Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) and selective use of adjuvant chemotherapy is currently considered the standard of care for locally advanced rectal cancer (LARC). Despite this, the concept of organ preservation is gradually challenging this approach. The management of complete clinical remission (cCR) lacks international consensus, leading scholars to develop their own perspectives based on well-designed studies and long-term data from large multicenter cohorts. To ensure appropriate treatment, this review focuses on the choice of neoadjuvant therapy, criteria for defining cCR, and treatment strategies for patients who achieve cCR after neoadjuvant therapy. By providing guidance on the accurate management of LARC patients after cCR, this review aims to prevent over- or under-treatment.

The protocol for treating locally advanced rectal cancer consists of the application of chemoradiotherapy (neoCRT) followed by surgical intervention. One issue for clinical oncologists is predicting the efficacy of neoCRT in order to adjust the dosage and avoid treatment toxicity in cases when surgery should be conducted promptly. Biomarkers may be used for this purpose along with in vivo cell-level images of the colorectal mucosa obtained by probe-based confocal laser endomicroscopy (pCLE) during colonoscopy. The aim of this article is to report our experience with Motiro, a computational framework that we developed for machine learning (ML) based analysis of pCLE videos for predicting neoCRT response in locally advanced rectal cancer patients. pCLE videos were collected from 47 patients who were diagnosed with locally advanced rectal cancer (T3/T4, or N+). The patients received neoCRT. Response to treatment by all patients was assessed by endoscopy along with biopsy and magnetic resonance imaging (MRI). Thirty-seven patients were classified as non-responsive to neoCRT because they presented a visible macroscopic neoplastic lesion, as confirmed by pCLE examination. Ten remaining patients were considered responsive to neoCRT because they presented lesions as a scar or small ulcer with negative biopsy, at post-treatment follow-up. Motiro was used for batch mode analysis of pCLE videos. It automatically characterized the tumoral region and its surroundings. That enabled classifying a patient as responsive or non-responsive to neoCRT based on pre-neoCRT pCLE videos. Motiro classified patients as responsive or non-responsive to neoCRT with an accuracy of ~ 0.62 when using images of the tumor. When using images of regions surrounding the tumor, it reached an accuracy of ~ 0.70. Feature analysis showed that spatial heterogeneity in fluorescence distribution within regions surrounding the tumor was the main contributor to predicting response to neoCRT. We developed a computational framework to predict response to neoCRT by locally advanced rectal cancer patients based on pCLE images acquired pre-neoCRT. We demonstrate that the analysis of the mucosa of the region surrounding the tumor provides stronger predictive power.

Watch-and-wait strategy has been increasingly accepted for patients with clinical complete response (cCR) after multimodal treatment for locally advanced rectal adenocarcinoma. Close follow-up is essential to the early detection of local regrowth. It was previously demonstrated that probe-based confocal laser endomicroscopy (pCLE) scoring using the combination of epithelial and vascular features might improve the diagnostic accuracy of cCR.

To validate the pCLE scoring system in the assessment of patients with cCR after neoadjuvant chemoradiotherapy (nCRxt) for advanced rectal adenocarcinoma.

Digital rectal examination, pelvic magnetic resonance imaging (MRI), and pCLE were performed in 43 patients with cCR, who presented either a scar (N = 33; 76.7%) or a small ulcer with no signs of tumor, and/or biopsy negative for malignancy (N = 10; 23.3%).

Twenty-five (58.1%) patients were men, and the mean age was 58.4 years. During the follow-up, 12/43 (27.9%) patients presented local regrowth and underwent salvage surgery. There was an association between pCLE diagnostic scoring and final histological report (for patients who underwent surgical resection) or final diagnosis at the latest follow-up (p = 0.0001), while this association was not observed with MRI (p = 0.49). pCLE sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 93.5%, 80%, 88.9%, and 86%, respectively. MRI sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 48.4%, 66.7%, 78.9%, and 53.5%, respectively.

pCLE scoring system based on epithelial and vascular features improved the diagnosis of sustained cCR and might be recommended during follow-up. pCLE might add some valuable contribution for identifying local regrowth. Trial Registration This protocol was registered at the Clinical Trials (ClinicalTrials.gov identifier NCT02284802).

