Adding hormone therapy to postprostatectomy radiotherapy may provide little survival benefit for most men with prostate cancer, especially those with very low prostate-specific antigen (PSA) levels before treatment. In the study, reported at the 2026 ASCO Genitourinary Cancers Symposium,¹ men with low PSA levels prior to postprostatectomy radiotherapy who received either short-term or long-term hormone therapy with radiotherapy derived no survival advantage over postprostatectomy radiotherapy alone. Those with higher pre-radiotherapy PSA levels did see some benefit, however, suggesting that adding hormones in this group might be worthwhile.

“Who needs hormone therapy with [postprostatectomy] radiotherapy for a survival benefit? Patients with a PSA level of more than 0.5 ng/mL prior to radiation. How long does hormone therapy need to be? For most patients, short-term hormone therapy—4 to 6 months—will suffice,” said Amar U. Kishan, MD, Professor and Executive Vice Chair of Radiation Oncology at the David Geffen School of Medicine at UCLA, at the symposium. The results were concurrently published in The Lancet.²

Amar U. Kishan, MD

As Dr. Kishan explained, hormone therapy can improve radiotherapy outcomes for men with intact prostates but whether it has similar benefit for men receiving radiotherapy after prostatectomy is unclear.Whereas this approach has improved endpoints that are based on biochemical progression, these outcomes are not surrogates for overall survival. Only one trial, RTOG 9601,³ demonstrated an overall survival benefit and it was a trial of late salvage.

“It’s important to quantify the overall survival benefit because hormone therapy is associated with significant adverse impacts on quality of life, cardiovascular function, metabolic status, musculoskeletal health, sexual function, and neurocognitive function,” Dr. Kishan said. “In fact, mounting evidence suggests that any potential cancer-specific benefit of adding hormone therapy can be offset by increasing other-cause mortality in patients who have nonaggressive disease.”

Aim of POSEIDON

To better understand the impact of hormone therapy in this setting—to understand “who needs hormone therapy with [postprostatectomy] radiotherapy and how long does it need to be,” as Dr. Kishan said—the researchers conducted a large-scale, individual patient-level meta-analysis that allows a more granular evaluation of potential interaction thresholds, nonlinear associations, and subgroup-specific effects. To this end, they launched the POSEIDON individual patient data (IPD) meta-analysis. The meta-analysis included all published randomized trials that drew data from the international MARCAP Consortium (Meta-Analysis of Randomised Trials in Cancer of the Prostate).⁴

Information was extracted for 6,057 patients with prostate cancer enrolled in six randomized trials comparing postprostatectomy radiotherapy alone to radiotherapy combined with either short-term (4-6 months) or long-term (24 months) hormone therapy, including RTOG 9601, GETUG-AFU-16, RADICALS (three trials), and RTOG 0534. The studies looked at radiation with or without hormone therapy in 5,026 men (median PSA 0.3 ng/mL), including those receiving radiation only or with short-term hormone therapy (n = 3,938; median PSA 0.3 ng/mL) or long-term hormone therapy (n = 1,088; median PSA 0.5 ng/mL). Patients were followed for a median of 9 years.

Key Finding: No Overall Survival Benefit

Overall, after 10 years, 83.6% of men who received postoperative radiotherapy alone were alive compared with 84.3% of those who received postoperative radiotherapy plus hormone therapy (hazard ratio [HR] 0.87, P = .06). “More important than any hazard ratio or confidence interval is the absolute benefit, which was projected at 10 years to be only 0.7%,” Dr. Kishan noted.

The finding carried this important caveat, however: preradiotherapy PSA level was critical. Whereas men with low PSA levels (≤ 0.5 ng/mL) saw no benefit from hormone therapy, those with higher PSA levels experienced modest improvements in survival, suggesting that hormone therapy may only be worthwhile for that group, Dr. Kishan said.

Metastasis-free survival, however, did demonstrate significance, at 10 years being 74.1% with radiotherapy alone and 77.9% with the addition of hormonal therapy, an absolute benefit of about 3.8% (HR, 0.79; P < .001). Extensive analysis determined, however, that metastasis-free survival could not be considered a surrogate for overall survival, he added.

The study also examined the duration of hormone therapy and found no significant interaction. Long-term therapy did indicate a small survival benefit, particularly for men with higher PSA levels (median PSA > 0.5 ng/mL) after prostatectomy (HR, 0.79; P = .049); extending short-term therapy to long-term therapy did not further improve survival, although it did appear to lower the risk of metastasis.

Interaction With PSA Level

The evaluation of subgroups did reveal an interesting picture for PSA levels, Dr. Kishan said. The study prestratified men according to four levels of preradiation PSA level and examined outcomes. The analysis suggested no benefit to overall survival or metastasis-free survival from the addition of short-term hormone therapy for any PSA < 2.4 ng/mL. For the addition of long-term hormone therapy, for men with elevated PSA (≥1.6 ng/mL), an advantage for overall survival and metastasis-free survival emerged.

An exploratory analysis of the 1,523 patients randomized to short-term vs long-term hormone therapy (aimed at “reconciling” this finding with that of the primary analysis, Dr. Kishan said) showed no benefit for prolonging therapy (HR, 0.89; P = .37). The number needed to treat was shown to be 125 for patients with low PSA (≤ 0.2 ng/mL) but 25 for those with PSA > 1.0 ng/mL.

