Cardiovascular and Thromboembolic Events in Patients With Localized Prostate Cancer Receiving Intensified Neoadjuvant Androgen Deprivation: A Systematic Review and Meta-Analysis

• Published in: Clinical genitourinary cancer 2024-06, Vol.22 (3), p.102088-102088, Article 102088
• Main Authors: Felício de Campos, Eduardo, Xavier, Camila Bragança, Queiroz, Marcello Moro, Firmino Lima Júnior, Nildevande, Ilario, Eder Nisi, Coelho, Rafael Ferreira, Nahas, William Carlos, Bastos, Diogo Assed, Fontes Jardim, Denis Leonardo
• Format: Article
• Language: English
• Subjects: Androgen Antagonists - administration & dosage; Androgen Antagonists - adverse effects; Androgen Antagonists - therapeutic use; Androgen deprivation therapy; Cardiovascular Diseases - chemically induced; Cardiovascular Diseases - etiology; Cardiovascular toxicity; Clinical Trials, Phase II as Topic; Humans; Male; Neoadjuvant hormone therapy; Neoadjuvant Therapy - adverse effects; Postoperative Complications - epidemiology; Postoperative Complications - etiology; Prostatectomy - adverse effects; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Radical prostatectomy; Randomized Controlled Trials as Topic; Thromboembolic adverse events; Thromboembolism - chemically induced; Thromboembolism - etiology
• ISSN: 1558-7673; 1938-0682
• DOI: 10.1016/j.clgc.2024.102088

•Cardiovascular and thromboembolic adverse events of intense neoadjuvant hormone therapy are underreported in clinical trials.•We conducted a systematic review to evaluate the incidence of cardiovascular and thromboembolic events among patients with localized prostate cancer receiving neoadjuvant ARSIs prior to prostatectomy in prospective trials.•Our results corroborate the pre-clinical hypothesis of an increased risk of cardiovascular and thromboembolic adverse events associated with neoadjuvant hormone therapy following radical prostatectomy.•Relevant incidence of high-grade hypertension adverse events was observed, with significant increase in the proportion of events with the combination therapy. Several phase II trials have investigated neoadjuvant novel androgen receptor signaling inhibitors (ARSIs) in combination with androgen deprivation therapy (ADT) followed by radical prostatectomy (RP) in prostate cancer (PC) patients. However, data regarding complications of intense hormone therapy and surgical complications are scarce. Our objective was to evaluate the occurrence of cardiovascular (CV) and thromboembolic (TE) adverse events (AE) in patients with localized PC who have received intense neoadjuvant ADT followed by prostatectomy. A comprehensive search in MEDLINE, Embase, Scopus and conference abstracts was performed. The strategies were developed and applied for each electronic database on March 7th, 2023. Eligible studies included randomized and single-arm trials testing ARSIs prior to prostatectomy that adequately reported safety data regarding CV and TE AE, peri-operative complications, and mortality during therapy. Pooled incidence (PI) of AE with 95% confidence interval (95% CI) was estimated using a random effects model. Quality assessment and reporting followed Cochrane Collaboration Handbook and PRISMA guidelines. PROSPERO: CRD42022344104. Nine randomized controlled trials and three single-arm phase II trials were included, comprising 702 patients (702 patients for CV AE and 522 for perioperative complications). The neoadjuvant regimen was classified as monotherapy with ARSI (100 patients), combination therapy with ADT + ARSI (383 patients), or ADT + ARSI + ARSI (219 patients). The PI of TE within the perioperative interval was 4.2% (95% CI = 2.6%-6.6%, I2 = 0.0%, P = .65), and the PI for CV AE was 4.6% (95% CI = 3.1%-6.7%, I2 = 0.0%, P = .71). Seven deaths were reported, resulting in a PI of 2.2% (95% CI = 1.3%-3.8%, I2 = 0.0%, P = .99