European urology oncology最新文献

Background and objective: Enzalutamide is a potent androgen receptor signalling inhibitor, effectively used for the treatment of different stages of prostate cancer. Side effects occur frequently at the registered dose, whilst a lower dose might be equally effective. Therefore, the aim of this study is to determine the effect of a reduced dose of enzalutamide on side effects in frail patients with prostate cancer.

Methods: This multicentre randomised trial compared the standard enzalutamide dose of 160 mg once daily (OD) with a reduced dose of 120 mg OD in frail patients with prostate cancer. Fatigue, cognitive side effects, and depressive symptoms were measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire, Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaire, and Geriatric Depression Scale-15 (GDS-15). Linear mixed-effect models were used to study differences in side effects over time between both groups.

Key findings and limitations: In total, 52 patients were included in the analysis (25 reduced dose and 27 standard dose). Patients treated with the reduced dose had significantly lower fatigue after 24 wk than those with the standard dose (difference FACIT-Fatigue 6.2; 95% confidence interval 1.4-11.0; p = 0.01). Patients treated with the reduced dose showed stable fatigue, cognitive side effects, and depressive symptoms over time, whilst patients with the standard dose showed significantly worse side effects after 24 wk than at baseline.

Conclusions and clinical implications: A reduced dose of enzalutamide results in less fatigue, cognitive side effects, and depressive symptoms in frail patients with prostate cancer than the standard dose, without any indication of interference with efficacy endpoints.

Patient summary: In this report, we looked at the side effects of enzalutamide at two dose levels. We found that, in frail patients, three tablets a day result in less fatigue than four tablets a day. Patients treated with four tablets a day showed an increase in fatigue, cognitive side effects, and depression. We conclude that a lower dose of three tablets can be used to alleviate side effects without indications for less efficacy.

Background and objective: A hilar location for a renal tumour is sometimes viewed as a limiting factor for safe partial nephrectomy. Our aim was to evaluate perioperative, oncological, and functional outcomes of robot-assisted partial nephrectomy (RAPN) for hilar tumours (RAPN-H) in comparison to RAPN for nonhilar tumours (RAPN-NH).

Methods: We conducted an observational, multicentre cohort study using prospectively collected data from the French Research Network on Kidney Cancer (UroCCR). The registry includes data for 3551 patients who underwent RAPN for localised or locally advanced renal masses between 2010 and 2023 in 29 hospitals in France. We studied the impact of a hilar location on surgery, postoperative renal function, tumour characteristics, and survival. We also compared rates of trifecta achievement (warm ischaemia time [WIT] <25 min, negative surgical margins, and no perioperative complications) between the groups. Finally, we performed a subgroup analysis of RAPN without vascular clamping. Variables were compared in univariable analysis and using multivariable linear, logistic, and Cox proportional-hazards models adjusted for relevant patient and tumour covariates.

Key findings and limitations: The analytical population included 3451 patients, of whom 2773 underwent RAPN-NH and 678 underwent RAPN-H. Longer WIT (β = 2.4 min; p < 0.01), longer operative time (β = 11.4 min; p < 0.01) and a higher risk of postoperative complications (odds ratio 1.33; p = 0.05) were observed in the hilar group. Blood loss, the perioperative transfusion rate, postoperative changes in the estimated glomerular filtration rate, and trifecta achievement rates were comparable between the groups (p > 0.05). At mean follow-up of 31.9 mo, there was no significant difference in recurrence-free survival (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.58-1.2; p = 0.3), cancer-specific survival (HR 1.1, 95% CI 0.48-2.6; p = 0.79), or overall survival (HR 0.89, 95% CI 0.52-1.53; p = 0.69).

Conclusions and clinical implications: Patient and tumour characteristics rather than just hilar location should be the main determinants of the optimal surgical strategy for hilar tumours.

Patient summary: We found that kidney tumours located close to major kidney blood vessels led to a longer operation and a higher risk of complications during robot-assisted surgery to remove the tumour. However, tumours in these locations were not related to a higher risk of kidney function loss, cancer recurrence, or death.

Urologists suffer from one of the highest rates of burnout, with negative effects for both physicians and patients. We share simple mindfulness-based strategies as invaluable tools for improving mental health, regulating physical and emotional responses to stressors, and strengthening resilience.

Background: The risk of early-onset and clinically aggressive prostate cancer is elevated in carriers of certain rare pathogenic germline mutations. The utility of augmenting traditional prostate-specific antigen (PSA)-based screening measures with multiparametric magnetic resonance imaging (MRI) in this population is not yet known.

