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BACKGROUND: Radiotherapy reduces local recurrence in locally advanced rectal cancer, but may cause harm in patients who do not experience recurrence. The aim was to investigate the impact of radiotherapy on long-term quality of life after curative treatment for rectal cancer, i.e. in patients without a recurrence during the follow-up. METHODS: All patients operated on for rectal cancer in Norway under 75 years of age between 30 September 2007 and 1 October 2020 were identified using the Cancer Registry of Norway. Exclusion criteria were distant metastasis, recurrence and dementia. The primary outcome measure was the Gastrointestinal Quality of Life Index. Secondary outcome measures included the 36-item Short Form Survey. Inverse probability weights based on a multiple logistic regression model were used to balance prechosen covariates between the radiotherapy and no radiotherapy groups when assessing differences in outcomes. RESULTS: Of 5014 invited patients, 2142 (43%) eligible patients answered the questionnaires. Of these 762 (36%) were treated with neoadjuvant radiotherapy plus surgery and 1380 (64%) with surgery alone. The mean follow-up time was 6.4 and 7.4 years respectively. After propensity score matching, the Gastrointestinal Quality of Life Index differed significantly between irradiated and non-irradiated patients ((mean(s.d.), mean score 103.8(19.4) versus 110.8(19.6) respectively, mean difference: -6.96 (95% c.i. -8.72 to -5.19); P < 0.001). Among patients without a stoma the mean difference was -8.1 points, whereas it was -5.7 for patients with a stoma. The radiotherapy group also scored significantly lower in 7 of 8 36-item Short Form Survey domains compared with the surgery alone group. CONCLUSION: Long-term quality of life was significantly lower in patients without a recurrence during the follow-up who received radiotherapy compared with patients who did not. These findings warrant a critical re-evaluation of the use of radiotherapy both in traditional neoadjuvant treatment and in modern organ-preserving treatment regimens.

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Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer. Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were selected.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARHGAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the patients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expression.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups. Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue (P<0.001).The expression level of ARHGAP8 was correlated with tumor stage (P=0.024),lymph node metastasis (P=0.007),and age (P=0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue (P<0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue (P=0.011).The expression of ARHGAP8 was correlated with tumor size (P=0.010) and pathological stage (P=0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 patients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91% (29/44) patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy (P<0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86%,which was higher than that (53.33%) in the patients with high protein level of ARHGAP8 (P=0.033). Conclusion ARHGAP8 is highly expressed in the rectal cancer tissue.The patients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and development of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.

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BACKGROUND: Robotic three-dimensional magnified visual effects and field of view stabilization have enabled precise surgical operations. Intracorporeal anastomosis in right-sided colorectal cancer surgery is expected to shorten operation times, avoid paralytic ileus, and shorten wound lengths; however, there are few reports of intracorporeal anvil fixation for intestinal anastomosis in left-sided colorectal cancer surgery. Herein, we introduce a simple, novel procedure for using robotic purse-string suture (RPSS) in intracorporeal anastomosis with the double-stapling technique in rectal and sigmoid cancer surgery and report short-term outcomes. METHODS: From September 2022 to April 2024, 105 consecutive patients underwent robotic surgery with double-stapling technique anastomosis for rectal or sigmoid colon cancer at our institution. Their data were retrospectively analyzed. Intracorporeal anastomosis with the double-stapling technique using RPSS was performed in 26 patients (the RPSS group), while the double-stapling technique anastomosis with extracorporeal anvil fixation was performed in 79 patients (the EC group). A 1:1 propensity score-matched analysis was performed (matching criteria: sex, age, body mass index (BMI), tumor location and tumor size) using a caliper 0.3. In the RPSS group, after tumor-specific or total mesorectal excision, specimens were extracted from the umbilical wound with simultaneous anvil placement in the body cavity. The oral colonic stump was robotically excised and robotically circumferentially stitched with 3-0 Prolene in all layers. After anvil insertion into the stump, the bowel wall of the colon was completely sewn onto the central rod of the anvil. Reconstructions were anastomosed using the double-stapling technique. RESULTS: The matched cohort contained 23 patients in each group. The RPSS group had significantly less bleeding than the EC group (p = 0.038). Super-low anterior resection (SLAR) in the RPSS group had shorter total operative times than those in the EC group (p = 0.045). The RPSS group experienced no perioperative complications greater than Clavien-Dindo grade III or any anastomosis-related complications. CONCLUSIONS: The RPSS technique can be performed safely without any anastomosis-related complications and reduces the total operative times in SLAR and blood loss through total robotic surgery. This may be a useful modality for robotic colorectal surgery.

