Individual prognosis assessment is of paramount importance for treatment decision-making and active surveillance in cancer patients. We aimed to propose a radiomic model based on pre- and post-therapy MRI features for predicting disease-free survival (DFS) in locally advanced rectal cancer (LARC) following neoadjuvant chemoradiotherapy (nCRT) and subsequent surgical resection.

This retrospective study included a total of 126 LARC patients, which were randomly assigned to a training set (n = 84) and a validation set (n = 42). All patients underwent pre- and post-nCRT MRI scans. Radiomic features were extracted from higher resolution T2-weighted images. Pearson correlation analysis and ANOVA or Relief were utilized for identifying radiomic features associated with DFS. Pre-treatment, post-treatment, and delta radscores were constructed by machine learning algorithms. An individualized nomogram was developed based on significant radscores and clinical variables using multivariate Cox regression analysis. Predictive performance was evaluated by the C-index, calibration curve, and decision curve analysis.

The results demonstrated that in the validation set, the clinical model including pre-surgery carcinoembryonic antigen (CEA), chemotherapy after radiotherapy, and pathological stage yielded a C-index of 0.755 (95% confidence interval [CI]: 0.739-0.771). While the optimal pre-, post-, and delta-radscores achieved C-indices of 0.724 (95%CI: 0.701-0.747), 0.701 (95%CI: 0.671-0.731), and 0.625 (95%CI: 0.589-0.661), respectively. The nomogram integrating pre-surgery CEA, pathological stage, alongside pre- and post-nCRT radscore, obtained the highest C-index of 0.833 (95%CI: 0.815-0.851). The calibration curve and decision curves exhibited good calibration and clinical usefulness of the nomogram. Furthermore, the nomogram categorized patients into high- and low-risk groups exhibiting distinct DFS (both P < 0.0001).

The nomogram incorporating pre- and post-therapy radscores and clinical factors could predict DFS in patients with LARC, which helps clinicians in optimizing decision-making and surveillance in real-world settings.

Extramural vascular invasion (EMVI) is associated with distant recurrence after treatment of locogionally advanced rectal adenocarcinomas (LARCs), but its use as a marker for response to neoadjuvant therapy is less well understood. We examined the relationship between EMVI and tumor or nodal category downstaging after treatment of LARCs with neoadjuvant therapy.

Patients with EMVI categorized on initial staging pelvic MRI for LARC who underwent curative-intent surgery after neoadjuvant therapy at MD Anderson Cancer Center from 2016 to 2022 were identified. Patients received either preoperative chemoradiation or total neoadjuvant therapy (TNT). Associations between EMVI and demographic, radiologic, and clinicopathologic variables were analyzed.

EMVI was associated with higher rates of lymphovascular invasion (LVI) (46.2% vs. 27.8%, P = .001) and perineural invasion (PNI) (51.9% vs. 28.4%, P < .001) on final pathology. Patients with EMVI were more likely to have cT4 tumors (31.7% vs. 16.3%, P = .004) and cN+ status (86.8% vs. 66.3%, P = .001) and more likely to be treated with TNT rather than chemoradiation alone (62.3% vs. 41.9%, P = .005). EMVI was associated with a lower rate of pathologic complete or near-complete response (20.1% vs. 34.2%, P = .018), downstaging to ypT0-2 from cT3/4 tumors (14.9% vs. 44.4%, P = .0001), and downstaging to ypN0 from cN+ status (47.9% vs. 66.4%, P = .015).

Rectal tumors with EMVI are more likely to have higher clinical stage, less likely to respond to neoadjuvant therapy despite increased use of TNT, and more likely to have high-risk features for recurrence. This suggests EMVI is a marker of disease with poorer response to neoadjuvant therapy. Disease biology should be strongly considered in treatment decision-making, and new treatment strategies are needed to improve disease response.

As patients with rectal cancer with clinical complete response (cCR) after neoadjuvant therapy may be safely spared Total Mesorectal Excision (TME), strategies to maximize cCR are needed.

We conducted a single-arm phase II study to determine whether dose-escalated short-course radiotherapy (25 Gy/5 fractions + 5 Gy/1 fraction boost) followed by eight cycles of FOLFOXIRI increased cCR rates among adult patients with > T2N0M0 or low T2N0 rectal cancer.

Between 2020 and 2023, we enrolled 37 patients, of whom 27 (73 %) had at least one high-risk feature (cT4, extramural vascular invasion [EMVI], N2, threatened circumferential resection margin, positive lateral node). At primary endpoint assessment, nine (24 %) patients had cCR on both endoscopy and MRI, and pursued organ preservation (OP). Fourteen (38 %) patients had cCR only on endoscopy, nine of whom pursued OP. Of the 18 patients who pursued OP, nine had local regrowth at two years from radiotherapy start, with two-year TME-free survival of 26 %. Baseline factors significantly associated with not achieving OP included age < 50 years and T4 disease. At mid-treatment restaging, patients who achieved OP were significantly less likely to have persistent node positivity, EMVI, and endoscopically visible tumor. Grade 3+ adverse events at least possibly attributed to chemotherapy and radiotherapy occured in 51% and 43% of patients, respectively.

Short-course radiotherapy with a boost followed by FOLFIXIRI results in OP in one-quarter of patients with high-risk rectal cancer, with poorer response among younger patients and T4 disease. Mid-treatment response may help guide timely decision-making regarding treatment.

There is controversy and limited data the management of rectosigmoid junction cancer (RSJC), especially the role of radiation. We aim to investigate the role of preoperative and postoperative radiation in RSJC and whether this cancer should be treated as a colon cancer or as a rectal cancer.

The data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and identified from 2000 to 2018.

Of the 50,779 patients, 87% were ≥50 years old, 56.2% were male, 80.8% were White. Regarding tumor characteristics, 76% were Grade II, while 22.7% had distant-stage. 16.4% of patients were treated with multimodal therapy (surgery with chemoradiation), 47.9% surgery alone, 6.5% of patients received preoperative radiation, and 9.9% received postoperative radiation. Regarding prognostic significance of pre-operative and postoperative radiation factors, we evaluated factors, such as age, gender, race, tumor size, histologic variants of adenocarcinoma, and tumor grade. Patients with distant-staged tumors who received preoperative radiation had lower mortality compared to those who received postoperative radiation (95% CI, 0.73 - 0.97, (hazard ratio (HR) = 0.85, p = 0.04). There were no survival differences for localized or regional disease regarding pre and postoperative radiation, or when sub-stratifying for any other significant demographic or tumor characteristics.

Surgery with adjuvant chemoradiation had the best prognosis for all demographic and tumor characteristics. Preoperative radiation had a good prognosis only in distant disease. However, further randomized evidence is required to demonstrate the efficacy of pre-and post-operative radiation in rectosigmoid junction cancer.

