Local excision after regrowth in rectal sparing: a review on iterative rectal preservation after neoadjuvant treatment.

Locally advanced rectal adenocarcinoma: Treatment sequences, intensification, and rectal organ preservation.

The management of rectal cancer has been transformed by advances in neoadjuvant treatments, leading to complete response in approximately 30% of cases and making a watch-and-wait (W&W) strategy feasible; however, this approach is associated with a local regrowth (LR) rate of up to 30%, and the management of LR remains non-standardized. We aimed to compare the oncological and quality-of-life outcomes of salvage total mesorectal excision (TME) versus local excision (LE) for LR following W&W in an expert colorectal surgery center. This retrospective analysis included prospectively registered patients with mid and low rectal cancer who achieved complete response after neoadjuvant treatment and were subsequently managed with a W&W strategy at Bordeaux University Hospital between 2015 and 2022. The choice of treatment for LR was based on patient preferences, comorbidities, and multidisciplinary team recommendations. A total of 103 patients were included in the W&W cohort. Among these patients, 33 (32%) developed LR, of whom 17 underwent TME, 13 underwent LE, and 3 presented with distant metastases and were not eligible for surgery. The new LR rate was significantly higher in the LE group compared with the TME group (4 vs. 0 patients; p=0.02). Additionally, 54% of patients in the LE group ultimately required salvage TME (n=7/13). The LE group reported poorer quality of life in terms of mobility (p=0.019) and anxiety/depression (p=0.001). A second attempt at organ preservation using LE after W&W failure may expose patients to increased oncological risk and inferior functional outcomes compared with those undergoing salvage TME. These findings highlight the need for cautious patient selection and standardized protocols when considering LE for LR following W&W.

In patient with a complete or near-complete clinical response after neoadjuvant treatment for locally advanced rectal cancer, the organ-sparing approach [watch & wait (W&W) or local excision (LE)] is a possible alternative to major rectal resection. Although, in case of local recurrence or regrowth, after these treatments, a total mesorectal excision (TME) can be operated. In this retrospective study, we selected 120 patients with locally advanced rectal cancer (LARC) who had a complete or near-complete clinical response after neoadjuvant treatment, from June 2011 to June 2021. Among them, 41 patients were managed by W&W approach, whereas 79 patients were managed by LE. Twenty-three patients underwent salvage TME for an unfavorable histology after LE (11 patients) or a local recurrence/regrowth (seven patients in LE group - five patients in W&W group), with a median follow-up of 42 months. Following salvage TME, no patients died within 30 days; serious adverse events occurred in four patients; 8 (34.8%) patients had a definitive stoma; 8 (34.8%) patients undergone to major surgery for unfavorable histology after LE - a complete response was confirmed. Notably active surveillance after rectal sparing allows prompt identifying signs of regrowth or relapse leading to a radical TME. Rectal sparing is a possible strategy for LARC patients although an active surveillance is necessary.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer.

Local excision of rectal cancer afterchemoradiation: feasibility depends on the primary stage

Patterns of care and surgical outcomes for early-stage rectal cancer in the United States.

