Many Men with Prostate Cancer May Not Need Long-Term Hormone Therapy, Large Study Finds

A major international study co-led by researchers at UCLA Health Jonsson Comprehensive Cancer Center has found that for most men with localized prostate cancer, extending hormone therapy (androgen deprivation therapy, or ADT) beyond 9 to 12 months provides little additional cancer protection—while increasing the risk of side effects and other health problems.

The findings of the study, supported in part by grants from the National Institutes of Health, were published in JAMA Oncology, suggest that many patients can safely receive shorter courses of ADT, with the ideal duration tailored to their individual risk. [1]

What Is ADT and Why Does Duration Matter?
Androgen deprivation therapy is a form of hormone treatment widely used alongside radiation therapy to slow the growth of prostate cancer by lowering testosterone levels. While ADT is effective at controlling cancer, it is associated with significant side effects, including bone and muscle loss, metabolic changes, and an increased risk of heart disease. Historically, treatment guidelines have varied, recommending anywhere from 4 to 36 months of ADT depending on cancer risk, but the optimal duration has remained unclear.

“Prostate cancer treatment should not be one-size-fits-all,” said Amar U. Kishan, MD, professor and executive vice chair of radiation oncology at UCLA and co-senior author of the study.

“These findings help doctors personalize therapy, balancing cancer control with potential side effects and other health risks,” Kishan added.

A Comprehensive Meta-Analysis
The research team conducted an individual patient data meta-analysis using the MARCAP Consortium*, combining data from 10,266 men enrolled in 13 international phase 3 clinical trials. Men in the study had received definitive radiotherapy with or without ADT, and were followed for a median of more than 11 years.

By systematically analyzing outcomes—including overall survival, cancer-specific survival, development of metastasis, and deaths from other causes—the investigators compared the benefits and risks associated with different durations of ADT.

Key Findings: Most Benefit Happens Early
The study found that most of the benefit from ADT is achieved within the first 9 to 12 months of therapy. Prolonging hormone treatment beyond this window brought only modest additional reductions in prostate cancer recurrence or death, but led to a steady increase in the risk of dying from other causes, such as cardiovascular or metabolic complications.

Risk-Based Recommendations:

• Low-Risk Patients: May not need ADT at all.
• Intermediate-Risk Patients: Most benefit from 6 to 12 months of ADT. Those with a single intermediate-risk factor may not require ADT, while those with two or more should consider 6–12 months.
• High-Risk Patients: Benefit plateaus at around 12 months of ADT. Longer therapy may not provide much additional protection.
• Very High-Risk Patients: May require longer durations, as the benefit from extended ADT remains undefined in this group.

The analysis revealed a nonlinear relationship: while increasing ADT duration initially improves outcomes, the gains diminish over time, and the risks of side effects continue to accumulate.

Why Does This Matter?

These results have immediate implications for how prostate cancer is managed:

• Personalized Care: Physicians can now tailor ADT duration based on a patient’s risk, overall health, age, and personal preferences, rather than following blanket recommendations.
• Reduced Side Effects: Shorter hormone therapy means fewer long-term complications, including bone thinning, muscle loss, fatigue, sexual dysfunction, and heart problems.
• Better Quality of Life: Avoiding unnecessarily prolonged ADT can help men maintain better overall health during and after cancer treatment.

“Shorter courses of hormone therapy may be sufficient for many patients, reducing side effects while maintaining effectiveness,” the authors concluded.

Study Details and Impact

• Population: 10,266 men (median age 70) with localized prostate cancer
• Design: Meta-analysis of 13 randomized controlled trials from 1980 to 2020
• Follow-Up: Median of 11.3 years
• Outcomes Measured: Overall survival, cancer-specific mortality, distant metastasis, other-cause mortality

Results showed that for men with one intermediate-risk factor, ADT was not necessary to prevent distant metastases at 10 years. For those with two or more intermediate-risk factors, 6 months was optimal, and for high-risk patients, 12 months was optimal. Extending ADT beyond these durations yielded diminishing returns for cancer control but increased other-cause mortality.

Clinical Implications: A Shift in Guidelines
The current study challenges the prevailing ‘longer is better’ approach and supports a more nuanced, risk-adapted strategy. Not only can many men avoid the burden of extended hormone therapy, but oncologists now have stronger evidence to support personalized recommendations.

“Physicians can use these findings to make more informed decisions about ADT duration, improving both the safety and quality of life for their patients,” Kishan said.

Looking Ahead
These findings underscore the importance of individualized treatment plans for prostate cancer. Men and their doctors now have new tools to weigh the benefits and risks of hormone therapy, aiming for the shortest effective duration based on personal and disease factors.

For men facing a diagnosis of localized prostate cancer, this research offers hope for effective cancer control with fewer side effects—marking a significant advance in the ongoing effort to improve both survival and quality of life.
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Note:* The MARCAP (Meta-Analysis of Randomized trials in Cancer of the Prostate) Consortium is a premier international collaboration that gathers individual patient data from randomized clinical trials to enhance treatment strategies for prostate cancer. Co-founded by Amar Kishan, MD and Daniel Spratt, MD it focuses on analyzing androgen deprivation therapy (ADT) and radiotherapy.

Reference
[1] Zaorsky NG, Sun Y, Nabid A, Zapatero A, Bolla M, Joseph D, Maingon P, Guerrero A, Gonzalez AA, San-Segundo CG, Cabeza Rodríguez MÁ, Sole JM, Olivé AP, Steigler A, Souhami L, Carrier N, Armstrong JG, Gillham C, Pisansky TM, Schipper M, Sandler HM, Efstathiou JA, Lawton C, de Reijke TM, Attard G, Roy S, Morgan SC, Malone S, Hall WA, Nguyen PL, Shoag JE, Vince RA Jr, Calaway A, Garcia JA, Barata PC, Mendiratta P, Brown JR, Valle L, Rettig M, Dess RT, Jackson WC, Martin T, Jia AY, Steinberg M, Romero T, Kishan AU, Spratt DE. Optimal Duration of Androgen Deprivation Therapy With Definitive Radiotherapy for Localized Prostate Cancer: A Meta-Analysis. JAMA Oncol. 2026 Jan 1;12(1):58-65. doi: 10.1001/jamaoncol.2025.4800. PMID: 41264309; PMCID: PMC12635924.

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