Chemoradiotherapy plus total mesorectal excision has been established as the standard treatment for locally advanced rectal cancer (LARC) and can achieve satisfactory local control. However, systemic control of LARC, especially in patients with risk factors for poor prognosis, is still of concern. As application of total neoadjuvant therapy (TNT) has been proposed as a potential solution, a clearer risk stratification of LARC to guide individual treatment is needed. Combination therapy such as targeted therapy or immunotherapy can be used to increase treatment intensity for high-risk LARC. In this review, we evaluate recent trials of several treatment modalities, specifically focusing on intensified TNT regimens for high-risk LARC with the goal of summarizing optimal clinical strategies and future study designs.

BackgroundNonoperative management in patients with rectal cancer with complete response to radiation therapy and chemotherapy is of increasing interest. Most of the data on nonoperative management have centered around patients treated with long-course chemoradiotherapy. The ability of short-course radiation-based treatment courses to achieve durable complete responses with sustained organ preservation is less defined. This study updates our institution's long-term experience with nonoperative management following upfront short-course radiation therapy and sequential/consolidation chemotherapy.MethodsWe retrospectively reviewed patients with nonmetastatic rectal cancer treated with sequential short-course radiation therapy and chemotherapy who reached complete response and were subsequently followed with nonoperative management. We report on disease control outcomes, including rates of regrowth and results of salvage surgery. We investigated characteristics associated with local tumor regrowth.ResultsOur study included 52 patients. The 2-year freedom from local regrowth for the entire cohort was 75%. Notably, patients with high-risk disease characteristics at diagnosis exhibited a trend toward a higher rate of local tumor regrowth. No patient with sustained clinical complete response developed metastatic disease. Of the twelve patients undergoing surgical salvage for regrowth of disease, ten were resected with complete/near-complete total mesorectal surgical specimens with negative margins.ConclusionsThe optimal approach to achieving sustained organ preservation through the use of radiation therapy and chemotherapy is not well defined. Our findings show the viability of neoadjuvant therapy incorporating short-course radiation therapy to achieve durable complete responses.

The individual chemotherapy- and radiotherapy-related toxicities between induction (iTNT) and consolidation total neoadjuvant therapy (cTNT) remain unclear. This network meta-analysis (NMA) comparing iTNT, cTNT, and traditional neoadjuvant chemoradiation (nCRT) evaluated the comparative treatment-related toxicities and compliance of the TNT schemas.

A systematic review of randomized clinical trials and nonrandomized studies of interventions was performed as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-NMA guidelines. A Bayesian NMA was conducted, and odds ratios (OR) with 95% credible intervals (CrI) are reported for all outcomes.

Eighteen studies including 5730 patients were identified. iTNT ranked highest on rate of rectal bleeding (cTNT: OR 0.23 95% CrI 0.05-0.93; nCRT: OR 0.33, 95% CrI 0.09-0.96), proctitis (cTNT: OR 0.2, 95% CrI 0.06-0.55; nCRT: OR 0.2, 95% CrI 0.06-0.51), and postoperative diarrhea (cTNT: OR 0.37, 95% CrI 0.18-0.73; nCRT: OR 0.33, 95% CrI 0.15-0.71); cTNT ranked highest on rate of vomiting (iTNT: OR 0.24, 95% CrI 0.05-0.96; nCRT: OR 0.29, 95% CrI 0.06-0.89) and a higher rate of lymphopenia than iTNT (iTNT: OR 0.56, 95% CrI 0.34-0.99). Radiotherapy compliance was highest in cTNT (iTNT: OR 0.23, 95% CrI 0.05-0.72; nCRT: OR 0.18, 95% CrI 0.04-0.58). There was no difference in overall toxicity and mortality, chemotherapy compliance, and remaining individual system-based toxicities and postoperative complications.

Across all treatment strategies, iTNT had higher radiation-related gastrointestinal toxicities and postoperative diarrhea; cTNT had higher vomiting and lymphopenia rates. While no treatment strategy was superior in chemotherapy compliance, radiotherapy compliance was ranked highest in cTNT.

An updated meta-analysis was conducted to evaluate the efficacy of radiotherapy in rectal cancer patients treated with total mesorectal excision (TME) or other types of surgery (non-TME-only).

The PubMed, Cochrane Library, and CNKI databases were searched. Data on overall survival (OS) were extracted.

Hazard ratios (HRs) for OS associated with preoperative radiotherapy, preoperative long-course concurrent chemoradiotherapy (LCCRT), preoperative radiotherapy alone, and postoperative radiotherapy in patients treated with TME were 1.02 [95% CI: 0.92-1.14, P = 0.65], 1.04 [95% CI: 0.93-1.16, P = 0.47], 0.87 [95% CI: 0.61-1.25, P = 0.46], and 1.18 [95% CI: 0.91-1.52, P = 0.20], respectively. HRs for OS associated with preoperative radiotherapy, preoperative LCCRT, preoperative radiotherapy alone, preoperative long-course RT (LCRT), and preoperative short-course radiotherapy (SCRT) in patients treated with non-TME-only surgery were 0.85 [95% CI: 0.79-0.90, P < 0.00001], 0.77 [95% CI: 0.63-0.94, P = 0.009], 0.86 [95% CI: 0.80-0.92, P < 0.0001], 0.83 [95% CI: 0.73-0.95, P = 0.005], and 0.84 [95% CI: 0.77-0.91, P= <0.0001], respectively. The HR for postoperative radiotherapy in patients treated with non-TME-only surgery was 1.08 [95% CI: 0.84-1.39, P = 0.57].

Preoperative radiotherapy, regardless of the regimen, improves the OS in patients treated with non-TME-only surgery, but not in those treated with TME. Postoperative radiotherapy does not improve OS.

This meta-analysis will serve as a reference for decision-making in multidisciplinary approaches for rectal cancer patients.

There is no standard surgical management for rectal cancer with synchronous resectable liver metastases. The aim of this study was to assess the oncologic outcomes of an adaptative and individualized strategy considering the extension of both tumoral sites in the management of rectal cancer with synchronous resectable liver metastases.

From 2011 to 2020, all consecutive patients treated for low/midrectal cancer with resectable synchronous resectable liver metastases in 4 French centers were included. The choice of strategy was not systematic but tailored on a case-by-case basis to the extension of rectal cancer and liver metastases, prioritizing the most advanced site. The success of the strategy was defined as complete resection of both tumor sites.

Among 83 included patients, most had locally advanced rectal cancer (cT3T4 = 96%) and a median of 3 liver metastases. Forty patients underwent a rectum-first strategy, 31 a liver-first strategy, and 12 a simultaneous resection strategy. Complete resection rate of both sites was 82%. After a 43-month follow-up, median overall survival was 58 months. One- and 3-year survival rates were 94% and 73%, with no difference between strategies (P = .650). In multivariate analysis, the only prognostic factor for overall survival was complete resection of both sites (P = .011, hazard ratio, 0.321; 95% confidence interval, 0.135-0.768), with a median overall survival of 72 months in these patients.

Extent-based tailored strategy for rectal cancer with synchronous resectable liver metastases, on the basis of disease extension, allows high rates of complete resection and favorable long-term survival outcomes. This individualized approach maximizes potential for curative outcomes in patients with metastatic rectal cancer.

Guidelines for resectable locally advanced rectal cancer (LARC) advocate for neoadjuvant radiotherapy (NRT) followed by surgery as the standard approach. However, recent trials have reported no oncological benefits of NRT-based therapy for middle or lower rectal cancer, raising the question of whether NRT followed by surgery remains the optimal treatment approach for resectable LARC overall.

To compare the outcomes of NRT followed by surgery vs up-front surgery for resectable LARC.

This cohort study, using a target trial emulation framework with nationwide registries in Taiwan, included patients undergoing curative resection for resectable LARC (cT1-2N1-2, cT3Nany) between January 1, 2014, and December 31, 2017, with follow-up until December 31, 2020. Data were analyzed from January 1, 2024, to February 15, 2025.

NRT.

The primary outcomes were overall survival (OS) and local recurrence (LR). The secondary outcome was intraoperative diverting stoma outcomes.

A total of 4099 patients were analyzed, including 1436 patients undergoing NRT followed by surgery (median [IQR] age, 62.0 [53.0-71.0] years; 1036 [72.1%] male) and 2663 patients undergoing up-front surgery (median [IQR] age, 65.0 [56.0-74.0] years; 1626 [61.1%] male). NRT followed by surgery, compared with up-front surgery, was associated with higher 3-year OS rates (88.5% vs 85.2%; hazard ratio [HR], 0.74; 95% CI, 0.59-0.92) but higher permanent diverting stoma rates (20.6% vs 11.1%; relative risk [RR], 1.91; 95% CI, 1.62-2.25); LR rates were not significantly different (5.7% vs 6.6%; HR, 0.78; 95% CI, 0.55-1.11). Subgroup analysis revealed that compared with up-front surgery, NRT followed by surgery was associated with improved outcomes in middle or lower rectal cancer but not upper rectal cancer (OS: HR, 1.54; 95% CI, 0.82-2.90; LR: HR, 1.08; 95% CI, 0.23-5.00). NRT followed by surgery was associated with significantly increased risks of permanent diverting stomas across different tumor heights, particularly in upper rectal cancer (RR, 3.54; 95% CI, 1.44-8.69).

In this cohort study of nationwide registries in Taiwan, NRT followed by surgery was associated with improved oncological outcomes for overall resectable LARC, with excessive diverting stoma nonreversal as the trade-off. However, the benefits of NRT were not observed for upper rectal cancer. These findings raise concerns about potential harm from NRT and advise caution when performing NRT for upper rectal cancer.

To assess the ability of clinical inflammatory models to predict tumor regression grade (TRG) in response to neoadjuvant chemoradiotherapy (NCRT) and survival in patients with locally advanced rectal cancer (LARC).

We retrospectively analyzed 161 patients with LARC who underwent NCRT followed by total mesorectal excision at Beijing Hospital between May 2007 and March 2022. By using logistic and Cox regression analyses, we developed prediction models for TRG in response to NCRT and overall survival (OS), respectively.

Multivariable logistic regression analysis indicated that variations in neutrophil, lymphocyte, and monocyte counts and pre-NCRT (preneoadjuvant chemoradiotherapy) CA19 - 9 levels independently predicted TRG in response to NCRT (all P < 0.05). Multivariate Cox regression analysis revealed that clinical tumor (cT) stage, pre-NCRT platelet count, CA19 - 9 level, number of lymph node metastases, and TRG could independently predict OS (all P < 0.05). On the basis of these results, we developed models to predict TRG and OS, respectively. The final predictive model for predicting the response to NCRT had areas under the curve (AUCs) of 0.783 and 0.809 in the training and testing cohorts, respectively; for predicting the 5-year OS rate, the AUC rates were 0.842 and 0.930 in the training and test sets, respectively. The calibration and decision curves showed favorable performance in our prediction models.

We combined inflammatory markers with tumor characteristics and successfully developed clinical prediction models for TRG in response to NCRT and OS in patients with LARC. Our findings offer insights for optimizing treatment in patients with LARC.

Randomized controlled trials have revealed that abdominoperineal resection leads to inferior oncological outcomes compared with low anterior resection, especially regarding local recurrence rates (LRRs). While neoadjuvant chemoradiotherapy can lower LRRs, it is linked to potential short- and long-term radiation-induced adverse effects. Consequently, meticulous patient selection for neoadjuvant chemoradiotherapy is imperative to balance benefits and risks.

This research encompassed individuals with rectal cancer (RC) who underwent abdominoperineal resection (APR) from January 2006 to December 2017. The cohort was categorized into two cohorts on the basis of tumor location: the anterior cohort and the nonanterior cohort. Propensity score matching (PSM) was employed to mitigate selection bias, and this resulted in 767 patients in both cohorts. The primary endpoint assessed was survival without local recurrence (LR).

Of the 2025 cases examined, 1806 were deemed eligible for inclusion. In the entire cohort, the incidence of LR was 9.9% (178/1806); the anterior cohort exhibited a higher rate of LR (15.2% versus 5.9%, p < 0.001). Multivariate examination revealed that anterior location was an independent risk factor (IRF) for LR (hazard ratio [HR] = 2.503, p < 0.001). In patients with stage II/III or T3/4, anterior location persisted as a predictor of increased LR. Neoadjuvant chemoradiotherapy for stage II and III tumors diminished the LR rate in anterior tumor locations (p = 0.017) but not in nonanterior locations (p = 0.390).

Anterior tumor location is an IRF for LR in RC patients. Tumor location can serve as a criterion for patient selection in neoadjuvant chemoradiotherapy.

The studies involving human participants were reviewed and approved by the National Cancer Center's Institute Research Medical Ethics Committee (23/180-3922, 11 May 2023). A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

This study aims to examine why we encounter a pathological circumferential resection margin (pCRM)-positive specimen whose preoperative MRI indicates negative mesorectal fascia involvement in middle to low rectal cancer.

Forty-four consecutive patients included in this study had c(yc)T1-3 primary rectal adenocarcinoma without mesorectal fascia involvement and underwent laparoscopic total mesorectal excision (TME) with curative intent in the Department of Gastrointestinal Surgery of Kansai Medical University Hospital from January 2014 to April 2018. We adopted three checkpoints to investigate the misleading point causing positive pCRM (≤ 1 mm). (1) c(yc)CRM diagnosis by two radiologists with more than 20 and 15 years of experience in rectal cancer MRI diagnosis. (2) The specimen was assessed using the TME score presented by Nagtegaal. (3) We compared the standard sectioning according to UK guidelines (group A; n = 26) with the specimen MRI image navigation-based section (group B; n = 18) in terms of estimation of pCRM by c(yc)CRM.

We achieved a "complete" resection specimen in all cases. A simple correlation coefficient in group B revealed a significant correlation between c(yc)CRM and pCRM (r = 0.663, p = 0.00513); this correlation was not significant in group A (r = 0.261, p = 0.19824). However, tests for differences between linear regression coefficients in groups A and B showed no significant differences (p = 0.12596). There were five cases of pCRM ≤ 1 mm: three in group A and two in group B. An anterior lesion caused pCRM ≤ 1 mm in three cases; the tumor deposits or extramural vascular invasion caused the other cases.

The cause of misleading pCRM was the inaccurate preoperative MRI diagnosis of c(yc)CRM.

Combining radiotherapy (RT) with immune checkpoint inhibitors (ICIs) is a promising strategy that can enhance the therapeutic efficacy of ICIs. However, little is known about RT-induced changes in the expression of immune checkpoints, such as PD-L1, and their clinical implications in colorectal cancer (CRC). This study aimed to investigate the association between responsiveness to RT and changes in PD-L1 expression in human CRC tissue and cell lines.

Tissue specimens from preoperative biopsy via sigmoidoscopy and surgical resection were obtained from 24 patients with locally advanced rectal cancer (LARC) who underwent neoadjuvant chemoradiation therapy (CRT) between August 2016 and December 2017. Immunohistochemistry for PD-L1 in formalin-fixed paraffin-embedded tissue was performed from the endoscopic biopsy and surgical specimens. RNA sequencing was performed using 11 pairs of human LARC tissues before and after irradiation. After exposing human CRC cells to radiation, we investigated changes in the expression levels of PD-L1 and its regulatory signaling pathways.

Patients were classified by tumor regression grade into responders (grade 2; 9 patients, 37.5 %) and non-responders (grades 3, 4, or 5; 15 patients, 62.5 %). In the non-responder group, 13 patients had low PD-L1 expression, but neoadjuvant CRT increased PD-L1 expression in 7 patients (53.9 %) (McNemar's test, p=0.034). CRT up-regulated PD-L1 in non-responder LARC tissues. Similarly, radiation increased PD-L1 in radioresistant DLD-1 cells more than in radiosensitive HCT116 cells, also affecting PD-L1-regulating genes and immune checkpoints in CRC cells. Conventional fractionated radiation treatment further increased PD-L1 in DLD-1 cells compared to HCT116 cells.

This study demonstrated that radiation induces an increase in PD-L1 expression, which is more pronounced in radioresistant CRC, proving the theoretical framework for a combined treatment strategy with a PD-L1 blockade for locally advanced rectal cancer.

Perihilar cholangiocarcinoma (phCCA) has excellent outcomes following liver transplantation (LT). Neoadjuvant radiation-based locoregional therapy is standard-of-care. Gemcitabine and cisplatin (gem/cis) combination systemic therapies have improved outcomes in advanced settings, but their efficacy pre-LT has not been studied.

We review our experience following neoadjuvant gem/cis alone versus radiation-based approaches. Patients with phCCA undergoing LT at a single center between January 2008 and February 2023 were identified retrospectively. Neoadjuvant therapy was categorized as gem/cis systemic therapy (ST) alone, or any ST and radiotherapy (RT). Outcomes were posttransplant overall survival (OS), recurrence-free survival (RFS), waitlist time, and pathologic tumor response.

During study period, 27 phCCA patients underwent LT. One patient decompensated with neoadjuvant therapy and was excluded. Median age was 61 y (interquartile range, 53-68 y) and 14 (54%) were male. Of 26 patients, 12 (46%) received ST and 14 (54%) RT. Six RT patients received gem/cis ST. Median waitlist time was 199 d (interquartile range, 98-405 d) and did not differ by neoadjuvant regimen. Explanted tumors were predominantly T1 stage, without lymphovascular invasion or nodal involvement. Neither pathologic features nor percent tumor necrosis differed by regimen. OS probabilities at 1 and 3 y were 84% and 55% for the cohort. There was no significant difference in OS and RFS when stratified by regimen.

Post-LT OS, RFS, waitlist time, and tumor response were similar in the 2 groups. Patients with phCCA who do not undergo RT may still be considered for LT under appropriate institution-based protocols that adhere to other established criteria.

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.

The 2024 updates of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for the diagnosis and treatment of colorectal cancer emphasize standardizing cancer treatment in China, highlighting the latest advancements in evidence-based medicine, healthcare resource access, and precision medicine in oncology. These updates address disparities in epidemiological trends, clinicopathological characteristics, tumor biology, treatment approaches, and drug selection for colorectal cancer patients across diverse regions and backgrounds. Key revisions include adjustments to evidence levels for intensive treatment strategies, updates to regimens for deficient mismatch repair (dMMR)/ microsatellite instability-high (MSI-H) patients, proficient mismatch repair (pMMR)/ microsatellite stability (MSS) patients who have failed standard therapies, and rectal cancer patients with low recurrence risk. Additionally, recommendations for digital rectal examination and DNA polymerase epsilon (POLE)/ DNA polymerase delta 1 (POLD1) gene mutation testing have been strengthened. The 2024 CSCO Guidelines are based on both Chinese and international clinical research, as well as expert consensus, ensuring their relevance and applicability in clinical practice, while maintaining a commitment to scientific rigor, impartiality, and timely updates.

Preoperative neoadjuvant chemoradiotherapy (nCRT) is considered to be the standard treatment strategy for locally advanced rectal cancer (LARC); however, the risk of adverse events and postoperative recurrence remains significant. This study aimed to evaluate the non-inferiority of neoadjuvant chemotherapy (nCT) compared with nCRT in patients with LARC and to assess the possibility of eliminating radiotherapy on the basis of guaranteed efficacy.

We searched the PubMed, Embase, and Cochrane Library databases to identify randomized controlled trials (RCTs) comparing the efficacy of nCRT and nCT for LARC. The study protocol was registered with the Prospective Register of Systematic Reviews (PROSPERO).

A total of 2706 patients from seven studies were included in the meta-analysis. There was no significant difference in overall survival (OS) or disease-free survival (DFS) between the nCT and nCRT groups. This study demonstrated a lower rate of infection (OR = 0.53, 95% CI = 0.34-0.82; P = 0.005), anastomotic leak (OR = 0.55, 95% CI = 0.34-0.87; P = 0.01), tumor regression grade (TRG) 0-1 (OR = 0.50, 95% CI = 0.36-0.69; P < 0.0001), preventive diverting ileostomy (OR = 0.41, 95% CI = 0.17-1.02; P = 0.05), and leukopenia (OR = 0.50, 95% CI = 0.25-1.01; P = 0.05) in the nCT group. However, there was no significant difference in the other toxic events, such as intestinal obstruction, urinary complications, diarrhea, and surgical or pathological outcomes, such as clinical fistula, sphincter preservation, postoperative mortality (≤ 60 d), R0 resection, ypStage 0-I, positive circumferential resection margin (CRM+), or pathological complete response (pCR) between the two groups.

This study indicated that OS and DFS were not lower in the nCT group than in the nCRT group. In addition, the nCT group had fewer complications. Preoperative nCT is expected to become a standard treatment option for most patients with stage II-III LARC. It is worth noting that radiotherapy cannot be ignored for some patients who need to ensure the conversion effect of neoadjuvant therapy and strongly request to preserve organ function.

This study aimed to develop and validate a nomogram that utilized macro- and microscopic tumor characteristics at baseline, including radiomics, pathomics, and biopsy-adapted immunoscore (ISB), to accurately predict distant metastasis (DM) in patients with locally advanced rectal cancer (LARC) who underwent neoadjuvant chemoradiotherapy (nCRT).

In total, 201 patients with LARC (91 months of median follow-up) were enrolled. Radiomics features were extracted from apparent diffusion coefficient maps and T2-weighted images. Pathomics features including global pattern (features of the entire image) and local pattern (features of the tumor nuclei) were extracted from whole-slide images of hematoxylin-eosin-stained biopsy specimens. ISB was calculated from the densities of CD3+ and CD8+ T cells in the tumor region using immunohistochemistry on biopsy specimens. The construction of a predictive model was carried out using the least absolute shrinkage and selection operator-Cox analysis, with performance metrics including the area under the curve (AUC) and concordance index (C-index) utilized for evaluation.

Compared with patients with moderate and high ISB, patients with low ISB exhibited significantly higher risk scores for radiomics and pathomics signatures. The nomogram showed respective C-indexes of 0.902 and 0.848 for 5-year DM-free survival in the training and test sets, along with corresponding AUC values of 0.950 and 0.872. Patients could be efficiently categorized into low- and high-risk groups for developing DM using the nomogram.

The nomogram integrating macroscopic radiological information and microscopic pathological information is effective for risk stratification at baseline in LARC treated with nCRT.

To investigate whether MRI risk factors can be used to predict clinical outcomes and whether MRI risk assessment can be used to select stage II-III rectal cancer patients who may benefit from neoadjuvant chemoradiotherapy (nCRT).

A total of 947 rectal cancer patients who underwent total mesorectal excision (TME) were retrospectively recruited. An MRI scoring system was established using the cumulative score of three risk factors (mesorectal fascia involvement, extramural venous invasion, and tumour deposits). Patients with mrT3c-T4 stage, N2 stage, or any risk factors were considered MRI high-risk cases of rectal cancer. Cox regression analysis was used to identify independent risk factors for overall survival (OS) and disease-free survival (DFS). Kaplan-Meier curves were generated to show the benefits of nCRT after propensity score matching (PSM).

OS and DFS were more favourable in the MRI low-risk group than in the MRI high-risk group, and the MRI scoring system facilitated prognostic stratification in stage II-III rectal cancer patients. NCRT significantly improved 3-year OS (89.1 % versus 78.8 %, p = 0.001) and 3-year DFS (73.4 % versus 68.0 %, p = 0.030) in the MRI high-risk group. After PSM, OS and DFS were improved in the MRI high-risk group with an MRI score of 1 (OS: HR = 0.432 [95 % CI: 0.214-0.871], p = 0.019; DFS: HR = 0.477 [95 % CI: 0.275-0.825], p = 0.008) and an MRI score of 2 (OS: HR = 0.276 [95 % CI: 0.130-0.586], p = 0.001; DFS: HR = 0.358 [95 % CI: 0.182-0.705], p = 0.003), whereas MRI low-risk patients did not obtain any survival benefit from nCRT.

MRI-defined high-risk patients with MRI scores of 1 or 2 may benefit from nCRT. Baseline MRI should be given more consideration in nCRT decision-making.

Total Neoadjuvant Therapy (TNT) is a promising strategy for treating locally advanced rectal cancer (LARC) and has started to replace the traditional neoadjuvant chemoradiotherapy (CRT). This review combines findings from pivotal studies that helped TNT to integrate into clinical practice. It emphasizes the efficacy of TNT in improving the disease-free and metastasis-free survival, pathologic complete response and, according to recent studies, a potential improvement in overall survival when compared to standard CRT. In addition, the review analyzes increased organ preservation by TNT and explores the trend towards personalized medicine with the use of TNT. Additionally, it investigates the possibility of excluding radiotherapy in some subgroups. Future directions include integration of immunotherapy, use of TNT in early-stage disease and determining optimal components of TNT, such as type of chemotherapy and type of radiotherapy.

Desmoplastic reaction is recognized as a prognostic factor in colorectal cancer. However, its significance in locally advanced rectal cancer after neoadjuvant chemoradiotherapy remains underexplored.

To assess the prognostic value of desmoplastic reaction in specimens from patients with advanced rectal cancer after chemoradiotherapy.

This was a retrospective study.

This study was conducted at a single comprehensive cancer center.

The study included 255 patients with advanced rectal cancer who underwent fluoropyrimidine-based chemoradiotherapy followed by total mesorectal excision from 2005 to 2014. Desmoplastic reaction was classified into mature, intermediate, and immature categories based on histological analysis.

The primary outcomes were recurrence-free survival and overall survival.

Desmoplastic reaction was classified as mature (69.0%), intermediate (5.5%), or immature (25.5%). The mature group had a higher percentage of good responders (34.1%) compared with the intermediate (0%) and immature (4.6%) groups ( p < 0.0001). The mature group correlated with better outcomes, with a higher 5-year recurrence-free survival (85.4%) and overall survival (93.0%) as compared with intermediate (45.1% and 76.2%, respectively) and immature (65.8% and 88.8%, respectively) groups. In the multivariable analysis, intermediate/immature desmoplastic reaction was significantly associated with poorer recurrence-free survival ( p = 0.03). Among poor responders, intermediate/immature desmoplastic reaction was associated with poorer recurrence-free survival ( p = 0.03). Adjuvant chemotherapy did not significantly improve the 5-year recurrence-free survival rate for the mature group (adjuvant chemotherapy vs no chemotherapy, 86.4% vs 84.8%; p = 0.64), with worse trends observed in the intermediate/immature combined group (55.9% vs 69.4%, respectively, p = 0.27).

The limitations include the subjective nature of the desmoplastic reaction assessment and the retrospective design of the study.

Desmoplastic reaction in surgical specimens after chemoradiotherapy is associated with responses to chemoradiotherapy and serves as a significant prognostic factor in advanced rectal cancer, particularly for those responding poorly to chemoradiotherapy. See Video Abstract .

ANTECEDENTES:La reacción desmoplásica se reconoce como un factor pronóstico en el cáncer colorrectal. Sin embargo, su importancia en el cáncer rectal localmente avanzado después de la quimiorradioterapia neoadyuvante sigue sin explorarse.OBJETIVO:Evaluar el valor pronóstico de la reacción desmoplásica en muestras de pacientes con cáncer rectal avanzado después de la quimiorradioterapia.DISEÑO:Este es un estudio retrospectivo.ESCENARIO:Este estudio se llevó a cabo en un solo centro oncológico integral.PACIENTES:El estudio incluyó a 255 pacientes con cáncer rectal avanzado que se sometieron a quimiorradioterapia basada en fluoropirimidina seguida de una escisión mesorrectal total entre 2005 y 2014. La reacción desmoplásica se clasificó en categorías madura, intermedia e inmadura según el análisis histológico.RESULTADOS PRINCIPALES:Los resultados primarios fueron la supervivencia sin recurrencia y la supervivencia general. RESULTADOS: La reacción desmoplásica se clasificó como madura (69,0%), intermedia (5,5%) o inmadura (25,5%). El grupo maduro tuvo un mayor porcentaje de buenos respondedores (34,1%) en comparación con los grupos intermedio (0%) e inmaduro (4,6%) (p < 0,0001). El grupo maduro se correlacionó con mejores resultados, con una mayor supervivencia libre de recurrencia a 5 años (85,4%) y supervivencia general (93,0%) en comparación con los grupos intermedio (45,1% y 76,2%, respectivamente) e inmaduro (65,8% y 88,8%, respectivamente). En el análisis multivariable, la reacción desmoplásica intermedia/inmadura se asoció significativamente con una peor supervivencia libre de recurrencia ( p = 0,03). Entre los malos respondedores, la reacción desmoplásica intermedia/inmadura se asoció con una peor supervivencia libre de recurrencia (p = 0,03). La quimioterapia adyuvante no mejoró significativamente la tasa de supervivencia sin recurrencia a 5 años para el grupo maduro (quimioterapia adyuvante vs. ninguna quimioterapia, 86,4% vs. 84,8%; p = 0,64), observándose tendencias peores en el grupo combinado intermedio/inmaduro (55,9% vs. 69,4%, respectivamente, p = 0,27).LIMITACIONES:Las limitaciones incluyen la naturaleza subjetiva de la evaluación de la reacción desmoplásica y el diseño retrospectivo del estudio.CONCLUSIONES:La reacción desmoplásica en muestras quirúrgicas después de la quimiorradioterapia se asocia con respuestas a la quimiorradioterapia y sirve como un factor pronóstico significativo en el cáncer rectal avanzado, particularmente para aquellos que responden mal a la quimiorradioterapia. (Traducción-Yesenia Rojas-Khalil ).

The peritumoral region possesses attributes that promote cancer growth and progression. However, the potential prognostic biomarkers in this region remain relatively underexplored in radiomics.

To investigate the prognostic value and importance of peritumoral radiomics in locally advanced rectal cancer (LARC).

This retrospective study included 409 patients with biopsy-confirmed LARC treated with neoadjuvant chemoradiotherapy and surgically. Patients were divided into training (n = 273) and validation (n = 136) sets. Based on intratumoral and peritumoral radiomic features extracted from pretreatment axial high-resolution small-field-of-view T2-weighted images, multivariate Cox models for progression-free survival (PFS) prediction were developed with or without clinicoradiological features and evaluated with Harrell's concordance index (C-index), calibration curve, and decision curve analyses. Risk stratification, Kaplan-Meier analysis, and permutation feature importance analysis were performed.

The comprehensive integrated clinical-radiological-omics model (ModelICRO) integrating seven peritumoral, three intratumoral, and four clinicoradiological features achieved the highest C-indices (0.836 and 0.801 in the training and validation sets, respectively). This model showed robust calibration and better clinical net benefits, effectively distinguished high-risk from low-risk patients (PFS: 97.2% vs 67.6% and 95.4% vs 64.8% in the training and validation sets, respectively; both P < 0.001). Three most influential predictors in the comprehensive ModelICRO were, in order, a peritumoral, an intratumoral, and a clinicoradiological feature. Notably, the peritumoral model outperformed the intratumoral model (C-index: 0.754 vs 0.670; P = 0.015); peritumoral features significantly enhanced the performance of models based on clinicoradiological or intratumoral features or their combinations.

Peritumoral radiomics holds greater prognostic value than intratumoral radiomics for predicting PFS in LARC. The comprehensive model may serve as a reliable tool for better stratification and management postoperatively.

Background: The use of adjuvant chemotherapy in patients with stage T3N0 rectal cancer following total mesorectal excision (TME) is debated. This study is aimed at investigating the clinical significance of negative lymph node (NLN) counts in patients with T3N0 rectal cancer, particularly in relation to adjuvant chemotherapy. Methods: This retrospective analysis examined 311 patients with T3N0 rectal cancer who underwent radical resection at the Sixth Affiliated Hospital of Sun Yat-sen University between August 2014 and December 2021. The optimal cutoff for NLN counts was determined using receiver operating characteristic (ROC) curves. Clinicopathological characteristics and clinical outcomes were compared between the high and low NLN groups. Overall survival (OS) and disease-free survival (DFS) were used to evaluate the efficacy of adjuvant chemotherapy. Results: The optimal cutoff for NLNs was 21. Of the 311 patients, 141 were categorized into the high NLN group and 170 into the low NLN group. Patients with NLNs ≥ 21 had significantly better 5-year OS (99.3% vs. 88.2%, p < 0.05) and 5-year DFS (92.2% vs. 79.4%, p < 0.05) compared to those with low NLNs. Multivariate Cox analysis revealed that NLN count was an independent prognostic factor for OS (hazard ratio (HR) = 0.078, 95% confidence interval (CI): 0.011-0.582, p = 0.013) and DFS (HR = 0.417, 95% CI: 0.213-0.815, p = 0.011). Subgroup analysis indicated that adjuvant chemotherapy significantly improved OS (p < 0.05) and DFS (p < 0.05) in the low NLN group. Conclusion: NLN count is an independent prognostic factor in patients with T3N0 rectal cancer. Patients with low NLN counts (NLN < 21) may benefit from adjuvant chemotherapy.

