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

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.