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ADT may increase cardiac mortality among men with unfavorable-risk prostate cancer, comorbidities
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The addition of androgen deprivation therapy to radiation appeared to increase the risk for overall and cardiac-specific mortality among men with unfavorable-risk prostate cancer and moderate to severe comorbidities, according to long-term results of a randomized trial.
The receipt of radiation without ADT increased mortality risk in men with few or no comorbidities; however, this association did not persist in the overall population.
“These findings give us reason to rethink how we manage prostate cancer in men with known heart disease,” Anthony V. D’Amico, MD, PhD, chief of genitourinary radiation oncology at Brigham and Women’s Hospital, said in a press release. “Men with significant heart disease that is not amenable to medical or surgical correction may be best served by radiation therapy alone.”
Earlier results from this trial showed a 6-month course of ADT plus radiation prolongs survival, and this combination is currently the standard treatment for men with unfavorable-risk prostate cancer. However, a post-randomization hypothesis-generating analysis suggested that men with moderate or severe comorbidity have no survival benefit with combined therapy.
Between December 1995 and April 2001, D’Amico and colleagues randomly assigned 206 men with unfavorable-risk prostate cancer to radiation therapy alone or with ADT.
Researchers used information collected at the time of randomization to assign a comorbidity score for each patient. Overall, 157 men had none or minimal comorbidity, and 49 had moderate or severe comorbidity.
Median follow-up was 16.62 years (interquartile range [IQR], 15.42-17.67).
At follow-up, 76% (n = 156) of men had died: 19% died of prostate cancer (n = 29), 25% died of cardiac causes (n = 39) and 56% died of other causes (n = 88).
A greater proportion of men with moderate or severe comorbidity died than men with minimal or no comorbidity (94% vs. 70%).
Men who received radiation therapy alone did not appear at increased risk for mortality (80 vs. 76 deaths; HR = 1.22; 95% CI, 0.89-1.67) or cardiac mortality (HR = 0.74; 95% CI, 0.4-1.39).
Researchers then evaluated outcomes based on comorbidity level in multivariable analyses.
Among men with none or minimal comorbidity, radiation therapy without ADT significantly increased overall mortality risk (HR = 1.51; 95% CI, 1.03-2.21) and prostate cancer mortality risk (HR = 4.3; 95% CI, 1.6-11.5) compared with the combination of radiation and ADT. There did not appear to be a difference in cardiac mortality (HR = 1.72; 95% CI, 0.64-4.58), whereas radiation therapy alone decreased other-cause mortality vs. radiation plus ADT in this cohort (HR = 0.6; 95% CI, 0.36-0.99).
Conversely, among men with moderate or severe comorbidity levels, radiation alone significantly decreased overall mortality risk (HR = 0.36; 95% CI, 0.19-0.67) and cardiac mortality risk (HR = 0.17; 95% CI, 0.06-0.46), with no difference in prostate cancer mortality (HR = 2.41; 95% CI, 0.23-25.21). However, radiation alone increased other-cause mortality in this cohort (HR = 2.79; 95% CI, 1.02-7.6).
The researchers acknowledged limitations of their study, including the potential that results from post-randomization analyses are sometimes based on low event rates.
“While there is a growing body of evidence to support active surveillance for men with low-risk prostate cancer, men who have unfavorable-risk cancer and significant comorbidity — notably heart disease — may be best served by considering radiation therapy alone or possibly active surveillance,” D’Amico said. “For these men, the adverse events of ADT may be life-threatening. More research is needed to better understand the newer forms of hormone therapy that do not lower testosterone and how they impact survival.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.
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