No meaningful benefit to adding hormone therapy to PORT in prostate cancer

The addition of hormone therapy, either short- or long-term, to postoperative radiotherapy (PORT) offers no survival advantage over PORT alone in prostate cancer, especially for men with very low pre-PORT prostate specific antigen (PSA) levels, according to the POSEIDON study.

In individual patient data meta-analysis of six phase III randomized controlled trials, the 10-year overall survival (OS) rate was 84.3 percent with the addition of hormone therapy vs 83.6 percent with PORT alone, with no evidence of OS benefit (hazard ratio [HR], 0.87, 95 percent confidence interval [CI], 0.76–1.01; p=0.06). [Lancet 2026;doi:10.1016/S0140-6736(26)00137-6]

The lack of an OS benefit with added hormone therapy was particularly observed in men with low pre-PORT PSA levels (≤0.2 ng/mL: HR, 1.14, 95 percent CI, 0.83–1.57; 0.21–0.50 ng/mL: HR, 0.94, 95 percent CI, 0.74–1.19).

In contrast, the addition of hormone therapy yielded a modest OS improvement in men with higher pre-PORT PSA levels (0.51–1.00 ng/mL: HR, 0.72, 95 percent CI, 0.54–0.96; >1.00 ng/mL: HR, 0.69, 95 percent CI, 0.48–0.98; p<0.05).

Additional analyses showed that compared with PORT alone, the addition of hormone therapy was associated with better metastasis-free survival (MFS) (HR, 0.79, 95 percent CI, 0.70−0.89; p<0.001). The respective 10-year MFS rates were 77.9 percent vs 74.1 percent.

Hormone therapy duration

Looking at the duration of hormone therapy, adding short-term therapy to PORT was associated with improved MFS (HR, 0.82, 95 percent CI, 0.71−0.95) but not OS (HR, 0.93, 95 percent CI, 0.77−1.11). Meanwhile, the addition of long-term hormone therapy to PORT conferred modest OS (HR, 0.79, 95 percent CI, 0.63–1.00; p=0.049) and MFS (HR, 0.74, 95 percent CI, 0.60–0.91; p=0.004) benefits.

Finally, extending the duration of hormone therapy from short to long term, as an addition to PORT, resulted in improved MFS (HR, 0.76, 95 percent CI, 0.61–0.95; p=0.02) but not OS (HR, 0.89, 95 percent CI, 0.68–1.16; p=0.37).

The pooled study population included 6,057 prostate cancer patients with a median follow-up of 9 years. Of these, 5,026 were included in the primary comparison of PORT with hormone therapy (n=2,810) vs PORT alone (n=2,216). No data integrity issues were identified. 

PORT adequate for most patients

“Overall, the POSEIDON results do not support the routine addition of hormone therapy to PORT for patients receiving adjuvant or early secondary radiotherapy (previously called salvage radiotherapy) and suggests that meaningful benefits in OS would primarily manifest for patients receiving very late secondary radiotherapy (PSA >1.6–2.0 ng/mL),” according to lead investigator Prof Amar Kishan from the University of California in Los Angeles, California, US.

For most patients with detectable but low PSA levels (<0.5 ng/mL), administering radiotherapy after radical prostatectomy “is highly effective on its own,” Kishan said. “By safely omitting hormone therapy in these patients, we can potentially spare them months of treatment that may substantially affect their quality of life without extending survival.”

Kishan highlighted a need to identify biomarkers to further guide the use of hormone therapy with PORT in this population.

In an accompanying editorial, Drs Ana Aparicio and Patrick Pilié, both from the University of Texas MD Anderson Cancer Center in Houston, Texas, US, wrote that POSEIDON “underscores an important adage in prostate cancer that more might not always be better.” [Lancet 2026;10.1016/S0140-6736(26)00368-5]

“For now, clinicians and patients will need to weigh the potential value of prolonging MFS by adding hormone therapy to PORT in light of Kishan and colleagues’ results signalling no OS benefit,” Aparicio and Pilié added.