Tumor deposits (TDs) and extramural venous invasion (EMVI) in locally advanced rectal cancer (LARC) are MRI-detectable markers that reflect the invasive and metastatic potential of tumors. However, both mrTDs and mrEMVI are closely associated with peritumoral vascular signals, and they show a high degree of statistical correlation. We developed a novel scoring system that integrates mrTDs and mrEMVI into a single parameter, simplifying the assessment process and capturing the prognostic value of both factors simultaneously.

We retrospectively included LARC patients who received neoadjuvant chemoradiotherapy at five centers and proposed a novel MRI-based scoring system, mrTE (derived from mrTDs and mrEMVI), to integrate the prognostic significance of mrEMVI and mrTDs in rectal cancer. The prognostic value of different mrTE scores was evaluated using Kaplan-Meier curves and the Cox model. The predictive accuracy of the new scoring system was evaluated using the integrated area under the ROC curve (iAUC).

A total of 1188 patients with LARC were included in the evaluation cohort to assess the reliability of the novel imaging scoring system. Based on the mrTE scores ranging from 0 to 2, the patients were categorized into three groups. The 3-year disease-free survival rates for the groups were 88.1%, 78.1%, and 51.9% (score 1 vs 0: HR 2.00, 95% CI 1.36-2.93, p < 0.001; score 2 vs 0: HR 4.75, 95% CI 3.61-6.26, p < 0.001). The mrTE scoring system demonstrated superior performance in predicting DFS compared to other clinical and imaging markers, with a higher predictive accuracy (iAUC = 0.707).

The mrTE scoring system simplifies the clinical assessment of relevant MR markers and has proven to be an effective tool for predicting the prognosis of LARC patients.

Over the past two decades, minimally invasive approaches in rectal surgery have changed the landscape of surgical interventions, impacting both malignant and benign pathologies. The dynamic nature of rectal cancer treatment owes much to innovations in surgical techniques, reflected in the expanding literature on available treatment modalities. Local excision, facilitated by minimally invasive surgery, offers curative potential for patients with early T1 rectal cancers and favorable pathologic features. For more complex cases, laparoscopic and robotic surgery have demonstrated significant efficacy and provided precise, durable outcomes while reducing perioperative morbidity and enhancing postoperative recovery. Additionally, advancements in imaging, surgical instrumentation, and enhanced recovery protocols have further optimized patient care. The integration of multidisciplinary care has also emerged as a cornerstone of treatment, emphasizing collaboration among surgeons, oncologists, and radiologists to deliver personalized, evidence-based care. This narrative review aims to elucidate current minimally invasive surgical techniques and approaches for rectal pathologies, spanning benign and malignant conditions, while also exploring future directions in the field, including the potential role of artificial intelligence and next-generation robotic platforms.

To determine whether quantitative parameters derived from dual-energy CT (DECT) could predict prognosis in patients with resectable rectal cancer (RC).

One hundred and thirty-four patients (recurrence/distant metastasis group, n = 36; non-metastasis/non-recurrence group, n = 98) with RC who underwent radical resection and DECT were retrospectively included. DECT quantitative parameters, including iodine concentration (IC), normalized iodine concentration (NIC), electron density (Rho), effective atomic number (Zeff), dual-energy index (DEI), the slope of the spectral Hounsfield unit curve (λHU) on arterial and venous phase images. Univariate and multivariate Cox proportional hazards models were employed to identify independent risk factors of prognosis. The area under the receiver operating characteristic curve (AUC) was used to assess the performance. Disease-free survival (DFS) curves were constructed using the Kaplan-Meier method.

Patients in the metastasis/recurrence group had higher Rho in arterial phase (A-Rho), NIC in venous phase (V-NIC), Rho in venous phase (V-Rho), Zeff in venous phase (V-Zeff), λHU in venous phase (V-λHU), pT stage, pN stage, serum carcinoembryonic antigen (CEA), carbohydrate antigen-199 levels and more frequent in extramural venous invasion than those in non-metastasis/non-recurrence group (all p < 0.05). V-NIC, V-λHU, and CEA were independent risk factors of recurrence/distant metastasis (all p < 0.05). The AUC of combined indicator integrating three independent risk factors achieved the best diagnostic performance (AUC = 0.900). In stratified survival analysis, patients with high V-NIC, V-λHU, and CEA had lower 3-year DFS than those with low V-NIC, V-λHU, and CEA.

Combining V-NIC, V-λHU, and CEA could be used to noninvasively predict prognosis in resectable RC.

Question TNM staging fails to accurately prognosticate; can quantitative parameters derived from dual-energy CT predict prognosis in patients with resectable rectal cancer? Findings Normalized iodine concentration (V-NIC) and the slope of the spectral Hounsfield unit curve in venous phase (V-λHU), and carcinoembryonic antigen (CEA) are independent risk factors for recurrence/metastasis. Clinical relevance The combined indicator integrating V-NIC, V-λHU, and CEA could predict 3-year disease-free survival in patients with resectable rectal cancer and could aid in postoperative survival risk stratification to guide personalized treatment.

Approximately 7% of patients with rectal cancer experience local recurrence within 5 years of curative surgery. A positive circumferential resection margin (CRM) is among the most significant risk factors. Other reported risk factors include histopathologic type, anastomotic leakage, positive distal margins, and more recently, the anterior localization of the tumor. In this retrospective cohort study, we aimed to assess risk factors for local recurrence in our institution, with a focus on tumor localization as an independent negative predictive factor.

From 2007 to 2018, all patients with stage II or III rectal cancer were included in this study. Patients underwent neoadjuvant chemoradiotherapy followed by surgical resection with total mesorectal excision. The tumor's anterior or posterior localization was assessed by preoperative endosonography or magnetic resonance imaging. Risk factors for local recurrence were assessed using univariate and multivariate regression analyses.

A total of 128 patients were included. The 3-year and 5-year local recurrence rates were 4.7% and 7%, respectively. In univariate and multivariate analyses, the histologic type of a poorly differentiated tumor (P=0.001) and a positive CRM (P=0.001) were correlated with local recurrence. Tumor localization (anterior or posterior) was not identified as a statistically significant factor associated with local recurrence.

Positive CRM and a poorly differentiated tumor histological subtype were found to be independent risk factors for local recurrence. In contrast to previous findings, anterior localization was not identified as an independent risk factor for local recurrence in our patient cohort.

Rectal eversion (RE) is a natural orifice specimen extraction (NOSE) method that allows anus-sparing resection in very low rectal tumors. This study aims to share the long-term results of RE in laparoscopic rectal resection performed with double stapling anastomosis.

A single-center retrospective cohort study was conducted for patients who underwent laparoscopic low anterior resection with RE. Age, sex, body mass index, American Society of Anesthesiologists (ASA) classification, type of surgery, distance of the tumor to the dentate line, specimen extraction site, cancer stage, preoperative chemoradiotherapy, postoperative complications, and postoperative clinical follow-up findings were recorded. Incontinence was assessed using the Wexner score (WS). Low anterior resection syndrome (LARS) is determined by the LARS score. A 7-point Likert scale was used to evaluate the satisfaction of the patients.

