Early Versus Delayed Androgen Deprivation Therapy for Biochemical Recurrence After Local Curative Treatment in Non-Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review of the Literature
Muneeb Uddin Karim, Steven Tisseverasinghe, Rodrigo Cartes, Constanza Martínez, Boris Bahoric, Tamim Niazi
Abstract
BACKGROUND: The ideal timing of androgen deprivation therapy (ADT) for patients with biochemical recurrence (BCR) of prostate cancer (PCa) remains controversial due to its side effects and uncertain impact on survival outcomes. METHODS: We performed a review of the current literature by comprehensively searching the PubMed, Embase, and Cochrane databases to determine the optimal timing of ADT initiation after biochemical recurrence. We selected 26 studies including systematic reviews, randomized controlled trials (RCTs), and retrospective studies, while also reviewing practice guidelines. RESULTS: Not all patients with BCR cancer experience clinical or radiological progression. While early ADT may delay progression, evidence of its effect on PCa-specific mortality remains inconclusive. The PSA thresholds for initiating ADT vary, complicating decision-making. Key predictors of progression include a short PSA doubling time (PSADT), a high Gleason score (GS), and a brief interval to BCR of PCa post-radiotherapy (RT). Combining ADT with androgen receptor pathway inhibitors (ARPIs) has been shown to improve metastasis-free survival in high-risk patients. CONCLUSION: The ideal timing of ADT initiation in BCR PCa remains uncertain. Early ADT can help control the progression, but its effect on PCa-specific mortality is unclear. Stratifying patients by their risk factors, such as their PSADT, GS, and time to BCR can guide individualized treatment. In high-risk patients, delaying ADT should be avoided, while combining ADT with an androgen receptor pathway inhibitor (ARPI) may further improve outcomes.