European urology oncology最新文献

Background and objective: The addition of docetaxel to radiotherapy (RT) and long-term androgen deprivation therapy (ADT) is not a standard of care for the treatment of high-risk localized prostate cancer (HRLPC). We performed an individual patient data (IPD) meta-analysis to assess the addition of docetaxel to RT and ADT in HRLPC.

Methods: IPD from patients with HRLPC (as defined by any of the following risk factors: Gleason score ≥8, prostate-specific antigen >20 ng/ml, cT3-T4, and/or N1) treated in trials evaluating RT + ADT ± docetaxel, available in the Intermediate Clinical Endpoints in Carcinoma of the Prostate (ICECaP) repository, were collated. The primary outcome was metastasis-free survival (MFS), and the secondary outcomes were overall survival (OS), event-free survival (EFS), prostate cancer-specific mortality (PCSM), and time to metastasis (TTM). Analyses were conducted using a one-stage IPD meta-analysis. Disease risk was defined as high (one risk factor) or very high (two to three risk factors and/or N1). Multivariable Cox proportional hazards and Fine-Gray competing risk models estimated the effect of addition of docetaxel to RT + ADT on each time-to-event outcome.

Key findings and limitations: A total of 1690 patients from four trials were included. Docetaxel did not lead to an overall benefit in MFS (hazard ratio [HR] 0.89), OS (HR 0.88), and TTM (HR 0.87), but there was a significant benefit in EFS (HR 0.87) and PCSM (HR 0.70). The 5- and 10-yr MFS rates were, respectively, 79% and 57% in patients treated with RT + ADT, and 84% and 62% in those who received RT + ADT + docetaxel. There was no clear evidence of a greater benefit of docetaxel in patients with very-high-risk disease than in those with high-risk disease (MFS: HR 0.87 vs 0.97; OS: HR 0.86 vs 0.95; EFS: HR 0.83 vs 0.93; TTM: HR 0.86 vs 0.92; and PCSM: HR 0.70 vs 0.73), with no statistically significant difference in treatment effect by risk group (all p-interaction >0.1).

Conclusions and clinical implications: Addition of docetaxel to RT + ADT did not lead to a significant benefit in MFS or OS. Clinical stratification together with biomarkers should be evaluated to determine whether biologic features can identify HRLPC patients who are more likely to benefit from intensification of therapy with docetaxel.

Background and objective: Recent Edinburgh-based research demonstrated high negative predictive value (NPV) for urinary dipstick testing for haematuria (UDH) in low-risk bladder cancer surveillance. This enabled a new protocol where flexible cystoscopy in surveillance years 2 and 4 is performed only if UDH is positive. Adopted across Scotland and included as aspirational in European Association of Urology guidelines, this protocol has yet to be validated in real-world settings. This study aims to evaluate the clinical outcomes of low-risk bladder cancer with the implementation of the new surveillance protocol.

Methods: The protocol began in December 2018. All patients with low-risk bladder cancer on initial transurethral resection of bladder tumour were included from January 2019 to February 2025. General practitioners conducted UDH in surveillance years 2 and 4; cystoscopy followed if positive. Patient and clinical data were prospectively recorded using a standardised institutional pro forma. This study performed the first clinical evaluation of the deintensified low-risk protocol. The study evaluated the recurrence and progression rates, NPV of UDH throughout surveillance, and number of check cystoscopies performed. The statistical analysis used Stata-BE version 19.0 for Mac.

Key findings and limitations: A total of 250 patients were observed with a recurrence rate of 14.4% and a progression rate of 1.6%, similar to preprotocol outcomes. The NPV of UDH remained above 94% throughout surveillance. Flexible cystoscopy use declined by 18.2%, saving at least £51 000. Limitations included a lack of randomisation, modest cohort sizes at 4 and 5 yr of surveillance, and absence of patient-reported outcomes.

