When Not to Treat with Androgen Deprivation Therapy

Mary-Ellen Taplin, MD

How to cite: Taplin ME. “When Not to Treat With Androgen Deprivation Therapy.” Grand Rounds in Urology. February, 2026. Accessed Oct 2026. https://grandroundsinurology.com/when-not-to-treat-with-androgen-deprivation-therapy/

Summary

Mary-Ellen Taplin, MD, Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts, outlines clinical scenarios in which androgen deprivation therapy (ADT) may be deferred or avoided, emphasizing individualized decision-making based on disease risk, comorbidities, and patient goals.

In oligometastatic prostate cancer treated with stereotactic body radiation therapy, no large randomized trials define the role of concurrent ADT. The RADIOSA phase 2 trial of stereotactic body radiation therapy with or without six months of luteinizing hormone-releasing hormone agonist therapy demonstrated improved clinical progression-free survival with ADT, but the study was small and individualized decision-making remains appropriate, particularly for patients wishing to delay hormone therapy.

Dr. Taplin reviews the cumulative side effects of ADT, including fatigue, metabolic changes, cardiovascular risk, cognitive decline, mood disturbance, and functional deterioration. Baseline comorbidities such as cardiovascular disease, neurologic disorders, obesity, uncontrolled diabetes, depression, and anxiety may increase risk of life-altering decline.

Primary ADT for localized prostate cancer in patients not receiving surgery or radiation is not associated with improvement in all-cause or prostate cancer–specific mortality in retrospective data. Hormone therapy alone in this setting should be avoided.

In intermediate-risk localized disease treated with radiation, predictive modeling using the Artera artificial intelligence-enabled test may help identify patients who derive benefit from short-term ADT versus those who do not. Clinical features must still guide interpretation.

In the salvage radiation setting after prostatectomy, older randomized trials show mixed results. Benefit from ADT depends on prostate-specific antigen (PSA) level, Gleason score, time to recurrence, PSA doubling time, age, comorbidities, and patient preference.

For patients with rising PSA after all local therapy and favorable features, delayed initiation or intermittent ADT may be appropriate. Shared decision-making remains central except in high-volume metastatic disease.

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ABOUT THE AUTHOR

Mary-Ellen Taplin, MD

Mary-Ellen Taplin, MD, is the Chair of the Executive Committee for Clinical Research in the Dana-Farber Cancer Institute (DFCI) and a Professor of Medicine at Harvard University in Boston, Massachusetts. In her role as Chair of the Executive Committee Clinical Research, Dr. Taplin oversees DFCI clinical research operations and mentors DFCI investigators in the development of trials that have the potential to improve outcomes for cancer patients. Her research in prostate cancer has focused on androgen receptor changes in the evolution of hormone-refractory prostate cancer and clinical trials of novel hormone therapy and chemotherapy with correlative molecular endpoints.

About The Author

Mary-Ellen Taplin, MD

Mary-Ellen Taplin, MD, is the Chair of the Executive Committee for Clinical Research in the Dana-Farber Cancer Institute (DFCI) and a Professor of Medicine at Harvard University in Boston, Massachusetts. In her role as Chair of the Executive Committee Clinical Research, Dr. Taplin oversees DFCI clinical research operations and mentors DFCI investigators in the development of trials that have the potential to improve outcomes for cancer patients. Her research in prostate cancer has focused on androgen receptor changes in the evolution of hormone-refractory prostate cancer and clinical trials of novel hormone therapy and chemotherapy with correlative molecular endpoints. Dr. Taplin earned her medical degree from the University of Massachusetts in Worcester. She completed a residency in Internal Medicine, serving as Chief Resident, at the University of Massachusetts Medical Center. Dr. Taplin then completed a fellowship in Hematology-Oncology at Beth Israel Hospital and Harvard Medical School in Boston, Massachusetts. Before joining the Dana-Farber Cancer Institute, Dr. Taplin served as an Assistant and then Associate Professor of Medicine at the University of Massachusetts. Dr. Taplin’s background includes comprehensive training in clinical practice, clinical trials, and correlative tumor analyses. As an academic Genitourinary Oncologist, her research interests are concentrated on prostate cancer. She has focused on molecular analyses of androgen receptor (AR) and AR signaling in both localized high-risk and castration resistant prostate cancer (CRPC). Dr. Taplin created a valuable tumor bank of prostate cancer metastasis biopsies at Dana-Farber Cancer Institute. She is the DFCI site lead for the Prostate Cancer Clinical Trials Consortium. She co-led the DFCI Stand Up to Cancer prostate cancer dream team that discovered the importance of mutations in DNA repair pathway genes in prostate cancer. Dr. Taplin has been awarded several Prostate Cancer Foundation challenge grants for her work. She is currently the primary investigator of many trials, including PROTEUS, a phase 3 trial evaluating the intensity of androgen deprivation therapy in localized high-risk prostate cancer and trials evaluating EZH2 inhibitors and novel AR antagonists in metastatic CRPC.

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