Open research questions in Colorectal Cancer Surgical Treatments

What the literature leaves open

• of stapler firings, intraoperative blood loss, and use of neoadjuvant therapy—could not be assessed because these data are not captured in the DPC da- https://doi.

  Effectiveness of Blood Perfusion Assessment by Indocyanine Green Fluorescence Angiography in the Prevention of Anastomotic Leakage after Rectal Cancer Surgery in Japan: A Retrospective Study Using the Diagnosis Procedure Combination Database · 2026 · DOI

• Given the limitations identified herein, prospective multicenter international studies are warranted to validate these findings across diverse health care systems and establish generalized evidence- based algorithms for NACT patient selection and its independent survival effect.

  Changes in the extensiveness of initial debulking surgery with increasing neoadjuvant chemotherapy use in advanced ovarian cancer: a nationwide population-based study · 2026 · DOI

• Additionally, cost-effectiveness analyses and investigations into enhanced recovery protocols and novel technologies aimed at reducing AL risk without diversion are warranted to optimize patient outcomes and resource allocation.

  Balancing benefit and burden: a critical appraisal of prophylactic ileostomy in laparoscopic low anterior resection · 2026 · DOI

• Finally, the proposed MRI-based score was evaluated in the context of specific neoadjuvant regimens, and its generalizability to other treatment protocols remains uncertain.

  MRI-guided risk stratification for neoadjuvant immunotherapy in rectal cancer · 2026 · DOI

• Key Points Question Reliable preoperative markers are lacking for accurate EMVI detection in rectal cancer, creating uncertainty in risk stratification and treatment decisions due to inconsistent MRI–pathology concordance.

  MRI versus histopathology in EMVI detection for rectal cancer: prognostic relevance and survival outcomes · 2026 · DOI

• MAC tumors tend to be larger, possess poorly defined planes, increase the risk of circumferential resection margin positivity, and are infrequently suitable for organ-preserving strategies such as watch-and-wait.

  Mucinous rectal adenocarcinoma and neoadjuvant therapy: Implications for surgical practice · 2026 · DOI

• and provide resection A major limitation of this study is the relatively short follow- up period, which makes it difficult to draw definitive conclusions regarding the long-term oncological safety of TA-ESPR for the treatment of low-grade rectal tumors.

  A multicenter clinical study on transanal endoscopic sphincter-preserving resection of low rectal tumors · 2026 · DOI

• However, the inclusion of patients who received adjuvant radiotherapy may have influenced the results, and the study primarily focused on patients with pancreatic head cancer, lacking data on the body and tail of the pancreas (10).

  Mapping local recurrence after radical resection of pancreatic body and tail cancer for target volume design · 2026 · DOI

• MMR or MSI status is the key marker for predicting immunotherapy efficacy, but strict treatment indications are necessary due to potential toxicity of immunotherapy.

  Chinese expert consensus on additional surgery following endoscopic resection for early colorectal cancer (2025 edition) · 2026 · DOI

• Criteria Category 1A evidence and partial Category 2A evidence: CSCO Guidelines classify Category 1A evidence, as well as partial high-consensus Category 2A evidence with good accessibility in China, as Grade I recommendations. Specifically, this includes interventions with well-defined indications, good accessibility, stable value in cancer treatment, and inclusion in the “National Basic Medical Insurance, Work-related Injury Insurance, and Maternity Insurance Drug Catalogue.” Category 1B evidence and partial Category 2A evidence: CSCO Guidelines categorize Category 1B evidence, as well as partial Category 2A evidence with high expert consensus but limited accessibility in China, as Grade II recommendations. Specifically, this includes randomized controlled trials conducted in China and internationally, which provide high-level evidence but may have limited accessibility or cost-effectiveness. Measures that demonstrate clear clinical benefits but are expensive may also be considered Grade II recommendations, taking into account the potential benefits for patients. Category 2B evidence and Category 3 evidence: For certain clinical practices that are commonly used or have exploratory value, although the evidence from evidence-based medicine is relatively limited, if the expert consensus deems them acceptable, they are classified as Grade III recommendations.