Non-operative management of rectal cancer is a feasible and appealing treatment option for patients who develop a complete response after neoadjuvant therapy. However, identifying patients who are complete responders is often a challenge. This review aims to present and discuss current evidence and recommendations regarding the assessment of treatment response in rectal cancer.

A review of the current literature on rectal cancer restaging was performed. Studies included in this review explored the optimal interval between the end of neoadjuvant therapy and restaging, as well as modalities of assessment and their diagnostic performance.

The current standard for restaging rectal cancer is a multimodal assessment with the digital rectal examination, endoscopy, and T2-weighted MRI with diffusion-weighted imaging. Other diagnostic procedures under investigation are PET/MRI, radiomics, confocal laser endomicroscopy, artificial intelligence-assisted endoscopy, cell-free DNA, and prediction models incorporating one or more of the above-mentioned exams.

Non-operative management of rectal cancer requires a multidisciplinary approach. Understanding of the robustness and limitations of each exam is critical to inform patient selection for that treatment strategy.

Reassessment tools of response to long-course neoadjuvant chemoradiation treatment (nCRT) in patients with locally advanced rectal cancer (LARC) are important in predicting complete response (CR) and thus deciding whether a wait-and-watch strategy can be implemented in these patients. Choosing which routine reassessment tools are optimal and when to use them is still unclear and will be researched in the study.

Altogether, 250 patients with LARC who received nCRT from 2013 to 2021 and were followed up were retrospectively reviewed. Common reassessment tools of response included digital rectal examination (DRE), clinical examination and symptoms, endoscopy, biopsy, magnetic resonance imaging (MRI), and blood biomarkers.

Overall, 27.20% (68/250) patients had a complete response and 72.80% (182/250) did not. The combination of MRI, endoscopy, and biopsy showed the best performance in terms of accuracy of 74% and area under the curve (AUC, 0.714, 95% CI 0.546-0.882). Reassessing through DRE and presence of symptoms failed to improve the efficacy of response reassessment. After 100 days, biopsy as an assessment tool would obtain a substantial rise in accuracy from 51.28 to 100% (p = 0.003).

The combination of MRI, endoscopy, and biopsy is suitable as the reassessment tool of response for applying a wait-and-watch strategy after long-course nCRT in patients with LARC. The accuracy of biopsy as reassessment tools would be improved if they were used over 100 days after nCRT in patients with rectal cancer.

In the last years, endoscopic techniques gained a crucial role in the treatment of colorectal flat lesions. At the same time, the importance of a reliable assessment of such lesions to predict the malignancy and the depth of invasion of the colonic wall emerged. The current unsolved dilemma about the endoscopic excision techniques concerns the necessity of a reliable submucosal invasive cancer assessment system that can stratify the risk of the post-procedural need for surgery. Accordingly, this narrative literature review aims to compare the available diagnostic strategies in predicting malignancy and to give a guide about the best techniques to employ. We performed a literature search using electronic databases (MEDLINE/PubMed, EMBASE, and Cochrane Library). We collected all articles about endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) registering the outcomes. Moreover, we analyzed all meta-analyses comparing EMR vs ESD outcomes for colorectal sessile or non-polypoid lesions of any size, preoperatively estimated as non-invasive. Seven meta-analysis studies, mainly Eastern, were included in the analysis comparing 124 studies and overall 22954 patients who underwent EMR and ESD procedures. Of these, eighty-two were retrospective, twenty-four perspective, nine case-control, and six cohorts, while three were randomized clinical trials. A total of 18118 EMR and 10379 ESD were completed for a whole of 28497 colorectal sessile or non-polypoid lesions > 5-10 mm in size. In conclusion, it is crucial to enhance the preoperative diagnostic workup, especially in deciding the most suitable endoscopic method for radical resection of flat colorectal lesions at risk of underlying malignancy. Additionally, the ESD necessitates further improvement because of the excessively time-consuming as well as the intraprocedural technical hindrances and related complications. We found a higher rate of en bloc resections and R0 for ESD than EMR for non-pedunculated colorectal lesions. Nevertheless, despite the lower local recurrence rates, ESD had greater perforation rates and needed lengthier procedural times. The prevailing risk for additional surgery in ESD rather than EMR for complications or oncologic reasons is still uncertain.