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BACKGROUND: Magnetic resonance-guided adaptive radiotherapy (MRgART) at MR-Linac allows for plan optimisation on the MR-based synthetic CT (sCT) images, adjusting the target and organs at risk according to the patient's daily anatomy. Conversely, conventional linac image-guided radiotherapy (IGRT) involves rigid realignment of regions of interest to the daily anatomy, followed by the delivery of the reference computed tomography (CT) plan. This study aims to evaluate the effectiveness of MRgART versus IGRT for rectal cancer patients undergoing short-course radiotherapy, while also assessing the dose accumulation process to support the findings and determine its usefulness in enhancing treatment accuracy. METHODS: Nineteen rectal cancer patients treated with a 1.5 Tesla MR-Linac with a prescription dose of 25 Gy (5 Gy x 5) and undergoing daily adapted radiotherapy by plan optimization based on online MR-based sCT images, were included in this retrospective study. For each adapted plan ([Formula: see text]), a second plan ([Formula: see text]) was generated by recalculating the reference CT plan on the daily MR-based sCT images after rigid registration with the reference CT images to simulate the IGRT workflow. Dosimetry of [Formula: see text] and[Formula: see text]was compared for each fraction. Cumulative doses on the first and last fractions were evaluated for both workflows. The dosimetry per single fraction and the cumulative doses were compared using dose-volume histogram parameters. RESULTS: Ninety-five fractions delivered with MRgART were compared to corresponding simulated IGRT fractions. All MRgART fractions fulfilled the target clinical requirements. IGRT treatments did not meet the expected target coverage for 63 out of 94 fractions (67.0%), with 13 fractions showing a V95 median point percentage decrease of 2.78% (range, 1.65-4.16%), and 55 fractions exceeding the V107% threshold with a median value of 15.4 cc (range, 6.0-43.8 cc). For the bladder, the median [Formula: see text] values were 18.18 Gy for the adaptive fractions and 19.60 Gy for the IGRT fractions. Similarly the median [Formula: see text] values for the small bowel were 23.40 Gy and 25.69 Gy, respectively. No statistically significant differences were observed in the doses accumulated on the first or last fraction for the adaptive workflow, with results consistent with the single adaptive fractions. In contrast, accumulated doses in the IGRT workflow showed significant variations mitigating the high dose constraint, nevertheless, more than half of the patients still did not meet clinical requirements. CONCLUSIONS: MRgART for short-course rectal cancer treatments ensures that the dose delivered matches each fraction of the planned dose and the results are confirmed by the dose accumulation process, which therefore seems redundant. In contrast, IGRT may lead to target dose discrepancies and non-compliance with organs at risk constraints and dose accumulation can still highlight notable dosimetric differences.

