561P - Risk of colorectal cancer and premalignant lesions after kidney transplantation

Background

Improved survival of kidney transplant recipients has led to an increased cancer risk, including colorectal cancer (CRC). We hypothesize that impaired immunosurveillance allows progression of sessile serrated lesions (SSL), leading to a higher incidence of immunogenic mismatch repair deficient (dMMR), but not mismatch repair proficient (pMMR) CRC.

Methods

The nationwide Dutch transplant, pathology, and cancer registries were linked by probabilistic matching to retrieve clinical data of all transplant patients between 2000-2022. A standardized incidence ratio (SIR) was calculated for CRC adjusted for age, sex, and incidence year. Mismatch repair (MMR) status was determined through immunohistochemistry and risk ratios (RR) were estimated. Premalignant lesions were identified within the Dutch CRC screening program. Kidney transplant patients were 1:4 matched to controls based on age, sex, and year of screening.

Results

20 181 kidney transplant patients were identified between 2000-2022 (Table). The mean recipient age was 48 years and 60% were male. 218 tumors were observed, resulting in a SIR of 1.11 (95% CI: 0.96-1.26). In the 162 transplant patients in which MMR status was determined, dMMR occurred more frequently compared to the general population, RR 2.1 (95% CI: 1.6-2.7). Polyps were identified in 488 kidney transplant patients and matched to 1952 patients without kidney transplantation. SSL with dysplasia occurred more often in the transplantation cohort, RR 2.3 (95% CI: 1.3-3.9).

Table: 561P

Incidence of CRC

Conclusions

This population-wide study suggests an increased risk to develop dMMR CRC, in all stages, after kidney transplantation but not pMMR CRC. Furthermore, we show an increased incidence of dysplasia in SSL, in which dMMR frequently occurs. This illustrates that unchecked immunosurveillance in transplant patients is clinically apparent in precancerous and cancerous lesions. These findings could change the manner of CRC screening and management of kidney transplant patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

University Medical Center Utrecht.

Funding

Has not received any funding.

Disclosure

M. Koopman: Financial Interests, Institutional, Advisory Board, advisory board and speaker: Pierre Fabre; Financial Interests, Institutional, Advisory Board: MSD, Bayer; Financial Interests, Institutional, Advisory Board, Advisory Board, speaker: Servier; Financial Interests, Institutional, Invited Speaker: Merck, Bristol Myers Squibb; Financial Interests, Institutional, Trial Chair: Servier; Financial Interests, Institutional, Research Grant: Servier, Roche, Bayer, Bristol Myers Squibb, Merck, Personal Genomics Diagnostics, Sirtex, Pierre Fabre; Financial Interests, Institutional, Funding: Pierre Fabre, Amgen, Nordic Pharma, Novartis, Merck, Servier, Bristol Myers Squibb; Non-Financial Interests, Leadership Role, vice-chair of DCCG: Dutch Colorectal Cancer Group; Non-Financial Interests, Advisory Role, Member of KWF scientific board: KWF; Non-Financial Interests, Other, ESMO faculty member for the Gastro-Intestinal Tumours – colorectal cancer: ESMO; Non-Financial Interests, Advisory Role, expert member of committee “regie op registers dure geneesmiddelen” ZINNL: ZiNNL; Non-Financial Interests, Advisory Role, CRC expert on Kanker.nl platform for answering online CRC questions of CRC (non) patients: Patient respresentative organisation (Kanker.nl); Non-Financial Interests, Leadership Role, chair of RWD & DH working group: ESMO; Other, PI of the Dutch Prospective Colorectal Cancer Cohort study: PLCRC project. G.M. Bol: Financial Interests, Institutional, Research Grant: Bayer, Pierre Fabre, Terumo. All other authors have declared no conflicts of interest.