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Assessment of Age, Period, and Birth Cohort Effects and Trends in Merkel Cell Carcinoma Incidence in the United States

Educational Objective
To evaluate the associations of patient age, calendar period of diagnosis, and birth cohort with the increasing incidence of Merkel cell carcinoma and provide new incidence projections to 2030.
1 Credit CME
Key Points

Question  What are the associations of age, calendar period of diagnosis, and birth cohort with the increasing incidence of Merkel cell carcinoma (MCC), and how can they inform projected incidence rates?

Findings  This cross-sectional study of 3720 patients with MCC found that, although birth cohort effects continue to increase over time, the effect owing to period of diagnosis has started to plateau. The projected incidence rate is estimated to be 3023 new cases of MCC in 2020.

Meaning  The initial increase found in this cross-sectional study in the incidence of MCC was likely owing in part to increased detection (period effect), but the continued increase will likely be associated with changes in risk factors (birth cohort effects) and the aging population (age effects).


Importance  Merkel cell carcinoma is an aggressive, cutaneous, neuroendocrine cancer that is increasing in incidence. Understanding why the incidence of Merkel cell carcinoma is increasing through underlying factors, such as age effects, calendar period of diagnosis effects, and birth cohort effects, can help guide resource allocation and design of screening programs.

Objectives  To evaluate the associations of patient age, calendar period of diagnosis, and birth cohort with the increasing incidence of Merkel cell carcinoma and to provide new incidence projections to 2030.

Design, Setting, and Participants  A cross-sectional retrospective study with age-period-cohort analysis and incidence projection modeling using data from the Surveillance, Epidemiology, and End Results Program database of 9 registries from 1987 to 2016 was conducted among 3720 patients with Merkel cell carcinoma. Statistical analysis was conducted from October 20, 2019, to July 29, 2020.

Exposures  Age effects (ie, physiology), period of diagnosis effects (ie, changes in diagnostics and clinical awareness), and birth cohort effects (ie, environmental risk factors) over time were assessed.

Main Outcomes and Measures  Incidence rates of Merkel cell carcinoma.

Results  Among the 3720 patients in the study (2200 male patients [59.1%]; median age, 77 years [interquartile range, 68-84 years]), during the period from 2012 to 2016, the age-adjusted Merkel cell carcinoma incidence rate was 0.66 per 100 000 (95% CI, 0.62-0.70), which represented a 3.5-times (95% CI, 3.0-4.2) increase from 1987 to 1991. The incidence of Merkel cell carcinoma increased with patient age across calendar periods and birth cohorts; the highest incidence rate was observed for those aged 85 years or older, with an age-adjusted rate from 2012 to 2016 of 14.6 per 100 000 for men and 5.5 per 100 000 for women. Although the birth cohort effect has continued to increase over time, the calendar period of diagnosis effect has started to plateau. It is projected that there will be 3023 new cases of Merkel cell carcinoma in 2020 and 5130 new cases in 2030, increased from an estimated 1933 cases in 2010.

Conclusions and Relevance  The slowing down of the period effect (ie, changes in diagnostics and awareness) found in this longitudinal cohort study suggests that part of the initial increased incidence of Merkel cell carcinoma was associated with increased detection. However, the projected increase in incidence rate is likely associated with the aging population and increasing risk factor exposure in more recent birth cohorts.

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Article Information

Accepted for Publication: August 15, 2020.

Published Online: November 4, 2020. doi:10.1001/jamadermatol.2020.4102

Corresponding Author: Yawei Zhang, MD, PhD, MPH, Department of Environmental Health Sciences, Yale School of Public Health, 60 College St, Ste 440, New Haven, CT 06510 (yawei.zhang@yale.edu).

Author Contributions: Mr Jacobs and Ms Huang. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Mr Jacobs and Ms Huang contributed equally to this work.

Concept and design: Jacobs, Kluger, Judson, Zhang.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Jacobs, Huang, Olino.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Jacobs, Huang.

Obtained funding: Jacobs, Judson.

Administrative, technical, or material support: Kluger, Judson.

Supervision: Olino, Kluger, Judson, Zhang.

Conflict of Interest Disclosures: Dr Weiss reported receiving grants from the National Institutes of Health/National Cancer Institute (K12 CA215110) and the Yale Specialized Programs of Research Excellence in Lung Cancer Career Enhancement Program and personal fees from Magellan Rx, Array Biopharma, University of Connecticut School of Pharmacy, and Baptist Health/Miami Cancer Institute during the conduct of the study. Dr Kluger reported receiving grants from Apexigen; grants and personal fees from Merck and Bristol-Myers Squibb; and personal fees from Nektar, Roche-Genentech, Pfizer, Iovanvce, Immunocore, Celldex, Array Biopharma, Instil Bio, and Elevate Bio outside the submitted work. No other disclosures were reported.

Funding/Support: This work was made possible by the William U. Gardner Memorial Student Fellowship at the Yale School of Medicine.

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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