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

Abstract

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

Acknowledgments

The study received financial support from Amgen Incorporated, CA, USA and the Department of Clinical Epidemiology Research Fund, Aarhus University Hospital, Denmark.

Disclosure

The authors report no conflicts of interest in this work. Authors K Cetin, A Daniels and J Acquavella are employed by Amgen Incorporated. The Department of Clinical Epidemiology is involved in studies with research grant funding from various other companies that are administered by Aarhus University Hospital. None of these other studies have any relation to the present study.