Age, comorbidity, and PSA doubling time (PSADT) influence the long-term risk and cause of death among men with non-metastatic castration-resistant prostate cancer (nmCPRC), according to a new study.

“Integrating simple clinical variables such as these into decision making represents a key component of precision medicine that is too often ignored,” a team led by Timothy J. Daskivich, MD, of Cedars-Sinai Medical Center in Los Angeles, concluded in Prostate Cancer and Prostatic Diseases. “We strongly believe that these factors should be taken into account when counseling patients about prognosis, and they may be important in selecting subgroups for future clinical trials in men with nmCRPC.”

The study included 1238 men diagnosed with nmCPRC from 2000 to 2015. The median follow-up after onset of CRPC was 33.5 months. During follow-up, 569 patients (46%) died from prostate cancer (PCa) and 320 (26%) died from other causes (other-cause mortality, OCM).

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A Charlson comorbidity index (CCI) of 3 or higher, compared with a CCI of 0, was associated with a 2.7-, 2.0-, and 2.5-fold increased risk of non-PCa death among men aged less 70, 70 to 79, and 80 years or older, respectively. Among men in these age groups, a PSADT of 9 months or longer, compared with less than 9 months, was associated with an approximately 50%, 40%, and 40% decreased risk of PCa-specific mortality (PCSM), respectively.

According to Dr Daskivich and his collaborators, PCSM and OCM were relatively equal competitors for death among patients with a PSADT of 9 months or longer, except among men aged 80 years or more with a CCI of 3 or greater. In these men, OCM was the predominant cause of death. Among patients with a PSADT of less than 9 months, PCSM was the predominant cause of death across all age and comorbidity groups.

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“We found that a combination of age, comorbidity, and PSADT could strongly risk stratify cause of death among these men,” the authors wrote.

In acknowledging study limitations, Dr Daskivich and his colleagues pointed out that, because of the retrospective nature of their investigation, important predictors of prognosis such as functional status and fraility were not available. In addition, their study population only included patients from Veterans Affairs medical centers, which may affect external generalizability to other patient populations. Another limitation was that the work-up of patients for metastatic disease at the time of CRPC diagnosis was at the discretion of treating physicians, and thus not uniform. This may have affected the homogeneity of their study population, they noted.


Whitney CA, Howard LE, Freedland SJ, et al. Impact of age, comorbidity, and PSA doubling time on long-term competing risks for mortality among men with non-metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2018; published online ahead of print.