European urology oncology最新文献

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.

The 2021 updated International Germ Cell Cancer Collaborative Group classification for seminomatous germ cell tumours confirmed and refined the original classification, introducing the notion that lactate dehydrogenase (LDH) elevation above 2.5 times the upper limit of normal separates the good-risk prognostic group into two distinct subgroups, with clearly inferior survival outcomes for the high-LDH subgroup. Validation of this prognostic factor has understandably opened the question of the optimal management for patients with high-LDH good-risk seminoma. In the absence of prospective evidence, guideline-recommended management options have not changed. However, there is evidence from the testicular cancer community that management trends might have been influenced by the poor prognosis associated with elevated LDH. The Testicular Cancer Guidelines Panel of the European Association of Urology has undertaken a global survey among oncologists and onco-urologists to document management trends and differences. PATIENT SUMMARY: Levels of an enzyme called LDH (lactate dehydrogenase) can differ among patients with testicular cancer that has good prognosis. Recent evidence shows worse outcomes for patients with higher LDH. This information should be used to update clinical guidelines and to tailor personalised treatment plans for these patients.

Background and objective: Recent randomized controlled trials have demonstrated the efficacy of five-fraction stereotactic body radiotherapy (5F-SBRT) for prostate cancer (PC), but there is no comparative evidence for fewer fractions. We compare outcomes of prostate two-fraction SBRT (2F-SBRT) and 5F-SBRT using prospective data for patients with intermediate-risk (IR) PC.

Methods: This meta-analysis of individual patient data evaluated IR-PC from four prospective trials of prostate SBRT (two trials each of 2F- and 5F-SBRT). The primary endpoint was the cumulative incidence of biochemical failure (BCF). Secondary endpoints included the cumulative incidence of distant metastases (DM) and patient-reported quality of life (QoL).

Key findings and limitations: Of the 199 patients meeting the eligibility criteria, 143 (72%) were in the 5F-SBRT group and 56 (28%) were in the 2F-SBRT group. Median follow-up was 9.4 years. There was no significant difference in BCF with a 5-year cumulative incidence of 3.6% (95% CI 0-8.6%) in the 2F-SBRT group and 6.0% (95% CI 1.8-10.2%) in the 5F-SBRT group (p = 0.73). There was no significant difference in DM incidence. We found no differences in acute and late urinary or bowel QoL. Limitations include the non-randomized comparison.

Conclusions and clinical implications: We report the first prospective comparison of prostate 2F-SBRT and 5F-SBRT. We found no significant difference in efficacy, or in urinary or bowel QoL. This meta-analysis further encourages the potential of 2F-SBRT to be a standard-of-care option for IR PC.