Rescuing ADT and ARPI: Benefits from Toxicities

How to cite: Hahn AW. “Rescuing ADT and ARPI: Benefits from Toxicities.” February, 2026. Accessed Apr 2026. https://grandroundsinurology.com/rescuing-adt-and-arpi-benefits-from-toxicities/

Summary

Andrew W. Hahn, MD, Assistant Professor of Genitourinary Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, provides a structured approach to managing toxicities associated with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs), emphasizing attribution, dose modification, switching strategies, and selective de-intensification.

Testosterone suppression remains the backbone of prostate cancer treatment. In metastatic hormone-sensitive prostate cancer, ADT combined with an ARPI is the minimum standard of care, producing substantial reductions in disease progression and mortality risk. However, treatment intensification increases toxicity burden.

Dr. Hahn distinguishes class effects of ADT from agent-specific toxicities of ARPIs. ADT is associated with fatigue, hot flashes, metabolic syndrome, cardiovascular risk, bone loss, anemia, gynecomastia, and cognitive changes. ARPIs have distinct pharmacologic profiles and adverse event patterns. Abiraterone may cause mineralocorticoid excess and hepatotoxicity. Enzalutamide is associated with neurocognitive and musculoskeletal effects. Apalutamide commonly produces rash.

Management begins with evaluation for non-drug causes, followed by a short interruption of the ARPI to determine attribution. If symptoms resolve, dose reduction is considered. Recurrent toxicity may prompt switching to an alternative agent, including darolutamide. Persistent toxicity across agents may necessitate de-intensification of treatment.

Finite-duration therapy is presented as a strategy to mitigate long-term adverse effects, particularly cognitive impact. Testosterone recovery is described as a patient-centered outcome, with preference for relugolix when finite therapy is planned due to more rapid recovery compared with agonists. Early discontinuation of ADT near the end of planned combination radiation-based therapy may facilitate testosterone recovery, though prospective non-inferiority data are lacking.

ARPI monotherapy is discussed in selected contexts, including in patients with biochemical recurrence and frail older patients. As therapeutic intensification continues, attribution and management of adverse events will become increasingly complex.

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