It is unknown whether the historical survival disadvantage of African American metastatic prostate cancer (mPCa) patients persists in abiraterone and androgen receptor pathway inhibitors (ARPIs) eras. In Surveillance, Epidemiology, and End Results (SEER) database (2017–2021), African American and Caucasian mPCa patients aged 40–80 years treated across abiraterone (2017–2018) and ARPI (2019–2021) eras were identified. Age- and sex-matched controls were generated (Social Security Administration life tables and Monte Carlo simulation). Years of life lost (YLL) were quantified for mPCa patients and controls. Subsequently, propensity score matching (PSM) and multivariable competing-risks regression (CRR) models were used. In abiraterone era, YLL were 8.1 in African Americans vs. 5.4 in Caucasians (Δ: 2.7). In ARPI era, YLL were 4.6 in African Americans vs. 2.6 in Caucasians (Δ: 2.0). The 24-months cancer-specific mortality (CSM) was 30.3

The widespread use of cross-sectional imaging has increased the incidental detection of small renal masses (SRMs). In this context, overtreatment represents a major concern, particularly for lesions < 2 cm. Most evidence derives from retrospective registries, whereas prospective data remain limited. This multi-center, prospective, non-randomized clinical trial was conducted in five European centers between January 2015 and July 2021. Seventy-six patients aged > 50 years with asymptomatic, unilateral SRM < 2 cm were enrolled and followed under a structured prospective active surveillance (AS) protocol with periodic axial imaging. Active treatment was recommended according to predefined progression criteria or patient preference. The primary endpoint was event-free survival (EFS); secondary endpoints included treatment-free survival (TFS), overall survival (OS), and cancer-specific mortality (CSM). 69 patients were included in the analyses. After a median follow-up of 88 months, 8-year EFS and TFS were 66

686 Background: Over the past 3 decades, treatment of mUC has been transformed by 3 landmark backbone therapies: platinum-based chemotherapy (PBC), immune-checkpoint inhibitors (ICIs), and antibody–drug conjugates (ADCs), either alone or in combination therapies. Temporal trends of OS improvement in patients (pts) with mUC are instrumental to identify research gaps and unmet needs. Methods: We used the TriNetX research database to conduct a retrospective, large-scale outcome analysis of pts with mUC who received ≥1 line of treatment across worldwide healthcare institutions. Pts were stratified into 3 therapeutic temporal periods: PBC era (1999–2015), ICIs era (2016–2018), and ADC era (2019–2025). Baseline clinical and demographic characteristics were compared using standard statistics. Kaplan–Meier analysis estimated OS, and propensity score matching (PSM) adjusted for sex, age, stage at diagnosis, lines of treatment and comorbidities. Results: Among 4,720 pts with mUC, 2,383 received 1st-line therapy between 1999 and 2025 and were included in the analysis. Overall, 783, 663, and 937 pts were treated in the PBC, ICI, and ADC eras. Median age was 70 years across PBC, ICI, and ADC eras, respectively; the proportion of male pts was 72.9%, 69.4%, and 73.1%. Across treatment eras, 51.7% of pts in PBC era received PBC (49.3% non-PBC), 32% in the ICI era received ICIs (35.3% only PBC, 32.6% non-PBC), and 20% in the ADC era received ADCs (20.9% only PBC, 30.2% only non-PBC, 28.9% ICIs). Regarding subsequent therapies, in the PBC, ICI, and ADC eras, 51.4%, 52.6%, and 53.2% of pts received 2nd-line and 25.4%, 25.9%, and 26.7% 3rd-line therapy, respectively. The three cohorts yielded no significant differences in sex, race, comorbidities, lines of treatment, or stage at diagnosis (all p > 0.05). Median OS was 13.5 months (mo) in the PBC era, 17.5 mo in the ICIs era, and 21.1 mo in the ADC era with a significant difference between the ADC vs PBC eras (p = 0.0017). After PSM, median OS was 13.4, 17.3, and 22.3 mo in the PBC, ICI, and ADC eras, respectively, with the difference between the PBC vs ADC eras remaining significant (p = 0.005). Notably, a subgroup analysis of pts who received only chemotherapy (PBC or non-PBC) in their respective temporal period showed a median of OS 13.5, 14.6, and 17.1 mo in the PBC, ICI, and ADC eras, respectively, with a trend toward significance for the PBC vs ADC eras comparison (p = 0.006). Conclusions: OS in mUC has significantly improved over the past 3 decades, with the greatest gains observed in the ADC era during which an over 7.5 month improvement in median OS was observed (vs PBC era). Notably, improvements were seen even among many pts not receiving era-specific systemic therapies, suggesting that advances in diagnostics, staging, supportive care, and healthcare delivery —should be considered when interpreting real-world survival gains.

