European urology oncology最新文献

Prostate cancer can make men feel socially isolated, even from friends and family, leading to feelings of loneliness that negatively impact their health and quality of life. Group-based exercise shows promise in addressing the social, emotional, and physical needs of men with prostate cancer.

Background and objective: We conducted a prostate cancer (PC) survey to provide a better understanding of the patient journey, expectations, and attitudes related to treatment.

Methods: This large-scale digital survey of patients with localized or advanced PC from Germany, the UK, and the USA assessed their demographics, diagnosis, treatment history, perception of therapy, medical care team involvement, and health-related quality of life (HRQoL). The survey was designed and interpreted by a large multistakeholder group. Descriptive statistics were primarily used. Univariate and multivariate analyses of the impact on HRQoL by demographic and clinical factors, including disease and treatment history, were examined using simple and multiple linear regression analyses, respectively.

Key findings and limitations: Overall, 15 824 participants completed the survey and 14 812 reported their disease status (79.6% had localized and 20.4% had advanced PC). Across the three countries, there were similarities and differences in diagnosis, treatment patterns, and medical specialists involved. Diagnosis by routine screening was more common in Germany and the USA than in the UK. For localized disease, the most common treatment was prostatectomy in Germany and the USA, and radiotherapy in the UK. Hormone therapy was the most common treatment for advanced disease across countries. Overall, treatment satisfaction was high but decreased over time. Patients not on active treatment generally had negative perceptions of treatment types and their impact on HRQoL. Advanced disease and multiple comorbidities were identified as the predictors of worse HRQoL.

Conclusions and clinical implications: This study highlights differences in the PC patient journey in Germany, the UK, and the USA. HRQoL did not differ between countries but was affected by advanced disease status and comorbidity burden. A common approach to PC diagnosis, treatment practices, and guidelines could improve outcomes.

Background and objective: In men with prostate cancer, one-third of deaths occur before the age of 75 yr. There remains a need to characterize heritable and environmental risk factors for these early deaths. This study aims to improve risk stratification for early lethal outcomes among prostate cancer patients with genetic factors beyond family history and with modifiable factors.

Methods: This study included 966 prostate cancer patients, enriched for high-risk localized disease and with germline genetic data, in two prospective cohorts. Three genetic factors (family history of prostate cancer, polygenic risk score [PRS] in the top 20%, and rare variants in DNA repair genes) and a lifestyle score were examined for their association with early lethal (metastases/prostate cancer death before the age of 75 yr) compared with nonlethal cases using logistic regression and by calculating 10-yr lethal disease risks.

Key findings and limitations: In total, 289 lethal, including 77 early lethal, cases were observed (median age at the end follow-up: 84.3 yr). Early lethal cases had higher percentages of men with a family history (23% vs 15%), a high PRS (47% vs 36%), and rare variants (14% vs 7.8%). Having two or more genetic factors was strongly associated with increased odds of early lethal disease (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.8-7.0) and linked to higher 10-yr lethal disease risks in high-risk localized patients diagnosed before the age of 75 yr. Healthy men with none of the genetic factors had the lowest odds of early lethal disease (OR, 0.3: 95% CI, 0.1-0.7), compared with unhealthy men with any genetic factor. The pattterns were similar for early fatal disease. The study had limited data for more detailed analyses.

Conclusions and clinical implications: The combination of family history with rare variants, a PRS, and lifestyle factors may improve the identification of prostate cancer patients at risk of early lethal and fatal disease.

Background and objective: Stereotactic ablative radiotherapy (SAbR) has shown promise in controlling oligometastatic renal cell carcinoma (omRCC). Careful patient selection is critical, and yet the selection criteria remain unknown for patients who will not be harmed by delayed systemic therapy using SAbR. Here, we analyzed long-term follow-up of omRCC patients treated with SAbR to derive the predictors of survival benefit.

Methods: We retrospectively reviewed patients with up to five omRCC sites treated with sequential SAbR from November 2007 to July 2022. Overall survival (OS), progression-free survival (PFS), local control (LC), and toxicity were analyzed. The predictors of PFS were analyzed using a univariate analysis and a Cox proportional hazard (CPH) model-based machine learning approach.

Key findings and limitations: We analyzed 153 patients who underwent SAbR to 337 metastases with a median follow-up of 27 mo. The median OS and PFS were 61.3 and 32 mo, respectively. The rate of grade ≥3 toxicity was 1.3%, and the 3-yr rate of LC was 98%. Patients with bone and brain metastases had lower PFS on the univariate analysis. When compared with historical controls, the delayed-onset PFS with first-line systemic therapy in this cohort was not compromised. The CPH model found bone, brain, and number of metastases at diagnosis to be the predictors of PFS, with a C-index of 0.66 and 1-yr area under the curve of 0.68.

Conclusions and clinical implications: For selected patients, SAbR is effective in controlling omRCC for >2 yr and can delay systemic therapy without compromising patient outcome. Bone and brain metastases, as well as an increasing number of metastases are poor predictive factors for omRCC patients treated with sequential SAbR who may benefit from upfront systemic therapy. Prospective studies are required to verify these findings.

Inactivation of the VHL gene leads to HIF accumulation, angiogenesis, and genomic instability. In this phase 1b/2 study, we assessed the safety and antitumor activity of axitinib combined with talazoparib in treatment-refractory clear-cell renal cell carcinoma (ccRCC). Patients received escalating doses of talazoparib with a fixed standard dose of axitinib in a 3 + 3 design. This was followed by a dose expansion phase in a separate cohort. The primary endpoints were determination of the recommended phase 2 dose (RP2D) and the objective response rate. From 2020 to 2023, 23 patients with ccRCC were enrolled: 15 in the dose escalation cohort and eight in the dose expansion cohort. The RP2D was identified as talazoparib 1 mg daily with axitinib 5 mg twice daily. At the RP2D, 13/14 patients discontinued treatment because of disease progression. Median progression-free survival was 6.1 mo (95% confidence interval 3.5-8.4). Thirteen patients (56%) experienced at least one grade 3+ treatment-emergent adverse event (AE), while nine (39%) experienced at least one treatment-related grade ≥3 AE, of which diarrhea, nausea, and anemia were the most common. This is the first report on a VEGFR-targeted tyrosine kinase inhibitor combined with a PARP inhibitor for ccRCC. While our results demonstrate the safety of this strategy, the combination did not meet a predefined efficacy threshold for continued evaluation. This trial is registered on Clinicaltrials.gov as NCT04337970.

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.