A pancancer analysis of the clinical and genomic characteristics of multiple primary cancers

Abstract

Multiple primary cancer (MPC) denotes individuals with two or more malignant tumors occurring simultaneously or successively. Herein, a total of 11,000 pancancer patients in TCGA database (1993–2013) were divided into MPC or non-MPC groups based on their history of other malignant tumors. The incidence of MPC has risen to 8.5–13.1% since 2000. Elderly individuals, males, early-stage cancer patients, and African Americans and Caucasians are identified as independent risk factors (p < 0.0001). Non-MPC patients exhibit significantly longer overall survival (OS) and disease-free survival (DFS) (p = 0.0038 and p = 0.0014). Age (p < 0.001) and tumor staging at initial diagnosis (p < 0.001) contribute to this difference. In our center, MPC was identified in 380 out of 801 tumor events based on SEER criteria. The peak occurrence of secondary primary was about 1–5 years after the first primary tumor, with a second small peak around 10–15 years. Multiple tumors commonly occur in the same organ (e.g., breast and lung), constituting 12.6%. Certain cancer types, notably skin cutaneous melanoma (SKCM), exhibit significantly higher tumor mutational burden (TMB) in the MPC group (17.31 vs. 6.55 mutations/MB, p < 0.001), with high TMB associated with improved survival (p < 0.001). High TMB in MPC may serve as a predictor for potential immunotherapy application.