Rethinking lymphadenectomy in the immunotherapy era of colorectal cancer: A hypothesis-generating perspective.

BACKGROUND

Lymphadenectomy is traditionally central to curative colorectal cancer (CRC) surgery, with ≥ 12 retrieved lymph nodes being a well-recognised quality indicator influencing staging and local control. However, contemporary immunology reframes tumour-draining lymph nodes (TDLNs) as active co-ordinators of anti-tumour immunity.

AIM: This article examines whether routine lymphadenectomy may theoretically impair systemic immune surveillance and immune checkpoint inhibitor (ICI) response, a concern most applicable to mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) disease.

MATERIALS AND

METHODS

A review of surgical, oncological and immunological literature was performed, including comparison to breast cancer and melanoma, where sentinel lymph node biopsy (SLNB) and nodal preservation are standard.

RESULTS

Retrospective CRC datasets demonstrate improved survival with increased nodal yield, though causality remains unproven and confounded by tumour biology, surgical quality and centre volume. Preclinical studies indicate TDLNs are essential for ongoing systemic immunity and optimal ICI effectiveness with early human data reporting improved outcomes with adjuvant immunotherapy. Evidence from breast cancer and melanoma provides indirect support for the concept of nodal preservation (SLNB ± observation) maintaining outcomes while reducing surgical morbidity, although lymphatic anatomy and systemic therapy differ from CRC.

DISCUSSION: These concepts require further research to evaluate whether CRC surgical strategy in the immunotherapy era may need to balance oncological clearance against immune preservation. Selective nodal surgery guided by sentinel mapping or molecular tracers, integration with neoadjuvant and adjuvant immunotherapy trials, and molecular staging to reduce reliance on large nodal harvests represent key areas for investigation.

CONCLUSION

Prospective, stratified trials, especially in dMMR/MSI-H vs. MSS cohorts, are needed to define when or if less may be more.