Radiation Therapy With or Without Hormonal Therapy for Prostate Cancer

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Radiation Therapy With or Without Hormonal Therapy for Prostate Cancer

In a small study, men without comorbidities benefited from ADT, but men with moderate-to-severe comorbidities did not.

In several randomized trials, researchers have demonstrated improvement in both disease-specific and overall survival among prostate cancer patients with poor risk features when they are treated with androgen-deprivation therapy (ADT) plus external-beam radiotherapy versus radiotherapy alone. However, although adding ADT to radiotherapy provides clear benefit to some patients, recent evidence has suggested an association between use of ADT and substantial cardiac morbidity and mortality.

To evaluate the effects of ADT on men with comorbid illnesses, investigators from several Boston centers randomized 206 men (median age, 72) with prostate cancer (T1b–T2b, N0, M0) and at least one unfavorable prognostic feature (prostate-specific antigen level >10 ng/mL, Gleason score 7–10, or radiographic evidence of extracapsular extension or seminal vesicle invasion) to 6 months of ADT (a luteinizing hormone–releasing hormone agonist plus an antiandrogen) plus three-dimensional conformal radiotherapy or to radiotherapy alone. Comorbidity classification for each patient was completed after randomization (but before treatment) using the Adult Comorbidity Evaluation 27 instrument, which is a validated comorbidity index for cancer patients. The main outcome measure during follow-up was all-cause mortality.

At enrollment, 157 men had no-to-minimal comorbidity; 49 had moderate-to-severe comorbidity. Men with moderate-to-severe comorbidity scores were distributed equally between the two treatment groups. During a median follow-up of 7.6 years, 74 men died (44 in the radiotherapy-only group and 30 in the radiotherapy-plus-ADT group). Forty-two deaths occurred in men with no-to-minimal comorbidities (27% of the group), and 32 occurred in men with moderate-to-severe comorbidities (64% of the group); of these deaths, 17 (40%) and 1 (3%), respectively, were due to prostate cancer, which suggested that prostate cancer was not a major contributor to all-cause mortality in men with moderate-to-severe comorbidities. A significantly higher risk for all-cause mortality was noted in men who received radiotherapy alone compared with those who received combined therapy (hazard ratio, 1.8; 95% confidence interval, 1.1–2.9; P=0.01). However, the higher risk in the radiotherapy-alone group was attributable largely to men with no-to-minimal comorbidity (P<0.001); among men with moderate-to-severe comorbidity, no difference in all-cause mortality was observed between treatment arms (P=0.08).

Comment: Although this was a relatively small trial, the investigators reconfirmed previous observations — that patients with poor risk features who are treated with external-beam radiotherapy gain a survival advantage from 6 months of ADT. However, in the post hoc analysis, the researchers also demonstrated that men with moderate-to-severe comorbidities failed to benefit from ADT. The major question remaining is whether and how ADT interacts with various conditions that lead to high comorbidity scores.

— Robert Dreicer, MD, MS, FACP

Published in Journal Watch Oncology and Hematology January 22, 2008