Duration of androgen deprivation with radiotherapy for high-risk or locally advanced prostate cancer: A network meta-analysis

Abstract

Objective: To evaluate various outcomes of different lengths of androgen deprivation therapy in high- and very-high-risk prostate cancer, we conducted a network meta-analysis of randomized trials. The treatment of high-risk PC comprises the use of radical radiotherapy associated with various durations of androgen deprivation therapy, with luteinizing hormone releasing hormone analogues initiated during or immediately before the beginning of radiation. Methods and Materials: This study followed the PRISMA extension statement to report network meta-analyses. We systematically searched online databases, including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, for all randomized trials published up to April 2022. The primary outcomes were overall survival, prostate cancer-specific mortality, and metastasis-free survival. Network meta-analyses were performed under a Bayesian framework using the “gemtc” package ( https://gemtc.drugis.org ). Results: The network meta-analysis included 12 studies (10 treatments) on overall survival outcomes. None of the arms showed superiority to radiotherapy alone with respect to overall deaths. Nine studies and 10 treatment arms had prostate cancer-specific mortality data. Overall, 36 months of adjuvant androgen deprivation therapy resulted in a better outcome than radiotherapy alone, three months of neoadjuvant androgen deprivation therapy, or 12 or 24 months of adjuvant androgen reprivation therapy, and it was the better treatment (73%) in terms of cancer mortality. Treatment involving luteinizing hormone releasing hormone analogues for 6 months before and during radiotherapy ranked the highest in reducing distant metastases (42%). Conclusions: We found that 36 months of adjuvant androgen deprivation therapy after radiotherapy was the optimal duration of endocrine treatment with regard to cancer mortality for high-risk and locally advanced prostate cancer.

Analysis of Clinical Trials and Review of Recent Advances in Therapy Decisions for Locally Advanced Prostate Cancer

“…Several drugs are available that target androgen receptor signaling, including enzalutamide, apalutamide, and darolutamide. These drugs have been shown to improve survival in patients with metastatic prostate cancer and are being studied in men with locally advanced disease, particularly in combination with radiation therapy [ 40 , 41 ], although the longer term effects on changes to muscle mass and adiposity are unknown [ 42 ].…”