European urology oncology最新文献

Genomic testing has potential to improve clinical decision-making for men with prostate cancer, but is understudied for active surveillance (AS), the standard management option for favorable-risk disease. We investigated whether Decipher scores are associated with AS outcomes in a cohort of patients on AS with at least two biopsies and a Decipher test. Decipher high-risk was defined as a score ≥0.6. Primary outcomes were any upgrading (any increase in grade group [GG]), major upgrading (GG ≥3), and unfavorable histology on subsequent biopsy. Multivariable Cox proportional-hazards regression models were generated for the cohort of 486 patients. On diagnostic biopsy, 78% had low risk and 22% had intermediate risk according to Cancer of the Prostate Risk Assessment (CAPRA) scores, and 12% had high risk according to Decipher. Decipher scores were associated with major upgrading after adjusting for CAPRA scores (hazard ratio [HR] 3.37, 95% confidence interval [CI] 1.17-9.69); high Decipher risk was associated with major upgrading after adjustment for either the CAPRA score (HR 2.00, 95% CI 1.14-3.49) or clinicodemographic variables (HR 2.65, 95% CI 1.36-5.17). The Decipher score was associated with unfavorable histology after adjustment for the CAPRA score (HR 3.68, 95% CI 1.03-13.08); high Decipher risk was associated with unfavorable histology after adjustment for clinicodemographic variables (HR 4.53, 95% CI 2.03-10.15) but not after adjustment for the CAPRA score. No association was observed for any upgrading. Deintensification of surveillance may be warranted for patients with lower Decipher risk.

Background and objective: Our aim was to identify key prognostic factors for recurrence and progression of upper tract urothelial carcinoma (UTUC) after endoscopic kidney-sparing surgery (eKSS), and to provide a reliable, easy-to-use, risk stratification model.

Methods: We used data from a retrospective multicenter database for 358 patients with UTUC who underwent eKSS with curative intent between 2010 and 2021. A scoring system to predict recurrence-free survival (RFS) and progression-free survival (PFS) was developed using regression analyses. The discriminative ability of the score was estimated using the C index.

Key findings and limitations: The analysis included 223 patients, of whom 106 (48%) had recurrence and 37 (17%) had progression at median follow-up of 39 mo. Scoring systems were created that included synchronous bladder cancer (BCA; hazard ratio [HR] 1.52), high grade at biopsy (HR 1.38), multifocal UTUC (HR 1.12), and history of UTUC (HR 1.43) as factors for RFS, and synchronous BCA (HR 1.44), high grade at biopsy (HR 1.38), size ≥2 cm (HR 1.23), and positive cytology (HR 1.64) as factors for PFS. The C index was 0.60 for 5-yr RFS and 0.64 for 5-yr PFS. Three risk groups for each model were identified. The 5-yr cumulative incidence rates for the low-risk, intermediate-risk, and high-risk groups were 37%, 58%, and 70% for recurrence, and 4%, 18%, and 30% for progression, respectively. Limitations include the lack of external validation, a heterogeneous eKSS cohort, and limited follow-up.

Conclusions and clinical implications: We propose a novel risk stratification model for patients with UTUC treated with eKSS that includes key predictors for recurrence and progression and an intermediate-risk UTUC category with distinct outcomes.

Background and objective: Radiotherapy (RT) is a key curative option for localized prostate cancer (PC). However, data on late genitourinary toxicity, especially adverse events requiring urgent care or hospitalization, remain limited. The aim of the Italian Registry of Radiotherapy-Associated Disorders and Urological Treatment & Evaluation (IRRADIaTE) is to characterize the burden and management of severe genitourinary adverse events following prostate RT across multiple high-volume centers in Italy.

Methods: A prospective, observational, multicenter registry was established in 2024 across 20 Italian institutions. Men with localized PC previously treated with curative, adjuvant, or salvage RT who presented with late (≥6 mo) genitourinary complications requiring urgent medical attention were enrolled. Demographics, treatment details, and outcomes were collected. Toxicity grading followed Common Terminology Criteria for Adverse Events. Primary endpoints were prespecified as (1) the cumulative incidence of grade 3-5 events with death as a competing risk and (2) hospitalization-free survival from RT completion. Analyses were descriptive and adjusted for prespecified confounders only. Key findings and limitations Among 321 patients, 50% received primary RT, and 50% postprostatectomy RT. At the time of admission, 43% presented with grade 3-5 genitourinary toxicity. Over 5 yr, the hospitalization-free survival rate declined from 86% to 42%. Higher cumulative incidence of severe events was observed in the primary RT group. The percentage of patients who did not require major surgery to manage RT-related complications decreased from 81% (95% confidence interval [CI] 76-97%) at 12 mo after RT to 66% (95% CI 48-79%) at 60 mo. Differences in baseline age and comorbidity profiles between the RT treatment settings must be acknowledged. Because the registry enrolls only men presenting with complications, population-level incidence and causal effects cannot be inferred.

