The impact of mismatch repair status on accuracy of clinical staging in stage II/III rectal cancer in daily practice

Abstract

BACKGROUND: Accurate clinical staging of rectal cancer (RC) is critical for guiding neoadjuvant treatment decisions. In colon cancer, mismatch repair deficient (dMMR) tumours have shown a higher risk of overstaging, but the impact of mismatch repair (MMR) status on staging accuracy in RC remains unclear. This study assessed the accuracy of clinical T and N staging compared to pathological staging in dMMR versus proficient MMR (pMMR) RC patients in the Netherlands. METHODS: Data from 2908 patients diagnosed with stage II/III RC between 2015 and 2022, treated with upfront surgery or short-course radiotherapy (SCRT) followed directly by surgery, and with known MMR status (50 dMMR, 2858 pMMR) were obtained from the Netherlands Cancer Registry. Discrepancies between clinical and pathological T and N stage and TNM risk category were classified as over-, under-, or correctly staged. RESULTS: T stage was overstaged in 47.8 % of dMMR tumours versus 37.1 % of pMMR tumours, while understaging was similar (6.5 % vs 7.5 %). N stage overstaging was more frequent in dMMR (34.7 %) than in pMMR tumours (21.6 %), while understaging was less frequent in dMMR (2.0 %) than in pMMR (18.1 %). TNM risk category was overstaged in 34.0 % of dMMR versus 23.8 % of pMMR tumours, while understaging occurred in 12.0 % vs 23.7 %, respectively. CONCLUSIONS: In RC patients treated with upfront surgery or with SCRT followed directly by surgery, pMMR tumours were more prone to clinical understaging, while dMMR tumours were more frequently overstaged. MMR status should be taken into account in clinical staging for better prognosis estimation and appropriate treatment advice.