550P - The impact of mismatch repair status on accuracy of clinical staging in upfront resected stage II/III rectal cancer in the Netherlands

Background

Accurate staging of rectal cancer is of high importance, especially regarding neoadjuvant decision-making. In colon cancer, mismatch repair deficient (dMMR) tumors have already shown to be at risk for overstaging, mainly for lymph nodes. Clinical staging of rectal tumors has been standardized through ESGAR guidelines, but clarity on the influence of MMR status on accuracy of clinical staging is lacking. The aim of this abstract is to assess the accuracy of clinical T and N staging compared to pathological staging in dMMR versus MMR proficient (pMMR) rectal cancer (RC) patients in the Netherlands, using real-word data.

Methods

Data of 2922 patients (53% clinical stage II & 47% stage III RC), with upfront surgery or with 5x5Gy followed by direct surgery were included for a fair comparison of clinical and pathological staging to avoid confounding effect of down-staging. Patients diagnosed between 2015-2022 and a known MMR status (n = 50 dMMR and n = 2872 pMMR) were obtained from the Netherlands Cancer Registry. TNM risk categories were defined as low (T1-3bN0/Nx) intermediate (T1-3dN1 or T3c-dN0) and high (T4a-b or N2) risk. Discrepancy in clinical versus pathological T-, N-stage and TNM risk category was used to define over-, under-, or correct staging. Differences in staging was compared between pMMR and dMMR tumors using Fisher’s exact tests.

Results

Overstaging of TNM risk category was present in 25% of pMMR tumors compared to 40% of dMMR tumors (p=0.03), while understaging occurred in 22% versus 11%, respectively (p = 0.1). Additionally, overstaging of N-stage was seen in 22% of pMMR tumors versus 35% of dMMR tumors (p=0.04), where understaging of N-stage was more present in pMMR tumors compared to dMMR (respectively 17% vs 4%, p = 0.01).

Conclusions

In patients diagnosed with RC, with upfront surgery or with 5x5Gy and direct surgery, pMMR tumors were more often understaged and dMMR tumors more overstaged. This suggests taking MMR status into account when assessing primary clinical stage in RC patients, as accurate staging is important for prognosis estimation and treatment decisions. Future studies should guide the way towards development of specific staging criteria according to MMR status to prevent staging failure.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

University Medical Center Utrecht.

Funding

GSK.

Disclosure

I.A. Franken: Financial Interests, Institutional, Research Grant: DoMore Diagnostics. F.H. van der Baan: Financial Interests, Institutional, Research Funding: Personal Genomic Diagnostics. 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, BMS; 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 Farma, Novartis, merck, servier, BMS; Non-Financial Interests, Leadership Role, vice-chair of DCCG: Dutch Colorectal Cancer Group; 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. Vink: Financial Interests, Institutional, Research Grant: BMS, Merck, Servier, Personal Genome Diagnostics, Bayer, Sirtex, Pierre Fabre, Delfi Diagnostics. M. Intven: Financial Interests, Personal, Full or part-time Employment: UMC Utrecht; Non-Financial Interests, Personal, Leadership Role: Dutch Society for Radiotherapy and Oncology; Financial Interests, Institutional, Project Lead, also Research Funding and Research Grant: Dutch Cancer Society; Financial Interests, Institutional, Steering Committee Member, also Invited Speaker: Elektra. J.M.L. Roodhart: Financial Interests, Institutional, Research Grant: Bayer, Cleara, Servier, GSK, Hub 4 organoids, Pierre Fabre, Servier, Xilis, DoMore diagnostics, Delphi, PGDx; Financial Interests, Institutional, Member of Board of Directors: Foundation Hubrecht Organoid Biobank; Financial Interests, Institutional, Coordinating PI: AMGEN, GSK, BMS, Pfizer, Nutricia. All other authors have declared no conflicts of interest.