Researchers from the UCLA Health Jonsson Comprehensive Cancer Center have conducted a groundbreaking study indicating that incorporating hormone therapy alongside radiotherapy following prostate surgery delivers minimal survival advantages for the majority of prostate cancer patients, particularly those exhibiting extremely low levels of prostate-specific antigen (PSA) prior to undergoing treatment. The investigation revealed that individuals with minimal PSA concentrations before starting radiotherapy experienced no enhancements in overall survival, regardless of whether the hormone therapy was administered for a short duration or extended over a longer period. Conversely, patients presenting with elevated PSA levels prior to radiation treatment demonstrated slight gains in both survival rates and metastasis-free survival, implying that hormone therapy could prove advantageous mainly for this subgroup at higher risk.
These findings were recently published in The Lancet and showcased by Dr. Amar Kishan, who serves as a professor and executive vice chair in the Department of Radiation Oncology at UCLA’s David Geffen School of Medicine, during the plenary session at the American Society of Clinical Oncology Genitourinary Cancers Symposium held in San Francisco.
Understanding the Role of Hormone Therapy Post-Surgery
Hormone therapy functions by interfering with testosterone’s capacity to promote prostate cancer cell growth and facilitate tumor repair mechanisms. While previous research has demonstrated that combining this therapy with radiotherapy yields improved results in patients whose prostates remain intact, its efficacy in cases where radiotherapy follows surgical removal of the prostate has been a subject of ongoing debate, according to Kishan, the study’s lead author and co-director of the cancer molecular imaging, nanotechnology, and theranostics program at the UCLA Health Jonsson Comprehensive Cancer Center.
Furthermore, hormone therapy is associated with a range of substantial adverse effects, such as profound fatigue, hot flashes, sexual dysfunction, increased body weight, bone density reduction, and metabolic alterations that elevate the risk of cardiovascular issues. The study’s results indicate that for the majority of men who have undergone prostatectomy and subsequently show detectable yet low PSA levels (less than 0.5 ng/mL), radiotherapy alone post-surgery is exceptionally effective. This allows clinicians to confidently forgo hormone therapy in these cases, thereby avoiding several months of potentially debilitating treatment that fails to prolong life expectancy but could significantly diminish quality of life.
MARCAP Consortium: A Comprehensive Meta-Analysis
In an effort to thoroughly evaluate the effects of hormone therapy in this specific clinical context, the research team performed an extensive individual patient-level meta-analysis utilizing data from the MARCAP Consortium. This international collaborative initiative, co-led by Kishan, focuses on assessing long-term outcomes from various randomized clinical trials.
The analysis incorporated information from 6,057 male participants across six randomized controlled trials. These trials compared outcomes between groups receiving postoperative radiotherapy by itself and those receiving radiotherapy in conjunction with either short-term hormone therapy (lasting 4 to 6 months) or long-term hormone therapy (extending to 24 months). By aggregating detailed individual patient data instead of depending on aggregated trial summaries, the investigators gained the ability to scrutinize outcomes with heightened precision, particularly exploring how PSA levels measured before radiation influenced the potential benefits of the added therapy.
Participants in the study were monitored for a median duration of nine years, providing robust data on long-term metrics including overall survival, freedom from metastasis, and recurrence rates. This extended follow-up period also facilitated direct head-to-head comparisons between short-term and long-term hormone therapy regimens to ascertain if prolonging the treatment duration led to superior results.
Key Findings on Survival and PSA Levels
Overall, the data showed that 83.6% of men treated with postoperative radiotherapy alone remained alive at the 10-year mark, a figure nearly identical to the 84.3% survival rate observed among those who also received hormone therapy in addition to radiotherapy.
A pivotal factor emerged from the analysis: pre-radiotherapy PSA levels, which quantify prostate-specific antigen in the bloodstream following prostate removal surgery. For men with low PSA readings (≤0.5 ng/mL) before radiotherapy, the addition of hormone therapy conferred no discernible advantages. On the other hand, those with higher PSA concentrations exhibited modest enhancements in survival outcomes, reinforcing the notion that hormone therapy’s value is primarily reserved for patients with more pronounced biochemical recurrence indicators.
The duration of hormone therapy was another aspect under scrutiny. Short-term administration failed to yield improvements in overall survival, although it was associated with a minor decrease in the likelihood of cancer metastasis. Long-term therapy, meanwhile, provided a subtle boost to survival, especially among men with higher post-prostatectomy PSA levels. Nonetheless, statistical modeling by the researchers indicated that prolonging short-term therapy into a long-term course did not yield additional survival benefits, despite a slight reduction in metastasis risk.
Toward Personalized Prostate Cancer Treatment
Our primary objective remains eradicating cancer while simultaneously minimizing patient harm, emphasized Kishan. This research advances the paradigm of personalized medicine in prostate cancer management. Through precise identification of patients who genuinely derive benefit from hormone therapy, healthcare providers can optimize treatment strategies, eliminate superfluous therapies, and prioritize enhancements in patients’ holistic health and well-being.
Leveraging these insights, current investigations are refining this precision medicine approach even further. For instance, initiatives like the BALANCE Trial are seeking to discover specific biomarkers that can more accurately predict which individuals post-surgery stand to gain the most from hormone therapy, thereby enabling even more customized and effective treatment protocols.
Additional contributors from UCLA include Tahmineh Romero Kalbasi, Dr. Michael Steinberg, Dr. Luca Valle, Dr. Kekoa Taparra, Dr. Matthew Rettig, Dr. Adam Singer, Dr. Robert Reiter, Dr. Scott Eggener, Dr. Wayne Brisbane, and Dr. Nicholas Nickols.
The study, titled “Hormone therapy use and duration with postoperative radiotherapy for recurrent prostate cancer: an individual patient data meta-analysis,” appears in The Lancet (2026), with DOI: 10.1016/S0140-6736(26)00137-6.
