European urology oncology最新文献

Background and objective: Low-grade, stage Ta (TaLG) non-muscle-invasive bladder cancer (NMIBC) is generally nonaggressive; yet, some patients experience recurrence or progression. We previously identified long noncoding RNA cluster 2 (LC2) as an aggressive TaLG subgroup via consensus clustering, which required a cohort-level analysis. We developed a single-sample transcriptome classifier for patient-level LC2 identification.

Methods: Using the UROMOL cohort (n = 276) for training/testing and the Hurst (Stage-stratified molecular profiling of non-muscle-invasive bladder cancer enhances biological, clinical, and therapeutic insight. Cell Rep Med 2021;2:100472) cohort (n = 72) for validation, we performed feature selection via median absolute deviation and nested cross-validation. An elastic net regression model (α = 0.5) was trained using ten-fold cross-validation. Performance was evaluated through a pathway analysis, with prognostic significance assessed by Kaplan-Meier and univariable Cox regression.

Key findings and limitations: Biological characterization revealed that LC2 tumors exhibited higher proliferation (G2M/E2F signatures), elevated FGFR3 pathway activity, and reduced sonic hedgehog signaling and immune activity (p < 0.001). The classifier identified 7/72 LC2 tumors in the Hurst cohort. LC2-TaLG patients had significantly worse recurrence-free survival (log-rank p < 0.001). On univariable Cox regression analysis, LC2 status was strongly associated with recurrence (hazard ratio 4.52, 95% confidence interval 1.78-11.5; p = 0.001). LC2-predicted tumors in the Hurst cohort showed similar biological patterns.

Conclusions and clinical implications: We developed a single-sample transcriptomic classifier identifying aggressive TaLG NMIBC, demonstrating reproducibility across platforms. If validated, this model has the potential to support clinical decision-making.

Background and objective: Patients with locally advanced bladder cancer have a poor prognosis despite radical surgery. Early data on neoadjuvant immunotherapy are promising, with possible synergistic effects with radiation therapy. Therefore, this prospective multicenter phase 2 trial evaluated, for the first time, the feasibility, safety, and efficacy of neoadjuvant radioimmunotherapy before radical cystectomy.

Methods: Patients with locally advanced urothelial bladder cancer (cT3/4 cN0/N+ cM0) eligible for radical cystectomy but unfit or refusing neoadjuvant cisplatin-based chemotherapy were included in this prospective phase 2 trial. Patients received four cycles of nivolumab 240 mg every 2 wk combined with radiotherapy of the pelvis with a maximum dose of 50.4 Gy. Patients underwent radical cystectomy with pelvic lymphadenectomy between weeks 11 and 15. The primary endpoint was feasibility, defined as a minimum completed treatment rate of >70% at the end of week 15.

Key findings and limitations: Thirty-three patients were included. For the primary endpoint and efficacy analysis, 31 patients were eligible. The trial met its primary endpoint with a completed treatment rate of 87% (27/31). The pathological response rates were 39% with ypT0 ypN0 cM0, 58% with ≤ypT1 ypN0 cM0, and 74% with ≤ypT2 ypN0 cM0. Immune-related adverse events of all grades occurred in 55%, and grade 3/4 adverse events occurred in 33% of patients. There were no treatment-related deaths.

Conclusions and clinical implications: By meeting its primary endpoint, this trial demonstrated for the first time the feasibility and safety of neoadjuvant radioimmunotherapy prior to radical cystectomy in patients with locally advanced bladder cancer, warranting further investigation in a randomized setting.

Background and objective: Poly ADP-ribose polymerase (PARP) inhibitors have become an important treatment option for metastatic castration-resistant prostate cancer (mCRPC), targeting PARP1-mediated DNA repair. We investigated [¹⁸F]PARPi positron emission tomography (PET) uptake as a predictive biomarker of mCRPC.

Methods: We retrospectively analyzed 15 mCRPC patients who underwent [¹⁸F]PARPi PET/computed tomography (CT) examinations and were subsequently treated with PARP inhibitors andrs; homologous recombination repair alterations were detected in two patients. Lesions exhibiting uptake above the background were segmented and quantified. Target to background ratios (TBRs) were derived using the abdominal aorta as a blood pool to normalize interpatient biodistribution. Baseline uptake metrics were correlated with the percentage of prostate-specific antigen (PSA) response.

Key findings and limitations: Most patients presented with osseous metastases (n = 13) on [¹⁸F]PARPi PET, followed by nodal (n = 9), visceral (n = 3), and prostatic (n = 1) lesions. During PARP inhibition, of the 15 patients, six achieved a ≥50% PSA decline, eight showed a <50% decline, and one experienced a >100% PSA increase. The median time to PSA nadir was 40 d (interquartile range [IQR] 20-76 d). The percentage of PSA change correlated well with [¹⁸F]PARPi PET mean, peak, and maximum TBRs of bone lesions (all r = 0.72-0.79; all p < 0.05), with weaker, nonsignificant correlations for nodal lesions (r = 0.49-0.53; all p > 0.05). Five patients discontinued treatment due to adverse events (AEs) after a median of 28 d (IQR 27-69 d). Patients without AEs (n = 3) exhibited higher bone lesion TBRs than those with AEs (n = 12, p < 0.05). The limitations of this study are its retrospective nature and small sample size.

