The Impact of Longitudinal Surveillance on Tumor Thickness for Melanoma-Prone Families with and without Pathogenic Germline Variants of CDKN2A and CDK4

Cancer Epidemiol Biomarkers Prev. 2021 Apr;30(4):676-681. doi: 10.1158/1055-9965.EPI-20-1521.

Abstract

Background: Skin cancer screening is routinely performed for members of melanoma-prone families, but longitudinal studies evaluating the efficacy of surveillance in this high-risk population are lacking.

Methods: We evaluated thickness for first primary melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) enrolled in NCT00040352 (NCI familial melanoma study) from 1976 through 2014; enrolled patients received routine skin cancer screening and education about skin self-exams. We used linear and ordinal logistic regression models adjusted for gender and age with a generalized estimating equations approach to report changes in thickness and tumor (T) stage over time, comparing outcomes for NCI cases diagnosed before (pre-study) versus after study participation (prospective) and for NCI cases versus nonfamilial cases [Surveillance, Epidemiology, and End Results (SEER) 9 registries].

Results: Tumor thickness was evaluated for 293 NCI (pre-study = 246; prospective = 47) patients. Compared with NCI pre-study cases, NCI prospective melanomas were thinner (0.6 vs. 1.1 mm; P < 0.001) and more likely to be T1 stage [39/47 (83%) vs. 98/246 (40%); P < 0.001]. Similar findings (P < 0.05) were observed for familial cases with and without germline CDKN2A and CDK4 mutations. Peters-Belson modeling suggested that calendar period effects of decreasing thickness in the general population (SEER 9) did not fully explain thickness trends in NCI families.

Conclusions: Participation in a longitudinal surveillance program providing skin cancer screening and education about skin self-exams was associated with thinner melanomas for members of melanoma-prone families.

Impact: The study findings support the clinical benefit of screening (physician and self) for this high-risk population.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Cyclin-Dependent Kinase 4*
  • Cyclin-Dependent Kinase Inhibitor p16*
  • Female
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation
  • Humans
  • Longitudinal Studies
  • Male
  • Mass Screening
  • Melanoma / epidemiology
  • Melanoma / genetics*
  • Melanoma / pathology*
  • Middle Aged
  • Neoplasm Staging
  • Population Surveillance
  • SEER Program
  • Self-Examination
  • Skin Neoplasms / epidemiology
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology*
  • United States / epidemiology

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4

Associated data

  • ClinicalTrials.gov/NCT00040352