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Background: Combination of androgen deprivation therapy (ADT) with external beam radiation therapy (EBRT) is a standard of care for patients with intermediate-risk prostate cancer (PCa). However, 6 months of ADT generates multiple side effects impacting quality of life (QoL). Darolutamide (an androgen receptor targeting agent [ARTA]) is associated with low blood-brain barrier penetrance and less drug-drug interaction., Objective: To assess the efficacy of a combination of 6 months of darolutamide with EBRT to treat patients with unfavorable intermediate-risk PCa., Design, Setting, and Participants: The DARIUS trial is a multicenter randomized non comparative phase 2 trial, randomizing the 6-months darolutamide + EBRT arm versus 6-months ADT + EBRT in patients with unfavorable intermediate-risk PCa., Outcome Measurements and Statistical Analysis: The primary endpoint is a biological response defined as prostate-specific antigen ≤0.1 ng/ml at month six of darolutamide or ADT. The key secondary endpoints are biochemical recurrence-free survival, disease-free survival, safety, and QoL. Ancillary studies using radiomics and genomic classifier are planned. Sixty-two patients will be included., Results and Limitations: In this population of patients requiring ADT combined with EBRT, the use of an ARTA alone, such as darolutamide, may demonstrate antitumoral efficacy while minimizing toxicity and maintaining QoL. Limitations are mainly inherent to the open-label design of this study., Conclusions: Six months of darolutamide + EBRT compared with 6 months of ADT + EBRT may be efficient in terms of a biological response, avoiding toxicity and altered QoL attributable to ADT in patients with unfavorable intermediate-risk PCa., Patient Summary: The ongoing DARIUS clinical trial assesses short-term (6 months) darolutamide treatment in association with external beam radiation therapy in men with localized prostate cancer. The trial investigates whether single-agent darolutamide can improve the biological response while maintaining a favorable tolerability profile., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background and Objective: Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa. Current research focuses on the description and validation of novel predictive biomarkers to improve precision medicine in mPCa. Our aim was to systematically review the current evidence on liquid biopsy biomarkers for predicting treatment response in mPCa., Methods: We systematically searched Medline, Web of Science, and evidence-based websites for publications on circulating biomarkers in mPCa between March 2013 and February 2024 for review. Endpoints were: prediction of overall survival, biochemical or radiographic progression-free survival after treatment (chemotherapy, androgen deprivation therapy, androgen receptor pathway inhibitors [ARPIs], immunotherapy, or PARP inhibitors [PARPIs]). For each biomarker, the level of evidence (LOE) for clinical validity was attributed: LOE IA and IB, high level of evidence; LOE IIB and IIC, intermediate level; and LOE IIIC and LOE IV-VD, weak level., Key Findings and Limitations: The predictive value of each biomarker for the response to several therapies was evaluated in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). In patients with mCRPC, BRCA1/2 or ATM mutations predicted response to ARPIs (LOE IB) and PARPIs (LOE IIB), while AR-V7 transcripts or AR-V7 protein levels in circulating tumor cells (CTCs) predicted response to ARPIs and taxanes (LOE IB). CTC quantification predicted response to cabazitaxel, abiraterone, and radium-223 (LOE IIB), while TP53 alterations predicted response to 177 Lu prostate-specific membrane antigen radioligand treatment (LOE IIB). AR copy number in circulating tumor DNA before the first treatment line and before subsequent lines predicted response to docetaxel, cabazitaxel, and ARPIs (LOE IIB). In mHSPC, DNA damage in lymphocytes was predictive of the response to radium-223 (LOE IIB)., Conclusions and Clinical Implications: BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies., Patient Summary: We reviewed studies assessing the value of biomarkers in blood or urine for management of metastatic prostate cancer. The evidence indicates that some biomarkers could help in selecting patients eligible for specific treatments., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background and Objective: The role of anatomical factors in predicting outcomes after radical prostatectomy (RP) remains unclear. This review aims to evaluate the impact of various anatomical factors on the perioperative outcomes of patients undergoing RP for localized prostate cancer (PCa)., Methods: A comprehensive literature search was conducted through January 2024 using the PubMed/Medline, Embase, and Web of Science databases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed to identify eligible studies. Data were extracted and pooled for a meta-analysis, with outcomes including operative time, blood loss, transfusion rates, overall complications, and positive surgical margins (PSMs). Heterogeneity was assessed using Cochrane Q test, and subgroup analyses were conducted to explore the influence of surgical approach., Key Findings and Limitations: A total of 91 studies met our inclusion criteria. Among the anatomical factors, prostate volume (PV), prostate weight, and median lobe (ML) were suitable for the meta-analysis. Larger prostates were associated with increased operative