Comorbidity May Reduce ADT Benefit for Localised Prostate Cancer

Patient comorbidity could help determine the optimal treatment regimen for men with unfavourable risk, localised prostate cancer

medwireNews: The survival benefit associated with adding androgen deprivation therapy (ADT) to radiotherapy for localised prostate cancer is limited to men in otherwise good health, say US researchers who challenge dual therapy in those with moderate or severe comorbidity.

In a research letter to JAMA, the team reports findings for 206 men with unfavourable risk prostate cancer who were randomly assigned to receive radiation alone or alongside 6 months of ADT.

Over a median of 16.62 years, 76% of the patients died, including 94% of the 49 men who had a moderate or severe Adult Comorbidity Evaluation 27 score and 70% of the 157 men with a score denoting no or minimal comorbidity.

Multivariate analysis demonstrated that comorbidity altered the impact of treatment on the risk of mortality, say Anthony D’Amico, from Brigham and Women’s Hospital in Boston, Massachusetts, and co-authors.

Specifically, men with moderate or severe comorbidity had significantly reduced rates of both overall mortality and cardiac mortality, defined as fatal myocardial infarction, if they received radiotherapy alone than if they were given combined treatment, with significant hazard ratios (HRs) of 0.36 and 0.17, respectively.

And the regimen given did not significantly impact on prostate cancer-related mortality – defined as castration-resistant metastatic disease, an increasing prostate-specific antigen level resistant to hormone therapy and need for chemotherapy – or other-cause mortality.

By contrast, men with no or minimal comorbidity had a significantly increased rate of overall and prostate cancer-specific mortality if treated with radiation alone than if given combined therapy, with HRs of 1.51 and 4.30, respectively. There was no significant difference in the treatment groups with regard to cardiac mortality or mortality associated with other causes.

“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 researchers comment.

“Nevertheless, the association of treatment with [radiation therapy] alone with decreased cardiac and overall mortality in men with moderate or severe comorbidity suggests that administering ADT to treat unfavorable-risk prostate cancer in these men should be carefully considered”, they conclude.


D’Amico AV, Chen M-H, Renswhaw A, et al. Long-term follow-up of a randomized trial of radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA 2015; 314: 1291–1293. doi:10.1001/jama.2015.8577

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