EP628 - Trends In Tumor Board Recommendations For MSI-H/dMMR Rectal Adenocarcinoma: Expanding Role Of Immunotherapy In Nonmetastatic Disease

Purpose/Background: Rectal cancer treatment has evolved significantly over the last few decades, specifically for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) rectal adenocarcinomas. While these tumors make up approximately 6-7% of rectal adenocarcinomas, treatment can be challenging due to treatment-resistant and aggressive tumors. Immune checkpoint inhibitors have transformed treatment for metastatic MSI-H/dMMR rectal cancers . Their role in the neoadjuvant setting for locally invasive rectal cancer is still evolving, with some recent studies supporting organ-preserving approaches in select patients. Our study assessed rectal cancer tumor board (TB) recommendations across 3 NAPRC-accredited institutions to assess evolving trends as regards MSI-H/dMMR rectal cancer patients.

Methods/Interventions: Data from 3 NAPRC approved tumor boards (TBs) in a single health care system was collected and entered into a REDCap database. Patients with rectal adenocarcinoma and confirmed MSI status (from 2022 to 2025) were selected and data from both the initial TB presentation and the mandated post-neoadjuvant treatment TB presentation were assessed.

Results/Outcomes: 368 rectal cancer patients had completed MSI testing with their initial TB presentation, with 12 patients presenting with MSI-H/dMMR tumors (3.3%). 42% proximal rectal tumors, 33% mid rectum and 25% distal rectum. Eight patients (67%) were recommended for neoadjuvant therapy after initial TB presentation, 50% to total neoadjuvant therapy (TNT) and 50% to immunotherapy, all were clinical stage III tumors. Of the patients recommended to TNT, 50% were unable to complete the treatment due to chemotherapy toxicity; one patient received immunotherapy after only completing short-course radiation with subsequent complete response and recommendation to watch-and-wait protocol. The additional three TNT patients had incomplete tumor response and were recommended to surgical resection. For the patients recommended to immunotherapy, one was lost to follow up, one is still undergoing treatment and two finished treatment with complete response and recommended to watch-and-wait protocol. All immunotherapy patients received a programmed cell death protein 1 (PD-1) inhibitor, one received a combination with a cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) inhibitor. Interestingly, the majority (75%) of the TNT patients presented initially in 2022, while the immunotherapy group presented later, in 2023-2025. There were also 4 additional MSI-H/dMMR patients recommended straight to surgery, 50% mid rectum and 50% proximal rectum lesions. Of the mid rectal lesions, one patient presented after piecemeal polypectomy requiring formal resection and the other had concomitant history of recurrent sigmoid diverticulitis. All patients recommended straight to surgery had node negative, nonmetastatic tumors.

Conclusion/Discussion: TB recommendations for MSI-H/dMMR rectal adenocarcinomas have increased the focus on immunotherapy-based and organ-preserving approaches since 2023. Immunotherapy produced complete clinical and radiographic responses among all patients that completed treatment, while TNT was limited by toxicity and incomplete tumor response. These findings highlight a shift towards the consideration and recommendation of immunotherapy in locally advanced MSI-H/dMMR rectal cancer within our health system and the need for continued evaluation of longer term outcomes with a larger cohort.