The risk of mortality from multiple primary cancers in colorectal cancer survivors: analysis of data from the South Australian Cancer Registry

Purpose
Colorectal cancer (CRC) survivors face an increased risk of multiple primary cancers (MPCs), but evidence on MPC-related mortality is limited.

Methods
Using data from the South Australian Cancer Registry (1982–2017), this retrospective study analysed CRC survivors diagnosed with MPCs, defined as distinct primary cancers arising ≥ 2 months after CRC diagnosis. Causes of death were categorised as index CRC, MPC, or non-cancer related. Poisson regression estimated cancer-specific mortality risk compared to the general population. Propensity score weighting was applied to balance covariate distribution between CRC survivors with and without MPC groups. A hazard ratio (HR) for all-cause mortality was estimated using a weighted dataset to assess the impact of MPC on overall survival.

Results
Among 26,093 CRC survivors (181,877 person-years follow-up), the age-standardised MPC-related mortality rate was 240 per 100,000 population. Gastrointestinal, lung, haematological, and urinary tract cancers were the most common MPC-related causes of death. CRC survivors had a 45% higher risk of dying from MPCs than the general population (standardised mortality ratio = 1.45, 95%CI 1.38–1.52). Adjusted analyses showed a 58% increase in all-cause mortality among CRC survivors with MPCs (HR = 1.58, 95%CI 1.51–1.65).

Conclusions
CRC survivors with MPC face significantly worse survival compared to those with a single primary CRC. Early detection and management of MPCs are essential for improving long-term survival in individuals diagnosed with CRC.