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PURPOSE: Robotic-assisted rectal surgery (RARS) and Laparoscopic-assisted rectal surgery are the two techniques that are increasingly used for rectal cancer, and both have their advantages and disadvantages. This meta-analysis will analyze the outcomes of both techniques to determine their relative performance and suitability. METHODS: An extensive search was carried out on PubMed, Cochrane, Scopus, Embase, and Google Scholar, followed by a meta-analysis of all randomized controlled trials (RCTs) to assess both approaches for rectal cancer. RESULTS: This meta-analysis is comprised of fifteen RCTs. The conversion to open surgery (RR = 0.53, 95% CI: 0.38-0.74, P = 0.0002) was significantly lower in the RARS group. The outcomes like anastomotic leak, postoperative ileus, postoperative urinary retention (POUR), surgical site infection (SSI), and intra-abdominal abscess showed no significant difference between the two groups. The reoperation rate (RR = 0.56, 95% CI: 0.34-0.95, P = 0.03) was lower in the robotic group. High heterogeneity was obtained when pooling data on operative time, length of hospital stay, and blood loss. Oncological outcomes, including local recurrence, the number of harvested lymph nodes (LN) and distal resection margin showed no significant distinction among both groups, while the positive circumferential resection margin (CRM) (RR = 0.67, 95% CI: 0.49-0.91, P = 0.01) was lower in the RARS group. RARS demonstrated a significantly higher rate of total mesorectal excision (TME) (RR = 1.07, 95% CI: 1.01-1.14, P = 0.03). CONCLUSION: RARS is safe and feasible for rectal cancer patients and may be superior or equivalent to Laparoscopic-assisted rectal surgery, but high-standard, large-scale trials are required to determine the best approach.

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Neoadjuvant radiotherapy is the standard care of locally advanced rectal cancer. Although a majority of patients received the same dose, the curative efficacy varies among individuals. In recent years, cancer treatment has entered the era of precise medical care, and how to identify patients for proper treatment by molecular signature is an important path of individualized therapy. This study aimed to establish and validate a genome-based model for adjusting radiation dose (GARD) for Chinese locally advanced rectal cancer through gene expression microarrays, and to evaluate the response of the GARD model in predicting the efficacy of neoadjuvant radiotherapy. Fresh-frozen primary tumor from 64 patients with locally advanced rectal cancer undergoing neoadjuvant radiotherapy from 2015 to 2018 were included. The gene expression profile was analyzed using Affymetrix 3000Dx gene-chip scanner. The radiosensitivity index (RSI) and GARD were calculated using the pGRT™ algorithm. Neoadjuvant rectal cancer score (NAR) was selected as efficacy evaluation indicators. Patients were divided into high and low NAR scoring groups, and two-sample t-test was used to analyze the differences in GARD values between different NAR subgroups. ROC curves were used to calculate the cut-off values and the area under the curve (AUC) for assessing the validity of the GARD models. The personalized radiation dose ( pGRT dose )can be computed using the formula nd = GARD / (α + ßd). Among patients, 1.5% T2, 46.3% T3, and 52.2% T4. Wherein pCR (n = 10; 15.6%) and no pCR (n = 54; 84.4%). The median NAR is 8.43 (rang from 0 to 50.34, IQR 3.75-14.98). NAR > 8.43 (n = 27; 42.2%) and NAR ≤ 8.43 (n = 37; 57.8%), suggesting that there are significant individual differences in clinical efficacy of patients with similar tumor stages and under the same treatment conditions. The median RSI is 0.48 (rang from 0.22 to 0.92, IQR 0.41-0.55). Median GARD was 18.40 rang from (rang from 2.26 to 37.52, IQR 14.94-22.28) within tumor tissue, suggesting individual differences in the efficacy of radiation therapy. The RSI value was significantly lower in the NAR low group (NAR ≤ 8.43) than in NAR high group (NAR > 8.43) (0.44 vs. 0.54, p = 0.0003). The GARD value was significantly higher in the NAR low group (NAR ≤ 8.43) than in NAR high group (NAR > 8.43) (21.01 vs. 15.88, p = 0.0004). Using the Receiver Operating Characteristic (ROC) curve analysis, a GARD threshold of 17 was identified as optimal, covering 37.5% of the 64-patient sample, with an area under the curve (AUC) of 0.75. In the external validation cohort, the high GARD score group demonstrated superior DFS compared to the low GARD score group(p < 0.001). Only 17% of patients had pGRT dose within the guideline recommended dose (45-50 Gy). The differences in NAR values among LARC patients receiving standard neoadjuvant radiotherapy suggest significant individual differences in clinical outcomes among patients with similar tumor stage and the same treatment conditions. Patients with a GARD value exceeding 17 exhibit a more favorable prognosis. Our results suggest that the gene expression-based pGRT™ algorithm has good efficacy prediction performance in preoperative concurrent radiotherapy for locally advanced rectal cancer, suggesting the potential clinical application of this method to guide the designation of individualized radiotherapy doses.

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AIM: Retrorectal tumors are rare and heterogeneous. They are often asymptomatic or present with nonspecific symptoms, making management challenging. This study examines the diagnosis and treatment of retrorectal tumors. METHODS: Between 2002 and 2022, 21 patients with retrorectal tumors were treated in our department. We analyzed patient characteristics, diagnosis and treatment modalities retrospectively. Additionally, a literature review (2002-2023, "retrorectal tumors" and "presacral tumors", 20 or more cases included) was performed. RESULTS: Of the 21 patients (median age 54 years, 62% female), 17 patients (81%) suffered from benign lesions and 4 (19%) from malignant lesions. Symptoms were mostly nonspecific, with pain being the most common (11/21 (52%)). Diagnosis was incidental in eight cases. Magnetic resonance imaging was performed in 20 (95%) and biopsy was obtained in 10 (48%). Twenty patients underwent surgery, mostly via a posterior approach (14/20 (70%)). At a mean follow-up of 42 months (median 10 months, range 1-166 months), the local recurrence rate was 19%. There was no mortality. Our Pubmed search identified 39 publications. CONCLUSION: Our data confirms the significant heterogeneity of retrorectal tumors, which poses a challenge to management, especially considering the often nonspecific symptoms. Regarding diagnosis and treatment, our data highlights the importance of MRI and surgical resection. In particular a malignancy rate of almost 20% warrants a surgical resection in case of the findings of a retrorectal tumour. A local recurrence rate of 19% supports the need for follow up.

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BACKGROUND: Colorectal cancer screening programmes have led to a shift towards early-stage colorectal cancer, which, in selected cases, can be treated using local excision. However, local excision followed by completion total mesorectal excision (two-stage approach) may be associated with less favourable outcomes than primary total mesorectal excision (one-stage approach). The aim of this population study was to determine the distribution of treatment strategies for early rectal cancer in the Netherlands and to compare the short-term outcomes of primary total mesorectal excision with those of local excision followed by completion total mesorectal excision. METHODS: Short-term data for patients with cT1-2 N0xM0 rectal cancer who underwent local excision only, primary total mesorectal excision, or local excision followed by completion total mesorectal excision between 2012 and 2020 in the Netherlands were collected from the Dutch Colorectal Audit. Patients were categorized according to treatment groups and logistic regressions were performed after multiple imputation and propensity score matching. The primary outcome was the end-ostomy rate. RESULTS: From 2015 to 2020, the proportion for the two-stage approach increased from 22.3% to 43.9%. After matching, 1062 patients were included. The end-ostomy rate was 16.8% for the primary total mesorectal excision group versus 29.6% for the local excision followed by completion total mesorectal excision group (P < 0.001). The primary total mesorectal excision group had a higher re-intervention rate than the local excision followed by completion total mesorectal excision group (16.7% versus 11.8%; P = 0.048). No differences were observed with regard to complications, conversion, diverting ostomies, radical resections, readmissions, and death. CONCLUSION: This study shows that, over time, cT1-2 rectal cancer has increasingly been treated using the two-stage approach. However, local excision followed by completion total mesorectal excision seems to be associated with an elevated end-ostomy rate. It is important that clinicians and patients are aware of this risk during shared decision-making.

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Background MRI plays a crucial role in restaging locally advanced rectal cancer treated with total neoadjuvant therapy (TNT); however, prospective studies have not evaluated its ability to accurately select patients for nonoperative management. Purpose To evaluate the ability of restaging MRI to predict oncologic outcomes and identify imaging features associated with residual disease (RD) after TNT. Materials and Methods This was a secondary analysis of the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial, which randomized participants from April 2014 to March 2020 with stages II or III rectal adenocarcinoma to undergo either induction or consolidation TNT. Participants enrolled in the OPRA trial who underwent restaging MRI were eligible for inclusion in the present study. Radiologists classified participants as having clinical complete response (cCR), near-complete clinical response (nCR), or incomplete clinical response (iCR) based on restaging MRI at a mean of 8 weeks ± 4 (SD) after treatment. Oncologic outcomes according to MRI response category were assessed using Kaplan-Meier curves. Logistic regression analysis was performed to identify imaging characteristics associated with RD. Results A total of 277 participants (median age, 58 years [IQR, 17 years]; 179 male) who were randomized in the OPRA trial had restaging MRI forms completed. The median follow-up duration was 4.1 years. Participants with cCR had higher rates of organ preservation compared with those with nCR (65.3% vs 41.6%, log-rank P < .001). Five-year disease-free survival for participants with cCR, nCR, and iCR was 81.8%, 67.6%, and 49.6%, respectively (log-rank P < .001). The MRI response category also predicted overall survival (log-rank P < .001), distant recurrence-free survival (log-rank P = .005), and local regrowth (log-rank P = .02). Among the 266 participants with at least 2 years of follow-up, 129 (48.5%) had RD. At multivariable analysis, the presence of restricted diffusion (odds ratio, 2.50; 95% CI: 1.22, 5.24) and abnormal nodal morphologic features (odds ratio, 5.04; 95% CI: 1.43, 23.9) remained independently associated with RD. Conclusion The MRI response category was predictive of organ preservation and survival. Restricted diffusion and abnormal nodal morphologic features on restaging MRI scans were associated with increased likelihood of residual tumor. ClinicalTrials.gov identifier: NCT02008656 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Milot in this issue.

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INTRODUCTION: Limited data exists on oncological outcomes following rectal cancer surgery in men who have previously been diagnosed with prostate cancer (PC). This study aimed to assess overall mortality and rectal cancer recurrence in men previously diagnosed with PC who underwent bowel resection. METHODS: Data from the Swedish Colorectal Cancer Registry identified men who had rectal cancer surgery between 2000 and 2016, and the National Prostate Cancer Registry was used to identify those with a prior PC diagnosis. Cox regression analysis with propensity score matching was employed for data analysis. The primary outcome was overall mortality. Secondary outcome was recurrence for rectal cancer. RESULTS: Out of 13,299 men undergoing bowel resection for rectal cancer between 2000 and 2016, 1130 had a history of PC. Overall mortality did not significantly differ between men with and without a prior PC diagnosis. Cox regression analyses with propensity score matching revealed that men with previously diagnosed low- or intermediate-risk (HR, 0.79; 95% CI, 0.70-0.90) and high-risk PC (HR, 0.85; 95% CI, 0.74-0.98) had lower overall mortality after rectal cancer surgery compared with men without a PC. There was no significant difference in rectal cancer recurrence between men with a previous low or intermediate-risk PC (HR, 0.92; 95% CI, 0.74-1.14) or high-risk PC (HR, 0.73; 95% CI, 0.52-1.01) compared with those without PC history. CONCLUSION: Men undergoing rectal cancer surgery with a previous diagnosis of prostate cancer do not experience an increased risk of rectal cancer recurrence or overall mortality compared with men without a previous history of prostate cancer.