PurposeLocal excision is an effective approach for managing rectal cancer exhibiting substantial regression after neoadjuvant chemoradiotherapy. The purpose of this study is to compare the outcomes between local excision and total mesorectal excision in rectal cancer patients achieving clinical complete or near-complete response after neoadjuvant chemoradiotherapy.MethodsThis is a retrospective cohort study that includes a consecutive series of rectal cancer patients who responded well to neoadjuvant chemoradiotherapy followed by surgery. A total of 180 rectal cancer patients at a single institution during a 12-year period are included. The main outcomes include short-term outcomes, oncological outcomes, and functional outcomes between the two groups.ResultsA total of 180 patients were included in the study. Sixty-one (33.9%) received local excision and 119 (66.1%) received total mesorectal excision. The baseline characteristics were generally balanced between the two groups. The local excision group demonstrated a significantly shorter operative time, less blood loss, and shorter hospital stay (p < 0.001). 3-year overall survival rates were 97.5% (95% CI, 0.93–1.00) and 95.5% (95% CI, 0.91–1.00) between the two groups (p = 0.38). The local excision group exhibited significantly higher 3-year local recurrence rates 15.7% (95% CI, 0.74–0.97) vs 4.2% (95% CI, 0.92–1.00) (p = 0.017), yet lower 3-year distant metastasis rates 9.6% (95% CI, 0.82–1.00) vs 12.6% (95% CI, 0.81–0.94) (p = 0.33) and lower 3-year disease-free survival rates 76.8% (95% CI, 0.64–0.92) vs 84.7% (95% CI, 0.78–0.92) (p = 0.56) comparing with the total mesorectal excision group. The local excision group demonstrated significantly better functional outcomes compared with the total mesorectal excision group (p < 0.001).ConclusionPatients who achieve either clinical complete or near-complete response after neoadjuvant chemoradiotherapy are suitable candidates for local excision. The local excision group demonstrated superior short-term and functional outcomes, and the oncological outcomes were not compromised.

Simple SummaryRectal cancer patients with a clinical complete response to neoadjuvant treatment are eligible for Watch and Wait as an alternative to total mesorectal excision. However, in patients with local regrowth, major surgery is still the standard of care. The present study evaluates the role of local excision for suspected local regrowth in a large Watch and Wait cohort, in terms of long-term outcomes. This study shows excellent overall survival and a good organ preservation rate. Patients who developed locoregional recurrence after initial local excision for regrowth were all successfully treated with salvage surgery. This study shows that local excision can provide maintenance of organ preservation without an obvious compromise in surgical or oncological safety. Local excision for suspected regrowth in patients following Watch and Wait can be a safe alternative for total mesorectal excision in selected patients with a strong wish to preserve their rectum.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.

A watch-and-wait approach for patients with rectal cancer and a clinical complete response after neoadjuvant chemoradiotherapy or radiotherapy is associated with better quality of life and functional outcome. Nevertheless, prospective data on both parameters are scarce. To prospectively evaluate quality of life and functional outcome, including bowel, urinary, and sexual function, of patients following a watch-and-wait approach. A total of 278 patients with rectal cancer and a clinical complete response or near-complete response after neoadjuvant chemoradiotherapy or radiotherapy were included in 2 prospective cohort studies: a single-center study (March 2014 to October 2017) and an ongoing multicenter study (from September 2017). Patients were observed by a watch-and-wait approach. Additional local excision or total mesorectal excision was performed for residual disease or regrowth. Data were analyzed between April 1, 2021, and August 27, 2021, for patients with a minimum follow-up of 24 months. Quality of life was evaluated with the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-C30 (EORTC-QLQ-C30), EORTC-QLQ-CR38, or EORTC-QLQ-CR29 and 36-Item Short-Form Health Survey. The score for the questionnaires and 36-Item Short-Form Health Survey ranges from 0 to 100. For some scales, a high score indicates a high level of functioning, and for others it indicates a high level of complaints and symptomatology. Functional outcome was assessed by the Low Anterior Resection Syndrome score, Vaizey incontinence score, International Prostate Symptom Score, International Index of Erectile Function, and Female Sexual Function Index. Of 278 patients included, 187 were male (67%), and the median age was 66 years (range, 34-85 years). In the first 24 months, 221 patients (80%) were observed by a watch-and-wait approach without requiring surgery, 18 patients (6%) underwent additional local excision, and 39 patients (14%) underwent total mesorectal excision. In general, patients observed by a watch-and-wait approach reported good quality of life, with limited variation over time. At 3 months, 56 of 221 patients (25.3%) reported major bowel dysfunction; at 12 months, 53 patients (24.0%) reported it; and at 24 months, 55 patients (24.9%) reported it. At 24 months, 48 of 151 male patients (31.8%) reported severe erectile dysfunction. For female patients, sexual satisfaction and overall sexual function decreased during follow-up. Patients who underwent local excision reported more major bowel dysfunction (10 of 18 patients [55.6%]) compared with those without additional surgery. Quality-of-life scores, however, were comparable. After total mesorectal excision, patients scored significantly worse on several quality-of-life subscales. Results of this study suggest that patients with rectal cancer who were observed by a watch-and-wait approach had good quality of life, with some patients reporting bowel and sexual dysfunction. Quality of life and functional outcome deteriorated when patients required surgery. These data will be useful in daily care to counsel patients on what to expect from a watch-and-wait approach.

