BACKGROUND:Transanal total mesorectal excision (TaTME) facilitates distal pelvic dissection and enables low anastomoses for mid and low rectal cancer, potentially avoiding permanent colostomy. However, its oncological safety remains unclear. The COLOR III trial aimed to compare oncological outcomes between TaTME and laparoscopic TME (LapTME). Here, we report the short-term secondary outcomes. METHODS:This international, multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial was conducted at 28 hospitals globally. Patients (aged ≥18 years) with (y)cT1-3N0-2M0 rectal adenocarcinoma located 10 cm or less from the anal verge were randomly assigned (2:1) to TaTME or LapTME through an interactive web-response system. Randomisation was done using minimisation with stratification for sex, BMI, tumour stage, tumour height, preoperative radiotherapy, and downstaging after chemoradiotherapy. Quality assurance included pre-trial video-based competency assessment and central MRI evaluation for patient eligibility. The primary endpoint, assessed for non-inferiority, is 3-year local recurrence. Short-term secondary endpoints included conversion, 90-day morbidity, anastomotic leakage, specimen quality, and circumferential resection margin (CRM) and distal resection margin (DRM) involvement. All analyses were conducted according to the modified intention-to-treat principle (analysed based on initial allocation but excluded from the analysis after randomisation if they did not undergo surgery or if they were ineligible for surgery after randomisation). The trial is registered at ClinicalTrials.gov (NCT02736942). Patient recruitment has been completed and long-term follow-up for the primary endpoint is ongoing. FINDINGS:Between Jan 2, 2017 and Jan 16, 2024, 1205 patients were screened for eligibility, of whom 1103 were randomly assigned (735 to TaTME and 367 to LapTME). The modified intention-to-treat population consisted of 711 patients in the TaTME group and 350 in the LapTME group. Patients were predominantly male (717 [68%] male patients vs 344 [32%] female patients), with a median age of 63·0 years (IQR 55·0-70·0) and a median BMI of 24·4 kg/m2 (22·2-26·9). Conversion was significantly less frequent with TaTME than with LapTME (four [1%] of 696 patients vs 56 [17%] of 339; adjusted odds ratio [OR] 0·03 [95% CI 0·01-0·08]). Postoperative complications within 90 days were similar between groups (138 [20%] of 689 with TaTME vs 59 [18%] of 335 with LapTME; adjusted OR 1·22 [95% CI 0·90-1·64]). Minor morbidity (Clavien-Dindo grade ≤2) occurred in 61 (9%) of 689 participants in the TaTME group versus 26 (8%) of 333 in the LapTME group, and major morbidity (Clavien-Dindo grade ≥3) in 77 (11%) of 689 versus 31 (9%) of 333 (adjusted OR 1·23 [95% CI 0·82-1·85]). The incidence of anastomotic leakage did not differ between treatment groups (68 [10%] of 689 patients in the TaTME group vs 27 [8%] of 333 patients in the LapTME group; adjusted OR 1·32 [95% CI 0·83-2·08]). Macroscopically complete resection was achieved in 583 (84%) of 692 TaTME specimens vs 291 (86%) of 339 LapTME specimens (adjusted OR 0·94 [95% CI 0·58-1·51]). Resection margin involvement was rare, with positive CRM in four (1%) of 611 TaTME procedures versus one (<1%) of 291 LapTME procedures, and positive DRM in seven (1%) of 690 versus one (<1%) of 334, respectively. INTERPRETATION:TaTME is a safe surgical technique for mid and low rectal cancer, achieving similar 90-day morbidity and complete resection rates to LapTME, while significantly reducing conversion rates. Long-term follow-up is needed to determine functional and oncological outcomes. FUNDING:Dutch Cancer Society, Ethicon EndoSurgery, Medtronic, Applied Medical, and Chinese Institutional funds.

Purpose Positive circumferential resection margin (CRM) is an important oncological quality indicator in rectal cancer surgery. This study aimed to explore factors associated with CRM positivity after transanal total mesorectal excision (taTME) using data from a multicenter registry. Methods Patients with rectal cancer who underwent primary taTME between 2017 and 2024 were identified from the Chinese TaTME Registry Collaborative. The primary outcome was pathological CRM positivity. Nine supervised machine learning algorithms were evaluated, including logistic regression, elastic net, decision tree, random forest, XGBoost, radial support vector machine, multilayer perceptron, LightGBM, and k-nearest neighbors. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), and model interpretation was performed using SHapley Additive exPlanations. Results A total of 1,625 patients from 32 institutions were included, and the CRM positivity rate was 2.77%. In the validation cohort, the radial support vector machine model showed the highest apparent AUC of 0.84. SHAP analysis identified pathological N stage, threatened mesorectal fascia on preoperative MRI, and intersphincteric resection as the most influential variables. Conclusion This exploratory analysis identified clinically plausible factors associated with CRM positivity after taTME. Because the models included intraoperative and postoperative variables, they should not be interpreted as preoperative decision-support tools. Further studies using preoperative-only variables and external validation are required.