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The treatment mode for patients with low rectal cancer (LRC) is still mainly surgical treatment. With the advancement of medical technology, the current surgical mode is more inclined towards super minimally invasive surgery (SMIS) that preserves organs and functions. SMIS belongs to organ preservation surgery, including non-full thickness and full-thickness resection under digestive endoscopy, laparoscopic or robotic full-thickness resection, and transanal minimally invasive surgery, which can cover all stages of TNM staging. The paper elaborates on the importance of preoperative accurate diagnosis and risk stratification in selecting appropriate SMIS methods, the new progress of imaging technology in accurately predicting lymph node metastasis, providing preoperative TNM staging and risk stratification, and guiding SMIS treatment. Finally, the paper introduces the SMIS surgical options for the treatment of LRC that have been developed and are currently in the clinical research stage, with the aim of maximizing the quality of life for LRC patients.

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Objective: To investigate the efficacy of Da Vinci robotic transanal minimally invasive surgery (R-TAMIS) for rectal neoplasms. Methods: The patients of rectal neoplasms who underwent R-TAMIS and were regularly followed up at the First Medical Center of Chinese PLA General Hospital from January 2021 to January 2024 were retropectively selected. Follow-up visits were conducted at 1, 2, and 4 weeks postoperatively, and then every 3 months until January 20, 2024. The perioperative situation, postoperative histopathological results, and follow-up status of the patients were observed. Results: A total of 17 patients were included, including 10 males and 7 females, aged 35-80 (59±13) years. Eleven patients underwent surgery using the da Vinci® Si robot, while 6 patients underwent surgery using the da Vinci® Xi robot. The height of the resected tumor from the anal verge [M (Q1, Q3)] was 3.5 (3.0, 3.8) cm. The total operative time was 55.0 (50.0, 55.0) minutes, the platform installation time was 32.5 (30.0, 35.0) minutes. The actual surgical operation time was 22.5 (20.0, 27.5) minutes. Intraoperative blood loss was 9.2 (5.0, 10.0) ml. The postoperative hospital stay was 3.2 (3.0, 3.8) days. The total treatment cost was (29 447±4 765) yuan. Two patients who achieved clinical complete remission after neoadjuvant chemoradiotherapy experienced incision dehiscence one week postoperatively, which was resolved after four weeks of rectal irrigation therapy. All surgical specimens were intact, and all resection margins were negative. A total of 44(31,73) weeks were followed up, without local recurrence or distant metastasis. Conclusion: Da Vinci robotic transanal minimally invasive local resection may be a safe and feasible treatment option for rectal neoplasms.