Dr. Kishan said that the study’s enrollment predated the use of prognostic biomarkers such as Decipher and advanced molecular imaging, such as PSMA PET, which now often guide decision-making. “This is a space where data from biomarker-driven trials like NRG-GU-006 [BALANCE] are going to be particularly helpful,” he said. 

DISCLOSURE: Dr. Kishan had disclosures for Boston Scientific, Janssen Oncology, Varian Medical Systems, Lantheus Medical Imaging.

REFERENCES

1. Kishan AU, et al: Hormone therapy use and duration with postoperative radiotherapy for recurrent prostate cancer. 2026 ASCO Genitourinary Cancers Symposium. Abstract 15. Presented February 26, 2026.

2. Kishan AU, et al: Hormone therapy use and duration with postoperative radiotherapy for recurrent prostate cancer. Lancet. Published online February 26, 2026.

3. Kishan AU, Sun Y, Hartman H, et al: Androgen deprivation therapy use and duration with definitive radiotherapy for localised prostate cancer. Lancet Oncol 23(2):304-316, 2022.

EXPERT POINT OF VIEW: Bridget F. Koontz, MD, FASTRO

The findings of POSEIDON,¹ according to invited discussant Bridget F. Koontz, MD, FASTRO, a radiation oncologist with AdventHealth Cancer Institute in Orlando, are “either practice-changing or practice-supporting, depending on how one currently practices.”

Dr. Koontz emphasized that the results are applicable only to patients with positron emission tomography (PET)-negative biochemical recurrence. Patients with PET-positive nodal or metastatic disease should be treated with radiation and hormone therapy.

Bridget F. Koontz, MD, FASTRO

As she pointed out, clinical practice guidelines for androgen deprivation therapy (ADT) in the postprostatectomy prostate cancer setting are “loose” and are based on evidence that has either been “conflicting or felt to be underpowered.” Of four large populations in whom postprostatectomy hormone therapy has been evaluated, only one showed an overall survival benefit, she noted.

“POSEIDON is a very robust, large-volume patient-level meta-analysis of over 5,000 patients with 9 years of follow-up, however, even in this dataset the addition of hormone therapy to postoperative radiotherapy did not provide an overall survival benefit,” she said. Favorable trends could also be seen in subsets with certain high-risk features, including very high Gleason grades, seminal vesicle involvement, and very young age, but these numbers were small.

“Not all patients need ADT as part of salvage postoperative radiotherapy,” Dr. Koontz concluded.“Postoperative radiotherapy is highly effective and the use of ADT should be focused on those who either have bad biology or a high risk of micrometastases.” 

DISCLOSURE: Dr. Koontz had disclosures for RayThera Therapeutics, Novartis, Blue Earth Diagnostics, Fuse Oncology, Myriad Genetics, and Demos MedicalPublishing.

REFERENCE

1. Kishan AU, Sun Y, Parker C, et al: Hormone therapy use and duration with postoperative radiotherapy for recurrent prostate cancer: An individual patient data meta-analysis. 2026 ASCO Genitourinary Cancers Symposium. Abstract 15. Presented February 26, 2026.

EXPERT POINT OF VIEW: Neha Vapiwala, MD, FASTRO, FACR, FASCO

In an interview with The ASCO Post, Neha Vapiwala, MD, FASTRO, FACR, FASCO, shared her thoughts on findings of POSEIDON.1 Dr. Vapiwala is President of the American Society for Radiation Oncology (ASTRO) and the Eli Glatstein, MD, Endowed Professor and Vice Chair of Radiation Oncology, at the University of Pennsylvania.

Neha Vapiwala, MD, FASTRO, FACR, FASCO

 “For many radiation oncologists, these findings largely reinforce current practice patterns that were informed by the trials included in this meta-analysis. In the setting of postprostatectomy radiotherapy, when PSA level is the primary driver of decision-making, short-term androgen deprivation therapy (ADT) is generally reserved for patients with higher PSA values, for example, 0.35 ng/mL or greater was suggested from secondary analysis of NRG [RTOG] 0534. With respect to long-term ADT, it is very uncommon these days for patients to present for postoperative radiotherapy with PSA levels above 1.6 ng/mL. Most patients are treated at substantially lower PSA values, and those with higher levels typically have additional high-risk pathologic or imaging features that would independently support consideration of longer-duration ADT.

“While the study’s focus was overall survival, metastasis-free survival is also highly meaningful to patients; it carries implications in terms of future treatments and the costs they can incur, financially, physically, and emotionally. This is especially true for younger patients who experience biochemical recurrence after surgery, as well as patients with high-risk pathologic features, such as Grade Group 4–5 disease or pT3b tumors.

“As the authors acknowledge, the included trials span a long period of time during which practice patterns and risk stratification tools evolved. We know PSA is a solid prognostic and predictive biomarker, but the field is moving increasingly toward incorporating other biomarkers, such as genomic classifiers and advanced PET imaging. Of note, PSA doubling time was not available in these data, which can be an important part of systemic therapy decision-making.

“The bottom line is that PSA alone does not typically dictate ADT decisions. These findings reinforce the value of personalizing treatment based on a broader clinical context.” 

DISCLOSURE: Dr. Vapiwala reported no conflicts of interest.

REFERENCE

1. Kishan AU, Sun Y, Parker C, et al: Hormone therapy use and duration with postoperative radiotherapy for recurrent prostate cancer. 2026 ASCO Genitourinary Cancers Symposium. Abstract 15. Presented February 26, 2026.