European urology oncology最新文献

Polygenic risk scores (PRSs) have generated considerable interest as a means of personalizing prostate cancer (PC) screening by stratifying individuals according to their genetic risk. The single-arm BARCODE1 study recently showed that PRS-based screening detected more PCs than prostate-specific antigen (PSA) testing or magnetic resonance imaging (MRI). The absence of a comparator arm limits the interpretability of this finding. We compared outcomes from BARCODE1 with those from two contemporaneous, large-scale screening trials-Göteborg-2 and ProScreen-that used MRI with or without a PC blood marker to risk-stratify men for biopsy. When standardized to 10 000 men tested, BARCODE1 biopsied more men (704 vs 386 and 338), diagnosed more low-grade PCs (126 vs 103 and 41), and detected fewer high-grade PCs (155 vs 178 and 165) versus Göteborg-2 and ProScreen. Combining PRS with PSA or MRI in BARCODE1 reduced the detection of high-grade PCs by 50-75% in comparison to Göteborg-2 and ProScreen. These findings reflect the limited risk discrimination of PRSs and their inability, unlike MRI and blood-based markers, to preferentially detect aggressive disease. PRS-based PC screening underperforms relative to current best practice and, on the basis of BARCODE1 data, should not be adopted in clinical practice.

Background and objective: Distal ureterectomy (DU) is a kidney-sparing option for low-risk upper tract urothelial carcinoma (UTUC) and may be considered for selected high-risk cases. Long-term outcomes and recurrence predictors remain poorly defined. Our aim was to evaluate oncological outcomes of DU and identify preoperative predictors of disease recurrence, with a particular focus on ipsilateral upper tract recurrence (iUTR).

Methods: This retrospective multicentre study included 450 patients with nonmetastatic UTUC in the distal ureter treated with DU and bladder cuff excision between 2010 and 2023. The primary endpoint was iUTR-free survival (iUTRFS). Secondary endpoints were intravesical recurrence-free survival (IVRFS), recurrence-free survival (RFS), cancer-specific survival (CSS), overall survival (OS), and perioperative outcomes. Survival outcomes were visualised using Kaplan-Meier curves, and multivariable Cox regression analyses were performed.

Key findings and limitations: The 5-yr survival estimates were 82% for iUTRFS, 49% for IVRFS, 81% for RFS, 89% for CSS, and 72% for OS. IVRFS, iUTRFS, CSS, and OS did not significantly differ between the low-risk and high-risk groups. iUTR occurred in 16% of patients, with one in four of these cases arising after 5 yr. Salvage radical nephroureterectomy was performed in 10% of patients. Preoperative double-J stenting (hazard ratio [HR] 2.85, 95% confidence interval [CI] 1.11-7.30), tumour size (HR 1.04, 95% CI 1.01-1.07) and endoscopic bladder cuff management (HR 9.73, 95% CI 1.66-56.89) were independent predictors of iUTR. Perioperative complications were rare, with only 7% graded as high grade within 90 d. Limitations include the retrospective design, lack of centralised pathology review, and variability in surgical technique.

Conclusions and clinical implications: DU provides favourable perioperative and long-term oncological outcomes and may also be appropriate for selected high-risk cases. iUTR is not uncommon, and prolonged upper tract follow-up is essential. Avoidance of preoperative stenting and endoscopic bladder cuff management may reduce the risk of iUTR.

Background and objective: The impact of biochemical recurrence (BCR) of prostate cancer after radical prostatectomy (RP) on overall mortality (OM) remains uncertain. Specifically, there are no patient-centered quantitative data on the impact of BCR on life expectancy. We compared OM and remaining lifetime between groups of patients with and without BCR after RP.

Methods: We identified 7820 participants who underwent RP, of whom 2846 (36%) had BCR. Associations between BCR and OM were assessed via Cox models with BCR as a time-dependent covariate. Years of life lost (YLL) associated with BCR (difference in remaining lifetime between the BCR and no-BCR groups) was estimated via Poisson regression. In secondary analyses the BCR group was stratified by prostate-specific antigen doubling time (PSADT).

Key findings and limitations: BCR was associated with modestly higher risk of OM on multivariable analysis (hazard ratio 1.29; p < 0.001). On PSADT stratification, only the BCR subgroups with PSADT of <3 mo or 3-8.9 mo had significantly higher OM risk in comparison to the group without BCR on multivariable analysis (both p < 0.001). At the median time to recurrence, remaining lifetime was 16.7 yr for the group without BCR and 15.3 yr for the BCR group (1.4 YLL). YLL stratified by PSADT subgroup was 6.8 yr for PSADT <3 mo, 2.8 yr for PSADT 3-8.9 mo, and <1 yr for PSADT >9 mo. Early salvage radiation and/or hormonal therapy was more common in the BCR subgroup with PSADT <9 mo (p < 0.001).

