Decreased Mortality in Men With Unfavorable-Risk Prostate Cancer and Moderate or Severe Comorbidities Treated With Radiotherapy Alone


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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 The Journal of the American Medical Association (JAMA). In the letter, Anthony V. D’Amico, MD, PhD, of Brigham and Women’s Hospital, Boston, and colleagues presented long-term follow-up to their randomized trial, reported in JAMA in 2008, which showed that 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 study builds on a “post-randomization hypothesis-generating analysis suggesting that men with moderate or severe comorbidity had no 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 randomized 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 died of cardiac causes (25%), and 88 died of other causes (56%).

Among men with moderate or severe comorbidity, 46 of 49 patients had died (94%), compared with 110 of 157 (70%) men with no or minimal comorbidity. “Survival did not differ in the radiotherapy-alone group vs the radiotherapy and androgen-deprivation therapy group, 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 none or minimal comorbidity was associated with significantly increased overall mortality (hazard ratio [HR], 1.51 [95% confidence interval (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 vs radiotherapy and androgen-deprivation therapy 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).

“Limitations include that the results from postrandomization analyses are hypothesis-generating and in some cases based on low event rates and therefore require validation,” the authors pointed out. “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.” ■

D’Amico AV, et al: JAMA 314:1291-1293, 2015.



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