Science, and PubMed archives were screened to identify all the relevant studies investigating the role of Rezum in the treatment of BPH. Randomized controlled trial (RCT), retrospective, prospective, observational, and comparative studies were included. Finally, 17 studies were included, five of which reporting data of a double blind Rezum RCT. Overall, 1,451 patients underwent Rezum procedure. All the studies performed a minimum of 3 months follow-up. Preoperatively, the mean International Prostate Symptom Score (IPSS) score was 19.8, mean Qmax was 9.2mL s1, and mean PVR was 142 cc. At 3 months after surgery, the mean IPSS score was 1.5, mean Qmax was 13.7mL s1, and mean PVR was 74 cc. Six studies investigated sexual function, most of them using the International Index of Erectile Function (IIEF)-5 questionnaire and a few also the Male Sexual Health Questionnaire (MSHQ). Preoperative mean IIEF-5 score was 18.5, and the mean MSHQ score was 7.4. At the 3 months follow-up, the mean IIEF-5 score was 16.4, and the mean MSHQ score was 9.62. None of the studies reported intraoperative complications. Rezum system is a novel minimally invasive treatment for symptomatic BPH using transurethral water vapor thermal energy. It represents a cost-effective and safe procedure with durable relief of lower urinary tract symptom, preservation of sexual function, low complications rate, and short recovery time.

Association between dietary flavonoids intake and prostate cancer risk: A case-control study in Sicily.

OBJECTIVES: The aim of this study is to test the association between dietary flavonoids intake and prostate cancer (PCa) in a sample of southern Italian individuals. DESIGN: A population-based case-control study on the association between PCa and dietary factors was conducted from January 2015 to December 2016, in a single institution. SETTING: Patients with elevated PSA (Prostate Specific Antigen) and/or suspicion of PCa underwent transperineal prostate biopsy (≥12 cores). A total of 118 histopathological-verified PCa cases were collected and matched with controls, which were selected from a sample of 2044 individuals randomly recruited among the same reference population. Finally, a total of 222 controls were selected. MAIN OUTCOME MEASURES: Prevalence of PCa. RESULTS: Consumption of certain groups of flavonoids significantly differed between controls and cases, in particular: flavonols (63.36 vs 37.14 mg/d, P < 0.001), flavanols (107.61 vs. 74.24 mg/d, P = .016), flavanones (40.92 vs. 81.32 mg/d, P < 0.001), catechins (63.36 vs. 36.18 mg/d, P = .006). In the multivariate model, flavanols and flavones were associated with reduced risk of PCa, despite not in the highest quartile of intake. Higher flavonol and catechin intake was consistently associated with reduced risk of PCa (Odds Ratio (OR) = 0.19, 95% CI: 0.06-0.56 and OR = 0.12, 95% CI: 0.04-0.36). In contrast, the highest intake of flavanones was positively associated with PCa. CONCLUSION: Flavonols and catechins have proved to be the most promising molecules for a potential protective role against PCa. Nevertheless, further research on flavanones is needed to better establish whether they are associated with PCa.