European urology oncology最新文献

Background and objective: Uptake of active surveillance for patients with Gleason grade group (GG) 2 prostate cancer (PCa) remains low. Magnetic resonance imaging (MRI) before biopsy would allow better patient selection, but there are no published data on this strategy. Our aim was to report one of the first European AS series of patients with GG 2 PCa selected via MRI before image-guided biopsy.

Methods: This multicenter study enrolled patients with GG 2 PCa managed with AS between 2016 and 2024 in ten reference centers in France, Spain, Italy, Switzerland, and Germany. Patients deemed unsuitable for curative treatment (ie, watchful waiting) were excluded. The primary endpoint was metastasis-free survival.

Key findings and limitations: A total of 139 patients with GG 2 PCa were included. Baseline MRI revealed a lesion with a Prostate Imaging-Reporting and Data System score of 4-5 in 81 patients (59%). Median event-free follow-up was 38 mo (interquartile range 20-63). Two cases of metastasis were observed, and there were no deaths due to PCa. The estimated 3-yr metastasis-free survival rate was 98.1% (95% confidence interval 95.5-100%). Overall, 56 patients underwent definitive treatment and 26 were reclassified as having GG 3 PCa during follow-up. Among the 28 patients who underwent radical prostatectomy, final pathology revealed adverse features (GG 3 and/or pT3a) in 13 cases (46%), but very aggressive disease (GG ≥4 and/or ≥pT3b and/or pN1) was noted in only two cases (7%). There were no statistically significant differences in outcomes between groups that did and did not meet the European Association of Urology inclusion criteria for AS (all log-rank tests p > 0.05).

Conclusions and clinical implications: In the era of prebiopsy MRI and image-guided biopsy, AS is a safe management option for selected patients with GG 2 PCa. Future studies should focus on redefining current inclusion criteria for AS in the targeted biopsy era, as many patients with GG 2 PCa are at low absolute risk of distant progression.

Background and objective: Patients with Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions are at a high risk of clinically significant prostate cancer (PCa), extracapsular extension, and biochemical recurrence (BCR) after local treatment. Managing these patients with active surveillance (AS) can be particularly challenging when targeted biopsies indicate favorable-risk tumors. This study aims to evaluate the outcomes of patients with PI-RADS 5 lesions managed with AS.

Methods: We analyzed data from 126 patients treated at 16 centers in France, Italy, Switzerland, and Belgium, whose initial magnetic resonance imaging revealed at least one PI-RADS 5 lesion and who subsequently underwent AS. The primary endpoint was BCR-free survival. The secondary endpoints included metastasis-free survival, time to biopsy grade reclassification, and time to AS discontinuation, along with their predictors.

Key findings and limitations: After a median follow-up of 36 mo after confirmatory biopsies (95% confidence interval [CI] 23-55), BCR was observed in five patients, with the median time not reached. The 5-yr BCR-free survival rate was 88% (95% CI 79-99%). No metastatic progression was reported. Seventeen patients experienced biopsy grade reclassification (median time not reached), and 55 patients discontinued AS. The median time to AS discontinuation was 55 mo (95% CI 46 mo-not applicable). The 5-yr AS discontinuation-free survival rate was 41% (95% CI 30.8-54.6%). On a multivariate Cox regression analysis, baseline prostate-specific antigen density and the percentage of positive biopsy cores were associated with biopsy grade reclassification, AS discontinuation, and BCR.

Conclusions and clinical implications: With strict monitoring, AS is a safe management option for patients with PI-RADS 5 lesions and favorable-risk PCa. Limitations are mainly inherent to the retrospective design of this study.

Background and objective: Conventional core needle biopsy for prostate cancer diagnosis can lead to diagnostic uncertainty and complications, prompting exploration of alternative risk assessment approaches that use clinical and imaging features. Our aim was to evaluate the effectiveness of machine learning (ML) models in reducing unnecessary biopsies.

Methods: We conducted a retrospective analysis of data for 1884 patients across two academic centers who underwent prostate magnetic resonance imaging and biopsy between 2016 and 2020 or 2004 and 2011. Twelve ML models were assessed for prediction of clinically significant prostate cancer (csPCa; Gleason grade group ≥2) using combinations of clinical features, including patient age, prostate-specific antigen level and density, Prostate Imaging-Reporting and Data System/Likert score, lesion volume, and gland volume. The models were trained and validated using a tenfold split for intrasite, intersite, and combined-site data sets. Model effectiveness was evaluated using the area under the receiver operating characteristic curve and decision curve analysis.

Key findings and limitations: The best-performing ML model would reduce the number of biopsies by 13.07% at a false-negative rate of 1.91%. Performance was consistent across sites, although the study is limited by the small number of centers and the absence of specific clinical data.

Conclusions and clinical implications: ML-enhanced clinical models provide an effective and generalizable approach for prediction of csPCa using standard clinical data. These models allow personalized risk assessment and follow-up, support clinical decision-making, and improve workflow efficiency.

Patient summary: Models that are enhanced by machine learning can predict the severity of prostate cancer and help doctors in tailoring treatments for individual patients. This approach can simplify health care decisions and improve clinical efficiency.

