Decreased Mortality for Men With Unfavorable-Risk Prostate Cancer and Moderate or Severe Comorbidities Treated With Radiotherapy Alone
Men with unfavorable-risk prostate cancer and moderate or severe comorbidities had significantly decreased overall and cardiac mortality when treated with radiotherapy alone vs radiotherapy and androgen-deprivation therapy, according to a study described in a research letter in JAMA. In the letter, D’Amico et al present long-term follow-up to their randomized trial, reported in JAMA in 2008, that showed 6 months of androgen-deprivation therapy and radiotherapy vs radiotherapy alone “prolongs survival and is the standard treatment for unfavorable-risk prostate cancer.”
The new findings build on a “post-randomization hypothesis-generating analysis suggesting that men with moderate or severe comorbidity had no increased survival from combined therapy,” the researchers noted. “Using updated data from our randomized trial, we compared overall survival and mortality from prostate cancer, cardiac, or other causes in all men and those within comorbidity subgroups by randomized treatment group,” the authors explained. Information collected before randomization was used to assign a comorbidity score.
A total of 206 men with unfavorable-risk prostate cancer were randomly assigned to receive radiotherapy alone or radiotherapy and 6 months of androgen-deprivation therapy at three academic and three community-based centers in Massachusetts between December 1, 1995, and April 15, 2001, At a median follow-up of 16.62 years, 156 men had died (76%); 29 died of prostate cancer (19%), 39 of cardiac causes (25%), and 88 of other causes (56%).
‘Opposite Effects of Treatment’
Among men with moderate or severe comorbidity, 46 of 49 had died (94%), compared to 110 of 157 (70%) of men with no or minimal comorbidity. Survival did not differ in the patients receiving radiotherapy alone vs those receiving radiotherapy and androgen-deprivation therapy, “but opposite effects of treatment on survival were observed in the comorbidity subgroups,” the authors reported.
“In multivariable analyses, [radiotherapy] alone vs [radiotherapy and androgen-deprivation therapy] in men with no or minimal comorbidity was associated with significantly increased overall mortality (hazard ratio [HR] = 1.51, 95% CI = 1.03–2.21, P = .04) and prostate cancer mortality (HR = 4.30, 95% CI = 1.60–11.50, P = .004), no difference in cardiac mortality (HR = 1.72, 95% CI = 0.64–4.58, P = .28), and decreased other-cause mortality (HR = 0.60, 95% CI = 0.36–0.99, P = .04),” the authors reported.
“Conversely, in men with moderate or severe comorbidity, [radiotherapy] alone vs [radiotherapy and androgen-deprivation therapy] was associated with significantly decreased overall mortality (HR = 0.36, 95% CI = 0.19–0.67, P = .001) and cardiac mortality (HR = 0.17, 95% CI = 0.06–0.46, P < .001),” the researchers wrote. This finding is in contrast to no association with overall mortality at a median follow-up of 7.6 years (HR = 0.54, 95% CI = 0.27–1.10, P = .08), as previously reported.
In addition, among men with moderate or severe comorbidity, radiotherapy alone was associated with no difference in prostate cancer mortality (HR = 2.41, 95% CI = 0.23–25.21, P = .46), and increased other-cause mortality (HR = 2.79, 95% CI = 1.02–7.60]; P = .05).
Carefully Consider Administering Androgen-Deprivation Therapy
The authors reported that the results from the postrandomization analyses are hypothesis-generating and require validation. “Nevertheless, the association of treatment with [radiotherapy] alone with decreased cardiac and overall mortality in men with moderate or severe comorbidity suggests that administering [androgen-deprivation therapy] to treat unfavorable-risk prostate cancer in these men should be carefully considered."
Anthony V. D’Amico, MD, PhD, of Brigham and Women’s Hospital, Boston, is the corresponding author for the JAMA article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
