Rectal cancer patients with a clinical complete response to neoadjuvant (chemo)radiation are eligible for Watch and Wait (W&W). For local regrowth, total mesorectal excision (TME) is considered the standard of care. This study evaluated local excision (LE) for suspected local regrowth. From 591 patients prospectively entered into a national W&W registry, 77 patients with LE for regrowth were included. Outcomes analyzed included histopathologic findings, locoregional recurrence, long-term organ preservation, and colostomy-free and overall survival. In total, 27/77 patients underwent early LE (<6 months after neoadjuvant radiotherapy) and 50/77 underwent late LE (≥6 months). Median follow-up was 53 (39–69) months. In 28/77 patients the LE specimen was histopathologically classified as ypT0 (including 9 adenomas); 11/77 were ypT1, and 38/77 were ypT2–3. After LE, 13/77 patients with ypT2–3 and/or irradical resection underwent completion TME. Subsequently, 14/64 patients without completion TME developed locoregional recurrence, and were successfully treated with salvage TME. Another 8/77 patients developed distant metastases. At 5 years, overall organ preservation was 63%, colostomy-free survival was 68%, and overall survival was 96%. There were no differences in outcomes between early or late LE. In W&W for rectal cancer, LE can be considered as an alternative to TME for suspected regrowth in selected patients who wish to preserve their rectum or avoid colostomy in distal rectal cancer.

Surgery for locally recurrent rectal cancer (LRRC) presents several challenges, which is why the percentage of inadequate resections of these tumors is high. In this exploratory study, we evaluate the use of image-guided surgical navigation during resection of LRRC. Patients who were scheduled to undergo surgical resection of LRRC who were deemed by the multidisciplinary team to be at a high risk of inadequate tumor resection were selected to undergo surgical navigation. The risk of inadequate surgery was further determined by the proximity of the tumor to critical anatomical structures. Workflow characteristics of the surgical navigation procedure were evaluated, while the surgical outcome was determined by the status of the resection margin. In total, 20 patients were analyzed. For all procedures, surgical navigation was completed successfully and demonstrated to be accurate, while no complications related to the surgical navigation were discerned. Radical resection was achieved in 14 cases (70%). In five cases (25%), a tumor-positive resection margin (R1) was anticipated during surgery, as extensive radical resection was determined to be compromised. These patients all received intraoperative brachytherapy. In one case (5%), an unexpected R1 resection was performed. Surgical navigation during resection of LRRC is thus safe and feasible and enables accurate surgical guidance.

Curative rectal cancer treatment has shifted toward organ preservation since the first report on watch and wait (W&W) as an alternative to total mesorectal excision (TME)¹. For patients with locally advanced rectal cancer and a cCR after neoadjuvant therapy, presumed benefits of omitting TME are improved functional outcomes and quality of life (QoL)². The majority of W&W studies have focused on chemoradiation (CRT) and have reported excellent long-term oncological outcomes, with approximately 15–25% local regrowth rates and a 5-year overall survival of 85%^3–5. To date, W&W has been mainly used in patients treated with CRT, rather than in patients treated with other neoadjuvant treatment regimens⁶. Short-course radiotherapy (SCRT) can be indicated for patients with intermediate-risk rectal cancer or for those with contraindications to CRT^7,8. Current standard practice after SCRT is (delayed) TME surgery, sometimes without a response evaluation. SCRT with immediate surgery is not expected to result in significant tumour down-staging, due to the absence of a time interval for tumour regression^9,10. However, when surgery is delayed after SCRT, pathological complete response rates of 8–10% are described^11–14. Therefore, the following question arises: does SCRT with delayed response evaluation play a role in organ preservation for rectal cancer?

Pretreatment response prediction is crucial to select those patients with rectal cancer who will benefit from organ preservation strategies following (intensified) neoadjuvant therapy and to avoid unnecessary toxicity in those who will not. The combination of individual predictors in multivariable prediction models might improve predictive accuracy. The aim of this systematic review was to summarize and critically appraise validated pretreatment prediction models (other than radiomics-based models or image-based deep learning models) for response to neoadjuvant therapy in patients with rectal cancer and provide evidence-based recommendations for future research. MEDLINE via Ovid, Embase.com, and Scopus were searched for eligible studies published up to November 2022. A total of 5006 studies were screened and 16 were included for data extraction and risk of bias assessment using Prediction model Risk Of Bias Assessment Tool (PROBAST). All selected models were unique and grouped into five predictor categories: clinical, combined, genetics, metabolites, and pathology. Studies generally included patients with intermediate or advanced tumor stages who were treated with neoadjuvant chemoradiotherapy. Evaluated outcomes were pathological complete response and pathological tumor response. All studies were considered to have a high risk of bias and none of the models were externally validated in an independent study. Discriminative performances, estimated with the area under the curve (AUC), ranged per predictor category from 0.60 to 0.70 (clinical), 0.78 to 0.81 (combined), 0.66 to 0.91 (genetics), 0.54 to 0.80 (metabolites), and 0.71 to 0.91 (pathology). Model calibration outcomes were reported in five studies. Two collagen feature-based models showed the best predictive performance (AUCs 0.83–0.91 and good calibration). In conclusion, some pretreatment models for response prediction in rectal cancer show encouraging predictive potential but, given the high risk of bias in these studies, their value should be evaluated in future, well-designed studies.

This review summarizes the current applications and benefits of imaging modalities for organ preservation in the treatment of rectal cancer. The concept of organ preservation in the treatment of rectal cancer has revolutionized the way rectal cancer is managed. Initially, organ preservation was limited to patients with locally advanced rectal cancer who needed neoadjuvant therapy to reduce tumor size before surgery and achieved complete response. However, neoadjuvant therapy is now increasingly utilized for smaller and less aggressive tumors to achieve primary organ preservation. Additionally, more intensive neoadjuvant strategies are employed to improve complete response rates and increase the chances of successful organ preservation. The selection of patients for organ preservation is a critical component of treatment, and imaging techniques such as digital rectal exam, endoscopy, and MRI are commonly used for this purpose. In this review, we provide an overview of what imaging modalities should be chosen and how they can aid in the selection and follow-up of patients undergoing organ-preserving strategies.