Genomic Classifier Predicts Benefit From Adding Hormone Therapy to Salvage Prostate Radiation

Men who have undergone prostatectomy for prostate cancer may later develop a detectable or rising prostate-specific antigen, prompting salvage radiation therapy. A key challenge is determining who is most likely to benefit from adding hormone therapy. Tumor biology may help identify patients at greater risk of progression or distant metastases and guide treatment intensification. New findings suggest that genetic profiling could help tailor hormone therapy after surgery.

Researchers at NRG Oncology (Philadelphia, PA, USA) evaluated the Luminal B (LumB) molecular subtype using the PAM50 genomic classifier in the NRG-RTOG 0534 “SPPORT” clinical trial. PAM50 classified prostate tumors as either LumB or non-LumB. Because LumB tumors are generally associated with more aggressive disease and increased androgen receptor signaling, the researchers examined whether this subtype was linked to a different response to hormone therapy.

The SPPORT trial compared prostate-bed radiation alone with prostate-bed radiation plus short-term androgen deprivation therapy (STADT), and with prostate-bed radiation plus STADT and pelvic lymph-node radiation therapy. Researchers analyzed prostate tissue from 709 patients to determine whether LumB status was associated with treatment benefit. 

After accounting for other factors that could influence outcomes, LumB tumors were linked to a higher risk of disease progression and distant metastases. Patients with LumB tumors also derived greater benefit from adding STADT, with or without pelvic lymph-node radiation, 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. At 10 years, the absolute improvement in metastasis-free survival was 20% for LumB patients, compared with -3% for non-LumB patients. The analysis was published in the International Journal of Radiation OncologyBiologyPhysics and presented during the Clinical Trials Session of the 2026 American Society for Radiation Oncology Annual Meeting in Boston.

“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,” said Phuoc T. Tran, M.D., Ph.D., of the University of Texas MD Anderson Cancer Center and lead author of the SPPORT analysis.

“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,” added Tran. 

Related Links
NRG Oncology