Background: Current evidence suggests that neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) alone is insufficient for magnetic resonance imaging (MRI)–suspected lateral lymph node metastasis (LLNM) in rectal cancer. However, whether upfront TME with lateral lymph node dissection (LLND) is adequate, and whether adding nCRT before planned LLND confers additional benefit, remains controversial. Methods: Between May 2021 and September 2022, a total of 342 patients from 20 Chinese centers were enrolled, of whom 293 were included in the final analysis and received either long-course nCRT plus TME with LLND or upfront TME+LLND. Groups were balanced by propensity score matching. The primary endpoint was 3-year recurrence-free survival (RFS). Findings: After matching, the nCRT group had significantly better 3-year RFS (HR 0.54; 95% CI. 0.32–0.92; P=0.023) and locoregional recurrence-free survival (HR 0.37; 95% CI, 0.19–0.74; P=0.005); distant metastasis-free survival did not differ (HR 0.74; 95% CI, 0.37–1.47; P=0.385). In patients with pretreatment positive lateral nodes (n=141), nCRT also improved RFS (HR 0.53; 95% CI, 0.28–0.99; P=0.049) and local control (HR 0.35; 95% CI, 0.15–0.77; P=0.010). Pathologic complete response in lateral nodes after nCRT was 44.7% (34/76). Overall postoperative complication rates were similar between groups (19.8% vs 16.0%; P=0.474), as were severe complications (grade III–V, 9.4% vs 8.5%; P=0.811). Interpretation: In MRI-suspected LLNM, adding nCRT to TME with LLND significantly improves RFS and local control without increasing morbidity. Upfront surgery alone is insufficient. These findings support a combined treatment paradigm and confirm the necessity of nCRT in these patients.

For patients with mismatch repair-proficient / microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC), the NECTAR (NEoadjuvant Chemoradiotherapy plus immunoTherapy for locally Advanced Rectal cancer) trial reported an encouraging pathological complete response (pCR) rate of 40.0%. Given that pMMR/MSS tumors are generally resistant to immunotherapy, this pCR rate highlights the potential of combination therapy to overcome primary resistance. Here, we report the 3-year survival outcomes of the NECTAR trial, using neoadjuvant chemoradiotherapy (NCRT) plus tislelizumab in pMMR/MSS LARC. In this phase 2, multi-center, single-arm trial, eligible pMMR/MSS LARC patients received three cycles of neoadjuvant programmed cell death protein 1 (PD-1) blockade, three cycles of chemotherapy, and long-course radiotherapy followed by total mesorectal excision (TME). This 3-year analysis evaluates disease-free survival (DFS) and safety. From June 2021 to November 2022, 50 patients were enrolled and 46 patients completed neoadjuvant therapy and TME. Of the 46 patients, 20 patients reached pCR. With a median follow-up of 44.2 months, the median DFS was not reached. The 3-year DFS rate was 89.1%. All patients who achieved pCR (20/46) remained DFS at 3 years. Patients with a low neoadjuvant rectal (NAR) score (<8) had the 3-year DFS rate of 100%, suggesting that overcoming therapeutic resistance in immunotherapy may translate into sustained survival benefits. No new grade ≥III treatment-related adverse events (trAEs) occurred during the 3-year follow-up. The 3-year survival outcomes demonstrate promising efficacy and safety of this NECTAR trial, which provides a promising therapeutic avenue for a patient population traditionally resistant to single-agent immunotherapy.

