Neoadjuvant Immunotherapy Followed by Surgery Compared with Upfront Surgery Alone in Operable Colon Cancer with Deficient Mismatch Repair: Modeling Oncological Outcomes and Numbers Needed to Treat.

Background: Trials on neoadjuvant immunotherapy in operable colon cancer with deficient mismatch repair (dMMR) reported high pathological response rates in the surgical specimen, but long-term survival is not known. Neoadjuvant immunotherapy as a stand-alone therapy without subsequent radical surgery is currently not investigated in colon cancer.

Objective: The aim of this study was to model outcomes between trial data and real-world patients after surgery.

Methods: We conducted a comparative modeling study between prospective trial data (NICHE-1) and a prospective, population-derived, translational cohort study (ACROBATICC) of patients with operable colon cancer and microsatellite instability (MSI) status. Comparison was performed across immune-cell infiltrates, stages, MSI, and patient demographics for adverse events, reported oncological outcomes, and modeling numbers needed to treat (NNT) to prevent recurrence.

Results: Patient characteristics between the dMMR tumors in the NICHE-1 (n = 21) and ACROBATICC (n = 43) cohorts differed, with older patients and fewer hereditary dMMRs in the 'real-life' ACROBATICC cohort. Higher expression of CD8+ in dMMR tumors compared with proficient mismatch repair (pMMR) tumors was statistically significant across both cohorts. At long-term follow-up, 2/43 patients with dMMR had died from recurrent colon cancer in the ACROBATICC cohort. Assuming a curative effect of neoadjuvant immunotherapy in addition to surgery in dMMR tumors, the NNT would be >20 patients for any additional survivor.

Conclusion: In unselected patients with colon cancer having dMMR, recurrence risk is very low after surgery. Assuming a curative effect of neoadjuvant immunotherapy beyond surgery alone, the NNT would be at least 20 patients to prevent one cancer death over surgery alone.