Background and objective: Management of metastatic renal cell carcinoma (mRCC) remains complex despite clinical guidelines. The aim of this Delphi study was to achieve consensus among RCC experts on the definition, diagnosis, and first-line treatments for mRCC.

Methods: Between May 2023 and April 2024, 14 experts from ten European countries completed two Delphi rounds of a 51-item questionnaire covering four topics: (1) oligometastatic RCC; (2) first-line treatment for metastatic clear-cell RCC; (3) treatment duration for metastatic clear-cell RCC; and (4) treatment of non-clear-cell RCC. Agreement was scored as absent/poor (<50%), fair (50-74%), or consensus (≥75%).

Key findings and limitations: Consensus was reached for 12 of 51 items (24%) in the first round and 25 of 49 items (51%) by the study end. Notably, 79% of experts defined oligometastatic RCC as five or fewer metastases and agreed that it typically does not require immediate systemic treatment. All experts (100%) emphasized the importance of clinical performance status in guiding treatment for metastatic clear-cell RCC, with 86% agreeing on additional factors such as International Society of Urological Pathology grade and sarcomatoid features. Nivolumab plus cabozantinib was favored for patients with brain or bone metastases (93% and 86% agreement, respectively), while there was fair agreement on pembrolizumab plus lenvatinib for patients with liver metastases. In addition, 71% supported stopping immune checkpoint inhibitors after 2 yr, while 86% agreed on the undefined duration of tyrosine kinase inhibitor therapy.

Conclusions and clinical implications: This Delphi study offers insights into mRCC management, and highlights the importance of multidisciplinary discussions for this challenging disease.

Background and objective: For inoperable patients, stereotactic body radiation therapy (SBRT) is a noninvasive treatment approach for primary renal cell carcinoma (RCC). We aimed to evaluate local control (LC) of primary RCC treated with SBRT.

Methods: This multicenter retrospective study involved 16 centers in Australia, France, Italy, and the Netherlands. The primary endpoint was the LC probability, and the secondary endpoints were progression-free survival, overall survival (OS), cumulative incidence of cancer-related deaths, toxicities, and renal function evolution after SBRT.

Key findings and limitations: A total of 144 patients, treated between 2008 and 2020, with a median follow-up of 43 mo (interquartile range [IQR], 24.0-81.2), were included. The median age was 76 yr (IQR, 67.0-82.0) and the median tumor size was 4.4 cm (IQR, 3.3-5.6). The median baseline estimated glomerular filtration rate (eGFR) was 60 ml/min/1.73 m². Of the patients, 40% had mild to moderate eGFR (30-60 ml/min). The two main treatment regimens were 42 Gy in three fractions and 26 Gy in one fraction. The LC probability was 98% at 1 yr (95% confidence interval [CI], 94-99) and 96% (95% CI, 92-99) at 5 yr. The median OS was 58 mo and the cumulative incidence of cancer-related deaths was 8% (95% CI, 3-15) at 5 yr. Seventy-one patients (49%) experienced at least one toxicity, including grade 1 in the majority (32%), grade 2 (14%), and grade 3 (1%). Two patients (1%) underwent dialysis (grade 4). The median eGFR loss was -7 ml/min (IQR, -17; 0) at the last follow-up.

Conclusions and clinical implications: This large series of primary RCC treated with SBRT demonstrates excellent LC and renal function preservation, and is associated with an acceptable toxicity profile. SBRT is an alternative treatment for inoperable patients.

Background and objective: The prostate-specific membrane antigen (PSMA) radioligand ¹⁷⁷Lu-PSMA-617 (LuPSMA) is approved for treatment of metastatic castration-resistant prostate cancer (mCRPC). PARP inhibitors (PARPi) are approved for patients with mCRPC and mutations in homologous recombination repair (HRR) pathway genes. Both modalities induce DNA damage and therefore may share mechanisms of resistance. We investigated whether PARPi exposure would reduce the subsequent efficacy of LuPSMA.

Methods: This retrospective study included 100 patients with a PARPi-qualifying HRR alteration treated with LuPSMA. Clinical outcomes on LuPSMA, including PSA₅₀ response, PSA progression-free survival (PFS), and overall survival (OS), were compared between those who had not previously received PARPi (PARPi-N) and those who had (PARPi-T). Subgroup analyses were performed for the most frequent HRR alterations (BRCA2 and ATM).

Key findings and limitations: PSA₅₀ responses on LuPSMA were similar between PARPi-N (n = 47) and PARPi-T (n = 53), although PSA PFS was longer in the PARPi-N group (9.1 vs 4.8 mo; p = 0.037). Among patients with BRCA2 alterations, the PARPi-N group had a better PSA₅₀ response rate (89% vs 35%; p = 0.009), PSA PFS (14 vs 2.9 mo; p = 0.026), and OS (19 vs 5.3 mo; p = 0.10). PARPi exposure did not influence LuPSMA outcomes among patients with ATM alterations. Limitations include the retrospective design and differences in prior lines of therapy between the groups.

Conclusions and clinical implications: PARPi exposure is associated with inferior LuPSMA outcomes, particularly for patients with BRCA2 alterations. These findings suggest potential cross-resistance and underscore the need for prospective studies assessing the optimal sequencing of these agents.