Conclusions and clinical implications: BCR after RP was significantly associated with a modest increased in the risk of OM and 1.4 YLL. In the BCR subgroup with PSADT <9 mo, the OM risk was dramatically higher, with 3-7 YLL, despite more frequent and earlier secondary treatment. These results quantify YLL associated with high-risk BCR for the first time, and can support patient-centered discussion and consideration of intensified salvage treatment validated in recent clinical trials and regimens recommended in clinical practice guidelines.

Background and objective: Muscle-invasive bladder cancer (MIBC) is a biologically heterogeneous disease with variable prognosis after radical cystectomy. While conventional clinicopathological parameters offer limited prognostic value, growing evidence highlights the role of the tumor immune microenvironment (TIME)-including immune cell composition and spatial architecture-as robust biomarkers for disease progression and outcomes.

Methods: The study included 251 consecutive patients with MIBC who underwent cystectomy (2004-2014, LMU Munich). Three 1-mm-diameter cores were sampled from the tumor invasive front and center in the cystectomy specimen. Six immune checkpoint proteins (ICPs; IDO, PD-L1, PD-1, LAG-3, TIM-3, and VISTA) were quantified digitally following immunohistochemical (IHC) staining. ICP-positive immune and tumor cells were stratified and densities were hierarchically clustered. Multivariable Cox models were then used to assess the association with overall (OS) and disease-free survival. The minimum tumor sample count needed to detect the maximum ICP expression per patient was estimated via a 1000-fold bootstrap resampling simulation.

Key findings and limitations: IDO⁺ and VISTA⁺ immune cells dominated the TIME, while PD-L1⁺ tumor cells exhibited a dichotomous expression pattern. Analysis of three spatially distinct cores was sufficient to recover maximal expression of low-abundance TIM-3⁺ and VISTA⁺ immune cells, while four cores were required for all other markers. ICP-based clustering revealed three TIME subtypes (CID1-3), of which CID3 was associated with markedly worse prognosis (median OS 18.5 vs 100.5 mo; p = 0.0007). This classification outperformed Union for International Cancer Control staging and improved patient stratification in late-stage MIBC.

Conclusions and clinical implications: A six-marker, multiregional ICP panel delivers a robust, stage-independent, actionable risk stratification in MIBC. At least four biopsies are advised for routine immune profiling; further longitudinal external validation is warranted.

Background and objective: High-risk prostate cancer (PCa) carries a substantial risk of recurrence and progression after radical prostatectomy (RP). The ARNEO trial previously showed that apalutamide (APA) plus degarelix (DEG) improved the rates of minimal residual disease (MRD) and organ-confined pathology (ypT2) compared with matching placebo (PBO). This study aims to assess the oncological and quality-of-life outcomes of neoadjuvant DEG + APA compared with DEG + PBO.

Methods: ARNEO was a double-blind, randomised, PBO-controlled phase 2 trial investigating neoadjuvant DEG + APA in high-risk PCa patients eligible for RP. Patients received 3 mo of neoadjuvant DEG + APA or DEG + PBO. No adjuvant or salvage therapy was given unless biochemical recurrence (BCR) occurred. Quality-of-life data were collected at predefined time points. The prespecified secondary endpoints included a between-arm comparison of testosterone recovery (testosterone ≥150 ng/ml), BCR within 3 yr (prostate-specific antigen ≥0.2 ng/ml), BCR-free survival (BCR-FS), and quality of life according to treatment allocation. Quality of life was assessed using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form, International Index of Erectile Function-5 items, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 questionnaires. Exploratory analyses included metastasis-free survival (MFS) and the relation of outcomes according to pathological outcomes.

Key findings and limitations: With a median follow-up of 54 mo, the 3-yr BCR rate was not significantly different between groups (24% with DEG + APA vs 39% with DEG + PBO; relative risk 0.63 [95% confidence interval {CI} 0.34-1.19], p = 0.18). BCR-FS was not associated with treatment allocation (hazard ratio 0.72 [95% CI 0.37-1.41]; p = 0.34) or MRD achieved (p = 0.93). However, BCR-FS was significantly longer in patients with ypT2 or specimen-confined disease (p ≤ 0.0001). Similar outcomes regarding 3-yr BCR rates and MFS were found. The median testosterone (>150 ng/dl) recovery time was 5 mo in both the groups (p = 0.36). Quality-of-life outcomes were not different at each time point (p > 0.47). Importantly, the ARNEO trial was powered for a difference in MRD rates (primary endpoint) and not for the reported secondary endpoints.

