Histopathological ultrastaging of mesocolic lymph nodes after colon cancer resection: A systematic review and meta-analysis.

BACKGROUND

In colon cancer (CC), lymph node (LN) (micro)metastases determine the need for adjuvant chemotherapy. Routine single-section hematoxylin and eosin (H&E) may miss (micro)metastases, resulting in understaging. Histopathological ultrastaging using serial sectioning (SS) and immunohistochemistry (IHC) can improve metastasis detection, for example in the context of organ-preserving surgery using a sentinel lymph node (SLN) procedure. This review evaluates SS and IHC for detecting LN (micro)metastases and aims to identify the ultrastaging method with the highest detection rate. Isolated tumor cells were analyzed separately and were not considered indicative of nodal upstaging.

METHODS

PubMed, Embase, and the Cochrane Library were searched. Studies were included if they evaluated histopathological ultrastaging alongside routine H&E in patients with CC and reported results separately. Risk of bias was assessed using QUADAS-2. Pooled proportions were calculated using random-effects models.

RESULTS

Thirty studies (n = 1822 patients) using SS and IHC were included. In SLN studies (n = 23), 21 % (95 % CI: 12-31 %) of 1070 patients had LN (micro)metastases. Among node-positive patients, 25 % (95 % CI: 6.0-50 %) were identified only by SLN ultrastaging. The absolute benefit of ultrastaging in the total cohort was small, 3.0 % (95 % CI: 1.0-5.0 %), with moderate heterogeneity. In non-SLN studies (n = 7), ultrastaging of all LNs upstaged 6.0 % (95 % CI: 2.0-13 %) of 752 patients, with high heterogeneity. IHC identified only one additional micrometastasis beyond SS. Protocol heterogeneity was considerable.

CONCLUSION

Histopathological ultrastaging detects (micro)metastases, but its clinical impact on adjuvant chemotherapy benefit remains uncertain. Protocol standardization is needed, and the added value of IHC beyond SS appears minimal.