European urology最新文献

Prostate-specific membrane antigen (PSMA)-targeting strategies in prostate cancer have evolved rapidly from early antibody-based approaches to highly effective diagnostic and therapeutic agents. While PSMA remains a central benchmark in metastatic disease, biological heterogeneity and therapy resistance underscore the need for continued innovation and rational combination strategies.

Intravesical bacillus Calmette-Guérin (BCG) therapy remains the cornerstone for high-risk non-muscle-invasive bladder cancer (NMIBC), but up to 40% of patients experience disease recurrence or progression within 2 yr. We conducted a systematic review and meta-analysis of three phase 3 randomized trials POTOMAC, CREST, and ALBAN; n = 2590) in BCG-naïve high-risk NMIBC disease treated with a combination of BCG and an immune checkpoint inhibitor (ICI). Overall risk of bias was low for all studies. Combination therapy with BCG maintenance was associated with better event-free survival (EFS) in comparison to BCG alone (pooled hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.60-0.99; Q = 3.29, p = 0.2). Using the HR for high-grade recurrence from ALBAN, the pooled estimate was directionally consistent, but not statistically significant (HR 0.78, 95% CI 0.58-1.04; Q = 3.94, p = 0.1). Overall survival was comparable between groups (HR 0.92, 95% CI 0.67-1.26). Grade ≥3 treatment-related adverse events were more frequent with combination therapy (risk ratio [RR] 3.66, 95% CI 2.56-5.24 for BCG induction only; RR 3.97, 95% CI 2.54-6.21 for BCG induction + maintenance). There was a moderate decline in patient-reported quality of life in the ICI + BCG maintenance arms. These findings are supported by moderate-certainty evidence for EFS. BCG monotherapy remains the benchmark for BCG-naïve high-risk NMIBC. ICI addition improves EFS but increases high-grade toxicity, which should prompt cautious and individualized adoption pending mature survival data.

Background and objective: Prostate-specific antigen (PSA)-based screening for prostate cancer (PCa) has limited accuracy, and it is linked to overdiagnosis. The PROSA trial aimed to evaluate whether a contrast-free biparametric magnetic resonance imaging (bpMRI)-first screening strategy improves the detection of clinically significant PCa (csPCa) as the primary outcome. The secondary outcomes included overall PCa detection, benefit-harm metrics, and cost effectiveness from a health care payer perspective.

Methods: This single-center, randomized controlled trial enrolled 816 asymptomatic men aged 49-69 yr (≥40 yr with a PCa family history). Participants were randomized into two arms: arm A underwent bpMRI regardless of the PSA levels; arm B received bpMRI only if PSA ≥3 ng/ml (or 2.5 ng/ml with a family history). Men with Prostate Imaging Reporting and Data System score ≥3 were directed to a targeted biopsy. Imaging and pathology assessors were blinded; csPCa is defined as International Society of Urological Pathology grade group ≥2. The primary outcomes included csPCa detection, benefit-harm metrics, and cost effectiveness from a health care payer perspective.

Key findings and limitations: Among 759 randomized men, biopsy and csPCa detection rates were higher in arm A (10.8% and 4.6%, respectively) than in arm B (5.2% and 1.8%, respectively), with a relative risk of 2.6 (95% confidence interval 1.1-6.1; p = 0.05) for the csPCa detection rate. Benefit-harm metrics favored the MRI-first strategy, showing higher grade selectivity (1.89 vs 1.75), biopsy efficiency (0.74 vs 0.54), and biopsy avoidance (23.1 vs 11.9). No serious adverse event was recorded. The MRI-first strategy yielded an incremental cost-effectiveness ratio of €2201.75 per csPCa case detected. Limitations include single-round design and short follow-up.

Conclusions and clinical implications: In this randomized screening trial, a contrast-free MRI-first pathway improved csPCa detection, enhanced benefit-harm metrics, and showed favorable cost effectiveness.

Background and objective: In EMPIRE-1, [¹⁸F]-fluciclovine positron emission tomography (PET) imaging to guide salvage radiotherapy (RT) for prostate cancer recurrence after prostatectomy resulted in an improvement in event-free survival (EFS) over conventional imaging alone. The aim of EMPIRE-2 was to explore the impact of RT dose escalation to sites of uptake on PET in comparison to EMPIRE-1.

Methods: EMPIRE-2 was a randomized trial of [¹⁸F]-fluciclovine versus [⁶⁸Ga]-PSMA-11 in a cohort of men with biochemical progression after prostatectomy and negative conventional imaging findings. After stratification, patients were randomized to RT guided by [¹⁸F]-fluciclovine PET (arm 1) or [⁶⁸Ga]-PSMA-11 PET (arm 2). PET findings were used for treatment decisions and for RT dose escalation (≤76.0 Gy to the prostate bed and ≤56.0 Gy to the pelvis). The primary endpoint was 2-yr EFS in comparison to the [¹⁸F]-fluciclovine RT arm in EMPIRE-1. The secondary endpoint was a planned EFS comparison for [¹⁸F]-fluciclovine versus [⁶⁸Ga]-PSMA-11 in EMPIRE-2.

Key findings and limitations: In the cohort of 140 patients, 59 randomized to arm 1 patients and 60 randomized to arm 2 completed RT. Median follow-up was 2.6 yr (interquartile range 1.8-4.0). The 2-yr EFS rates were 87% for the overall EMPIRE-2 cohort versus 80% for the EMPIRE-1 comparison cohort (difference 7.7%, 95% confidence interval [CI] 4.7-12%; p = 0.01). After propensity score weighting, the corresponding 2-yr EFS rates were 84% versus 73% (difference 11%, 95% CI 3.6-24%; p = 0.01). The 2-yr EFS rates in the EMPIRE-2 study arms were 87% for [¹⁸F]-fluciclovine versus 88% for [⁶⁸Ga]-PSMA-11 (difference 0.7%, 95% CI 0.3-1.3%; p > 0.9).

Conclusions and clinical implications: Use of either [¹⁸F]-fluciclovine or [⁶⁸Ga]-PSMA-11 imaging to guide RT dose escalation to sites of PET uptake in the prostate bed and/or pelvis was associated with an improvement in EFS in comparison to a prior trial without dose escalation.