BACKGROUND:Hemostatic drugs are frequently prescribed after colorectal cancer (CRC) surgery to prevent bleeding. However, in real-world practice, their net clinical benefit and thrombotic safety remain uncertain. This study aimed to evaluate the effectiveness and safety of prophylactic postoperative hemostatic drug use after CRC surgery. METHODS:This retrospective analysis was based on a prospectively collected multicenter CRC-venous thromboembolism (VTE) database involving 46 tertiary centers across 17 provinces in China between May 2021 and May 2022. Adults who underwent elective curative CRC surgery were included and followed up for 28 days. Exposure was defined as initiation of any prophylactic postoperative hemostatic drug (tranexamic acid, hemocoagulase, or carbazochrome sodium sulfonate) within 0-48 h after surgery in the absence of active bleeding at the first administration. Primary outcome was postoperative bleeding within 28 days; a surrogate outcome was hemoglobin decrease (dHb) ≥20 g/L. The secondary outcome was imaging-confirmed VTE, defined as postoperative DVT and/or PE; DVT was systematically screened within prespecified follow-up windows, whereas PE was assessed when clinically suspected. Inverse probability of treatment weighting (IPTW) based on propensity scores was used to balance baseline covariates, followed by weighted logistic regression. RESULTS:Among 1810 patients, 322 (17.8%) received prophylactic postoperative hemostatic drugs. After IPTW, all covariates achieved adequate balance, with standardized mean differences <0.10. Hemostatic drug use was not associated with reduced postoperative bleeding (2.9% vs. 1.7%; weighted odds ratio [OR]: 1.72, 95% confidence interval [CI]: 0.77-3.86) or dHb ≥20 g/L (21.4% vs. 26.1%; weighted OR: 0.77, 95% CI: 0.55-1.06). In contrast, hemostatic drug use was associated with a higher postoperative VTE rate (13.8% vs. 9.5%; weighted OR: 1.51, 95% CI: 1.02-2.24), mainly driven by DVT without PE, whereas PE events were rare and did not differ significantly between groups. Additional analyses showed that this association was also observed for symptomatic VTE (4.7% vs. 2.3%; weighted OR: 2.12, 95% CI: 1.03-4.37), whereas the association for asymptomatic/screening-detected VTE was not statistically significant after IPTW. Most VTE events with a DVT component involved distal DVT. Sensitivity analyses using winsorized weights yielded consistent estimates, and Propensity score trimming excluded no participants, supporting adequate overlap. In multivariable analysis, tumor-node-metastasis stage III-IV (OR: 3.20, 95% CI: 1.31-7.79) and intraoperative blood loss ≥50 mL (OR: 3.15, 95% CI: 1.20-8.22) were independent predictors of postoperative bleeding. CONCLUSIONS:In this retrospective analysis of a prospectively collected multicenter database, routine prophylactic postoperative hemostatic drug use after CRC surgery was not associated with a lower bleeding risk, but was associated with a higher postoperative VTE rate. Given the limited number of symptomatic events, the predominance of distal DVT, and the potential for residual confounding, this finding should be interpreted as a hypothesis-generating thrombotic safety signal rather than definitive causal evidence. Prophylactic hemostatic drugs should be used individually, with careful consideration of thrombotic risk.

The Tianhe Procedure is a functional sphincter-preserving surgical approach developed for patients with rectal cancer following radiotherapy. This technique involves proximal extended resection of the colon beyond the pelvic cavity, followed by anastomosis of the non-irradiated proximal colon to the distal rectum or anal canal. This strategy aims to reduce the incidence of anastomotic complications and postoperative bowel dysfunction. However, there is currently a lack of standardized practice guidelines for implementing the Tianhe Procedure in China. Therefore, the Chinese Radiation Intestinal Injury Research Group, the Colorectal Surgery Group of Surgery Branch of the Chinese Medical Association, the Anorectal Branch of Chinese Medical Doctor Association, the Colorectal Cancer Committee of the Chinese Medical Doctor Association, the Colorectal Cancer Committee of China Anti-cancer Association, and the Gastrointestinal Surgical Branch of Guangdong Medical Doctor Association have jointly convened a panel of national experts to discuss and establish this standardized surgical procedure. This standard, based on the latest evidence from literature, research advancements, and expert experience, focuses on key aspects of the Tianhe Procedure, including its precise definition, indications, critical procedural steps, postoperative complications, and functional rehabilitation strategies. It aims to promote standardized implementation and broader clinical adoption of this innovative surgical technique.

