Using Medicare Claims to Examine Long-term Prostate Cancer Risk of Finasteride in the Prostate Cancer Prevention Trial

Abstract

Background: Investigators have used administrative claims to better understand cancer outcomes when a research question cannot feasibly be examined within a study. The Prostate Cancer Prevention Trial (PCPT) showed that seven years of finasteride reduced prostate cancer (PC) risk by 25% in men age 55 years or older. However, it was unclear whether the observed reduction in PC for finasteride participants would be maintained after finasteride discontinuation.

Methods: We examined PC diagnoses identified by PCPT study records and Medicare claims (finasteride = 9423, placebo = 9457). A Medicare-defined PC diagnosis algorithm was defined using diagnosis and procedure codes. Multivariable Cox regression was used to examine time to PC within prespecified follow-up windows (<6.5, 6.5-7.5, and >7.5 years) using time-dependent covariates interacting with intervention assignment to account for the PCPT protocol-specified end-of-study biopsy at seven years. All statistical tests were two-sided.

Results: Median follow-up using the linked database was 16 years. Overall, finasteride arm participants had a 21.1% decrease in the hazard ratio of PC (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.74 to 0.84, P < .001). The beneficial effect of finasteride in reducing the hazard ratio of PC was most pronounced in the first 7.5 years (HR = 0.71, 95% CI = 0.66 to 0.77, P < .001), consistent with the original study findings; after 7.5 years, there was no increased risk of PC for finasteride arm participants (HR = 1.10, 95% CI = 0.96 to 1.26, P = .18).

Conclusions: Finasteride provides a substantial reduction in PC through 16 years of follow-up. There was no strong evidence that the benefit of finasteride diminished after the end-of-study follow-up. Utilizing Medicare claims to augment PCPT follow-up illustrates how the novel use of secondary data sources can enhance the ability to detect long-term outcomes from prospective studies.

Figure 1.

Cumulative incidence of prostate cancer by type of database. Cumulative incidence of prostate cancer was identified using SWOG clinical records alone (A) compared with using the combination of SWOG clinical records and Medicare claims data (B) by intervention arm (finasteride vs placebo). Cumulative incidence curves are drawn on the same scale. The time point of 7.5 years is highlighted to indicate the end of case ascertainment on the main component of the Prostate Cancer Prevention Trial. The time point of 6.5 years is also highlighted to indicate the beginning of the end-of-study biopsy window. The curves representing the cumulative incidence of death as a competing risk were suppressed to emphasize the examination of the cumulative incidence of prostate cancer diagnoses. PCPT = Prostate Cancer Prevention Trial.

Figure 2.

Forest plot of the hazard ratio of time to prostate cancer for finasteride vs placebo. The vertical line indicates the line of equal hazard (1.0). The boxes indicate the estimated hazard ratio, and the horizontal lines around each box indicate the 95% confidence intervals. Hazard ratios to the left of the line of equal hazard indicate reduced hazard (ie, risk) of prostate cancer for participants in the finasteride arm, and to the right, reduced hazard of prostate cancer for participants in the placebo arm. Hazard ratios and P values were from multivariable Cox regression analyses adjusted for age (55–59, 60–64, 65+ years), race (black, nonblack), and family history of prostate cancer. The primary comparison between 0–7.5 years vs >7.5 years is shown above the horizontal blue bar, including the test for heterogeneity (interaction test). All statistical tests were two-sided. HR = hazard ratio.

Figure 3.

Cumulative incidence of prostate cancer by arm and follow-up time period. A) Initial 6.5 years of follow-up only. B) Those individuals with no prostate cancer event prior to 6.5 years, with time at 6.5 years set to zero and follow-up censored at 7.5 years. C) Individuals with no prostate cancer event prior to 7.5 years, with time at 7.5 years set to zero. For each panel, the curves representing the cumulative incidence of death as a competing risk were suppressed to emphasize the examination of the cumulative incidence of prostate cancer diagnoses. P values were derived from Cox regression with a change point and were two-sided. There was no evidence that the proportional hazards assumption was violated within any time window (Panel A, p = .50; Panel B, p = .23; Panel C, p = .51). CI = confidence interval; HR = hazard ratio.