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

• Type of Material: Article
• Authors: Deirdre P. Cronin-Fenton, Arhus Universitetshospital; Sussie Antonsen, Arhus Universitetshospital; Karynsa Cetin, Amgen Incorporated; John Acquavella, Amgen Incorporated; Andre Daniels, Amgen Incorporated; Timothy Lash, Emory University
• Language: English
• Date: 2013-10-31
• Publisher: Dove Medical Press
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Cronin-Fenton et al.
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.2147/CLEP.S49713
• Title of Journal or Parent Work: Clinical Epidemiology
• ISSN: 1179-1349
• Volume: 5
• Start Page: 429
• End Page: 437
• Grant/Funding Information: The study received financial support from Amgen Incorporated, CA, USA and the Department of Clinical Epidemiology Research Fund, Aarhus University Hospital, Denmark.
• Keywords: new primary cancer; competing risks; prostate cancer; multiple comparisons; incidence rate; cancer epidemiology; cohort study
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Oncology

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.