A meta-analysis involving more than 6000 men suggested that adding hormone therapy (HT) to radiation after radical prostatectomy improves overall survival (OS) in those with higher pre-radiation prostate-specific antigen (PSA) levels.

This finding seemed to hold whether men received radiation as adjuvant therapy — about 20% of the study population — or for salvage after biochemical recurrence, which made up the remainder of the study participants.

Adding HT to definitive radiotherapy is known to improve OS in localized prostate cancer, but it hasn’t been clear if it does the same when added to radiotherapy after prostatectomy.

Methods and Results

The meta-analysis, dubbed POSEIDON, sought to resolve the issue by pooling individual patient-level data, including PSAs, from trials that pitted radiation alone vs with HT. Lead investigator Amar Kishan, MD, presented the findings at the American Society of Clinical Oncology Genitourinary Cancers Symposium 2026, which were also published in The Lancet.

The 6057 patients were followed for a median of 9 years. The majority had pathological Gleason scores of 7 and positive surgical margins. They were treated in the pre-PSMA PET era and were negative on conventional imaging.

In general, adding HT to postoperative radiotherapy (PORT) did not significantly improve OS (hazard ratio, 0.87; 95% CI, 0.76-1.01; P = .06). However, a trend toward improved OS emerged with increasing pre-radiation PSAs, reaching statistical significance when PSAs exceeded 0.5 ng/mL. Whether men had short (4-6 month) or long HT (24 months) didn’t seem to matter.

Patients who have particularly elevated pre-PORT PSA levels (> 1.6-2.0 ng/mL) appear to derive the greatest potential benefits from the addition of HT, the investigators concluded in The Lancet. 

Study Takeaways

Kishan, a radiation oncologist at the University of California, Los Angeles, advised on how he thinks his study findings should be used in practice.

“Who needs hormone therapy with postoperative radiation? Only patients with a pre-radiation PSA greater than 0.5 have an OS benefit. How long does hormone therapy need to be? For most patients, short-term hormone therapy is sufficient,” he said, at the meeting.

Kishan was aiming at a general rule based on a concern that many men with lower PSA values are overtreated with HT during salvage radiation, which carries the risk for cardiovascular and other potentially fatal complications unrelated to their tumor. 

When pressed by his audience, he acknowledged that in some cases, such as in young men, HT during salvage radiation might make sense.

“We can’t have a one-size-fits-all approach,” he said, but Kishan also noted that high-risk patients were only maybe 15% of the study population, so a general rule is still useful.

Even so, study discussant Bridget Koontz, MD, radiation oncologist at Advent Health, Orlando, was concerned about the outliers who could benefit.

“When a pre-radiation PSA was less than 0.51, there was no benefit from concurrent” androgen deprivation therapy (ADT), but “while not significant, there were cases with patients with certain high-risk features, such as very high Gleason grade or seminal vesicle involvement, which trended towards a benefit. And in the very young age group, they also suggested that there may be a benefit,” she noted.

“Not all patients need ADT as part of salvage postoperative radiotherapy,” but “it’s important that we use common sense in men who have high-risk features,” Koontz responded.

The majority of men treated with HT in the trials received ADT with gonadotropin-releasing hormone agonist medications, but some were treated with less potent androgen receptor antagonist monotherapies like bicalutamide. It was one of the study’s limitations in addition to, among others, the lack of modern PSMA PET staging.

The study was funded by the National Institutes of Health. Kishan reported numerous industry ties, including to Boston Scientific and Janssen. Koontz has ties to Rythera Therapeutics, Novartis, Sumitomo, and other companies.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com.