UH Seidman Cancer Researchers: What is the ideal duration of hormone therapy for the treatment of prostate cancer

• Researchers analyzed individual patient data from 13 randomized phase III trials, and learned the benefit of androgen deprivation therapy (ADT) increases in a non-linear fashion.
  
  
• While longer ADT durations improve cancer outcomes, they also increase risk of death from other causes. Thus, there is a plateau in the overall benefit, depending on ADT duration.
  
  
• Clinicians can now have more informed, patient-centered discussions that weigh absolute benefit, life expectancy, comorbidities, and patient preferences when selecting ADT duration.
  
  
• Replaces a "one-size-fits-all" approach with a personalized strategy that balances cancer control against treatment-related harm.
  
  
• Results published in JAMA Oncology.

CLEVELAND- Hormone therapy is commonly combined with radiation therapy for prostate cancer, but patients are often unsure how long it should be continued and why. A new study published in JAMA Oncologyfrom researchers at University Hospitals Seidman Cancertried to find the answer to that question.

First author and UH Seidman Cancer Center radiation oncologist Nicholas G Zaorsky, MD, MS (Vice Chair for Education, Department of Radiation Oncology, UH Cleveland Medical Center) said, "We set out to determine the optimal duration of ADT when combined with definitive radiotherapy for men with localized prostate cancer. Although ADT is known to improve survival, the ideal length of treatment has remained unclear because different trials used different durations, patient adherence was inconsistent and longer courses of ADT are associated with significant side effects."

This uncertainty makes it difficult for clinicians to balance maximizing cancer control with minimizing harm, making this an important and unresolved problem in prostate cancer care.

"We learned that the benefit of ADT increases in a nonlinear fashion. While longer durations improve cancer outcomes, the incremental benefit plateaus after approximately 9-12 months for high risk patients. Beyond this point, additional ADT provides diminishing cancer control while continuing to increase the risk of non-prostate cancer death," said senior author Daniel Spratt, MD, Vincent K. Smith Chair of Radiation Oncology, UH Seidman Cancer Center and Associate Chief Scientific Officer, UH Cleveland Medical Center. "Our study was the first of its kind to account for treatment compliance, as up to 50% of men on clinical trials prescribed long-term ADT stop early due to poor tolerability" says Dr. Spratt.

Optimal duration of ADT varies by disease risk:

• Patients with one intermediate-risk factor (a surrogate for favorable intermediate risk disease) often gain little benefit from ADT.
• Those with multiple intermediate-risk factors (a surrogate for unfavorable intermediate risk disease) benefit most from about 4-6 months. An ongoing clinical trial is using a DNA signature / genomic classifier to fine-tune this recommendation.
• High-risk patients benefit most from approximately 9-12 months. An ongoing clinical trial is using a genomic classifier to fine-tune this recommendation.

The significance of this work is that it replaces a "one-size-fits-all" approach with a personalized strategy that balances cancer control against treatment-related harm.

Many patients-particularly those with intermediate-risk disease and some with high-risk disease-can safely receive shorter courses of ADT (compared to those historically recommended in guidelines) without compromising cancer control. This reduces exposure to side effects such as cardiovascular disease, metabolic complications, bone loss, and fatigue, improving quality of life.

Clinicians can now have more informed, patient-centered discussions that weigh absolute benefit, life expectancy, comorbidities, and patient preferences when selecting ADT duration.

For complete study: https://jamanetwork.com/journals/jamaoncology/article-abstract/2841671