Multiple Primary Cancers in Colorectal Cancer Survivors: A Comprehensive Narrative Review of Epidemiology, Genetics and Clinical Implications

Authors:
Open Access
Publisher website
Google Scholar
Abstract
With rising global incidence and improved survival, colorectal cancer (CRC) survivors face an increasing risk of developing multiple primary cancers (MPCs). Despite the growing clinical significance, the epidemiology, molecular basis and optimal clinical management of MPCs remain incompletely understood. This narrative review summarises historical perspectives on the definition of MPCs and synthesises current epidemiological, clinical and molecular evidence on MPCs among CRC survivors, focusing on incidence, risk factors, biological mechanisms, mortality and clinical implications of MPCs in CRC survivors. Available evidence indicate that up to 20% of CRC survivors develop one or more subsequent MPCs, with risk influenced by age at diagnosis of the index CRC, sex, tumour characteristics, comorbidities and variation in tumour coding practices. Survivors diagnosed before the age of 50 years have the highest risk of MPCs. The most commonly reported MPCs include gastrointestinal, prostate, breast, lung, urinary tract, haematological and gynaecological cancers. The presence of MPCs is associated with substantially poorer outcomes and increased mortality, with deaths frequently attributable to lung, gastrointestinal, prostate, urinary tract and haematological cancers. The molecular mechanisms underlying MPC development are poorly understood. Although germline pathogenic variants account for a subset of cases, evidence suggest that somatic mutations, tumour mutational burden and field cancerisation may contribute to the development of multiple malignancies. However, no consistent molecular drivers of MPCs have been identified. Clinical management is further complicated by the absence of evidence‐based guidelines, under‐representation of cancer survivors in clinical trials, biological heterogeneity of tumours and the complexity of synchronous and metachronous disease presentations. In conclusion, MPCs represent an increasingly important challenge in CRC survivorship and contribute substantially to long‐term morbidity and mortality. Future advances will require integration of large‐scale clinical and molecular datasets, improved understanding of underlying biological mechanisms and development of risk‐stratified surveillance and treatment strategies. Progress in preclinical disease models and targeted therapies may ultimately improve outcomes for the growing survivor population.

This publication has 122 references indexed in Scilit: