Watch and Wait (WW) strategy is currently used for mid/low rectal adenocarcinoma after neoadjuvant treatment (NAT). Local regrowth (LR) is a well-known risk, but its impact on distant metastasis (DM) is increasingly debated. This study aimed to assess the rate of DM after local excision (LE) for near-complete clinical response (ncCR) at restaging versus salvage surgery for regrowth following WW.

Retrospective analysis of DM rates from a prospective international registry, comparing patients with ncCR after NAT who underwent LE and patients with initial complete clinical response (cCR) and WW strategy, who underwent salvage surgery for regrowth. The primary endpoint was the 5-year distant metastasis-free survival (5y-DMFS). Univariate/Multivariate analysis were performed to identify risk factors of DM.

Among 138 patients included, 59 had LE for ncCR and 79 had salvage surgery after regrowth including TME (n = 23), APR (n = 30) and LE (n = 26). The 5y-DMFS was lower in patients with surgery at regrowth, 71 % vs. 93 % (p = 0.006). LR was the only independent risk factor associated with DM (OR:3.89; 95 % CI:1.34-11.25; p = 0.012). When only patients managed by salvage LE for LR are considered, 5y-DMFS was equivalent to LE at restaging (87 vs. 93; p = 0.442).

Patients with rectal cancer undergoing LE for ncCR after NAT have a significantly lower rate of DM compared to patients undergoing salvage surgery after LR within WW approach. Patients managed by LE for regrowth may represent a distinct subgroup where the risk of subsequent DM is equivalent to patients managed by LE at restage.

With the results of several recently published clinical trials, this guideline focused update provides evidence-based recommendations for the indications and dose-fractionation regimens for neoadjuvant radiation therapy (RT), optimal sequencing of RT and systemic therapy in the context of total neoadjuvant therapy (TNT), and considerations for selective omission of RT and surgery for rectal cancer.

The American Society for Radiation Oncology convened a multidisciplinary task force to update 3 key questions that focused on the role of RT for patients with operable rectal cancer. The key questions addressed (1) indications for neoadjuvant RT, (2) selection of neoadjuvant regimens, and (3) indications for consideration of a nonoperative management (NOM) or local excision approach after definitive/preoperative chemoradiation. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation.

For patients with stage II-III rectal cancer, neoadjuvant RT was strongly recommended; however, among patients deemed at lower risk of locoregional recurrence, consideration of omission of neoadjuvant RT was conditionally recommended in favor of neoadjuvant chemotherapy with a favorable treatment response or upfront surgery. For patients with T3-T4 and node-positive rectal cancer undergoing neoadjuvant RT, a TNT approach was strongly recommended. Among patients with higher risk of locoregional recurrence, TNT with chemotherapy before or after long-course chemoradiation was strongly recommended, whereas TNT with short-course RT followed by chemotherapy was conditionally recommended. For patients with rectal cancer for whom NOM is a priority, concurrent chemoradiation followed by consolidation chemotherapy was strongly recommended. Selection of RT dose-fractionation regimen, sequencing of therapies, and consideration of NOM should be determined by multidisciplinary consensus and based on disease extent, disease location, patient preferences, and quality of life considerations.

The task force proposed recommendations to inform best clinical practices on the use of RT for rectal cancer with strong emphasis on multidisciplinary care. Future studies should focus on further addressing optimal treatment regimens to allow for more personalized recommendations based on individual risk stratification and patient priorities regarding quality of life.

Neoadjuvant chemoradiotherapy followed by radical surgery is the common treatment for patients with locally advanced rectal cancer. Presently, for patients with complete clinical response after neoadjuvant chemoradiotherapy, organ preservation ("watch-and-wait" and local excision strategies) has been increasingly favored. However, the optimal treatment for patients with complete clinical response remains unclear.

This study aimed to use Bayesian meta-analysis to determine the best treatment for patients with locally advanced rectal cancer with complete clinical response among radical surgery, local excision, and watch-and-wait strategies.

PubMed, Web of Science, Cochrane Library, and Embase (Ovid) databases were searched for literature published through December 31, 2023.

Studies that compared 2 or more treatments for patients with complete clinical response were included.

The analysis was completed via Bayesian meta-analysis using a random-effects model.

Surgery-related complications, local recurrence, distant metastasis, and 5-year overall and disease-free survival rates.

Eleven articles met the inclusion criteria. The watch-and-wait group and local excision group exhibited a higher rate of tumor recurrence compared to the radical surgery group (watch-and-wait vs radical surgery: OR, 9.10 [95% CI, 3.30-32.3]; local excision vs radical surgery: OR, 2.93 [95% CI, 1.05-9.95]). The distant metastasis, overall survival, and disease-free survival rates of the 3 treatments were not statistically different. The radical surgery group had the most number of stomas and had the greatest risk of morbidity than the watch-and-wait group (watch-and-wait vs radical surgery: OR, 0.00 [95% CI, 0.00-0.12]).

The study included only 1 randomized controlled trial compared to 10 observational studies, which could affect overall quality. Funnel plots of disease-free survival rates and stoma suggest significant publication bias among studies that compared radical surgery with the watch-and-wait strategy.

The watch-and-wait strategy could be optimal for patients with locally advanced rectal cancer with complete clinical response after neoadjuvant chemoradiotherapy.

The adoption of a watch and wait (W&W) approach in patients with rectal cancer, and a complete clinical response (cCR) following neoadjuvant therapy, is increasing worldwide. Despite this, pragmatic unbiased outcome data is limited. This study aimed to investigate national outcomes associated with W&W in Aotearoa New Zealand (AoNZ).

A national retrospective study of patients with adenocarcinoma of the rectum managed with a W&W approach between January 2015 and December 2022 in AoNZ was performed by STRATA, a student and trainee led collaborative network. The Cancer Registry and the New Zealand Ministry of Health National Minimum Data Set were linked to identify patients who had rectal cancer and who were treated with neoadjuvant therapy but not rectal resection. Research teams across 17 AoNZ hospitals then screened these patients for inclusion and data collection.

One thousand five hundred and eighteen patients were screened across 17 hospitals, 133 met inclusion criteria. Median age was 71 years. Median follow-up was 2.2 years. The 2-year cumulative incidence of local regrowth was 18.2% (95% CI 10.7%-25.1%), of which 92% was present in the bowel wall, and 68% underwent surgery, all with curative intent. The 2-year cumulative distant metastasis rate was 8.8% (95% CI 3.0%-14.2%) and the 2-year overall survival was 94.8% (95% CI 90.4%-99.4%).

This nationwide study of a W&W approach has clinical outcomes similar to the international literature. This data will help guide further implementation of a W&W approach in the management of patients with rectal cancer and inform both clinicians and patients.

Rectal cancer is a significant global health concern, particularly amongst the elderly population, with rectal cancer accounting for approximately one-third of cancer cases in this population. Older adults often present with advanced disease stages and unique clinical manifestations, such as tumors closer to the anal verge and with greater size. Diagnosis typically involves a series of screening and imaging strategies, culminating in accurate staging through pelvic MRI, endoscopic ultrasound, and CT scan. Management of rectal cancer in older adults emphasizes individualized treatment plans that consider both the cancer stage and the patient's overall health status, including frailty and comorbidities. A multidisciplinary approach, including a mandatory geriatric assessment, is essential for optimizing outcomes, in order to improve survival and quality of life for elderly patients with rectal cancer.

Total mesorectal excision is the standard surgery for locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT), but it may lead to high complication rates and poor quality of life. This study evaluates whether transanal endoscopic microsurgery (TEM), as a partial resection procedure, can enhance quality of life for clinical complete response (cCR) or near-cCR patients without compromising survival.

Between May 2017 to September 2021, 80 patients with T3-4N0M0 or TanyN+M0 mid-low rectal cancer achieving cCR or near-cCR post-nCRT were prospectively included at 6 Chinese centers. Patients underwent either TEM (Group A, n = 38) or radical surgery (Group B, n = 41). Clinicopathological, oncological, and functional outcomes were analyzed.

Postoperative histology revealed 22 ypT0 (57.9 %), 5 ypT1 (13.2 %), 10 ypT2 (26.3 %), and 1 ypT3 (2.6 %) cases in group A and 20 pCR (48.8 %), 1 T0N1 (2.4 %), 5 T1N0 (12.2 %), 12 T2-3N0 (29.3 %), 3 T2-3N1 (7.3 %) cases in group B. After a 60-month median follow-up, local recurrence occurred in 2 patients (5.26 %) in Group A and none in Group B. Distant metastases occurred in 8 patients (21.05 %) in group A and 7 (17.07 %) in group B. There was no significant difference between the two groups in 5-year disease-free survival (P = 0.658) or 5-year overall survival (P = 0.465). Group A showed significantly faster recovery (P < 0.001) and better sphincter function per Wexner (1 vs. 4, P = 0.001) and LARS (0 vs. 17, P < 0.001) scores than Group B.

TEM may be an effective approach for assessing residual tumors in LARC patients with cCR or near-cCR. This approach offers an option for those requiring sphincter preservation, with no significant compromise in long-term oncological outcomes observed in our study.

MRI plays a critical role in the local staging, restaging, surveillance, and risk stratification of patients, ensuring they receive the most tailored therapy. As such, radiologists must be familiar not only with the key MRI findings that influence management decisions but also with the appropriate MRI protocols and structured reporting. Given the complexity of selecting the optimal therapy for each patient-which often requires multidisciplinary discussions-radiologists should be well-versed in relevant treatment strategies and surgical terms, understanding their significance in guiding patient care. In this manuscript, we review the most common treatment options for managing patients with rectal adenocarcinoma, emphasizing key MRI principles and protocol characteristics for accurate staging. We also highlight important anatomical landmarks and essential factors to be described during baseline assessment. Additionally, we discuss crucial information for restaging and surveillance.

Organ preservation (OP) strategies are gaining interest in improving the quality of life in the management of rectal cancer, particularly for tumors located in the distal or middle rectum. The optimal OP protocol is still not standardized and relies on randomized trials. This review summarizes past and ongoing studies on OP protocols for adenocarcinoma of the distal and middle rectum.

We searched for articles and abstracts on randomized clinical trials investigating OP approaches for rectal cancer, including data presented at the LUCARRE Congress held in Nice on November 25, 2023, covering ongoing and recently published trials on rectal preservation.

Our review's findings are presented in four tables: the first evaluates key trials with overall survival (OS) as the primary endpoint; the second provides an overview of past Phase III trials; the third reviews Phase II/III trials that specifically focus on local excisions (LE); and finally, the fourth summarizes ongoing trials. Each table is accompanied by detailed comments elucidating the significance and implications of the presented data, alongside a review of current guidelines.

We highlight the growing interest in OP strategies for rectal cancer management to enhance patients' quality of life. Despite the lack of international consensus on the optimal OP protocol, past and ongoing randomized trials provide valuable findings into the evolving management strategies of rectal cancer treatment. The presented data supports the role of randomized phase III trials to provide evidence for a change in clinical practice.

Local resection (LR) in rectal cancer is indicated in stage T1N0M0 without unfavorable pathological factors, achieving oncologically satisfactory outcomes through transanal endoscopic surgery techniques. However, the initial step involves accurate staging and selection of these tumors through specific tests conducted in specialized colorectal units. For T2N0M0 tumors and T1 tumors with poor prognostic factors, the standard treatment is total mesorectal excision (TME), a procedure associated with high postoperative morbidity and mortality, functional impairments, and reduced quality of life. Therefore, new organ-preservation strategies are being explored as alternatives to TME. These include neoadjuvant therapy combined with LR, which has shown promising results, and neoadjuvant therapy followed by a "Watch and Wait" approach -where patients with complete clinical response are selected for strict surveillance- as an ideal future treatment, although there are still current challenges to be addressed.

Advancements in cancer care have significantly extended the life expectancy of rectal cancer patients and the impact of treatment-related toxicity on long-term quality of life has become a crucial factor in determining the most suitable type of neoadjuvant therapy, particularly for patients who are likely to undergo surgery. While radiotherapy has traditionally been regarded as the cornerstone for achieving improved local control in rectal cancer, it is accompanied by a range of associated complications, including bowel and bladder dysfunction, gonadal ablation, and Low Anterior Resection Syndrome. De-escalation of treatment is undoubtedly beneficial for many patients, and this approach should be tailored to consider their expectations while prioritizing patient care in decision-making. Although there is inadequate data to support the oncologic safety of a watch-and-wait approach without radiation or to omit radiation in patients with suspicious lateral pelvic lymph nodes, sufficient evidence exists to justify de-escalation by avoiding radiation before surgery in many other patients who respond well to chemotherapy.

In contrast to significant advances in organ preservation in locally advanced rectal cancer, the contemporary management of early-stage rectal cancer, including the frequency of abdominoperineal resections, remains largely unexplored in the United States. Therefore, we assessed the utilization of neoadjuvant therapy and oncological resections in early-stage rectal cancer patients.

This is a retrospective cohort study of patients with cT1-T3N0 rectal cancer who underwent proctectomies between 2016 and 2022 in the National Surgical Quality Improvement Project proctectomy files. Multivariable logistic regression was used to identify factors associated with abdominoperineal resections and Kendall's tau statistics to evaluate clinical-pathological staging agreement.

In all, 3078 patients (29.6% cT1-2N0, 70.4% cT3N0) were included with 55.3% of tumours <5 cm from the anal verge. Overall, 58.2% received neoadjuvant therapy within 3 months of surgery (30.6% for cT1-T2N0 vs. 69.8% for cT3N0, P < 0.001), and 58.6% underwent abdominoperineal resection (55.5% for cT1-T2N0 vs. 59.9% for cT3N0, P = 0.058). The adjusted odds of undergoing abdominoperineal resection were associated with increasing age (OR 1.4 per every 10-year increase; 95% CI 1.2-1.5), cT3N0 tumours (OR 1.7; 95% CI 1.1-2.7) and tumour location <5 cm from the anal verge (OR 10.6; 95% CI 7.7-14.7). There was a weak clinical-pathological T staging correlation (Kendal tau coefficient 0.25; 95% CI 0.20-0.29).

In this large cohort of patients with early-stage rectal cancer with high rates of neoadjuvant therapy, over half of patients underwent abdominoperineal resection and one in five had a pathological complete response. These findings underscore opportunities for organ preservation in early-stage rectal cancer, suggesting that treatments typically reserved for locally advanced disease may extend to early stages with the completion of ongoing clinical trials.

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.

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.

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.

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.

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.

Non-radical management is an option for good responders to neoadjuvant chemoradiotherapy in mid-to-low rectal cancer. This study aimed to analyze risk factors for lymph node metastasis in patients with ypT2 rectal cancer, exploring the possibility of non-radical management.

We included patients with ypT2 rectal cancer who received neoadjuvant chemoradiotherapy followed by total mesorectal excision between January 2004 and December 2022. Clinicopathological parameters were evaluated to identify risk factors for lymph node metastasis.

Among the 198 patients, 158 (79.8%) had ypT2N0 and 40 (20.2%) had ypT2N+. In univariable analyses, the risk factors of lymph node metastasis were perineural invasion (48.0% vs. 16.3% without perineural invasion, P < 0.001), female sex (30.0% vs. 14.8% with male sex, P = 0.011), and clinically positive nodes after neoadjuvant chemoradiotherapy (32.6% vs. 16.4% with negative nodes, P = 0.017). These factors were confirmed as independent risk factors in multivariable analyses: perineural invasion (odds ratio [OR]: 4.50; 95% confidence interval [CI]: 1.79-11.29; P < 0.001), female sex (OR: 2.62; 95% CI: 1.24-5.52; P = 0.012) and clinical node involvement after neoadjuvant chemoradiotherapy (OR: 2.28; 95% CI: 1.03-5.05; P = 0.012). The rate of lymph node metastasis in patients with ypT2 rectal cancer without any of these three risk factors was 12.5%.

This study revealed a high probability of lymph node metastasis in patients with ypT2 rectal cancer, even in the absence of identifiable risk factors. We confirm that lymph node metastasis should be considered in ypT2 rectal cancer.

For patients with rectal cancer, the standard approach of chemotherapy, radiation therapy, and surgery (trimodality therapy) is associated with significant long-term toxicity and/or colostomy for most patients. Patient options focused on quality of life (QOL) have dramatically improved, but there remains limited guidance regarding comparative effectiveness. This systematic review and associated guidelines evaluate how various treatment strategies compare to each other in terms of oncologic outcomes and QOL. Cochrane and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology were used to search for prospective and retrospective trials and meta-analyses of adequate quality within the Ovid Medline database between January 1, 2012, and June 15, 2023. These studies informed the expert panel, which rated the appropriateness of various treatments in 6 clinical scenarios through a well-established consensus methodology (modified Delphi). The search process yielded 197 articles that advised voting. Increasing data have shown that nonoperative management (NOM) and primary surgery result in QOL benefits noted over trimodality therapy without detriment to oncologic outcomes. For patients with rectal cancer for whom total mesorectal excision would result in permanent colostomy or inadequate bowel continence, NOM was strongly recommended as usually appropriate. Restaging with tumor response assessment approximately 8 to 12 weeks after completion of radiation therapy/chemoradiation therapy was deemed a necessary component of NOM. The panel recommended active surveillance in the setting of a near-complete or complete response. In the setting of NOM, 54 to 56 Gy in 27 to 31 fractions concurrent with chemotherapy and followed by consolidation chemotherapy was recommended. The panel strongly recommends primary surgery as usually appropriate for a T3N0 high rectal tumor for which low anterior resection and adequate bowel function is possible, with adjuvant chemotherapy considered if N+. Recent data support NOM and primary surgery as important options that should be offered to eligible patients. Considering the complexity of multidisciplinary management, patients should be discussed in a multidisciplinary setting, and therapy should be tailored to individual patient goals/values.

Total mesorectal excision remains the gold standard for the management of rectal cancer however local excision of early rectal cancer is gaining popularity due to lower morbidity and higher acceptance by the elderly and frail patients.

To investigate the results of local excision of rectal cancer by transanal endoscopic microsurgery (TEMS) approach carried out at three large cancer centers in the United Kingdom.

TEMS database was retrospectively reviewed to assess demographics, operative findings and post operative clinical and oncological outcomes. This is a retrospective review of the prospective databases, which included all patients operated with TEMS approach, for early rectal cancer (Node-negative T1-T2), selected T3 in unfit/frail patients.

Two hundred and twenty-two patients underwent TEMS surgery. This included 144 males (64.9%) and 78 females (35.1%), Median age was 71 years. The median distance of the tumours from the anal verge 4.5 cm. Median tumour size was 2.6 cm. The most frequent operative position of the patient was lithotomy (32.3%), Full-thickness rectal wall excision was done in 204 patients. Median operating time was 90 minutes. Average blood loss was minimal. There were two 90-day mortalities. Complete excision of the tumour with free microscopic margins by > 1mm were accomplished in 171 patients (76.7%). Salvage total mesorectal excision was performed in 42 patients (19.8%). Median disease-free survival was 65 months (range: 3-146 months) (82.8%), and median overall survival was 59 months (0-146 months).

TEMS provides a promising option for early rectal cancers (Large adenomas-cT1/cT2N0), and selected therapy-responding cancers. Full-thickness complete excision of the tumour is mandatory to avoid jeopardising the oncological outcomes.

Local 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.

This 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.

A 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).

Patients 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.

We aimed to evaluate outcomes of organ preservation by local excision (LE) compared to proctectomy following neoadjuvant therapy for rectal cancer.

This retrospective observational study using the National Cancer Database (NCDB) included patients with locally advanced non-metastatic rectal cancer (ypT0-1 tumors) treated with neoadjuvant therapy between 2004 and 2019. Outcomes of patients who underwent LE or proctectomy were compared. 1:1 propensity score matching including patient demographics, clinical and therapeutic factors was used to minimize selection bias. Main outcome was overall survival (OS).

11,256 of 318,548 patients were included, 526 (4.6%) of whom underwent LE. After matching, mean 5-year OS was similar between the groups (54.1 vs. 54.2 months; p = 0.881). Positive resection margins (1.2% vs. 0.6%; p = 0.45), pathologic T stage (p = 0.07), 30-day mortality (0.6% vs. 0.6%; p = 1), and 90-day mortality (1.5% vs. 1.2%; p = 0.75) were comparable between the groups. Length of stay (1 vs. 6 days; p < 0.001) and 30-day readmission rate (5.3% vs. 10.3%; p = 0.02) were lower in LE patients. Multivariate analysis of predictors of OS demonstrated male sex (HR 1.38, 95% CI 1.08-1.77; p = 0.009), higher Charlson score (HR 1.52, 95% CI 1.29-1.79; p < 0.001), poorly differentiated carcinoma (HR 1.61, 95% CI 1.08-2.39; p = 0.02), mucinous carcinoma (HR 3.53, 95% CI 1.72-7.24; p < 0.001), and pathological T1 (HR 1.45, 95% CI 1.14-1.84; p = 0.002) were independent predictors of increased mortality. LE did not correlate with worse OS (HR 0.91, 95% CI 0.42-1.97; p = 0.82).

Our findings show no overall significant survival difference between LE and total mesorectal excision, including ypT1 tumors. Moreover, patients with poorly differentiated or mucinous adenocarcinomas generally had poorer outcomes, regardless of surgical method.

It is accepted that tumor stage and size can influence response to neoadjuvant therapy in locally advanced rectal cancer (LARC). Studies on organ preservation to date have included a wide variety of size and TNM stage tumors. The aim of this study was to report tumor response based on each relevant TNM stage and tumor size.

Patients treated with LARC from 2014 to 2021 with cT2-3NxM0 tumors who received neoadjuvant chemoradiotherapy with or without induction chemotherapy were included. Tumors were staged and tumor size calculated on pelvic MRI at the time of diagnosis (cTNM). Tumor size was based on the largest dimension taken on the longest axis of each tumor. Clinical response was defined on the basis of post-treatment pelvic MRI and pathological response following surgery, when performed. Statistical analysis was performed using IBM SPSS Statistics™, version 20. Data from 432 patients were analyzed as follows: cT2N0 (n = 51), cT2N+ (n = 36), cT3N0 (n = 76), cT3N+ (n = 270).

The rate of complete or near-complete response (cCR or nCR) varied from 77% in cT2N0 ≤ 3 cm to 20% in cT3N+ > 4 cm. Organ preservation without recurrence at 2 years was achieved in 86% of patients with cT2N0, 50% in cT2N+, 39% in cT3N0, and 12% in cT3N+.

There is significant variation in tumor response according to tumor stage and size. Tumor response appears inversely proportional to increasing TNM stage and tumor size. This data can support both refinement of selective patient recruitment to organ preservation programs and shared decision-making.

Local resection (LR) is an alternative to total mesorectal excision (TME) that avoids its associated morbidity to the detriment of oncological radicality in early stages of rectal cancer. There are several conditioning factors for the success of this strategy, such as poor prognosis histological factors (PPHF), involvement of resection margins, clinical under staging, or complications that may lead to the indication for radical surgery with TME.

An international multicenter prospective observational open-label study has been designed. Consecutive patients diagnosed with early rectal cancer (cT1N0 on MRI +/- endorectal ultrasound) whose lower limit is a maximum of 2 cm proximal to the ano-rectal junction will be included. The primary objective of the study is to determine the overall prevalence of PPHF after LR and requiring TME or postoperative radio-chemotherapy.

The prevalence of PPHF conditioning the success of LR in early distal rectal cancer has been scarcely studied in the literature, and there are very few prospective data. Considering the increasing interest in the watch and wait strategy in rectal cancer and its possible application in early-stage tumors, it seems necessary to know this information. The results of this study will help guide clinical practice in patients with early distal rectal cancer. It will also provide quality information for the design of future comparative studies to improve organ preservation success in these patients.

NCT05927584.

Transanal minimally invasive surgery (TAMIS) can be utilized to manage a wide variety of rectal lesions but can be technically demanding with traditional laparoscopic equipment. Robotic platforms such as the da Vinci Single Port system can reduce the technical barriers of TAMIS and allow more complicated lesions to be addressed. Robotic TAMIS with the SP system follows similar indications for local excision of benign and malignant lesions as conventional TAMIS or even transanal endoscopic microsurgery. We describe our initial experience using the SP system and provide technical suggestions for how to incorporate this technology. We also address innovations in flexible endoscopic robotic surgery that we anticipate will allow for increased use of organ preservation of the colon and rectum, as well as possibly expand the use of natural orifice surgery.

Prospective randomized trials have not yet identified baseline features predictive of organ preservation in locally advanced rectal cancers treated with total neoadjuvant therapy and a selective watch-and-wait strategy.

This was a secondary analysis of the OPRA trial, which randomized patients with stage II-III rectal adenocarcinoma to receive either induction or consolidation total neoadjuvant therapy. Patients were recommended for total mesorectal excision, or watch and wait based on clinical response at 8 ± 4 weeks after completing treatment. Standardized baseline clinical and radiological variables were collected prospectively. Survival outcomes, including total mesorectal excision-free survival, disease-free survival, and overall survival, were assessed by intention-to-treat analysis. Cox proportional hazards models were used to evaluate associations between baseline variables and survival outcomes.

Of the 324 patients randomized for the OPRA trial, 38 (11.7%) had cT4 tumours, 230 (71.0%) cN-positive disease, 101 (32.5%) mesorectal fascia involvement, and 64 (19.8%) extramural venous invasion. Several baseline features were independently associated with recommendation for total mesorectal excision on multivariable analysis: nodal disease (HR 1.66, 95% c.i. 1.12 to 2.48), extramural venous invasion (HR 1.57, 1.07 to 2.29), mesorectal fascia involvement (HR 1.45, 1.01 to 2.09), and tumour length (HR 1.11, 1.00 to 1.22). Of these, nodal disease (HR 2.02, 1.15 to 3.53) and mesorectal fascia involvement (HR 2.02, 1.26 to 3.26) also predicted worse disease-free survival. Age (HR 1.03, 1.00 to 1.06) was associated with overall survival.

Baseline MRI features, including nodal disease, extramural venous invasion, mesorectal fascia involvement, and tumour length, independently predict the likelihood of organ preservation after completion of total neoadjuvant therapy. Mesorectal fascia involvement and nodal disease are associated with disease-free survival.

Debate persists regarding the feasibility of adopting an organ-preserving strategy as the treatment modality for clinical T2N0 rectal cancer. This study aimed to compare the outcomes of attempting organ-preserving strategies versus radical surgery in patients with clinical T2N0 mid to low rectal cancer.

Patients diagnosed with clinical T2N0 rectal cancer, with lesions located within 8 cm from the anal verge as determined by pre-treatment magnetic resonance imaging between January 2010 and December 2020 were included.

Of 119 patients, 91 and 28 were categorized into the organ-preserving attempt group and the radical surgery group, respectively. The median follow-up duration was 48.8 months (range, 0-134 months). The organ-preserving attempt group exhibited a reduced incidence of stoma formation (44.0% vs. 75.0%; p = 0.004) and a lower occurrence of grade 3 or higher surgical complications (5.8% vs. 21.4%; p = 0.025). Univariate analyses revealed no significant association between treatment strategy and 3-year local recurrence-free survival (organ-preserving attempt 87.9% vs. radical surgery 96.2%; p = 0.129), or 3-year disease-free survival (79.6% vs. 84.9%; p = 0.429). Multivariate analysis did not identify any independent prognostic factors associated with oncologic outcomes.

Compared with radical surgery, attempted organ preservation resulted in lower incidences of stoma formation and severe surgical complications, whereas oncological outcomes were comparable. Attempting organ preservation may be a safe alternative to radical surgery for clinical T2N0 mid to low rectal cancer.

Managing patients with obstructing rectal cancer is challenging due to the risks of gastrointestinal obstruction and perforation. This study evaluates the outcomes of pre-emptive laparoscopic colostomy creation in patients with locally advanced rectal and anal cancer to prevent symptoms and facilitate therapy initiation.

This retrospective cohort study includes patients with locally advanced rectal or anal cancer assessed by our Colorectal Multidisciplinary Team from January 2017 to February 2024. Patients who underwent pre-emptive laparoscopic colostomy were compared to a control group of non-obstructing rectal cancer patients who started direct oncological treatment. The primary endpoint was the time from diagnosis to the initiation of oncological treatments. The secondary endpoints were the rate and timing of subsequent radical resection, surgical morbidity and hospital stay. A Weibull regression was used to evaluate the time differences between the groups.

There were 37 patients who received pre-emptive laparoscopic colostomy, compared to 207 control patients. The mean time from diagnosis to the start of neoadjuvant therapy was 38.3 ± 2.3 days. Despite higher rates of malnutrition and more advanced stages in the colostomy group, no significant differences were observed in the time to start therapy (p = 0.083) or time to radical resection (p = 0.187) between the groups. The laparoscopic procedure showed low rates of postoperative complications and acceptable lengths of stay.

Pre-emptive laparoscopic colostomy is a feasible approach for managing obstructing rectal or anal cancer. Treatment timelines were not extended compared to timelines for non-obstructing cases, despite differences in nutritional status and staging. Further prospective studies with larger cohorts are needed to validate these findings and refine treatment protocols for obstructing gastrointestinal malignancies.

Rectal-sparing approaches for patients with rectal cancer who achieved a complete or major response following neoadjuvant therapy constitute a paradigm of a potential shift in the management of patients with rectal cancer; however, their role remains controversial. The aim of this study was to investigate the feasibility of rectal-sparing approaches to preserve the rectum without impairing the outcomes.

This prospective, multicenter, observational study investigated the outcomes of patients with clinical stage II-III mid-low rectal adenocarcinoma treated with any neoadjuvant therapy, and either transanal local excision or watch-and-wait approach, based on tumor response (major or complete) and patient/surgeon choice. The primary endpoint of the study was rectum preservation at a minimum follow-up of 2 years. Secondary endpoints were overall, disease-free, local and distant recurrence-free, and stoma-free survival at 3 years.

Of the 178 patients enrolled in 16 centers, 112 (62.9%) were managed with local excision and 66 (37.1%) with watch-and-wait. At a median (interquartile range) follow-up of 36.1 (30.6-45.6) months, the rectum was preserved in 144 (80.9%) patients. The 3-year rectum-sparing, overall survival, disease-free survival, local recurrence-free survival, and distant recurrence-free survival was 80.6% (95% CI 73.9-85.8), 97.6% (95% CI 93.6-99.1), 90.0% (95% CI 84.3-93.7), 94.7% (95% CI 90.1-97.2), and 94.6% (95% CI 89.9-97.2), respectively. The 3-year stoma-free survival was 95.0% (95% CI 89.5-97.6). The 3-year regrowth-free survival in the watch-and-wait group was 71.8% (95% CI 59.9-81.2).

In rectal cancer patients with major or complete clinical response after neoadjuvant therapy, the rectum can be preserved in about 80% of cases, without compromising the outcomes.

Despite decreased incidence rates in average-age onset patients in high-income economies, colorectal cancer is the third most diagnosed cancer in the world, with increasing rates in emerging economies. Furthermore, early onset colorectal cancer (age ≤50 years) is of increasing concern globally. Over the past decade, research advances have increased biological knowledge, treatment options, and overall survival rates. The increase in life expectancy is attributed to an increase in effective systemic therapy, improved treatment selection, and expanded locoregional surgical options. Ongoing developments are focused on the role of sphincter preservation, precision oncology for molecular alterations, use of circulating tumour DNA, analysis of the gut microbiome, as well as the role of locoregional strategies for colorectal cancer liver metastases. This overview is to provide a general multidisciplinary perspective of clinical advances in colorectal cancer.

This manuscript offers a detailed description of our successful tips for mastering transanal robotic surgery. It covers various aspects, including patient positioning, management of abdominal pressures to maintain a stable pneumorectum, platform positioning, camera alignment, trocar positioning to minimize collisions, instruments used, and approaches to tumor resection.

Although total mesorectal excision (TME) remains the standard of care for rectal cancer, including early-stage T1/T2 rectal adenocarcinoma, local excision may be warranted for these early-stage tumors in a select group of patients who may decline surgery or may be nonoptimal surgical candidates. Operative approaches for transanal local excision include transanal endoscopic microsurgery or transanal minimally invasive surgery for tumors <4 cm, occupying <40% of the rectal circumference and <10 cm from the dentate line. The use of preoperative chemoradiation therapy may help to downstage tumors and allow for more limited resections, and chemoradiation may also be employed postoperatively. Local excision approaches appear to result in improved quality of life compared with TME, but limited resections may also compromise survival rates compared with TME. Multidisciplinary management and shared decision-making can allow for the desired patient outcomes.

Transanal minimally invasive surgery (TAMIS) is a surgical alternative to proctectomy in the management of complex rectal polyps and early rectal cancers. In 2016, our institution introduced a TAMIS programme. The purpose of this study was to evaluate changes in practice and outcomes in our institution in the 3 years before and after the implementation of TAMIS. We conducted a retrospective analysis of a prospective database of patients who underwent proctectomy or TAMIS for the management of complex rectal polyps or early rectal cancers at our institution between 2013 and 2018. 96 patients were included in this study (41 proctectomy vs 55 TAMIS). A significant reduction was noted in the number of proctectomies performed in the 3 years after the implementation of TAMIS as compared to the 3 years before (13 vs 28) ( P  < 0.001); 43% of patients ( n  = 12) who underwent proctectomy in the period prior to implementation of TAMIS were American Society of Anaesthesiologists grade III, as compared to only 15% ( n  = 2) of patients during the period following TAMIS implementation ( P  = 0.02). TAMIS was associated with a significant reduction in length of inpatient stay ( P  < 0.001). Oncological outcomes were comparable between groups (log rank P  = 0.83). Our findings support TAMIS as a safe and effective alternative to radical resection. The availability of TAMIS has resulted in a significant reduction in the number of comorbid patients undergoing proctectomy at our institution. Consequently, we have observed a significant reduction in postoperative complications over this time period.

