Diagnosis of Clinical Complete Response by Probe-Based Confocal Laser Endomicroscopy (pCLE) After Chemoradiation for Advanced Rectal Cancer

Background Neoadjuvant chemoradiotherapy (nCRxt) followed by radical surgery is the optimal treatment for advanced rectal adenocarcinoma. Patients with clinical complete response (cCR) may be followed closely without immediate surgery. Probe-based confocal laser endomicroscopy (pCLE) is a real-time in vivo method that allows acquisition of optical biopsies with 1000 times magnification, evaluating both epithelial and vascular patterns. Aim To evaluate the role of pCLE in the diagnosis of cCR after nCRxt for advanced rectal adenocarcinoma. Methods pCLE was performed in 47 patients with locally advanced rectal adenocarcinoma (T3/T4, or N+) who underwent nCRxt (5-fluorouracil, 5040 cGy). Results Twenty-seven (57.5%) patients were men, and the mean age was 62.8 years. Thirty-seven had partial response confirmed by pCLE. Ten (21.3%) patients had good endoscopic response and presented small ulcer (n = 5) or residual scar (n = 5). After nCRxt, the essential features to differentiate malignancy from post-radiation alterations at pCLE were the presence of irregular crypts, budding, back-to-back glands, cribriform pattern, increased vessel/crypt ratio, and fluorescein leakage. A scoring system was created considering these epithelial and vascular features, with high accuracy for differentiating patients with complete response from those with residual neoplasia (p < 0.00001). pCLE sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 100%, 71.4%, 95.2%, 100%, and 95.7%, respectively. Conclusions (1) pCLE evaluation of epithelial and vascular features may improve the diagnosis of cCR and may alter patient management; (2) pCLE might be valuable for identifying patients with advanced rectal cancer who will benefit from watch and wait strategy, avoiding immediate surgical treatment.