Objective: To evaluate MRI-based screening in comparison with traditional PSA-based screening among individuals at an elevated genetic risk for prostate cancer.

Design, setting, and participants: Male germline carriers of pathogenic/likely pathogenic variants in any of 19 prostate cancer risk genes between the ages of 35 and 74 yr with no prior history of prostate cancer were recruited. Intervention Enrolled participants underwent screening with annual PSA, digital rectal examination (DRE), and triennial multiparametric MRI. Individuals with abnormal DRE, elevated age-adjusted PSA (>1.5 ng/ml for 35-49 yr, >2.0 ng/ml for 50-54 yr, and >3.0 ng/ml for 55-74 yr), or suspicious multiparametric MRI (Prostate Imaging Reporting and Data System [PI-RADS] ≥3 lesion) were offered prostate biopsy. Outcome measurements and statistical analysis Endpoints were diagnosis of any and clinically significant prostate cancer, and alternative screening strategies were compared by a decision curve analysis.

Results and limitations: To date, 101 males have completed the first round of screening. The greatest proportion of participants are carriers of BRCA2 (n = 44), BRCA1 (n = 35), and ATM (n = 7) variants. Twenty-one have undergone biopsy, resulting in the detection of nine cases of cancer (seven clinically significant). For the detection of clinically significant prostate cancer, abnormal MRI (PI-RADS ≥3) demonstrated 100% sensitivity (7/7) with a negative predictive value (NPV) of 100%, whereas PSA-based screening alone had 57% (4/7) sensitivity with an NPV of 73%. Of six screening strategies evaluated in the decision curve analysis, MRI-based screening alone achieved superior net benefit at all threshold probabilities compared with PSA screening-detecting one additional cancer case per 7.5 patients, while avoiding more unnecessary biopsies at the same threshold probability.

Conclusions: Disease prevalence is high among carriers of prostate cancer-associated pathogenic germline mutations. Early results suggest that MRI-based screening enhances early detection of clinically significant disease beyond PSA screening alone.

Patient summary: In this study, we present the interim results from the PROGRESS prostate cancer screening trial. We found that in certain germline carriers of prostate cancer risk mutations, magnetic resonance imaging-based screening enhances detection of prostate cancer while reducing biopsies triggered, in comparison with traditional prostate-specific antigen screening strategies.

Telemedicine, virtual conferences, and reducing waste in the operating room are ways in which urologists can reduce their environmental impact in daily practice. Patient counseling should also consider advice that simultaneously promotes overall, urological, and planetary health, such as plant-based diets and active transport.

Current standard-of-care systemic therapy options for locally advanced and metastatic bladder cancer (BC), which are predominantly based on cisplatin-gemcitabine combinations, are limited by significant treatment failure rates and frailty-based patient ineligibility. We previously addressed the urgent clinical need for better-tolerated BC therapeutic strategies using a drug screening approach, which identified outstanding antineoplastic activity of clofarabine in preclinical models of BC. To further assess clofarabine as a potential BC therapy component, we conducted head-to-head comparisons of responses to clofarabine versus gemcitabine in preclinical in vitro and in vivo models of BC, complemented by in silico analyses. In vitro data suggest a distinct correlation between the two antimetabolites, with higher cytotoxicity of gemcitabine, especially against several nonmalignant cell types, including keratinocytes and endothelial cells. Accordingly, tolerance of clofarabine (oral or intraperitoneal application) was distinctly better than for gemcitabine (intraperitoneal) in patient-derived xenograft models of BC. Clofarabine also exhibited distinctly superior anticancer efficacy, even at dosing regimens optimized for gemcitabine. Neither complete remission nor cure, both of which were observed with clofarabine, were achieved with any tolerable gemcitabine regimen. Taken together, our findings demonstrate that clofarabine has a better therapeutic window than gemcitabine, further emphasizing its potential as a candidate for drug repurposing in BC. PATIENT SUMMARY: We compared the anticancer activity of clofarabine, a drug used for treatment of leukemia but not bladder cancer, and gemcitabine, a drug currently used for chemotherapy against bladder cancer. Using cell cultures and mouse models, we found that clofarabine was better tolerated and more efficacious than gemcitabine, and even cured implanted tumors in mouse models. Our results suggest that clofarabine, alone or in combination schemes, might be superior to gemcitabine for the treatment of bladder cancer.