As watch and wait has become an attractive management alternative among patients with rectal cancer who achieve a clinical complete response to neoadjuvant chemoradiation, the focus of organ preservation has now shifted toward the use of this approach in patients with early rectal cancer. These patients would otherwise be treated without the use of neoadjuvant therapy for oncological reasons. The sole purpose of any neoadjuvant treatment here would be the achievement of a complete clinical response in an attempt to avoid total mesorectal excision. This has become particularly interesting after the incorporation of total neoadjuvant therapy regimens. These regimens have resulted in significantly higher rates of complete tumor regression and therefore become an interesting alternative among early rectal cancer patients where organ preservation is desired. The present review provides an overview of the currently available evidence and the preliminary experience with this rather controversial approach.

Transanal minimally invasive surgery (TAMIS) is an advanced technique for excision of early rectal cancers. Robotic TAMIS (r-TAMIS) has been introduced as technical improvement and potential alternative to total mesorectal excision (TME) in early rectal cancers and in frail patients. This study reports the perioperative and short-term oncological outcomes of r-TAMIS for local excision of early-stage rectal cancers.

Retrospective analysis of a prospectively collected r-TAMIS database (July 2021-July 2023). Demographics, clinicopathological features, short-term outcomes, recurrences, and survival were investigated.

Twenty patients were included. Median age and body mass index were 69.5 (62.0-77.7) years and 31.0 (21.0-36.5) kg/m2. Male sex was prevalent (n = 12, 60.0%). ASA III accounted for 66.7%. Median distance from anal verge was 7.5 (5.0-11.7) cm. Median operation time was 90.0 (60.0-112.5) minutes. Blood loss was minimal. There were no conversions. Median postoperative stay was 2.0 (1.0-3.0) days. Minor and major complication rates were 25.0% and 0%, respectively. Seventeen (85.0%) patients had an adenocarcinoma whilst three patients had an adenoma. R0 rate was 90.0%. Most tumours were pT1 (55.0%), followed by pT2 (25.0%). One patient (5.0%) had a pT3 tumour. Specimen and tumour maximal median diameter were 51.0 (41.0-62.0) mm and 21.5 (17.2-42.0) mm, respectively. Median specimen area was 193.1 (134.3-323.3) cm2. Median follow-up was 15.5 (10.0-24.0) months. One patient developed local recurrence (5.0%).

r-TAMIS, with strict postoperative surveillance, is a safe and feasible approach for local excision of early rectal cancer and may have a role in surgically unfit and elderly patients who refuse or cannot undergo TME surgery. Future prospective multicentre large-scale studies are needed to report the long-term oncological outcomes.

The aim of this study was to assess the significant risk factors that predict lymph node metastasis in ypT0 patients with locally advanced rectal cancer following chemoradiotherapy (CRT). Additionally, the study aimed to identify high-risk groups who would not be suitable candidates for a rectal-preserving strategy, despite achieving a complete tumour response.

Between 2013 and 2021, 226 ypT0 patients with stages II/III rectal cancer underwent CRT and radical surgery were enrolled. Two groups of patients were evaluated: those with lymph nodes metastasis and those without. The selection of variables for multivariable logistic regression was conducted through bivariate logistic regression analysis. Furthermore, the determination of optimal cutoff values for risk factors was achieved using ROC curve analysis.

Nearly 8% (18/226) of patients with ypT0 had positive lymph nodes (LN) on final pathology. Four variables resulted as being independent factors of LN metastasis: pre-CRT tumour movability (OR = 8.618, P = 0.003), pre-CRT maximal LN size (OR = 28.474, P = 0.004), post-CRT tumour vertical length (OR = 1.492, P = 0.050), post-CRT anaemia (OR = 10.288, P = 0.001). The optimal cutoff point of pre-CRT maximal LN size and post-CRT tumour vertical length was 7.50 mm and 3.05 cm, respectively.

The prevalence of lymph node metastasis remains at 8% among patients who achieve pathological complete regression of the primary tumour. In instances where patients are considered appropriate candidates for a rectal-preserving strategy after clinical complete remission, careful consideration should be given to the selection of this strategy if specific risk factors are present. These risk factors encompass a maximal LN size surpassing 7.50 mm prior to CRT, a fixed tumour prior to CRT, a tumour vertical length exceeding 3.05 cm after CRT, and the existence of anaemia subsequent to CRT.

The introduction of total mesorectal excision into the radical surgery of rectal cancer has significantly improved the oncological outcome with longer survival and lower local recurrence. Traditional treatment modalities of distal rectal cancer, relying on radical surgery, while effective, take their own set of risks, including surgical complications, potential damage to the anus, and surrounding structure owing to the pursuit of thorough resection. The progress of operating methods as well as the integration of systemic therapies and radiotherapy into the peri-operative period, particularly the exciting clinical complete response of patients after neoadjuvant treatment, have paved the way for organ preservation strategy. The non-inferiority oncological outcome of "watch and wait" compared with radical surgery underscores the potential of organ preservation not only to control local recurrence but also to reduce the need for treatments followed by structure destruction, hopefully improving the long-term quality of life. Radical radiotherapy provides another treatment option for patients unwilling or unable to undergo surgery. Organ preservation points out the direction of treatment for distal rectal cancer, while additional researches are needed to answer remaining questions about its optimal use.

Radical excision (RE) for rectal cancer carries a higher risk of mortality and morbidity, while local excision (LE) could decrease these postoperative risks. However, the long-term benefit of LE is still debatable.

To study the effectiveness of LE versus RE in T1 and T2 rectal cancer.

A systematic review and meta-analysis was conducted using key databases like PubMed and ClinicalTrials.gov. Only cohort studies and randomized controlled trials were included. RevMan 5.4 tool was used for data analysis. Both clinical and statistical heterogeneity of the studies were assessed, and I2 >75% was considered as highly heterogeneous. The primary outcomes being measured were 5-year overall survival (OS) and 5-year disease free survival (DFS). A subgroup analysis of patients with T1-only was also conducted, without adjuvant chemo/radiotherapy.