The authors have provided a novel hybrid approach in a selected group of locally advanced ultra-low rectal cancers, using neoadjuvant chemoradiation followed by local excision in responders and a delayed Total Mesorectal Excision (TME) and restorative proctectomy, showing that medium-term survival is possible with acceptable functional outcome [1]. Although it is clear that the neoadjuvant approach has acceptable toxicity—with the majority of patients showing significant tumor downsizing and creating a better chance for sphincter preservation—the selection criteria for these patients still remain subjective. Here, the alternatives in those showing a partial clinical response (pCR) include radical resection, transanal local excision and a ‘wait and see' policy but the data are contradictory in the matter of assisting individual patient management [2]. One problem is that some data show relatively high recurrence rates in clinical complete responders when a ‘wait and see' strategy is followed, while studies are heterogeneous in their staging and inclusion criteria and there are differences in what constitutes a pCR. In this respect, there is only partial agreement between pcR and complete clinical response (cCR) cases [3]. This inconsistency of cCR diagnosis most probably also explains some reportedly high rates of local perirectal lymph node metastases in some series, which precludes either a ‘wait and see' plan of action or one combined with local excision [4]. Despite the encouraging results from Wang et al., which mirror those recently reported from Beijing using a neoadjuvant approach followed by TME for distal rectal cancers, [5] the numbers are at this stage too small to result in adequate conclusions regarding this hybrid approach, where four out of nine cases still had lymph node involvement despite a partial response. Although it would appear that objective tumor shrinkage—as measured by magnetic resonance imaging (MRI) or even by barium enema—may assist in correlating with the final histological response [6], our assessment of responders who were less likely to have involved perirectal lymph nodes is still limited, where early FDG-PET responsiveness not only correlates with pathological response but also with relapse-free survival when TME is performed after neoadjuvant therapy for locally advanced cases [7]. Proof of the prognostic benefit of local excision as an interim procedure can only await the results of clinical randomized trials in which there is a standardization of cCR and pCR and its value will be affected by histological tumor type [8] with less tumor regression in mucinous variants, as well as by tumor location (anterior versus posterior tumors) [9]. The advantage of the approach by Wang et al. in this reported study will be that of using the local excision as a prognostic marker for response, since Borschitz et al. have shown a very low locoregional recurrence rate (under 2%) with a near-complete or complete pCR with local excision alone [10] and outcomes that are equivalent to those undergoing routine TME surgery [11]. Despite this approach, however, the high morbidity of a local excisional policy alone should be considered, suggesting that TEM alone remains an unacceptable policy [12]. It is at present hard to justify this ‘triple approach' by Wang and colleagues over conventional TME in distal locally advanced cases with sphincter preservation, although clearly the data are in line with the very low local recurrence rates after complete response [13]. The follow-up in these patients also needs to be comparatively long, as the median time for tumor regrowth can exceed five years [14]. The likelihood is that advances will come more from rigorous patient selection in advanced low tumors with a better definition of cCR by clinical, endoscopic and metabolic imaging, along with histological local excision, to better identify those patients most suited to a subsequent TME or to an observational policy. Further, the data supporting a ‘wait and see' policy in earlier responsive tumors, where salvage surgery may be performed for endoluminal recurrence, cannot effectively be extrapolated to those more advanced T3 or T4 tumors, in which initial nodal positivity can be high and residual nodal disease can be moderate. Locoregional recurrence in such cases will be a feature of residual local lymph node disease that would mandate a restorative TME where possible. In all of this, the best time to assess response currently remains unknown, as does the exact timing of subsequent surgery, which is being investigated by the ongoing {type:clinical-trial,attrs:{text:NCT 01037049,term_id:NCT01037049}}NCT 01037049 UK trial that compares surgery at 6 and at 12 weeks after neoadjuvant therapy. In this regard, more extended periods before definitive surgery may actually permit a greater recorded pCR rate [15]. Conflict of interest: none declared.