A total of 17 patients underwent resection by RE for rectal tumors. Of the 11 patients included in the study, 4 were female and 7 were male. The mean age was 66.09±15.04 years. The mean follow-up was 64.18±16.83 months. The mean tumor diameter was 3.1 cm (range: 0.9 to 7.2 cm). The mean distance of the tumor from the dentate line was 2.7 cm (range: 1.2 to 5.6 cm). No anastomotic leak was observed in any patient. One patient had an anastomotic stenosis and was treated with balloon dilatation. The median LARS score was 16 (range 0 to 32) and 64% of the patients had no LARS. Two patients had minor LARS and 2 patients had major LARS. The median Wexner score was 3.5 (range 0 to 14). The median Likert scale was 7 (range 5 to 7). It was found that 55% of the patients were extremely satisfied, 18% were satisfied, and 27% were slightly satisfied with their surgery. There were no dissatisfied patients.

RE is a safe NOSE technique in laparoscopic double stapling anastomosis for rectal resection. There is a high level of long-term patient satisfaction with anus-sparing procedures via RE, even in the presence of various symptoms.

Colorectal cancer is the third leading cause of cancer death worldwide. In China, the incidence and mortality of colorectal cancer are increasing, in which low rectal cancer is more common. Ultra-low rectal cancer refers to rectal cancer where the distance between the tumor and the anus is less than 5 cm, it accounts for about 70%-80% of rectal tumors. Intersphincteric resection (ISR), an important technical means for anal preservation of ultra-low rectal cancer, although could reduce the pain of patients during the surgical process, increase the anal preservation rate of patients and improve the life quality of patients, still has many adverse effects such as the high incidence of anorectal anastomotic leakage and high anterior resection syndrome. Many modified ISRs have emerged due to the limitations and adverse reactions of traditional ISR surgery. the purpose of this article is to review the progress of ISR surgery to improve its use in treatment.

The potential oncological benefit of extending the waiting period between neoadjuvant radiochemotherapy and surgical resection for rectal cancer is debated.

To evaluate the impact of prolonging this waiting period on the 5-year oncological prognosis and 2-year functional result of locally advanced rectal adenocarcinoma.

Phase III, multicenter, randomized, open-label, parallel-group, controlled trial.

Patients were enrolled from 24 colorectal centers.

Patients with nonmetastatic mid or lower cT3/T4Nx or cTxN+ rectal adenocarcinoma who had received radiochemotherapy (45-50 Gy radiation dose with fluorouracil or capecitabine).

Patients were randomly assigned to undergo total mesorectal excision either 7 weeks or 11 weeks after radiochemotherapy.

Overall survival and disease-free survival at 5-year follow-up and low anterior resection syndrome score assessed after 2 years of follow-up.

Among 265 patients enrolled, 133 were randomized in the 7-week group and 132 in the 11-week group. Twelve patients were excluded because they did not undergo resection. Among 253 patients analyzed, 5-year overall survival was not different between the 2 groups (81.6% in the 7-week group vs 82.6% in the 11-week group, p = 0.827), and neither was the 5-year disease-free survival (70.4% in the 7-week group vs 69.5% in the 11-week group, p = 0.856). No difference was observed between the 2 groups for distant recurrence (27.4% in the 7-week group vs 25.7% in the 11-week group, p = 0.777) or local recurrence (8.4% in the 7-week group vs 10.2% in the 11-week group, p = 0.543). The low anterior resection syndrome score was similar between the 7-week (25.0; interquartile range, 15.0-34.0) and 11-week groups (23.0; interquartile range, 14.2-32.0; p = 0.743).

The response rate to the low anterior resection syndrome questionnaire was only 52%.

Extending the waiting period between radiochemotherapy and resection from 7 to 11 weeks does not change the 5-year oncological prognosis in rectal cancer or the 2-year low anterior resection occurrence. See Video Abstract.

ANTECEDENTES:Se debate el posible beneficio oncológico de prolongar el periodo de espera entre la radioquimioterapia neoadyuvante y la resección quirúrgica del cáncer de recto.OBJETIVO:Evaluar el impacto de la prolongación de este periodo de espera sobre el pronóstico oncológico a 5 años y el resultado funcional a 2 años del adenocarcinoma rectal localmente avanzado.DISEÑO:Ensayo controlado de fase III, multicéntrico, aleatorizado, abierto, de grupos paralelos.LUGAR:Se reclutaron pacientes de 24 centros colorrectales.PACIENTES:Pacientes con adenocarcinoma rectal de tercio medio o inferior, no metastásico cT3-4 o TxN+ que habían recibido radioquimioterapia (45 a 50 Gy con fluorouracilo o capecitabina).INTERVENCIÓN:Se asignaron aleatoriamente a los pacientes para ser sometidos a una escisión mesorrectal total 7 semanas (W7) u 11 semanas (W11) después de la radioquimioterapia.MEDIDAS DE RESULTADOS PRINCIPALES:Supervivencia global y supervivencia libre de enfermedad a los 5 años de seguimiento y puntuación del síndrome de resección anterior baja evaluada a los 2 años de seguimiento.RESULTADOS:De los 265 pacientes reclutados, 133 fueron asignados aleatoriamente al grupo de 7 semanas y 132 al grupo de 11 semanas. Doce pacientes fueron excluidos porque no fueron sometidos a resección. Entre los 253 pacientes analizados, la supervivencia global a 5 años no fue diferente entre los dos grupos (81,6% en el grupo de 7 semanas frente a 82,6% en el grupo de 11 semanas, p = 0,827), así como para la supervivencia libre de enfermedad a 5 años (70,4% en el grupo de 7 semanas frente a 69,5% en el grupo de 11 semanas, p = 0,856). No se observaron diferencias entre los dos grupos en cuanto a la recidiva a distancia (27,4% en el grupo de 7 semanas frente a 25,7% en el grupo de 11 semanas, p = 0,777) o la recidiva local (8,4% en el grupo de 7 semanas frente a 10,2% en el grupo de 11 semanas, p = 0,543). La puntuación del síndrome de resección anterior baja fue similar entre los grupos de 7 semanas (25,0 IQR [15,0-34,0]) y 11 semanas (23,0 IQR [14,2-32,0], p = 0,743).LIMITACIONES:La tasa de respuesta al cuestionario LARS fue sólo del 52%.CONCLUSIONES:Ampliar el periodo de espera entre radioquimioterapia y resección de 7 a 11 semanas no modifica el pronóstico oncológico a 5 años en cáncer de recto ni la baja incidencia de resección anterior a 2 años. (Traducción-Dr Osvaldo Gauto ).