The benefit (or lack thereof) of early, aggressive treatment in men ≥ 66 years


A new study published on line in the journal Cancer has shown that (a) the cancer-specific survival benefit associated with aggressive treatment for early-stage prostate cancer is reduced with increasing co-morbidity at time of diagnosis, and (b) patients with Charlson scores ≥ 3 gain no survival benefit from aggressive treatment.

These new data, just reported by Daskivitch et al., are not surprising. Rather, they provide the final confirmation of the long-held presumption that older and sicker men with limited life expectancies were highly unlikely to gain a survival benefit from aggressive forms of first-line treatment for localized prostate cancer. Additional commentary on this study, with specific remarks about the implications of the study data, can be found on the Science Codex web site.

Daskivitch et al. looked at data from 140,553 men, all aged ≥ 66 years, who had been diagnosed with early-stage prostate cancer between 1991 and 2007. These data were extracted from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database.

They were able to show that

  • For men with a Charlson score of 0, 1, or 2, aggressive first-line treatment for localized prostate cancer was associated with a significantly lower risk of prostate cancer-specific mortality.
  • For men with a Charlson score of ≥ 3, aggressive first-line treatment for localized prostate cancer was not associated with a significantly lower risk of prostate cancer-specific mortality.
  • The absolute reduction in 15-year prostate cancer-specific mortality between men who received aggressive versus non-aggressive treatment was
    • 6.1 percent for men with a Charlson score of 0
    • 4.3 percent for men with a Charlson score of 1
    • 3.9 percent for men with a Charlson score of 2
    • 0.9 percent for men with a Charlson score of ≥3
  • For men with a Charlson score of 0, 1, or 2 who had well-differentiated and moderately-differentiated tumors, aggressive treatment was again associated with a lower risk of prostate cancer-specific mortality.
  • For men with a Charlson score of ≥ 3 who had well-differentiated and moderately-differentiated tumors, aggressive treatment was again not associated with a lower risk of prostate cancer-specific mortality.
  • The absolute reduction in 15-year prostate cancer-specific mortality between men who had well-differentiated and moderately-differentiated tumors and who received aggressive versus non-aggressive treatment was
    • 3.8 percent for men with a Charlson score of 0
    • 3.0 percent for men with a Charlson score of 1
    • 1.9 percent for men with a Charlson score of 2
    • −0.5 percent for men with a Charlson score of ≥ 3

It is also worth noting that the 15-year survival benefit from immediate and aggressive treatment is relatively small among this large group of men who are 66 years of age or older — even among men whose Charlson scores are 0 to 2. In other words, yes, there is a 6.1 percent absolute reduction in risk of prostate cancer-specific mortality among men with a Charlson score of 0, but that has to be weighed against the risks associated with the side effects of such treatment — which are well understood to be considerable.

What these data from Daskivich et al. offer us is a better way to understand just how much real benefit is on offer from immediate treatment of older males as compared to the side effects. These decisions are always very personal: some are going to see the glass as being half full and would want to pursue the aggressive treatment opportunity based on these data; others may justifiably see the glass as being half empty and feel that some form of expectant management (active surveillance, watchful waiting, etc.) is a better way to have good quality of life given the limited survival benefit available from treatment.

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