Conclusions and clinical implications: The deintensified protocol appears safe, maintaining clinical outcomes whilst reducing procedural use and costs in low-risk bladder cancer.

Background and objective: Salvage radiotherapy (SRT) is often curative in men with biochemical recurrence (BCR) after radical prostatectomy (RP); however, a subset experiences progression. While the depth of prostate-specific antigen (PSA) nadir after SRT is a known prognostic factor, its combined role with time to nadir (TTN) in the salvage setting, in absence of androgen deprivation therapy (ADT), has not been evaluated systematically and the present study aims to evaluate it.

Methods: We retrospectively included RP patients treated with SRT across 15 European centers. No prior or concomitant ADT was allowed. Patients were stratified into four groups by PSA nadir (<0.1 vs ≥0.1 ng/ml) and TTN (<6 vs ≥6 mo). The primary endpoint was distant metastasis-free survival (DMFS). The secondary endpoint was BCR-free survival (BRFS).

Key findings and limitations: A total of 1189 patients were included in the study, with a median clinical follow-up of 4.4 (interquartile range, 2.7-6.4) yr, and 5-yr BRFS and DMFS probabilities of 62% (95% confidence interval [CI], 59-65%) and 89% (95% CI, 87-91%), respectively. Patients with favorable kinetics (nadir <0.1 ng/ml, TTN ≥6 mo; 56.3% of cohort) achieved a 5-yr DMFS rate of 96% (95% CI, 94-98%), while high-risk patients (nadir ≥0.1 ng/ml, TTN <6 mo; 14.7%) had poor outcomes (5-yr DMFS rate 63%; 95% CI, 55-72%). A multivariable analysis confirmed a nadir of ≥0.1 ng/ml (hazard ratio [HR] 10.1; 95% CI, 8.0-12.7 for BRFS, and HR 7.1; 95% CI, 4.5-11.2 for DMFS) and TTN <6 mo (HR 3.0; 95% CI, 2.3-3.8, and HR 1.8; 95% CI, 1.1-2.7, respectively) as independent adverse factors.

Conclusions and clinical implications: Our study showed that the combination of PSA nadir depth and TTN after SRT allows an improvement in prognostic stratification of SRT patients with BCR after RP. These findings might improve patient-tailored decisions between surveillance, active treatment, and treatment escalation.

Background and objective: Multidisciplinary tumor boards (MTBs) are the gold standard for oncological treatment planning, but their implementation is resource intensive. Large language models (LLMs) such as ChatGPT-4 and Claude 3.5 Sonnet have emerged as scalable tools for clinical decision support. As their comparative performance in urological oncology remains largely untested in prospective trials, this study aimed to prospectively evaluate them against real MTBs.

Methods: In this prospective, multicenter, noninferiority study (DRKS00034797), we evaluated whether therapeutic recommendations by ChatGPT-4 and Claude 3.5 Sonnet were noninferior to those of MTBs across 110 representative case scenarios involving locally advanced or metastatic genitourinary cancer. Standardized prompts elicited recommendations from both LLMs, which were rated independently by two blinded uro-oncologists using the validated modified System Causability Scale (mSCS). The predefined noninferiority margin was 0.15 mSCS points.

Key findings and limitations: The mean mSCS score of the MTBs was 0.849 (standard deviation [SD] = 0.157), setting the noninferiority margin at 0.699. Claude 3.5 Sonnet scored 0.731 (SD = 0.178; 95% confidence interval [CI]: 0.697-0.765), narrowly missing noninferiority. ChatGPT-4 scored 0.660 (SD = 0.193; 95% CI: 0.623-0.696), clearly below the margin. A subgroup analysis revealed better LLM performance in locally advanced versus metastatic cases (p < 0.05). Limitations include the use of synthetic cases and inherent LLM output variability.

Conclusions and clinical implications: Neither LLM matched the MTB standards. These findings highlight the current limitations of public LLMs, or of their use in our study, in supporting complex oncological decisions. This underscores the need for further validation and contextual refinement before integration into multidisciplinary care.

