The addition of 24 months of androgen-deprivation therapy to postoperative radiotherapy after radical prostatectomy provided a metastasis-free survival benefit and improved the time to salvage therapy in patients with prostate cancer, according to the preliminary results from the RADICALS-HD trial (ISRCTN40814031). These findings were presented during the Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2022.

“The new information from this study will ensure clinicians can better tailor treatment for patients with prostate cancer following surgery and help facilitate important discussion.”

— Chris C. Parker, MD

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“Until now, doctors and patients have had to depend largely on opinion regarding whether or not to choose hormones with their postoperative radiotherapy, and so these results will help doctors and patients in the future to have an evidence-based choice,” said Chris C. Parker, MD, consultant clinical oncologist at the Royal Marsden NHS Foundation Trust, and Professor, Prostate Oncology at the Institute of Cancer Research, London, in a press briefing at the Congress.

Key Study Results

When the investigators evaluated the duration of the added therapy, 24 months of androgen-deprivation therapy improved metastasis-free survival, compared with 6 months of androgen-deprivation therapy (hazard ratio [HR] = 0.77; 95% confidence interval [CI] = 0.61–0.97; P = .03), with a 10-year rate of metastasis-free survival of 78% vs 72%, respectively. Moreover, according to the study, the time to salvage therapy was delayed with longer androgen-deprivation therapy (HR = 0.73; 95% CI = 0.59–0.91); however, overall survival was not improved with a short course of therapy vs no androgen-deprivation therapy (HR = 0.88; 95% CI = 0.66–1.17).

When the study authors assessed the efficacy of short-course androgen-deprivation therapy with radiotherapy, vs radiotherapy alone, 6 months of androgen-deprivation therapy failed to improve metastasis-free survival (HR = 0.89; 95% CI = 0.69–1.14), with a 10-year metastasis-free survival rate of 79% vs 80%, respectively. Like the long-course therapy comparison, the time to salvage androgen-deprivation therapy was delayed with 6 months of androgen-deprivation therapy (HR = 0.54; 95% CI = 0.42–0.70); however, overall survival was not improved with a short course vs no androgen-deprivation therapy (HR = 0.88; 95% CI = 0.65–1.19).

“When men are getting radiotherapy for prostate cancer as their initial treatment, we know the addition of hormone therapy improves efficacy and survival. We also know longer courses of hormone therapy are more effective than shorter courses of therapy,” Dr. Parker stated. “However, when men are getting radiotherapy after surgery, we have much less data about the role of hormone therapy.”

Study Details

In the randomized, controlled trial, the investigators aimed to evaluate the use and duration of androgen-deprivation therapy with postoperative radiation therapy by randomly assigning patients to receive either no, 6 months (short course), or 24 months (long course) of androgen-deprivation therapy.

In two separate assessments, the investigators compared radiation alone vs short-course androgen-deprivation therapy (n = 1,480) and short-course vs long-course androgen-deprivation therapy (n = 1,523).

The trial was conducted in the UK, Canada, Denmark, and Ireland. Key eligibility criteria included the indication for radiation therapy after previous radical prostatectomy and no previous postoperative androgen-deprivation therapy. Metastasis-free survival served as the primary endpoint. Secondary endpoints included the time to salvage androgen-deprivation therapy and overall survival.

The median age of patients was 66 years. Overall, 23% of patients had pT3b/T4 disease, and the median prostate-specific antigen (PSA) level was 0.22 ng/mL before radiotherapy. Risk factors were more favorable in the no–androgen-deprivation vs short-course therapy arms, compared with the short- vs long-course therapy arms, according to the study details. Median follow-up was 9 years.

“The new information from this study will ensure clinicians can better tailor treatment for patients with prostate cancer following surgery and help facilitate important discussions,” Dr. Parker said in a press release. “This will mean some will receive a more effective treatment, whereas others will be spared unnecessary intervention. We already knew that patients with prostate cancer initially treated with radiotherapy benefit from hormone therapy. However, we did not know whether hormone therapy would also benefit those receiving radiotherapy after prostate surgery.” 

Disclosure: Dr. Parker reported institutional financial relationships with Bayer and Janssen and personal financial relationships with Myovant Sciences and Isotope Technologies Munich.