ObjectiveThis study aimed to assess the long-term results of the watch-and-wait (W&W) strategy in patients with clinical stage II/III mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer (CRC) who received neoadjuvant anti-PD-1 monotherapy.MethodsThis retrospective study enrolled stage II/III dMMR/MSI-H CRC patients from four Chinese tertiary hospitals between August 1, 2020 and February 28, 2025. All participants received neoadjuvant anti-PD-1 monotherapy followed by W&W approach. post hoc, endoscopic complete response (eCR) was defined as no suspicious mucosal lesion on white-light or chromoendoscopy (flat scar or normal mucosa allowed) and negative targeted biopsies from the primary tumor site. The primary outcomes were disease-free survival (DFS) and overall survival (OS). The study is registered in the Chinese Clinical Trial Registry (www.chictr.org.cn ChiCTR2500100474).ResultsA total of 49 patients managed with W&W strategy were enrolled, and all met the post hoc eCR criteria. Radiological evaluation showed clinical complete response in 21 patients (44%), partial response in 17 (35%) and stable disease in 10 (21%). One patient lacked evaluable imaging. Median neoadjuvant treatment duration was 6 months (IQR 4-8), with a median of 12 treatment cycles (IQR 8-16). Treatment-related adverse events were grade 1–2 in 14 patients (29%); no grade 3–4 events occurred. At a median follow-up of 35 months (range 9-60), no local regrowth, distant metastasis, or death was recorded. The estimated 3-year DFS and OS are both 100%.ConclusionIn this cohort, patients with dMMR/MSI-H CRC who met eCR after neoadjuvant anti-PD-1 monotherapy had excellent long-term outcomes when managed with W&W strategy. These findings support the potential utility of endoscopic assessment for selecting candidates for organ preservation, but prospective validation of standardized criteria is warranted.

In the past 5 years, clinical trials on immune checkpoint inhibitors (ICIs) for the treatment of locally advanced rectal cancer (LARC) have flourished globally, and China has become one of the leading regions in this field. In response to the breakthrough progress and accumulation of evidence from key clinical trials, the Chinese Society of Colorectal Surgery has recognised the need for updated consensus guidance on the development of perioperative and organ-preserving treatment strategies for LARC. This expert consensus guidance provided unified standards for the indications, medication regimens, efficacy evaluations and follow-up of ICIs in this population, with a focus mainly on perioperative management and organ-sparing strategies. The diagnostic part of this consensus guidance is based on the internationally recognised definition of mismatch repair/microsatellite instability detection and emphasises the importance of multidisciplinary teams in treatment decision-making. In terms of treatment, based on the results of key trials that have changed clinical practice in the past 5 years, this expert consensus provides graded recommendations for the duration of preoperative immunotherapy and the necessity of postoperative adjuvant therapy, local resection and organ preservation strategies. Moreover, we refined the management process for the safety of perioperative immunotherapy. This document aims to provide a reference for surgeons; internal medicine, radiation therapy, pathology and imaging physicians; patients and nursing staff involved in the treatment of LARC, as well as health policy makers.

Precise preoperative prediction of surgical complexity in robot-assisted total mesorectal excision (R-TME) is essential for optimizing surgical strategies. The current study aimed to construct an interpretable machine learning (ML) model to anticipate operative difficulty in sphincter-preserving R-TME. Retrospective data from 449 patients diagnosed with mid-to-low rectal cancer undergoing R-TME at Center A were analyzed. The dataset was partitioned randomly into training (n = 314) and internal validation (n = 135) groups using a 7:3 ratio. Additionally, external validation was conducted with a prospective cohort (n = 100) from multiple centers. Operative difficulty was quantified using a scoring system ranging from 0 to 13. Feature selection was performed employing Least Absolute Shrinkage and Selection Operator (LASSO) regression, followed by evaluation of five ML algorithms. Model accuracy and robustness were measured using metrics including the Area Under the Curve (AUC), calibration plots, decision curve analysis (DCA), and supplementary indicators. Interpretability of the predictive model was enhanced using SHapley Additive exPlanations (SHAP). Critical predictive factors comprised BMI, neoadjuvant treatment status, clinical staging, tumor distance to the anal verge, interspinous diameter, lateral mesorectal width, posterior mesorectal thickness, and two specific pelvic angle measurements. Among evaluated ML methods, Gradient Boosting Machine (GBM) demonstrated superior performance, achieving an AUC of 0.874 in the training cohort and 0.835 in internal validation. Calibration plots and DCA indicated excellent robustness and significant clinical applicability of the GBM model. Furthermore, external validation presented an AUC of 0.809, confirming the model’s generalizability. SHAP-based analysis delineated individual predictor impacts, facilitating the creation of an accessible online prediction instrument. This study successfully established and externally validated a transparent ML-based model to predict operative challenges in sphincter-preserving R-TME. This model can effectively aid surgeons in identifying anticipated difficulties prior to surgery, thereby enhancing clinical decision-making and improving surgical planning.

Aim To evaluate the value of trans-anal multipoint full-layer puncture biopsy (TMFP) in guiding organ preservation strategies and prognostic stratification for locally advanced rectal cancer (LARC) after neoadjuvant therapy. Method This prospective multicenter study was conducted across four tertiary centers in China. Sixty-one LARC patients after neoadjuvant chemoradiotherapy (± immunotherapy) who underwent in vivo TMFP were enrolled. Primary outcomes were TMFP-guided changes in treatment strategy (Watch-and-Wait, W&W, vs. surgery) and overall survival (OS). Results Among 61 patients, 20 achieved clinical complete response (cCR) and 41 were non-cCR. TMFP results significantly altered treatment decisions in non-cCR patients, with 48.8% (20/41) being TMFP-negative; half of these (10/20) successfully adopted a W&W strategy. The postoperative pCR rate in non-cCR but TMFP-negative patients who underwent surgery was 70% (7/10). TMFP demonstrated superior prognostic stratification compared to cCR: the OS of TMFP-negative patients was significantly better than that of TMFP-positive patients (P = 0.04), whereas no significant difference was found between cCR and non-cCR groups (P = 0.58). Among TMFP-negative patients, no survival difference was observed between the W&W and surgery groups (P = 0.40). The procedure was well-tolerated with a low complication rate. Conclusions TMFP serves as a pivotal clinical decision-making tool that safely expands organ preservation opportunities to a significant subset of non-cCR patients and provides powerful prognostic stratification, outperforming traditional cCR assessment. Integrating TMFP into the post-neoadjuvant workflow optimizes the balance between oncological safety and functional preservation.

3640 Background: Neoadjuvant chemoradiotherapy (nCRT) combined with PD-1 blockade has shown great potential for improving the clinical complete response (cCR) rate in low rectal cancer patients in a previous exploratory clinical trial. This study aimed to further verify the efficacy and safety of nCRT with PD-1 blockade in patients with pMMR/MSS low rectal cancer. Methods: We conducted a prospective, multicenter, randomized, open-label trial (NCT05215379) with two parallel groups across 11 centers. Patients with confirmed cT 1-3a N 0-1 M 0 rectal adenocarcinoma of the pMMR/-MSS type, with an inferior margin of 5 cm from the anal verge, were randomly assigned to either the intervention group, receiving 50 Gy (2 Gy/d*25d) radiotherapy, 4 cycles of PD-1 blockade (sintilimab) and 2 cycles of CAPOX, or the control group, receiving 50 Gy (2 Gy/d*25d) radiotherapy and 2 cycles of CAPOX. After completion of neoadjuvant treatment, patients were reassessed to determine clinical efficacy. If patients achieved cCR, the Watch-and-Wait (W&W) approach was performed. If near-cCR (ncCR) was achieved, patients were re-evaluated by a multidisciplinary team to determine whether W&W, local excision, or total mesorectal excision (TME) should be performed. Patients assessed with an incomplete clinical response (iCR) received TME. The primary endpoint was the cCR rate, and the key secondary endpoints included the organ preservation (W&W and local excision) rate, disease free survival (DFS), and overall survival (OS). Results: From July 2022 to December 2024, a total of 201 patients with low rectal cancer were screened at 11 medical centers and 180 patients were finally randomly assigned. A total of 169 patients were included in the primary analysis (85 patients in the intervention group and 84 in control group). The cCR rates were 36.5% in the intervention group compared to 17.9% in the control group (p=0.007). There were 48 and 51 patients who underwent surgery in the intervention and control groups, respectively, and the pathological complete response (pCR) rates were 25.0% and 15.7% (p=0.249). The overall complete response (cCR+pCR) rates were 50.6% and 27.4% (p=0.002) in the intervention and control groups. The overall occurrence rates of adverse events (AEs) were 72.9% in the intervention group compared to 66.3% in the control group (P>0.05), and the occurrence of severe AEs (Grade III or IV) was comparable between the two groups (7.1% vs 3.8%, p=0.34). Due to the limited follow-up duration, the DFS and OS data are immature. Conclusion: In this trial, the results showed that nCRT combined with sintilimab significantly improved the cCR rate in patients with pMMR/MSS low rectal cancer with a tolerable safety profile. Clinical trial information: NCT05215379 .

BACKGROUND Total mesorectal excision is the standard surgery for locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT), but it may lead to high complication rates and poor quality of life. This study evaluates whether transanal endoscopic microsurgery (TEM), as a partial resection procedure, can enhance quality of life for clinical complete response (cCR) or near-cCR patients without compromising survival. METHODS Between May 2017 to September 2021, 80 patients with T3-4N0M0 or TanyN+M0 mid-low rectal cancer achieving cCR or near-cCR post-nCRT were prospectively included at 6 Chinese centers. Patients underwent either TEM (Group A, n=38) or radical surgery (Group B, n=41). Clinicopathological, oncological, and functional outcomes were analyzed. RESULTS Postoperative histology revealed 22 ypT0 (57.9%), 5 ypT1 (13.2%), 10 ypT2 (26.3%), and 1 ypT3 (2.6%) cases in group A and 20 pCR (48.8%), 1 T0N1 (2.4%), 5 T1N0 (12.2%), 12 T2-3N0 (29.3%), 3 T2-3N1 (7.3%) cases in group B. After a 60-month median follow-up, local recurrence occurred in 2 patients (5.26%) in Group A and none in Group B. Distant metastases occurred in 8 patients (21.05%) in group A and 7 (17.07%) in group B. There was no significant difference between the two groups in 5-year disease-free survival (P=0.658) or 5-year overall survival (P=0.465). Group A showed significantly faster recovery (P<0.001) and better sphincter function per Wexner (1 vs. 4, P=0.001) and LARS (0 vs. 17, P<0.001) scores than Group B. CONCLUSION TEM may be an effective approach for assessing residual tumors in LARC patients with cCR or near-cCR. This approach offers an option for those requiring sphincter preservation, with no significant compromise in long-term oncological outcomes observed in our study.

3587 Background: Neoadjuvant chemoradiotherapy is currently the standard strategy for microsatellite stable (MSS) / mismatch repair-proficient (pMMR) locally advanced rectal cancer (LARC) patients. This study aimed to explore the safety and efficacy of combining specific (thymalfasin) and non-specific (tislelizumab) tumor immunotherapy with chemoradiotherapy in MSS/pMMR LARC. Methods: This trial is an open, prospective, multi-center, single-arm phase II clinical study assessing the efficacy and safety of neoadjuvant chemoradiotherapy combined with thymosin andtislelizumab in MSS/pMMR LARC. Stage II/III MSS/pMMR LARC patients (cT 3-4a N 0 M 0 and cT 1-4a N 1-2 M 0 ) with the tumor distal location ≤ 10 cm from anal verge at two centers in China were consecutively enrolled. Patients received chemoradiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week, 5 weeks; plus capecitabine 850-1000 mg/m 2 , bid, po, 5 days/week, day1-5), thymalfasin (4.8 mg, biw, ih, day 1 and day 4 from week 1-11) and three 21-day cycles tislelizumab (200 mg, iv.gtt, week 2, 5 and 8) as neoadjuvant therapy. Adjuvant therapies after neoadjuvant were nonuniformly specified and decided according to clinical experiences. The primary endpoint is the complete response (CR) rate, defined as the achievement of clinical complete response (cCR) after neoadjuvant therapy or pathological complete response (pCR) after total mesorectal excision (TME). Results: From Feb 2024 to Aug 2024, a total number of patients (n = 25) were enrolled and 3 patients were excluded because of T4b and dMMR. Finally, 2 patients were discontinued and 20 completed neoadjuvant therapy. The median age was 67.5 (from 36 to 74) years while the median tumor distal location was6.0 (from 3.5 to 8.5) cm. The CR, PD, and SD rate was 40.0% (8/20), 45.0% (9/20), and 15.0% (3/20) correspondingly, with the ORR rate of 85.0% (17/20). Grade 3 treatment-related adverse events (trAEs) including leukopenia and neutropenia were observed in 1 (5%) patient, while grade 1-2 trAEs were observed in 15(75.0%) patients. As for Dec 31, 2024, the EFS rate was 100% (20/20) with median follow-up time of 18.57 weeks (from 6.86 to 31.86). Conclusions: Neoadjuvant chemoradiotherapy plus thymalfasin and tislelizumab show promising anti-tumour activity in MSS/pMMR LARC patients, with manageable toxicities. This study suggests that such combination could be a promising therapeutic strategy for patients with MSS/pMMR LARC. Clinical trial information: NCT06056804 .