Background and objective: Current guidelines strongly recommend prostate-specific membrane antigen positron emission tomography (PSMA-PET) for staging high-risk prostate cancer (PCa) patients. This study aims to evaluate the impact of staging procedure (PSMA-PET vs conventional imaging) on short-term oncologic outcomes in a cohort of N0M0 high-risk PCa patients who underwent radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND).

Methods: We retrospectively included 1475 high-risk PCa patients who underwent RP and ePLND in 14 referral centers between 2014 and 2024. Each patient underwent either PSMA-PET (miN0M0) or conventional imaging (cN0M0). After a landmark analysis and 1:1 propensity score matching for age at diagnosis, year of surgery, initial serum prostate-specific antigen (PSA), cT stage, and International Society of Urological Pathology grade group at biopsy, the Kaplan-Meier methodology was used to assess biochemical recurrence (BCR)-free survival (BCR-FS) and multivariable Cox regression models to identify the predictors of BCR (time in months between the date of RP and the date of BCR).

Key findings and limitations: After propensity score matching, 463 (48.2%) versus 463 (90.1%) patients underwent PSMA-PET versus conventional imaging. PSA persistence was observed in 15 (3.2%) versus 64 (14%) miN0M0 patients at PSMA-PET versus cN0M0 patients at conventional imaging (p < 0.001). The BCR-FS rates at 36 mo were 90.9% and 82.2% in the PSMA-PET and conventional imaging cohorts, respectively. At multivariate Cox regression analyses, PSMA-PET (hazard ratio: 0.48; 95% confidence interval: 0.29-0.77) was an independent predictor of lower BCR rates (p = 0.003). In the PSMA-PET cohort, BCR-FS rates were similar between patients with one high-risk feature and those with two or more high-risk features, while in the conventional imaging cohort, two or more high-risk features were associated with significantly worse BCR-FS rates than one high-risk feature. Limitations include the retrospective design of the study.

Conclusions and clinical implications: Time to biochemical recurrence was longer in the miN0M0 cohort than in the cN0M0 cohort. Superior PSMA-PET staging accuracy seems to improve short-term oncologic outcomes of high-risk PCa patients following surgery.

Background and objective: Early-onset prostate cancer (PCa) is more frequent in men of African descent; yet, the biological mechanisms underlying susceptibility remain unclear. While most germline studies have focused on DNA repair genes (DRGs), alternative pathways may also contribute to tumor initiation, which we aim to assess in this study.

Methods: We analyzed 71 Afro-Caribbean men diagnosed with early-onset PCa (≤51 yr old for sporadic cases and ≤56 yr old for familial cases). Germline testing combined targeted sequencing of 175 genes-including major DRGs-with whole-exome sequencing in patients without DRG alterations. Variants were filtered for rarity (minor allele frequency <0.01 in African populations) and their clinical classification as pathogenic or likely pathogenic (P/LP; ClinVar and ACMG/AMP guidelines). Genes were grouped by biological function.

Key findings and limitations: Rare P/LP germline variants were identified in 37 patients (52.1%). Among these patients, ten carried a DRG variant (including one also harboring HOXB13 X285K), 26 carried at least one variant in immune-metabolic pathways (one also with HOXB13 X285K), and one carried only HOXB13 X285K. Recurrent truncating variants were found in FLG, PGAM2, and TYRP1. Although no statistically significant association was observed between molecular subgroups and clinical aggressiveness, DRG variants tended to occur in more high-risk tumors, whereas immune-metabolic alterations were more frequent in patients with low- or intermediate-risk disease.

Conclusions and clinical implications: This study reveals a broader germline landscape in early-onset PCa among men of African descent. Inherited immune-metabolic dysfunction may contribute to tumorigenesis through microenvironmental dysregulation, highlighting novel pathways for investigation in larger and ancestrally diverse cohorts.