Assessment of colorectal cancer recurrence risk following solid organ transplantation

Prior studies have reported solid organ transplant (SOT) recipients have increased rates of colorectal cancer (CRC). While this increased incidence is established, the recurrence risk following curative-intent treatment for post-SOT CRC remains poorly defined. Therefore, the aim of this study was to evaluate CRC recurrence in addition to exploring clinical and molecular factors associated with CRC recurrence in patients with prior SOT.

Multi-institutional retrospective cohort study of adult patients diagnosed with CRC following prior SOT between 2016-2025 at The Johns Hopkins Hospital and the University of Wisconsin Hospitals and Clinics. Demographic, clinical, molecular genomics, and immunosuppression data were obtained from electronic medical records. Recurrence risk was compared to population study benchmark recurrence rates using standardized incidence ratios (SIRs).

This study included 53 SOT recipients with subsequent CRC diagnosis. Recurrence rates exceeded population benchmarks across all disease stages, particularly in stage I and II disease demonstrating SIRs of 3.66 and 2.55 respectively. KRAS and APC mutations were associated with increased recurrence risk [hazard ratio (HR) =13.58, P=0.002; HR =5.03, P=0.02, respectively], while no patients with BRAF mutations recurred (n=8, P<0.001). All BRAF mutations occurred in tumors that were mismatch repair deficient (MMRd). Mismatch repair (MMR) status and immunosuppression characteristics did not predict disease recurrence in the study cohort.

SOT recipients showed a trend towards heightened CRC recurrence risk compared to population benchmarks. KRAS, APC, and BRAF mutational status all influenced recurrence risk in this cohort. Despite a lack of association between immunosuppression variables and recurrence, we suspect diminished immune surveillance is implicated in this elevated relapse risk. Strategies to address this, including immunosuppression reduction in the post-SOT CRC population, may be effective in reducing this elevated relapse risk but require validation in prospective multi-institutional studies.