BACKGROUND Rectal cancer has become one of the leading malignancies threatening people’s health. For locally advanced rectal cancer (LARC), the comprehensive strategy combining neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant chemotherapy has emerged as a standard treatment regimen, leading to favorable local control and long-term survival. However, in recent years, an increasing attention has been paid on the exploration of organ preservation strategies, aiming to enhance quality of life while maintaining optimal oncological treatment outcomes. Local excision (LE), compared with low anterior resection (LAR) or abdominal-perineal resection (APR) was introduced dating back to 1970’s. LE has historically been linked to a heightened risk of recurrence compared to TME, potentially due to occult lymph node metastasis and intraluminal recurrence. Recent evidence has demonstrated that LE might be an alternative approach, instead of LAR or APR, in cases with favorable tumor regression after NCRT with potentially better quality of life. Therefore, a retrospective analysis of clinicopathological data from mid-low LARC patients who underwent LE after NCRT was conducted, aiming to evaluate the treatment's efficacy, safety, and oncologic prognosis. AIM To explore the safety, efficacy, and long-term prognosis of LE in patients with mid-low rectal cancer who had a good response to NCRT. METHODS Patients with LE between 2012 to 2021 were retrospectively collected from the rectal cancer database from Gastro-intestinal Ward III in Peking University Cancer Hospital. The clinicopathological features, postoperative complications, and long-term prognosis of these patients were analyzed. The Kaplan-Meier method was used to create cancer-specific survival curve, and the log-rank test was used to compare the differences regarding outcomes. RESULTS A total of 33 patients were included in this study. The median interval between NCRT and surgery was 25.4 (range: 8.7-164.4) weeks. The median operation time was 57 (20.0-137.0) minutes. The initial clinical T staging (cT): 9 (27.3%) patients were cT2, 19 (57.6%) patients were cT3, and 5 (15.2%) patients were cT4; The initial N staging (cN): 8 patients (24.2%) were cN negative, 25 patients (75.8%) were cN positive; The initial M stage (cM): 2 patients (6.1%) had distant metastasis (ycM1), 31 (93.9%) patients had no distant metastasis (cM0). The pathological results: 18 (54.5%) patients were pathological T0 stage (ypT0), 6 (18.2%) patients were ypT1, 7 (21.2%) patients were ypT2, and 2 (6.1%) patients were ypT3. For 9 cT2 patients, 5 (5/9, 55.6%) had a postoperative pathological result of ypT0. For 19 cT3 patients, 11 (57.9%) patients were ypT0, and 2 (40%) were ypT0 in 5 cT4 patients. The most common complication was chronic perineal pain (71.4%, 5/7), followed by bleeding (43%, 3/7), stenosis (14.3%, 1/7), and fecal incontinence (14.3%, 1/7). The median follow-up time was 42.0 (4.0-93.5) months. For 31 patients with cM0, the 5-year disease-free survival (DFS) rate, 5-year local recurrence-free survival (LRFS) rate, and 5-year overall survival (OS) rate were 88.4%, 96.7%, and 92.9%, respectively. There were significant differences between the ycT groups concerning either DFS (P = 0.042) or OS (P = 0.002) in the Kaplan-Meier analysis. The LRFS curve of ycT ≤ T1 patients was better than that of ycT ≥ T2 patients, and the P value was very close to 0.05 (P = 0.070). The DFS curve of patients with ypT ≤ T1 was better than that of patients with ypT ≥ T2, but the P value was not statistically significant (P = 0.560). There was a significant difference between the ypT groups concerning OS (P = 0.014) in the Kaplan-Meier analysis. The LRFS curve of ypT ≤ T1 patients was better than that of ypT ≥ T2 patients, and the P value was very close to 0.05 (P = 0.070). Two patients with initial cM1 were alive at the last follow-up. CONCLUSION LE for rectal cancer with significant tumor regression after NCRT can obtain better safety, efficiency, and oncological outcome. Minimally invasive or nonsurgical treatment with patient participation in decision-making can be performed for highly selected patients. Further investigation from multiple centers will bring better understanding of potential advantages regarding local resection.

