Paolo Gontero

Objectives: To evaluate biochemical recurrence‐free survival (BRFS) and metastasis‐free survival (MFS) as potential intermediate clinical endpoints (ICEs) for overall survival (OS) in patients undergoing salvage radical prostatectomy (sRP). Patients and Methods: Evaluable patients were selected from a retrospective dataset, resulting in a cohort of 879 patients with recurrent, non‐metastatic, hormone‐sensitive prostate cancer treated with sRP at 13 centres. ICE surrogacy was evaluated using a two‐stage approach: (i) at the individual‐patient level by fitting Clayton copula models and estimating Kendall's ( >0.7 indicating a strong association) and (ii) at the centre level, by fitting weighted linear regression of 5‐year OS on 3‐year BRFS and MFS. Results: The two‐step analysis included 759 patients for BRFS (366 events) and 476 for MFS (137 events), with median follow‐up of 37 months (95% confidence interval [CI] 36–42 months) and 34 months (95% CI 31–37 months), respectively. At the individual‐patient level, MFS showed a strong association with OS (Kendall's 0.85, 95% CI 0.82–0.88), which was not observed for BRFS (Kendall's 0.63, 95% CI 0.56–0.69). At the centre level, neither 3‐year BRFS ( R ² = 0.15; slope = 0.34, P = 0.2) nor 3‐year MFS ( R ² = 0.21; slope = 0.26, P = 0.14) predicted 5‐year OS with sufficient explanatory power. Limitations include the fact that centre‐level analysis was based on single‐arm associations rather than on treatment‐effect surrogacy across arms, and retrospective data collection. Conclusions: The BRFS should not be used as a surrogate endpoint in the sRP setting. MFS requires further validation in future prospective studies to confirm its association with OS. Patient‐reported outcomes, such as quality‐of‐life and treatment‐related toxicity, should be considered in parallel with OS.

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a bothersome condition characterized by pelvic pain and lower urinary tract symptoms (LUTS). Phytotherapy can be used to treat this challenging condition. The aim of this study was to investigate the role of an oral combination of bovine colostrum, Serenoa repens extract and other anti-inflammatory elements in the treatment of CP/CPPS patients. Methods: Our study was a prospective, observational, single-arm study that enrolled patients > 18 years with a history consistent with CP/CPPS, a Chronic Prostatitis Symptom Index (CPSI) pain domain score ≥ 5 and a Meares–Stamey microbiological test negative for bacterial infection. Pelvic or genital pain was measured via the Numeric Pain Rating Scale (NPRS) and validated questionnaires. All patients were treated with an oral combination of colostrum, Serenoa repens extract and other anti-inflammatory elements for 6 months. Follow-up visits were scheduled at 3 and 6 months. Pre- and post-treatment variables were compared by means of the Wilcoxon signed-rank nonparametric test. Results: We included 42 patients in our analysis. The median (Inter-Quartile Range, IQR) age was 42 (28–51) years. Compared with baseline, after 3 months we observed a significant reduction in pain: total CPSI score of 16 (12–21) vs. 22 (17–26), p < 0.001, −6 points (−27.3%); CPSI score of “pain” domain 7 (5–9) vs. 8 (7–11), p < 0.001, −1 point (−12.5%). Moreover, quality of life improved: CPSI “quality of life” domain 6 (4–9) vs. 8 (7–10), p < 0.001. After 6 months, a significant reduction in pain was maintained: total CPSI score 19 (10–23), p < 0.001, −3 points (−13.65%); and CPSI “pain” domain 7 (4–9), p < 0.001, −1 point (−12.5%). After 6 months, a mild reduction in urinary symptoms was also reported. During the observation period, five patients discontinued treatment, two of them because of gastrointestinal intolerance. Conclusions: The daily oral administration of bovine colostrum, Serenoa repens and other anti-inflammatory elements showed a potential in improving pain and other urinary symptoms and was generally well tolerated by patients affected by CP/CPPS.