Cancer immunotherapy has revolutionized oncology by leveraging the immune system to combat tumors. Among various biomarkers, neoantigens and tumor mutational burden (TMB) have emerged as critical factors in tailoring personalized treatments. Neoantigens are tumor-specific peptides displayed on cancer cell surfaces, derived from somatic mutations. Recognized as "non-self" by the immune system, they trigger T-cell responses and enable therapies like personalized vaccines and adoptive T-cell transfer. Critically, neoantigen potential correlates with TMB, which quantifies the total somatic mutations within a tumor genome. A higher TMB generally correlates with a greater likelihood of generating immunogenic neoantigens, making it a predictive biomarker for the efficacy of immune checkpoint inhibitors (ICI). Progress in high-throughput sequencing, bioinformatics, and immuno-peptidomics has significantly enhanced the accuracy of neoantigen prediction, including assessments of major histocompatibility complex (MHC) binding affinity and T-cell receptor recognition. Clinically, neoantigen-based therapies have shown efficacy in early trials, with strategies such as mRNA vaccines demonstrating synergy with ICI by boosting T-cell activation and overcoming immune suppression. Combining neoantigen-based therapies with chemotherapy and radiotherapy harnesses synergistic mechanisms to enhance efficacy, overcome resistance, and emerge as a pivotal oncology research focus. The integration of TMB into clinical practice has received regulatory approval as a biomarker for stratifying patients for ICI therapies. Furthermore, advanced methodologies like liquid biopsy and single-cell technologies have streamlined TMB measurement, improving its predictive value for personalized immunotherapy. Collectively, neoantigens and TMB have optimized the evolution of precision immuno-oncology by providing frameworks that maximize therapeutic efficacy, overcome resistance mechanisms, and advance durable cancer remission.​

Radiotherapy displays unique antitumor synergism with immune checkpoint inhibitors, which is indicated by high pathological complete response (pCR) rates from single-arm trials of locally advanced rectal cancer (LARC). Here we test the efficacy and safety of the radiation–immune checkpoint inhibitor combination in patients with LARC in a phase 2, randomized trial conducted in eight major colorectal cancer centers in Beijing. In total, 186 eligible all-comer (proficient mismatch repair and deficient mismatch repair) participants were enrolled. The patients were randomly assigned to receive neoadjuvant chemoradiation + concurrent/sequential PD-1 blockade (experiment groups A/B) or neoadjuvant chemoradiation alone (control group). Radical surgeries were scheduled after neoadjuvant treatments. The primary endpoint was the pCR rate. The pCR rates were 27.1 NCT05245474 ). In a multicenter, open-label, randomized phase 2 trial, neoadjuvant chemoradiation with PD-1 blockade elicited a pathological complete response rate superior to that with neoadjuvant chemoradiation alone in patients with locally advanced rectal cancer.

PURPOSE:The clinical benefit of incorporating oxaliplatin into conventional neoadjuvant chemoradiotherapy (nCRT) for patients with high-risk locally advanced rectal cancer (LARC) remains controversial. METHODS AND MATERIALS:This multicenter, open-label, randomized controlled trial enrolled 505 patients with high-risk LARC, defined by the presence of at least 1 of the following adverse features: clinical T4 stage, clinical N2 stage, high tumor grade, extramural vascular invasion, involvement of the mesorectal fascia, or perianal musculature involvement. Enrollment took place between August 2017 and April 2022. Patients were randomly assigned to receive long-course radiation therapy combined with a 3-cycle chemotherapy regimen of capecitabine and oxaliplatin (CapeOX group; n = 248) or capecitabine alone (Cape group; n = 257). The primary endpoint was 3-year disease-free survival (3y-DFS). RESULTS:Following nCRT, radical surgery was performed in 91.5% of the CapeOX group and 92.2% in the Cape group (P = .778). Pathologic complete response rates were comparable between the CapeOX and Cape groups (25.5% vs 25.3%; P = .954). A significantly greater proportion of patients in the CapeOX group achieved marked tumor regression (College of American Pathologists (CAP 0-1)) compared with the Cape group (58.6% vs 46.8%; P = .011). The incidence of grade 3 to 4 treatment-related toxicities was similar between the groups (CapeOX: 14.1% vs Cape: 9.3%; P = .095). After a median follow-up of 37 months, 3y-DFS and 3-year overall survival rates were comparable between the groups (both P > .050). Overall, patients who achieved CAP 0 to 1 had significantly better 3y-DFS than those with CAP 2 to 3 (89.0% vs 80.9%; P = .018). CONCLUSIONS:The addition of oxaliplatin to conventional nCRT may enhance pathologic tumor regression in patients with high-risk LARC without a significant increase in severe adverse events. However, this intensified 3-cycle chemotherapy regimen did not translate into a long-term survival benefit.