Conclusions and clinical implications: Baseline [¹⁸F]PARPi uptake in mCRPC lesions was associated with a PSA response to PARP inhibition. Higher TBRs particularly in bone lesions predicted a greater PSA decline. These findings support [¹⁸F]PARPi PET/CT as a promising tool for patient selection and therapy monitoring, warranting prospective trials with histopathological validation and survival endpoints.

Counselling a patient with a localised renal mass (LRM) can be complex. While many models can predict various outcomes (nature of the mass, survival, technical points of the intervention), none is widely used. We conducted a systematic review of models that could potentially be used to assist patients' decision-making for LRMs (PROSPERO 1048873). Among 6833 records screened, 284 met the inclusion criteria covering nine broad categories (benign vs malignant, specific pathology, grade, adverse pathology, survival, genomics, renal function, complications, technical factors), of which 101 used existing nomograms (predominantly nephrometry scores). Of the 195 studies that developed an original model, 79 (40.5%) provided a nomogram that could be used for patient decision-making, while 105 (53.8%) provided no validation for the new model. We conducted an online survey that was completed by 31 clinicians and 35 patients/carers and identified six priority areas when considering treatment for a newly diagnosed LRM. Twenty models covered aspects of these priority areas, but no single model adequately covered them all. Further research is required for proper assessment of clinician and patient/carer priorities, but the results from our review and the survey that included multiple stakeholders provide clarity on clinical utility across the heterogeneous field of models available. The design of future models should include clinically relevant outputs, should clearly state the nature of the development cohort and model performance, and should ideally provide a user-friendly version of the model via which patients can obtain relevant information.

Background and objective: Targeted plus perilesional biopsies are recommended for men with prostate lesions visible on magnetic resonance imaging. However, available data are mainly retrospective, without predefined biopsy scheme protocols. The MRI-Integrated Regional and targeted Approach, recommendations, and Guidelines for prostate biopsies (MIRAGE) study is the first prospective European study designed to evaluate the outcomes when perilesional biopsies are incorporated deliberately into the biopsy protocol.

Methods: MIRAGE was a prospective, observational, multicenter study conducted across ten European centers between January and June 2025. We enrolled 912 men with a single Prostate Imaging Reporting and Data System (PI-RADS) ≥3 lesion. Targeted and perilesional biopsies were mandated, while distant biopsies (ie, cores taken beyond the perilesional zone) were left to the discretion of investigators. Detection rates of Gleason grade (GG) group ≥2 and 1 lesions were calculated separately for each scheme: targeted, perilesional, and distant biopsies.

Key findings and limitations: Targeted biopsy detected GG group ≥2 lesions in 380 men (41%). Compared with targeted biopsy alone, perilesional sampling increased GG group ≥2 lesion detection by +3.6% at the cost of +1% GG group 1 lesion detection. The greatest benefit of perilesional sampling was observed in biopsy-naïve men and those with PI-RADS 4-5 lesions. Conversely, in those with PI-RADS 3 or a prior negative biopsy, perilesional sampling yielded more cases of GG group 1 than of GG group ≥2. Distant sampling provided minimal incremental GG group ≥2 (contralateral: +1.6%; ipsilateral: +1.4%) but more GG group 1 (contralateral: +2.5%; ipsilateral: +2.9%) cases.

Conclusions and clinical implications: The MIRAGE study provides prospective evidence that, when a targeted plus perilesional biopsy strategy is applied, distant biopsies add minimal diagnostic benefit and should be omitted.

Background and objective: Adherence to European Association of Urology (EAU) guideline-recommended management of non-muscle-invasive bladder cancer (NMIBC) is essential for optimal outcomes. We quantified real-world adherence to early instillation (EI), second-look transurethral resection of bladder tumor (re-TURBT), and risk-adapted intravesical therapy, and assessed their impact on oncological outcomes.

Methods: We retrospectively analyzed 2194 consecutive NMIBC patients treated with TURBT at six European tertiary centers (2014-2021). Eligibility for EI, re-TURBT, and intravesical instillations was defined using the EAU criteria. Adherence was evaluated through Sankey plots. Recurrence-free survival (RFS) and progression-free survival (PFS) were assessed using Kaplan-Meier analyses with inverse probability of treatment weighting and compared by adherence status. Cox regression models were also fitted.

Key findings and limitations: Tumor stage distribution was as follows: 63% Ta, 32% T1, and 5.4% Tis stage; 60% were of high grade. Risk distribution was as follows: 22% low, 27% intermediate, 38% high, and 13% very high. EI was recommended in 1333 patients and performed in 290 (22%) patients. Re-TURBT was indicated in 1006 patients and performed in 445 (44%) patients. Intravesical instillations were recommended in 1713 patients and initiated in 497 (29%) patients. Adherence to EI (79% vs 61%; hazard ratio [HR] 0.60), re-TURBT (70% vs 54%; HR 0.53), and instillations (72% vs 53%; HR 0.49) was associated with superior RFS; re-TURBT (94% vs 87%; HR 0.41) and instillations (95% vs 89%; HR 0.47) also improved PFS (all p < 0.001). Nonadherence reasons were not reported.

Conclusions and clinical implications: In real-world practice, adherence to EAU-recommended NMIBC management remains low; yet, it is associated with more favorable outcomes. Improving delivery of guideline-based care through standardized pathways should be a priority in NMIBC management.