Histopathological factors help to predict lymph node metastases more efficiently than extra-nodal recurrences in submucosa invading pT1 colorectal cancer.

The therapeutic management of patients with endoscopic resection of colorectal cancer invading the submucosa (i.e. pT1 CRC) depends on the balance between the risk of cancer relapse and the risk of surgery-related morbidity and mortality. The aim of our study was to report on the histopathological risk factors predicting lymph node metastases and recurrences in an exhaustive case series comprising every pT1 CRC (of adenocarcinoma subtype only) diagnosed in Finistère (France) during 5-years. For 312 patients with at least 46 months follow-up included in the digestive cancers registry database, histopathological factors required for risk stratification in pT1 CRC were reviewed. Patients were treated by endoscopic resection only (51 cases), surgery only (138 cases), endoscopic resection followed by surgery (102 cases) or transanal resection (21 cases). Lymph node metastases were diagnosed in 19 patients whereas 15 patients had an extra-nodal recurrence (7 local recurrences only, 4 distant metastases only and 4 combining local and distant recurrences). Four patients with distant metastases died of their cancer. Poor tumor differentiation, vascular invasion and high grade tumor budding on HES slides were notably identified as strong risk-factors of lymph node metastases but the prediction of extra-nodal recurrences (local, distant and sometimes fatal) was less obvious, albeit it was more frequent in patients treated by transanal resection than with other treatment strategies. Beyond good performances in predicting lymph node metastases and guiding therapeutic decision in patients with pT1 CRC, our study points that extra-nodal recurrence of cancer is more difficult to predict and requires further investigations.

High reproducibility is attainable in assessing histoprognostic parameters of pT1 colorectal cancer using routine histopathology slides and immunohistochemistry analyses.

Assessment of the risk of lymph node invasion and tumour recurrence is critical to determine whether additional surgery is required in patients with endoscopically-removed pT1 colorectal cancer (CRC). A reproducible assessment of this risk of recurrence based on histopathological parameters is crucial for relevant therapeutic decisions. The inter-observer reproducibility of these parameters was the subject of our study. Two pathologists independently analysed 163 endoscopically-removed pT1 CRC recorded in a local digestive cancer registry database (Finistère, France). Using haematoxylin-eosin-saffron (HES) and immunohistochemistry slides, they evaluated several parameters related to the risk of tumour recurrence according to the international pT1 CRC-dedicated guidelines. Based on Kappa and intra-class correlation coefficients, good to very good inter-observer agreement was obtained by analysing vertical and lateral margins, submucosal invasion, tumour differentiation and lymphovascular invasion. The reproducibility of tumour budding quantification was only fair on the basis of HES slides but reached a very good agreement using cytokeratin immunohistochemistry. Dual colour cytokeratin and podoplanin immunohistochemistry also improved inter-observer agreement for the detection of lymphovascular invasion. All patients with loco-regional nodal metastases (7 of 101 who underwent complementary surgery) or distant metastases (3 patients) were diagnosed as having a high risk of recurrence and requiring an additional surgery by the two observers. Our study showed that good to very good inter-observer agreement is achievable in evaluating the pathological parameters of recurrence risk in endoscopically-removed pT1 CRC. In addition to HES slides, the detection of lymphovascular invasion and tumour budding can benefit with more reproducible immunohistochemical analyses.