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Importance: Patients with locally advanced rectal cancer and persistent lymph node metastases (PLNM) after neoadjuvant treatment are at high risk of developing locoregional and distant metastasis, yet optimal postsurgical treatment of these patients is limited. Objective: To analyze the association of PLNM with pretreatment clinical parameters, intensity of neoadjuvant treatment, and long-term oncological outcomes. Design, Setting, and Participants: This cohort study is a post-hoc analysis of 3 randomized clinical trials (Surgical Oncology Working Group of Germany [CAO], Radiological Oncology Working Group of Germany [ARO], and Working Group for Internal Oncology in the German Cancer Society [AIO]) conducted in Germany in 1994, 2004, and 2012 that included 1948 patients with locally advanced rectal cancer recruited between February 1995 and January 2018. Statistical analysis was conducted between September 2023 and February 2024. Exposures: Receiving preoperative fluorouracil-based chemoradiotherapy (CRT, comprising the preoperative group of CAO/ARO/AIO-94 and the control group of CAO/ARO/AIO-04), fluorouracil-based CRT plus oxaliplatin (experimental group of CAO/ARO/AIO-04), or total neoadjuvant treatment (TNT) with fluorouracil-based CRT plus oxaliplatin with induction or consolidation leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin chemotherapy within the CAO/ARO/AIO-12 trial. Main Outcome and Measures: The associations of PLNM with clinical parameters, intensity of neoadjuvant treatment, and cumulative incidences of LR, DM, and overall survival were assessed. Results: A total of 1888 patients (1333 male participants [70.6%]; median [range] age, 62 [19-84] years) with locally advanced rectal adenocarcinoma (clinical tumor stage 3 to 4 and/or clinically node-positive) treated within 3 consecutive clinical trials were analyzed. A total of 522 (29%) experienced PLNM; 378 had lymph node stage (ypN) 1 (20%) after neoadjuvant treatment (ypN) 1 (20%), and 174 had ypN2 (9%). Age, clinical T-stage, N-stage, grading, carcinoembryonic antigen levels, and time interval from completion of CRT to surgery were significantly associated with PLNM, whereas sex and tumor location were not. The percentage of patients with ypN2 stage was almost halved after TNT (18 of 293 patients [6%]) compared with patients treated with fluorouracil-based CRT (114 of 1009 patients [11.3%]; χ26 = 16.693; P = .01). After a median (IQR) follow-up of 54 (37-62) months, 5-year overall survival was 86.1% (95% CI, 83.9%-88.4%) for ypN0, 74.0% (95% CI, 83.9%-88.4%) for ypN1, and 43% for ypN2 (95% CI, 35.4%-52.2%) (P < .001). The 5-year cumulative incidences of locoregional and distant metastases were, respectively, 3% (95% CI, 2.1%-4.2%) and 20% (95% CI, 18%-23%) for ypN0, 6% (95% CI, 3.4%-8.8%) and 40% (95% CI, 34%-46%) for ypN1, and 19% (95% CI, 13%-26%) and 72% (95% CI, 63%-79%) for ypN2 (both P < .001). Conclusions and Relevance: In this cohort study, PLNM unmasked an unfavorable phenotype of rectal cancer at high risk for treatment failure. More aggressive adjuvant treatment might be considered; however, risk-adapted surveillance strategies and early recurrence-directed surgery, if feasible, are important strategies in this group of patients with CRT- and/or chemotherapy-resistant disease.

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STUDY OBJECTIVE: Advanced rectal cancer is a common cause of perineal pain and research on the use of radiofrequency therapy for the treatment of this pain is limited. In the present study, we aimed to compare the effectiveness and safety of conventional radiofrequency (CRF) and high-voltage long-term pulsed radiofrequency (H-PRF) of radiofrequency therapy in the management of perineal pain in advanced rectal cancer. DESIGN: Randomized, Double-Blind Controlled Trial. SETTING: Sichuan Cancer Hospital & Institute and Yanjiang District People's Hospital in Sichuan, China. PARTICIPANTS: A total of 72 patients with advanced rectal cancer experiencing perineal pain who were accepted for radiofrequency treatment. INTERVENTIONS: Patients were assigned randomly (1:1) assigned to either the group CRF or H-PRF in a double-blind trial. MEASUREMENTS AND MAIN RESULTS: The primary focus was on assessing perineal pain using numeric rating scales (NRS) scores at various time points. Secondary outcomes included the duration of maintaining a sitting position, depression scores, sleep quality, consumption of Oral Morphine Equivalent and Pregabalin, and the incidence of perineal numbness. A total of 57 patients (28 patients in the group CRF and 29 patients in the group H-PRF) were investigated. At all observation time points postoperatively, both groups of patients exhibited significant reductions in pain, enhancements in depression, improvements in sleep quality, and increased duration of sitting compared to their baseline measurements (P<0.05). During the 3 months and 6 months follow-up period, the group CRF exhibited significant reduction in pain, improvement in depression, sleep quality, and increased the time of keeping a sitting position compared with the group H-PRF (P<0.05). The consumption of oral morphine equivalent and Pregabalin as well as the incidence of perineal numbness were not significantly different between groups (P > 0.05). CONCLUSION: Our results demonstrate that application of CRF and H-PRF in ganglion impar to reduce perineal pain and improve the quality of life of patients with advanced rectal cancer is safe and effective. However, the long-term effect of CRF is better compared with that of H-PRF. TRIAL REGISTRATION: https://www.chictr.org.cn/ (ChiCTR2200061800) on 02/07/2022. This study adheres to CONSORT guidelines.