Conclusions and clinical implications: Late genitourinary toxicity after prostate RT is substantial and often resource-intensive. Differences observed by treatment setting are associational; attribution of causal mechanisms and treatment effects requires dedicated causal-inference studies.

Background and objective: Our aim was to identify potential prognostic factors for overall survival (OS) for patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy (NAC) and cystectomy in the VESPER trial (NCT01812369).

Methods: We focused on the NAC VESPER population (n = 437), including 218 patients who received dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin, and 219 who received gemcitabine and cisplatin. Tumor slides and formalin-fixed, paraffin-embedded blocks were available for central review in 297 cases of urothelial carcinoma. We investigated the effect of clinical, biological, pathological, and molecular characteristics on OS.

Key findings and limitations: Univariate analysis identified creatinine clearance, lymphovascular invasion, perineural invasion, and molecular subtype as factors with prognostic relevance for OS. Basal/squamous molecular subtype was the only covariate with the entire confidence interval greater than 0.5 for the time-dependent area under the receiver operating characteristic curve at 1, 3, and 5 yr, which suggests high prognostic value. Multivariable analysis demonstrated that these four prognostic factors were complementary for OS prediction. We did not observe a major difference in the 5-yr OS rate between groups with none of these factors (72%, 95% confidence interval [CI] 63-82%) or only one factor (67%, 95% CI 59-76%). By contrast, the 5-yr OS rate was lower for the group with two or more factors (38%, 95% CI 28-53%).

Conclusions and clinical implications: We identified four factors prognostic for OS for patients with MIBC treated with NAC in VESPER. Basal molecular subtype was the most significant prognostic factor for OS, as it was independent of the treatment arm, and showed high prognostic value, in particular during the first year after randomization.

Background and objective: Muscle-invasive bladder cancer (MIBC) may present de novo (primary MIBC [pMIBC]) or progress from non-muscle-invasive disease (secondary MIBC [sMIBC]). While sMIBC has been associated with adverse outcomes after radical cystectomy, its prognostic impact in patients undergoing trimodal therapy (TMT) is unclear. We aimed to compare the outcomes between pMIBC and sMIBC in a multicenter cohort treated with bladder-preserving TMT.

Methods: We conducted a retrospective study including patients with MIBC treated with curative-intent TMT. Eligible patients had stage ≥T2 disease and completed TMT without discontinuation. Patients were classified as those having pMIBC (≥T2 at diagnosis) or sMIBC (progression after prior non-muscle-invasive bladder cancer [NMIBC]). The primary endpoint was recurrence-free survival; the secondary endpoints were metastasis-free survival, cancer-specific survival (CSS), overall survival, and treatment-related toxicity. Survival was assessed using Kaplan-Meier methods and multivariable Cox regression.

Key findings and limitations: Among 294 patients (234 with pMIBC and 60 with sMIBC), the median age was 77 yr. The median follow-up was 34 mo for pMIBC and 24 mo for sMIBC. The 3-yr CSS rate was 78% for pMIBC and 79% for sMIBC. After adjustment for clinical covariates, sMIBC was not associated with an increased risk of recurrence (hazard ratio [HR] 1.35, 95% confidence interval [CI] 0.85-2.13) and cancer-specific death (HR 0.88, 95% CI 0.44-1.76). Toxicities were mostly of grade 1-2; grade ≥3 events were rare. Limitations include the retrospective design, a smaller sMIBC subgroup, and a relatively short follow-up.

Conclusions and clinical implications: Outcomes after TMT were broadly similar between pMIBC and sMIBC, although overall survival was lower in patients with secondary disease. A prior NMIBC history should therefore not preclude consideration of bladder-preserving therapy in appropriately selected patients.