Cancer Research Lab

The addition of androgen suppression therapy to radiation therapy for treatment of prostate cancer fails to improve survival among men with serious co-existing illness, according to a study in the Journal of the American Medical Association for January 23.

Recent evidence suggests that androgen suppression therapy increases the risk of cardiovascular events in men of advanced age, lead author Dr. Anthony V. D’Amico of Brigham and Women’s Hospital in Boston and his associates note.

To examine the interaction between comorbidity and treatment outcome, they obtained long-term follow-up data from a trial in which men with prostate cancer had been randomly assigned to receive radiation therapy alone or radiation therapy and androgen suppression therapy combined.

The study included 206 patients, median age 72.5 years, with localized prostate cancer and at least one of four unfavorable prognostic factors - PSA > 10 ng/mL, a biopsy Gleason score of 7-10, extracapsular extension, or seminal vesicle invasion. At baseline between 1995 and 2001, subjects were randomized to external beam radiation therapy alone or in combination with 6 months of androgen suppression therapy.

The authors determined comorbidity scores based on the severity of several clinically relevant ailments present at baseline.

Seventy-four men died during median follow-up of 7.6 years. For the group as a whole, the risk of all-cause mortality was significantly increased in the radiation therapy group (44 vs 30 deaths, hazard ratio 1.8, p = .01).

“However, the increased risk in all-cause mortality appeared to apply only to men randomized to radiation therapy with no or minimal comorbidity” (31 vs 11 deaths; HR 4.2, p < .001), Dr. D’Amico’s team reports.

For those with moderate or severe comorbidity, mortality rates did not differ significantly between treatment groups (13 vs 19 deaths, HR 0.54, p = .08).

“The clinical significance of this finding is that preexisting comorbid illness may increase the negative effects of specific anticancer treatments such as androgen suppression therapy,” Dr. D’Amico and his associates suggest.

As their study was a hypothesis-generating, post-randomization subgroup analysis, they recommend the findings be verified in a clinical trial specifically designed to assess the interaction of comorbidity with androgen suppression therapy treatment.

Furthermore, they add, studies should be designed to identify the impact of specific comorbid illnesses on life expectancy and health-related quality of life.