Prostate cancer biology helps identify hormone therapy candidates

A recent analysis of the NRG-RTOG 0534 "SPPORT" clinical trial evaluated the Luminal B (LumB) molecular subtype using the PAM50 genomic classifier to determine whether tumor biology could help identify patients most likely to benefit from hormone therapy. The analysis found that adding short-term androgen deprivation therapy (STADT), with or without pelvic lymph-node radiation therapy, provided a greater benefit in freedom from progression and metastasis-free survival among men with LumB tumors compared with those whose tumors were not classified as LumB.

LumB prostate cancers are generally associated with more aggressive disease and increased androgen receptor signaling, leading researchers to hypothesize that these tumors may be particularly responsive to hormone therapy. The SPPORT trial compared radiation to the prostate bed alone with radiation plus STADT and radiation plus STADT and pelvic lymph-node radiation in men who required salvage radiation therapy following a detectable or rising PSA after prostatectomy. These results were presented during the Clinical Trials Session of the 2026 American Society for Radiation Oncology Annual Meeting in Boston, Massachusetts.

These findings suggest that the biology of a patient's prostate cancer may help us better determine who is most likely to benefit from adding hormone therapy to salvage radiation. Future research should focus on validating PAM50 as a predictive biomarker and determining whether molecular testing can help us personalize treatment-identifying patients who may benefit from more intensive therapy while sparing others from treatment and its potential side effects when it is unlikely to provide meaningful benefit."

Phuoc T. Tran, MD, PhD, University of Texas MD Anderson Cancer Center and lead author of the SPPORT analysis

Researchers analyzed prostate tissue from 709 patients using PAM50 to determine whether tumors were Luminal B (LumB) or non-LumB. After accounting for other factors that could affect outcomes, LumB tumors were associated with a higher risk of disease progression and distant metastases. Importantly, adding short-term androgen deprivation therapy (STADT), with or without pelvic lymph-node radiation, to prostate-bed radiation provided a greater benefit for patients with LumB tumors than those with non-LumB tumors. At five years, the absolute improvement in freedom from progression was 31% for LumB patients compared with 10% for non-LumB patients (p=0.01), while the 10-year absolute improvement in metastasis-free survival was 20% compared with -3%, respectively (p=0.05).

This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), and U24CA196067 (NRG Specimen Bank) from the National Cancer Institute (NCI), part of National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.