Purpose: the prognostic value of positive surgical margins (PSMs) after radical prostatectomy (RP) remains debated, particularly when distinguishing focal from extensive involvement. Moreover, the interaction between margin status and other adverse pathological features, such as tumour stage, grade, and nodal status, is not fully defined. The study aims to evaluate the impact of focal and extensive PSMs on biochemical recurrence-free survival (BCRFS), stratified by pathological stage, Gleason grade, and nodal involvement. Methods: we retrospectively analyzed 1258 patients who underwent robot-assisted RP between 2017 and 2023, evaluating BCRFS as primary endpoint. Survival was analyzed using Kaplan–Meier and log-rank tests across margin categories (negative, focal, extensive). Analyses were stratified by pT stage (pT2–pT3b), ISUP grade (p < 0.01). In N + 5-year BCRFS was similarly poor in negative (~45%), focal (~42%), and extensive margins (~40%, p = 0.455). Conclusions: the prognostic impact of positive surgical margins depends on tumour biology. In organ-confined or ISUP ≤ 2 disease, focal PSMs show recurrence rates similar to negative margins and may be managed with observation. In locally advanced or ISUP ≥ 3 tumours, both focal and extensive PSMs carry a markedly higher risk of biochemical recurrence and might suggest an early intervention. PSMs lose discriminatory value in node-positive patients.

Purpose: To evaluate novel intravesical and systemic combination therapies for improving outcomes in BCG-naïve patients with non-muscle invasive bladder cancer (NMIBC), this systematic review and meta-analysis assessed first-line treatment strategies, including combinations with systemic immune-checkpoint inhibitors (ICIs). Methods: In this prospectively registered review (CRD420251163026), MEDLINE, Embase, Web of Science, and the ESMO 2025 abstract book were searched for randomized controlled trials (RCTs) evaluating first-line therapies in BCG-naïve NMIBC. Meta-analyses estimated HRs for recurrence-related time-to-event outcomes (disease-free and event-free survival). Grade ≥ 3 treatment-related adverse events were pooled as relative risks (RRs). Risk of bias was assessed using the Cochrane RoB 2 tool. Results: Out of 5202 records screened, six RCTs including 3485 patients were eligible. Modifications to intravesical BCG alone (three trials, n = 895) did not significantly improve recurrence-related outcomes. Systemic ICIs given additional to intravesical BCG significantly reduced recurrence-related events compared to BCG alone (HR 0.77, 95%CI 0.6–0.97, n = 1899; number needed to treat at two years: 25), but increased grade ≥ 3 treatment-related adverse events by a statistically and clinically significant margin (RR 3.97, 95% CI 2.53–6.22, n = 1879; number needed to treat to harm one patient: 5). Sensitivity analysis using the ALBAN alternative endpoint of high-grade recurrence-free survival yielded HR 0.78 (95% CI 0.59–1.02), not reaching statistical significance. Limitations included heterogeneity in trial design and endpoint definitions. Conclusion: In BCG-naïve NMIBC, systemic ICIs combined with intravesical BCG improve recurrence-related outcomes but are offset by a substantially increased risk of severe treatment-related adverse events. These findings highlight the need for careful, risk-based, biomarker-guided patient selection to balance over- and undertreatment within a shared decision-making process.

Boeri L, et al. World J Mens Health. 2026 ;44:e87. https://doi.org/10.5534/wjmh.260241

Tumor stroma can be actively shaped by tumor cells to adopt pro-tumorigenic properties, making it a focal point of cancer research. Among the stromal components, cancer-associated fibroblasts (CAFs) -- often the most abundant cell type in the tumor microenvironment (TME) -- play a pivotal role in promoting cancer progression through their interactions with tumor cells and other stromal components. Elucidating the mechanisms behind these interactions requires robust methods for isolating and characterizing CAFs, which can also lay the foundation for developing novel CAF-targeted cancer therapies. This study presents a method for isolating fibroblasts from both the tumor and the adjacent normal regions of radical prostatectomy specimens obtained from prostate cancer (PCa) patients. This approach enables the concurrent isolation of CAFs and their normal counterparts (NFs) from the same individual, providing a paired experimental system. Detailed protocols are provided for the maintenance of primary CAFs and NFs for downstream in vitro analyses, as well as for their immortalization to facilitate long-term studies. We also describe functional assays designed to compare the effects of CAFs and NFs on cancer cell behaviors, including proliferation, migration, and anchorage-independent growth. Two complementary approaches are detailed: treatment of cancer cells with fibroblast-derived conditioned media (CM), and direct co-culture of fibroblasts with tumor cells. Together, these methodologies represent a comprehensive toolkit for investigating the dynamic interplay between CAFs and tumor cells, not only in PCa but potentially across a range of human cancers. Moreover, molecular characterization of these interactions may reveal key mediators of CAF-driven oncogenesis, offering promising targets for therapeutic intervention.