A total of 18 studies were included for final meta-analysis. Four were RCTs, while the other 15 were retrospective cohort studies. One included study had data from both RCT and non-RCT study groups. Nine studies were multicentered or national studies while nine were unicentral.There was no difference in risk ratio (RR) between OS: RR 0.95, 95% Confidence Interval (CI) [0.91, 0.99] and DFS: RR 0.93, 95% CI [0.87, 1.01]. There were lower hazards ratios in OS: RR 1.41, 95% CI [1.14, 1.74] and DFS: RR 1.95, 95% CI [1.36, 2.78] with radical, as compared to LE. Lower recurrence rate was associated with RE. Random effect model was used due to clinical heterogeneity between studies (different surgical procedures, tumor staging, adjuvant chemo or radiotherapy).

LE for early-stage rectal cancer has lower 5-year OS and DFS than RE, with higher local recurrence rate. However, LE is associated with lower early postoperative mortality, morbidity and length of stay as compared to RE.

Cancer care guidelines based on clinical trial data in homogenous populations may not be applicable to all rectal cancer patients. The aim of this study was to evaluate whether patients enrolled in rectal cancer clinical trials (CTs) are representative of United States (U.S.) rectal cancer patients.

Prospective rectal cancer CTs from 2010 to 2019 in the United States were systematically reviewed. In trials with multiple arms reporting separate demographic variables, each arm was considered a separate CT group in the analysis. Demographic variables considered in the analysis were age, sex, race/ethnicity, facility location throughout the United States, rural vs urban geography, and facility type. Participant demographics from trial and the National Cancer Database (NCDB) participants were compared using chi-squared goodness of fit and one-sample t-test where applicable.

Of 50 CT groups identified, 42 (82%) studies reported mean or median age. Trial participants were younger compared to NCDB patients (P < .001 all studies). All but three trials had fewer female patients than NCDB (48.2% female, P < .001). Less than half the CT groups reported on race or ethnicity. Eighteen out of 22 trials (82%) had a smaller percentage of Black patients and 4 out of 8 (50%) trials had fewer Hispanic or Spanish origin patients than the NCDB. No CTs reported comorbidities, socioeconomic factors, or education. CT primary sites were largely at academic centers and in urban areas.

The present study supports the need for improved demographic representation and transparency in rectal cancer clinical trials.

Computed diffusion-weighted images (cDWI) of random b value could be derived from acquired DWI (aDWI) with at least two different b values. However, its comparison between aDWI and cDWI images in locally advanced rectal cancer (LARC) patients after neoadjuvant therapy (NT) is needed.

To compare the cDWI and aDWI in image quality, restaging, and treatment response of LARC after NT.

Retrospective.

Eighty-seven consecutive patients.

3.0 T/DWI.

All patients underwent two DWI sequences, including conventional acquisition with b = 0 and 1000 s/mm2 (aDWIb1000 ) and another with b = 0 and 700 s/mm2 on a 3.0-T MR scanner. The images of the latter were used to compute the diffusion images with b = 1000 s/mm2 (cDWIb1000 ). Four radiologists with 3, 4, 14, and 25 years of experience evaluated the images to compare the image quality, TN restaging performance, and treatment response between aDWIb1000 and cDWIb1000 .

Interclass correlation coefficients, weighted κ coefficient, paired Wilcoxon, and McNemar or Fisher test were used. A significance level of 0.05 was used.

The cDWIb1000 images were superior to the aDWIb1000 ones in both subjective and objective image quality. In T restaging, the overall diagnostic accuracy of cDWIb1000 images was higher than that of aDWIb1000 images (57.47% vs. 49.43%, P = 0.289 for the inexperienced radiologist; 77.01% vs. 63.22%, significant for the experienced radiologist), with better sensitivity in determining ypT0-Tis tumors. Additionally, it increased the sensitivity in detecting ypT2 tumors for the inexperienced radiologist and ypT3 tumors for the experienced radiologist. N restaging and treatment response were found to be similar between two sequences for both radiologists.

Compared to aDWIb1000 images, the computed ones might serve as a wise approach, providing comparable or better image quality, restaging performance, and treatment response assessment for LARC after NT.

3 TECHNICAL EFFICACY STAGE: 2.

Standard treatment for patients with intermediate or locally advanced rectal cancer is (chemo)radiotherapy followed by total mesorectal excision (TME) surgery. In recent years, organ preservation aiming at improving quality of life has been explored. Patients with a complete clinical response to (chemo)radiotherapy can be managed safely with a watch-and-wait approach. However, the optimal organ-preserving treatment strategy for patients with a good, but not complete clinical response remains unclear. The aim of the OPAXX study is to determine the rate of organ preservation that can be achieved in patients with rectal cancer with a good clinical response after neoadjuvant (chemo)radiotherapy by additional local treatment options.

The OPAXX study is a Dutch multicentre study that investigates the efficacy of two additional local treatments aiming at organ preservation in patients with a good, but not complete response to neoadjuvant treatment (ie near-complete response or a small residual tumour mass <3 cm). The sample size will be 168 patients in total. Patients will be randomised (1:1) between two parallel single-arm phase II studies: study arm 1 involves additional contact X-ray brachytherapy (an intraluminal radiation boost), while in study arm 2 the observation period is extended followed by a second response evaluation and optional transanal local excision. The primary endpoint of the study is the rate of successful organ preservation at 1 year following randomisation. Secondary endpoints include toxicity, morbidity, oncological and functional outcomes at 1 and 2 years of follow-up. Finally, an observational cohort study for patients who are not eligible for randomisation is conducted.

The trial protocol has been approved by the medical ethics committee of the Netherlands Cancer Institute (METC20.1276/M20PAX). Informed consent will be obtained from all participants. The trial results will be published in an international peer-reviewed journal.

NCT05772923.