Consensus recommendations for the management of locally advanced rectal cancer

Locally advanced rectal cancer (LARC) considerably impairs quality of life (QoL) and compromises prognosis. Immunotherapy induces complete responses in most patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-h) LARC, enabling organ preservation; however, challenges include access and inconsistent guideline recommendations. This Delphi study aimed to understand the unmet needs of patients with dMMR/MSI-h LARC and seek recommendations for appropriate diagnosis and management.

Europe-based clinical experts participated in a double-blinded modified Delphi panel, with two online surveys and a virtual consensus meeting. Consensus was defined as ≥80% rating their agreement or disagreement on a 9-point Likert scale.

Overall, 26 experts participated in the panel surveys, with 15 also participating in the final consensus meeting. Consensus was reached that dMMR/MSI-h LARC substantially affects QoL and a multidisciplinary team is needed for diagnosis, treatment planning, reflex mismatch repair/MSI testing, and staging. Panelists reached consensus that immunotherapy is an efficacious standard of care, offering high complete response rates, a favorable safety profile, and improved QoL. Consensus was also reached that unmet needs include long-term clinical data and biomarkers to predict treatment response and monitor for disease recurrence. Varied reimbursement policies across Europe underscore the need for updated guidelines and broader immunotherapy access.

Management recommendations include standardized use of immunotherapy as the preferred treatment approach due to its tolerability and efficacy. This informs the future treatment landscape direction and supports the need for long-term clinical data on immunotherapy use.