A complete or subcomplete tumour response (CTR) is observed in 10%-25% of patients with mid/low rectal cancer after neoadjuvant chemoradiotherapy (CRT). The aim of our study was to report a multicentric French experience in local excision (LE) after CRT. All patients who underwent LE for mid/low rectal cancer with suspected CTR after CRT, from 2006 to 2019 in seven GRECCAR centres were included. LE was considered adequate if the specimen showed a ypT0/Tis/T1R0 tumour, otherwise, a completion total mesorectal excision (TME) was discussed. Morbi-mortality, functional results and oncological outcomes were studied. A total of 257 patients were included. LE specimens showed 36% ypT0, 4% ypTis and 19% ypT1. Thus, 108 patients (42%) had theoretical indication of completion TME, which was performed in only 42 patients. Overall, 30-day morbidity after LE was 11%, including 2% Clavien-Dindo grade III or IV complications. After completion TME, 47% described major low anterior resection syndrome versus 5% after LE alone (p < 0.001). After a mean follow-up of 4 years (range 2-6 years), the recurrence rate was 11% after LE, 32% after completion TME and 20% in patients for whom completion TME was indicated but not performed (p = 0.021). TME remains the gold standard for mid/low rectal cancer after CRT. LE in selected patients is safe for operative and functional, but also oncological, results. However, completion TME was indicated in 42% of patients after LE, highlighting the difficulty of the preoperative diagnosis of CTR after CRT.

For treatment of early-stage rectal cancer, local (transanal) excision offers the advantages of lower rates of morbidity, mortality, and functional impairment in comparison with radical surgery such as total mesorectal excision (TME). Minimally invasive platforms facilitate removal of rectal tumors that are beyond the reach of conventional transanal excision techniques. The main drawback of local excision is the higher risk of local recurrence compared with TME. The risk of local recurrence is higher in patients with close resection margins, tumors penetrating beyond the submucosa, or tumors with unfavorable histologic features. In these patients, outcomes for immediate proactive TME are generally better than observation followed by reactive salvage TME in case of local recurrence. The use of neoadjuvant chemoradiotherapy may make local excision a viable option for T2 rectal tumors. As chemoradiation and local excision are being increasingly used for later-stage tumors, advances in imaging technologies will play a crucial role in facilitating careful patient selection. This review contains 5 figures, 5 tables and 37 references Key words: endocavitary contact radiotherapy, local excision, local recurrence, rectal cancer, salvage surgery, total mesorectal excision, transanal endoscopic operation, transanal excision, transanal minimally invasive surgery

For treatment of early-stage rectal cancer, local (transanal) excision offers the advantages of lower rates of morbidity, mortality, and functional impairment in comparison with radical surgery such as total mesorectal excision (TME). Minimally invasive platforms facilitate removal of rectal tumors that are beyond the reach of conventional transanal excision techniques. The main drawback of local excision is the higher risk of local recurrence compared with TME. The risk of local recurrence is higher in patients with close resection margins, tumors penetrating beyond the submucosa, or tumors with unfavorable histologic features. In these patients, outcomes for immediate proactive TME are generally better than observation followed by reactive salvage TME in case of local recurrence. The use of neoadjuvant chemoradiotherapy may make local excision a viable option for T2 rectal tumors. As chemoradiation and local excision are being increasingly used for later-stage tumors, advances in imaging technologies will play a crucial role in facilitating careful patient selection. This review contains 5 figures, 5 tables and 37 references Key words: endocavitary contact radiotherapy, local excision, local recurrence, rectal cancer, salvage surgery, total mesorectal excision, transanal endoscopic operation, transanal excision, transanal minimally invasive surgery

Risk of distant metastasis after local excision for near-complete response versus salvage surgery for local regrowth in rectal cancer: Results from an international registry.