Probe-Based Confocal Endomicroscopy May Improve the Diagnosis of Clinical Complete Response After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Neoplasia

Abstract

Introduction: Neoadjuvant chemoradiotherapy (nCRxt) followed by surgery represents the optimal approach for medium and distal advanced rectal tumors; however patients with clinical complete response (cCR) may be followed closely without surgery (watch and wait policy). Magnetic resonance imaging (MRI) and endoscopy have low sensitivity for the diagnosis of cCR. Probe-based confocal endomicroscopy (pCLE) represents a real time in vivo method allowing acquisition of optical biopsies with 1000 times magnification, evaluating both cellular and vascular patterns. Aim: to evaluate the contribution of pCLE in the diagnosis of cCR after nCRxt for advanced rectal cancer. Methods: We evaluated 40 patients with locally medium and distal advanced rectal neoplasia (T3 - T4, or N+) between October 2016 and February 2018 who underwent nCRxt (5-fluoroucacil, 5040 cGy), and who were submitted to pCLE. Cell irregularity, atypical glands, vascular enlargement and tortuosity were considered pCLE patterns of malignancy. pCLE was performed pre and post nCRxt, and guided tissue biopsies subsequently. Images of pCLE post nCRxt were recorded and blinded compared to the histology of the surgical specimens. Results: Twenty-one patients had tumor lesions located at medium rectum and 19 patients at distal rectum. Twenty-three (57.5%) patients were men. Mean age was: 63.15 years, varying from 36 to 82 years. Thirty-three had only partial nresponse, all of them confirmed by pCLE. Seven patients (17.5%) had good endoscopic response, and presented only a small ulcer (n=3) or residual scar (n=4). In this subgroup of patients, pCLE post nCRxt correctly diagnosed all but one (6/7 patients). Two negative pCLE patients were confirmed by surgical pathology. Three positive pCLE patients presented pathological residual disease in the surgical specimen. pCLE misdiagnosed one patient who was considered positive, however the surgical pathological result showed only mucin areas without neoplastic cells. One negative pCLE patient has been followed up for one year without any evidence of recurrence at endoscopy and MRI. pTNM stages of the subgroup were: 2 ypT0 ypN0, 1 ypT0 ypN1, 1 ypT1 ypN0, and 2 ypT2ypN0. Conclusion: 1. pCLE could be useful for improving the diagnosis of cCR, and may alter the patient management; 2. pCLE procedure might be valuable for identifying the patients with advanced rectal cancer who will benefit from watch and wait policy, avoiding surgical treatment and consequently achieving better quality of life.