Effectiveness of programmed cell death 1 blockade (anti-PD1) treatment plus neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer and proficient mismatch repair (pMMR-LARC) has been recently proven. However, the role of MRI in tumor restaging following anti-PD1 plus NCRT is less established. This study aims to evaluate the diagnostic performance and challenges of MRI for restaging pMMR-LARC patients after anti-PD1 plus NCRT treatment. This prospective multicenter study involved pMMR-LARC patients exhibiting following anti-PD1 plus NCRT treatment from 2021 to 2022. The evaluation of preoperative treatment response included assessments of complete response and near complete response (CR/nCR), N category, extramural venous invasion (EMVI) and mesorectal fascia (MRF), all of which were analyzed using MRI. The diagnostic accuracy was assessed using pathology as the reference standard. A cohort of 44 patients (mean age, 60.5 years ± 10.4 [SD]; 15 females) was evaluated. The pathologic CR/nCR rate was 75.0

BACKGROUND:Accurate risk stratification is essential to optimize neoadjuvant therapy for locally advanced rectal cancer (LARC) in the era of precision medicine. This study assessed the feasibility and safety of a circulating tumor DNA (ctDNA)-guided neoadjuvant strategy. METHODS:This interim analysis included patients with mid-low rectal adenocarcinoma (cT3-4N0M0 or cT1-4N1-2M0) from the multicenter, randomized CINTS-R trial using a 2:1 allocation to an experimental or control group. The control group received conventional nCRT (long-course radiotherapy with concurrent capecitabine followed by one XELOX cycle). In the experimental group, treatment was stratified as follows: (1) ctDNA-defined high-risk patients received TNT, consisting of the same nCRT followed by five additional XELOX cycles (six in total); (2) ctDNA-defined low-risk patients proceeded directly to surgery after nCRT; and (3) patients with dMMR/MSI-H/TMB-H tumors received neoadjuvant tislelizumab (≥6 cycles). The analysis focuses on feasibility and safety outcomes. RESULTS:Between February 2023 and September 2024, 349 patients were randomized and 316 included in analysis (experimental: 210; control: 106). Among the experimental group, 115 were ctDNA-high-risk and 89 ctDNA-low-risk. High-risk patients were significantly older and more often male, with larger tumors, longer tumor-to-anal verge distance, greater circumferential involvement, and higher EMVI rates (all p ＜0.05). Serious adverse events (SAEs, CTCAE v5.0, grade 3-4) occurred in 10.0 % vs. 6.6 % of patients in the experimental and control groups (p = 0.316). Notably, 15.7 % of TNT-treated patients discontinued chemotherapy due to SAEs, whereas all nCRT recipients completed treatment. CONCLUSION:This interim analysis demonstrates the feasibility and safety of a ctDNA-guided, risk-adapted neoadjuvant strategy for LARC. Final outcomes will further clarify its clinical efficacy. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT05601505.

INTRODUCTION:Retroperitoneal duodenal perforation is a rare but severe complication of endoscopic procedures such as ERCP and ESD, often leading to significant morbidity and mortality when diagnosed late. Previous studies have focused on early diagnosis, but data on delayed diagnosis cases are limited. This study presents four cases of delayed-diagnosis retroperitoneal duodenal perforation and introduces a novel surgical management strategy. PRESENTATION OF CASE:We report four cases diagnosed more than one month after the initial endoscopic procedure, with CT scans revealing extensive retroperitoneal fluid collections and secondary colonic perforation in some cases. Surgical interventions included right hemicolectomy and proximal jejunostomy to facilitate duodenal exposure and clearance of infectious debris. Outcomes varied, with some patients achieving full recovery while others succumbed to complications. DISCUSSION:The symptoms of retroperitoneal duodenal perforation are often subtle, leading to delayed diagnosis. Early surgical intervention is crucial if CT shows retroperitoneal fluid collections. Right hemicolectomy provides better duodenal exposure and facilitates effective debridement, improving outcomes. CONCLUSION:Early diagnosis and prompt surgical intervention, including right hemicolectomy, are essential for managing delayed retroperitoneal duodenal perforation. Further studies are needed to establish optimal management protocols for these complex cases.