Methods and rationale used in a matched cohort study of the incidence of new primary cancers following prostate cancer

Deirdre P Cronin-Fenton,¹ Sussie Antonsen,¹ Karynsa Cetin,² John Acquavella,² Andre Daniels,³ Timothy L Lash<sup>1,4

1</sup>Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; ²Center for Observational Research, Amgen Incorporated, Thousand Oaks, CA, USA; ³Global Regulatory Affairs and Safety, Amgen Incorporated, Thousand Oaks, CA, USA; ⁴Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA

Objectives: We describe several methodological issues that were addressed in conducting a Danish population-based matched cohort study comparing rates of new primary cancers (NPCs) in men with and without prostate cancer (PC).
Methods: We matched 30,220 men with PC to 151,100 men without PC (comparators) on age (±2 years) and PC diagnosis/index date. We focused on several methodological issues: 1) to address survival differences between the cohorts we compared rates with and without censoring comparators on the date their matched PC patient died or was censored; 2) to address diagnostic bias, we excluded men with a history of cancer from the comparator cohort; 3) to address prostate cancer immunity, we graphed the hazard of NPC in both cohorts, with and without prostate cancer as an outcome; 4) we used empirical Bayes methods to explore the effect of adjusting for multiple comparisons.
Results: After 18 months of follow-up, cumulative person-time was lower in the PC than comparator cohort due to higher mortality among PC patients. Terminating person-time in comparators at the matched PC patient's death or loss to follow-up resulted in comparable person-time up to 30 months of follow-up and lower person-time among comparators thereafter. The hazard of NPC was lower among men with PC than comparators throughout follow-up. There was little difference in rates beyond the first four years of follow-up after removing PC as an outcome. Empirical Bayes adjustment for multiple comparisons had little effect on the estimates.
Conclusion: Addressing the issues of competing risks, treatment interference or diagnostic bias, prostate cancer immunity due to radical prostatectomy, and multiple comparisons lowered the deficit rate of NPCs among men with a history of PC compared with those without PC. However, the differing rates of NPCs may also be due to risk factor differences between the cohorts.

Keywords: prostate cancer, cohort study, cancer epidemiology, new primary cancer, incidence rate, competing risks, multiple comparisons