Conclusions and clinical implications: At 3-yr follow-up, no differences were seen in the 3-yr BCR rate or BCR-FS between patients treated with neoadjuvant DEG + APA and those treated with DEG + PBO. Achieving MRD was not predictive of better outcomes, whereas ypT2 and specimen-confined disease were strongly associated with improved BCR-FS and MFS. Quality of life remained similar between groups at all time points.

Background and objective: It remains currently unknown whether the effectiveness of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is the same in patients with or without prior non-muscle invasive bladder cancer (NMIBC). This study aims to perform a real-world analysis of the predictive value of prior NMIBC for the effectiveness of NAC in patients undergoing RC for MIBC.

Methods: We included 2378 patients from the BLADRAC cohort who received RC with (n = 870; 37%) or without (n = 1508; 63%) NAC for primary (n = 1825; 77%) or secondary (n = 553; 23%) MIBC at 15 French centers from 2001 to 2023. Multivariable logistic regression models were fitted to identify the predictors of NAC delivery as well as those of pathological complete (pCR = [y]pT0N0) and pathological objective (pOR ≤[y]pT1N0) responses, while we assessed the predictors of recurrence-free (RFS), cancer-specific (CSS), and overall (OS) survival using multivariable Cox regression models. The heterogeneity of treatment effect of NAC according to the occurrence of prior NMIBC was determined further by testing the interaction terms between the occurrence of prior NMIBC and the effect of NAC within the models evaluating pathological and survival outcomes.

Key findings and limitations: Patients with secondary MIBC were significantly less likely to receive NAC (odds ratio [OR] = 0.63; 95% confidence interval [CI] = [0.5-0.79]; p < 0.001) than those with primary MIBC. The use of NAC was an independent predictor of better pCR (OR = 6.02; 95% CI = [4.63-7.83]; p < 0.001), pOR (OR = 5.08; 95% CI = [4.09-6.3]; p < 0.001), RFS (HR = 0.61; 95% CI = [0.53-0.71]; p < 0.001), CSS (HR = 0.57; 95% CI = [0.47-0.69]; p < 0.001), and OS (HR = 0.61; 95% CI = [0.51-0.72]; p < 0.001), while the occurrence of prior NMIBC was not significantly associated with any of these endpoints (all p > 0.05). There was no significant interaction between the occurrence of prior NMIBC and the impact of NAC on pCR, pOR, RFS, CSS, and OS (all p_interaction > 0.05). The study is limited by its retrospective design.

Conclusions and clinical implications: Our real-world data suggest that the occurrence of prior NMIBC could limit the access to NAC, while not predicting its effectiveness in patients treated with RC for localized MIBC.

Background and objective: Prostate-specific membrane antigen (PSMA) expression on positron emission tomography/computed tomography (PET/CT), semiquantitatively expressed as the standardised uptake value (SUV_max), is increasingly recognised as a prognostic factor and may predict metastatic progression after treatment. This study aims to evaluate the predictive value of SUV_max on preoperative PSMA PET/CT for metastatic development after robot-assisted radical prostatectomy (RARP).

Methods: This retrospective two-centre study included patients with nonmetastatic primary prostate cancer who underwent [⁶⁸Ga]Ga-PSMA-11 or [¹⁸F]DCFPyL PSMA PET/CT prior to RARP. The minimum follow-up period was 1 yr. Metastases were assessed by restaging PSMA PET/CT at biochemical recurrence. SUV_max was calculated for the dominant intraprostatic lesion on preoperative PSMA PET/CT. Multivariable Cox regression included SUV_max, clinical tumour stage (cT), initial prostate-specific antigen density, percentage positive biopsy cores, and biopsy International Society of Urological Pathology grade group. SUV_max thresholds and model performance were investigated.

Key findings and limitations: A total of 293 patients underwent preoperative PSMA PET/CT, of whom 53 developed metastases after a median follow-up of 39 mo (interquartile range [IQR] 29-54). SUV_max was higher in participants who developed metastases at 2-yr follow-up than in those without metastases (median 8.8; IQR 7.1-16 vs 7.8; IQR 5.7-13; p = 0.015). An SUV_max of >10 was associated with an increased metastatic risk (hazard ratio [HR] 1.81; 95% confidence interval [CI] 1.04-3.13; p = 0.035) and log-SUV_max independently predicted metastases (HR 2.80; 95% CI 1.02-7.70; p = 0.046). The limitations include potential selection and detection biases due to selective follow-up imaging and nonstandardised treatment decisions.

Conclusions and clinical implications: In patients with primary prostate cancer, preoperative SUV_max is associated with metastatic progression after RARP. An SUV_max of >10 may aid in risk stratification for adverse outcomes.

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.