time, blood loss, and complication rates, but with fewer PSMs (all p < 0.05). ML presence was not associated with a higher risk of complications. Heterogeneity was high across studies (Cochrane Q tests <0.05), reflecting inconsistent definitions and methods. In subgroup analyses, the open approach was associated with a longer operative time than robotic surgery for large prostates (p = 0.03) and a lower PSM rate (p < 0.001)., Conclusions and Clinical Implications: Anatomical factors, particularly PV, play a significant role in RP outcomes. Larger prostates are associated with higher complication rates but fewer PSMs. Further research with standardized outcome measures is necessary to clarify these relationships and guide clinical decision-making., Patient Summary: In this study, we examined how a patient's individual anatomy might affect the results of prostate surgery for cancer. We found that larger prostates tend to lead to longer surgeries and increased blood loss, but these also have a lower risk of leaving cancer cells behind. These findings could help doctors in better planning surgeries and improving patient outcomes., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: High-risk prostate cancer (PCa) patients frequently experience recurrence and progression after radical prostatectomy (RP). Neoadjuvant androgen deprivation therapy (ADT) has not demonstrated a clear oncological benefit and is not currently recommended., Objective: The SUGAR trial is the first phase 2, randomised, controlled, multicentre, noncommercial, open-label study investigating single-agent perioperative darolutamide compared with the standard of care (ie, upfront RP, without neoadjuvant ADT)., Design, Setting, and Participants: SUGAR aims to randomise 240 men affected by nonmetastatic PCa, with the major eligibility criteria being International Society of Urological Pathology grade group ≥4, seminal vesicle invasion at magnetic resonance imaging and/or clinically node-positive disease. Patients in the experimental arm will undergo neoadjuvant darolutamide monotherapy, RP, and adjuvant darolutamide, completing 9 mo of treatment., Outcome Measurements and Statistical Analysis: The primary endpoint is noncurable recurrence-free survival, an innovative and clinically meaningful measure; the secondary endpoints encompass safety; recurrence-free, metastasis-free, and overall survival; pathological response; and quality of life. A predictive biomarker analysis will also be performed., Results and Limitations: Initial data suggest that intensified neoadjuvant treatment with androgen receptor signalling inhibitors (ARSIs) is associated with a sustained pathological response and may improve outcomes, via tumour downstaging and micrometastasis eradication. ARSI monotherapy could further enhance tolerability., Conclusions: SUGAR will provide efficacy and safety information on perioperative darolutamide monotherapy compared with upfront RP, in a contemporary high-risk PCa population undergoing surgery., Patient Summary: The on-going SUGAR clinical trial evaluates 9 mo of darolutamide treatment in addition to radical prostatectomy, in men affected by prostate cancer with specific high-risk characteristics. It investigates whether this hormonal treatment can lower the rates of noncurable recurrences, maintaining a favourable tolerability profile., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: In the current era of immune checkpoint inhibitors (ICIs), the role and optimal timing of a nephrectomy in patients with metastatic renal cell carcinoma (mRCC) remain unknown., Objective: To assess the oncological outcomes of patients who responded to ICI-based treatments and were subsequently treated with a delayed nephrectomy., Design, Setting, and Participants: This national retrospective evaluation included 30 patients with mRCC who underwent a nephrectomy after a complete response (CR) or a major partial response (>80%) to ICI treatment at metastatic sites., Intervention: Partial or radical nephrectomy after a favorable response to ICI treatment., Outcome Measurements and Statistical Analysis: Disease-free survival (DFS), progression-free survival (PFS), overall survival (OS), and potential discontinuation of systemic treatment were assessed., Results and Limitations: ICI-based treatments included ipilimumab-nivolumab (40%), ICI + tyrosine kinase inhibitor (10%), and nivolumab (50%). A delayed nephrectomy was performed after a median ICI treatment duration of 10 mo. In 19 cases (63.3%), surgeons faced difficulties due to adhesions or inflammatory changes. A complete pathological response was observed in 16.7% of patients. After a median follow-up of 19.5 mo after nephrectomy, 76.7% of patients achieved DFS. At 1 yr, 66.7% of patients were free from systemic treatment. The PFS and OS rates were, respectively, 96.7% and 100% at 1 yr, and 78.3% and 86.1% at 2 yr. Patients with a CR at metastatic sites had a better prognosis than those with a major partial response, in terms of DFS (p = 0.022) and PFS (p = 0.014)., Conclusions: Despite potentially challenging surgery, a delayed nephrectomy for patients who responded to ICI treatment provided promising oncological outcomes, and the majority of patients could discontinue systemic treatment., Patient Summary: In this study, we evaluated the clinical outcome in patients who responded well to immunotherapy, and subsequently underwent kidney ablation surgery. Three-quarters of patients experienced no recurrence, and in most cases, medical treatment could be