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The anatomical dimensions and the shape of the pelvis influence surgical difficulty for rectal cancer. Compared to conventional laparoscopic surgery, robot-assisted surgery is expected to improve surgical outcomes due to the multi-joint movement of its surgical instruments. The aim of this study was to investigate the impact of pelvic anatomical indicators on short-term outcomes of patients with rectal cancer. A retrospective analysis was conducted using data from 129 patients with rectal cancer who underwent conventional laparoscopic low anterior resection (L-LAR) or robot-assisted low anterior resection (R-LAR) with total mesorectal excision or tumor-specific mesorectal excision between January 2014 and December 2022. The transverse diameter of the lesser pelvis and the sacral promontory angle were used as indicators of pelvic anatomy. The sacral promontory angle was not associated with age and sex while the pelvic width was smaller in male than in female. The pelvic width did not affect postoperative complications in both L-LAR and R-LAR. In contrast, postoperative urinary dysfunction occurred more frequently in patients with a small sacral promontory angle (p = 0.005) in L-LAR although there was no impact on short-term outcomes in R-LAR. Multivariate analysis demonstrated that a small sacral promontory angle was an independent predictive factor for urinary dysfunction (p = 0.032). Sharp angulation of the sacral promontory was a risk factor for UD after L-LAR. Robot-assisted surgery could overcome anatomical difficulties and reduce the incidence of UD.

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BACKGROUND: In locally advanced rectal cancer (LARC), optimizing neoadjuvant strategies, including the addition of concurrent chemotherapy and dose escalation of radiotherapy, is essential to improve tumor regression and subsequent implementation of anal preservation strategies. Currently, dose escalation studies in rectal cancer have focused on the primary lesions. However, a common source of recurrence in LARC is the metastasis of cancer cells to the proximal lymph nodes. In our trial, we implement simultaneous integrated boost (SIB) to both primary lesions and positive lymph nodes in the experimental group based on magnetic resonance-guided adaptive radiotherapy (MRgART), which allows for more precise (and consequently intense) targeting while sparing neighboring healthy tissue. The objective of this study is to evaluate the efficacy and safety of MRgART dose escalation to both primary lesions and positive lymph nodes, in comparison with the conventional radiotherapy of long-course concurrent chemoradiotherapy (LCCRT) group, in the neoadjuvant treatment of LARC. METHODS: This is a multi-center, randomized, controlled phase III trial (NCT06246344). 128 patients with LARC (cT3-4/N+) will be enrolled. During LCCRT, patients will be randomized to receive either MRgART with SIB (60-65 Gy in 25-28 fractions to primary lesions and positive lymph nodes; 50-50.4 Gy in 25-28 fractions to the pelvis) or intensity-modulated radiotherapy (50-50.4 Gy in 25-28 fractions). Both groups will receive concurrent chemotherapy with capecitabine and consolidation chemotherapy of either two cycles of CAPEOX or three cycles of FOLFOX between radiotherapy and surgery. The primary endpoints are pathological complete response (pCR) rate and surgical difficulty, while the secondary endpoints are clinical complete response (cCR) rate, 3-year and 5-year disease-free survival (DFS) and overall survival (OS) rates, acute and late toxicity and quality of life. DISCUSSION: Since dose escalation of both primary lesions and positive nodes in LARC is rare, we propose conducting a phase III trial to evaluate the efficacy and safety of SIB for both primary lesions and positive nodes in LARC based on MRgART. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with the Identifier: NCT06246344 (Registered 7th Feb 2024).

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BACKGROUND: 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. METHODS: 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). RESULTS: 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+. CONCLUSION: 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.

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