Adding hormone therapy to salvage RT found efficacious

The addition of hormonal therapy in post-RP is “practice changing,” study author says.

Radical prostatectomy patients who received 24 months of antiandrogen therapy with daily bicalutamide (Casodex) in addition to salvage radiation therapy had notably higher long-term overall survival rates and lower risk of metastasis and death from prostate cancer than those who received radiation therapy with placebo, according to a new study.

“Adding hormonal therapy to radiation after prostatectomy is practice changing. For the first time, we have identified a treatment-hormonal therapy-that can improve overall survival when combined with radiation for patients who have developed recurrent disease after radical prostatectomy,” said senior author Howard Sandler, MD, of the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai, Los Angeles.

The findings were published in the New England Journal of Medicine (2017; 376:417-28).

The study of 761 patients at 17 medical institutions in the U.S. and Canada tracked subjects for a 12-year period after the men had participated in RTOG 9601, a randomized clinical trial looking at the combined treatment. Eligible subjects had undergone prostatectomy with lymphadenectomy and had a tumor stage of T2 or T3, with no nodal involvement. They had PSA levels of 0.2 ng/mL to 4.0 ng/mL, and subsequent treatment with radiation therapy and either 24 months of bicalutamide, 150 mg daily, or daily placebo tablets.

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“The patients who were studied in the RTOG 9601 trial were standard patients seen in our clinics routinely: patients with detectable PSA after radical prostatectomy, who developed their first PSA rise about 1.5 years after surgery. Median PSA was 0.6 ng/mL and median age was 65 at the time of study entry,” Dr. Sandler said.

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At the end of 12 years, the authors found prostate cancer mortality was 5.4% in the active group, compared to 13.4% in the group that had radiation therapy only. Prostate cancer metastasis incidence was 14.5% for those who received hormone therapy and radiation, compared to 23% for radiation only.

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“While subset analysis can be helpful, it is important to note that overall the study showed a positive improvement in survival. However, those with higher PSAs, higher Gleason score, or those with positive surgical margins seemed to benefit the most,” Dr. Sandler said.

The most compelling reason to consider adding hormonal therapy, according to Dr. Sandler, is that patients who develop PSA recurrence after surgery are known to be at higher risk for clinically significant prostate cancer that can lead to distant metastases and death.

“The use of hormonal therapy reduced the risk of dying from prostate cancer by 50%!” he said.

Side effects were low in both arms. According to Dr. Sandler, bicalutamide, the hormone therapy used in RTOG 9601, caused gynecomastia. The good news, he said, is gynecomastia can be prevented by prophylactic low-dose radiation or pharmacologic therapy.

The take home message for urologists? For many patients with a detectable PSA after radical prostatectomy, there is a new standard of care: hormone therapy and radiotherapy, according to Dr. Sandler.

The National Cancer Institute and AstraZeneca supported the study. Dr. Sandler has been a consultant or adviser to Ferring, Janssen, and Sanofi.