discontinued., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Previous reports have shown an association between vasectomy and prostate cancer (PCa). However, there exist significant discrepancies between studies and systematic reviews due to a lack of strong causal association and residual confounding factors such as prostate-specific antigen (PSA) screening., Objective: To assess the association between vasectomy and PCa, in both unadjusted and PSA screen-adjusted studies., Evidence Acquisition: We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The PubMed, Scopus, and Web of Science databases were searched in January 2022 for studies that analyzed the association between vasectomy and PCa., Evidence Synthesis: A total of 37 studies including 16 931 805 patients met our inclusion criteria. A pooled analysis from all studies showed a significant association between vasectomy and any-grade PCa (odds ratio [OR] 1.23; 95% confidence interval [CI], 1.10-1.37; p  < 0.001; I 2  = 96%), localized PCa (OR 1.08; 95% CI, 1.06-1.11; p  < 0.00001; I 2  = 31%), or advanced PCa (OR 1.07; 95% CI, 1.02-1.13; p  = 0.006; I 2  = 0%). The association with PCa remained significant when the analyses were restricted to studies with a low risk of bias (OR 1.06; 95% CI, 1.02-1.10; p  = 0.02; I 2  = 48%) or cohort studies (OR 1.09; 95% CI, 1.04-1.13; p  < 0.0001; I 2  = 64%). Among studies adjusted for PSA screening, the association with localized PCa (OR 1.06; 95% CI, 1.03-1.09; p  < 0.001; I 2  = 0%) remained significant. Conversely, vasectomy was no longer associated with localized high-grade ( p  = 0.19), advanced ( p  = 0.22), and lethal ( p  = 0.42) PCa., Conclusions: Our meta-analysis found an association between vasectomy and any, mainly localized, PCa. However, the effect estimates of the association were increasingly close to null when examining studies of robust design and high quality. On exploratory analyses including studies, which adjusted for PSA screening, the association for aggressive and/or advanced PCa diminished., Patient Summary: In this study, we found an association between vasectomy and the risk of developing localized prostate cancer without being able to determine whether the procedure leads to a higher prostate cancer incidence., (© 2022 The Author(s).)

There are no countrywide data regarding the utilization of same-day-discharge (SDD) surgery for robot-assisted radical prostatectomy (RARP). We aimed to evaluate the annual number of SDD RARP procedures in France and to compare postoperative outcomes in SDD versus non-SDD centers. Data for all 9651 patients undergoing RARP in France in 2020 were extracted from the central database of the national healthcare system. Endpoints were length of hospital stay, patient age, center volume, lymph node dissection, and the hospital readmission rate. Overall, 184 SDD cases (1.9%) were reported in 14.2% of RARP centers. The annual RARP and SDD RARP caseload ranged from 41 to 485, and from one to 47, respectively, in SDD centers. SDD was significantly associated with higher-volume centers ( p < 0.001). No difference in readmission rate (7.9% vs 5.1%; p = 0.141) was observed for SDD versus non-SDD centers. Direct stay costs were estimated at €1457 in SDD centers compared to €2021 in non-SDD centers. The main limitation is the lack of detailed patient characteristics and readmission causes. This annual nationwide analysis suggests that SDD RARP remains infrequently used in routine practice in France despite being associated with comparable short-term outcomes after RARP and potential cost benefits., Patient Summary: We evaluated the use of robot-assisted removal of the prostate (RARP) with same-day hospital discharge in France for men with prostate cancer. In 2020, only 1.9% of the 9651 RARP procedures involved same-day discharge, even though the data show that this approach has lower costs and comparable safety., (© 2021 The Author(s).)

The evolution in the past decade of recommendations for prostate cancer (PCa) management, from screening to surgical treatment, may have affected the radical prostatectomy (RP) landscape. However, comprehensive data at a national level remain scarce. We extracted 5-yr data for RP patients in France from the central database of the national health care system. The primary endpoints were surgical approach (open [ORP], laparoscopic [LRP], and robot-assisted RP [RARP]), length of stay (LOS), and complication and readmission rates. The annual number of RPs was stable during the study period. The proportion of RARPs increased from 39.8% in 2015 to 52.6% in 2019, whereas the proportion of ORPs decreased from 34.4% to 24.5%. LOS continuously decreased over time irrespective of the surgical approach. The proportion of centres in the highest quartile of hospital volume increased from 22.0% to 28.3% ( p  = 0.006). LOS and complication and readmission rates were significantly lower ( p  < 0.001) in the LRP cohort at each time point. National trends confirmed that RARP progressively replaced ORP, with a stable number of annual RPs over time. Greater centralisation and better early postoperative outcomes were observed with laparoscopy., Patient Summary: We reviewed French data for patients undergoing removal of the prostate for prostate cancer between 2015 and 2019. We found that robot-assisted minimally invasive surgery has increased over time and the length of hospital stays has decreased. Rates of complications and readmission were lower with minimally invasive surgery., (© 2021 The Author(s).)