BACKGROUND:Although intermediate clinical endpoints (ICEs) may expedite completion of randomized controlled trials (RCTs) evaluating perioperative systemic treatments for localized muscle-invasive bladder cancer (MIBC), no validated surrogate for overall survival (OS) has been established. We aimed to assess the surrogacy of pathologic complete response (pCR), pathologic objective response (pOR), and disease-free survival (DFS) for OS. PATIENTS AND METHODS:We analyzed 4,828 patients with MIBC (cT2-T4N0M0) who underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) across 29 European centers (2001-2024). The inverse probability of treatment weighting (IPTW) approach was used to adjust for confounding between NAC and RC-only groups. Surrogacy was evaluated using: (1) adapted Prentice criteria to test whether each ICE remained a significant predictor of OS while the treatment effect disappeared in IPTW-adjusted multivariable Cox models; (2) the proportion of treatment effect explained (PTE); and (3) an emulated 2-stage meta-analytic framework to estimate the pseudo-trial-level R2 between treatment effects on each ICE and OS across 1,000 replicates of 5 random clusters. The surrogate threshold effect (STE) was calculated for ICEs demonstrating strong surrogacy (R2≥0.7). RESULTS:Overall, 1,288 (26.7%) patients received NAC followed by RC and 3,540 (73.3%) underwent RC alone. In IPTW-adjusted Cox regression analyses including NAC and each ICE separately, pCR (hazard ratio [HR], 0.32; 95% CI, 0.24-0.41; P<.001), pOR (HR, 0.26; 95% CI, 0.21-0.31; P<.001), and DFS (HR, 5.17; 95% CI, 4.56-5.86; P<.001) were independent predictors of OS. The PTE was 0.42 (95% CI, 0.22-0.54), 0.48 (95% CI, 0.24-0.58), and 0.84 (95% CI, 0.66-0.96) for pCR, pOR, and DFS, respectively. At the pseudo-trial level, the R2 was 0.22 (95% CI, 0.20-0.25), 0.33 (95% CI, 0.31-0.36), and 0.83 (95% CI, 0.81-0.84) for the correlation between treatment effects on pCR, pOR, and DFS and OS, respectively. The STE was 0.82 (95% CI, 0.81-0.84) for DFS. CONCLUSIONS:We observed uncertainty regarding the surrogacy of pCR and pOR in patients undergoing RC with or without NAC for localized MIBC. Only DFS consistently mediated the treatment effect on OS, supporting its use as a surrogate for RCT dimensioning when a recurrence or death risk reduction of ≥18% is expected.

Background: International guidelines recommend further diagnostic evaluation for patients with an elevated prostate-specific antigen (PSA; >4 ng/mL). However, real-world adherence to these recommendations remains poorly characterized. We aimed to quantify the proportion of patients receiving appropriate diagnostic work-up after an elevated PSA and to identify factors associated with adherence. Methods: We conducted a retrospective cohort study using the Epic Cosmos database (USA). Among 15,369,304 individuals undergoing PSA testing between 2017 and 2024, we included patients aged 40–75 years with at least 1 year of follow-up. Patients with prior prostate cancer, prostate MRI, or biopsy were excluded. The primary outcome was appropriate diagnostic work-up, defined as repeat PSA within 6 months and/or prostate MRI or biopsy within 12 months after an elevated PSA. Predictors included PSA level, age, race, Charlson Comorbidity Index, Area Deprivation Index, and ordering department. Findings: The final cohort included 1,002,947 patients. Overall, 49.1% received appropriate diagnostic work-up. Rates increased from 43.7% in 2017 to 55.5% in 2024. Patients receiving appropriate work-up had higher PSA levels (mean 5.5 vs 5.1 ng/mL; p<0.001) and were younger (mean 65 vs 66 years; p<0.001). They were more frequently White (73.1% vs 71.8%; p<0.001), had lower Area Deprivation Index (median 0.44 vs 0.46; p<0.001), fewer severe comorbidities (13.6% vs 14.5%; p<0.001), and were more often privately insured (39.1% vs 33.1%; p<0.001) and partnered (71.4% vs 67.9%; p<0.001). These associations were confirmed in multivariable analyses. Interpretation: In this large, contemporary cohort, approximately half of patients with elevated PSA did not receive guideline-concordant diagnostic evaluation. Despite modest improvement over time, substantial disparities persist, particularly across sociodemographic and clinical factors. These findings highlight an important gap in prostate cancer care and support the need for targeted strategies to improve adherence to diagnostic guidelines.Funding: None.