  The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update · 2024 · DOI

• Follow-up frequency ∙ Stage I: Every 6 months for 5 years ∙ Stages II-III: Every 3 months for 3 years; then every 6 months until 5 years postoperatively; annually after 5 years Follow-up contents (each time, unless otherwise specified) ∙ Physical examination, emphasizing DRE ∙ Blood CEA testing ∙ Liver ultrasound examination (for stages I-II) ∙ Contrast-enhanced pelvic MRI annually ∙ Contrast-enhanced thoracoabdominal CT annually (for stage III or in case of abnormal CEA, ultrasound) ∙ Colonoscopyc,d Follow-up/monitoring frequency: Every 3 months for the first 3 years, then every 6 months until 5 years, annually after 5 years, Follow-up/monitoring contents: ∙ Physical examination ∙ Blood CEA level ∙ Contrast-enhanced thoraco-abdominal CT and contrast-enhanced pelvic MRI every 6-12…

  The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update · 2024 · DOI

• ∙ PET/CT ∙ Surgical exploration with biopsyc ∙ Comprehensive discussion with MDTd ∙ Leeds classificatione ∙ Assessment of surgical resectabilityf ∙ Concurrent chemoradiotherapy, followed by surgery ± adjuvant chemotherapy ∙ Surgery (if intolerant to chemoradiotherapy) ∙ Chemotherapy alone (if intolerant to surgery) ∙ Surgery ± postoperative chemotherapy ∙ Chemotherapy alone (if intolerant to surgery) ∙ With previous chemoradiotherapy: palliative treatment ∙ Without previous chemoradiotherapy: chemoradiotherapy ∙ All patients should be evaluated for the possibility of re-resection after treatment Surgery ± postoperative…

  The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update · 2024 · DOI

• Nivolumab + Ipilimumabb (Category 2A) ∙ Anti-HER-2 therapy (HER-2 amplification)k (Category 2B) ∙ Cetuximab ± Irinotecan (Previously treated with Cetuximab) (Category 3) ∙ Raltitrexed (No previous Raltitrexed treatment) (Category 3) ∙ Best supportive care ∙ Other local treatments (Category 3) ∙ Irinotecan + Cetuximab + Vemurafenib (RAS wild-type/BRAF V600E mutation)e (Category 2B) ∙ BRAF inhibitor + Cetuximab ± MEK inhibitor (RAS wild-type/BRAF V600E mutation)e (Category 2B) ∙ Raltitrexed (No previous Raltitrexed treatment) (Category 3) ∙ Best supportive care ∙ Other local treatments (Category 3) Abbreviations: BRAF, v-raf murine sarcoma viral oncogene homolog B; RAS, rat sarcoma virus; MSI-H, microsatellite instability-high; dMMR, deficient mismatch repair; MSS, microsatellite stable; MEK, mitogen-activated protein kinase kinase; HER-2, human epidermal growth factor receptor. Notes for sections 3.2.1.2.1 to 3.2.1.2.4 aIn recent years, many retrospective studies have shown that the prognosis of patients with metastatic colon cancer located on the right side (from the cecum to the splenic flexure) is significantly worse than that of patients with left-sided (from the splenic flexure to the rectum) metastatic colon cancer. In RAS wild-type patients, the efficacy of anti-epidermal growth factor receptor (EGFR) monoclonal antibody (Cetuximab) is significantly correlated with tumor location, while no significant association has been observed between the efficacy of anti-vascular endothelial growth factor (VEGF) monoclonal antibody (Bevacizumab) and tumor location. Subgroup analysis of head-to-head randomized controlled trials comparing chemotherapy combined with Bevacizumab or Cetuximab has shown that in left-sided colon cancer, Cetuximab is superior to Bevacizumab in both ORR and OS. However, in right-sided colon cancer, although Cetuximab may have a certain advantage in ORR, Bevacizumab is superior in OS [114, 115]. bBased on the results of the KEYNOTE-177 study, Pembrolizumab was approved for use in China in June 2021. Pembrolizumab is indicated as a first-line monotherapy for patients with unresectable/metastatic colorectal cancer with KRAS, NRAS, and BRAF wild-type and MSI-H or dMMR. Based on other Chinesebased and foreign clinical trial results and NCCN guidelines, immune checkpoint inhibitors (PD-1/PD-L1) are recommended for MSI-H/dMMR advanced colorectal cancer patients in second-line and later-lines. Chinese-manufactured Envafolimab, Serplulimab, and Tislelizumab, as well as imported Pembrolizumab and Nivolumab, have been approved to treat unresectable/metastatic MSI-H/dMMR solid tumors in adults (including patients with advanced colorectal cancer who have failed standard treatment), which are therefore prioritized.

  The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update · 2024 · DOI

• ∙ Envafolimab, Serplulimab, Tislelizumab, or Pucotenlimabb (Category 2A) ∙ Pembrolizumab and Nivolumabl (Category 2A) ∙ Irinotecan ± Cetuximabc (Category 2A) ∙ Irinotecan + Raltitrexed (Fluorouracil intolerable) (Category 2A) ∙ Irinotecan + Capecitabine ± Bevacizumabd (Category 1B) ∙ Oxaliplatin + Raltitrexed (Fluorouracil intolerable) (Category 2A) Other local treatments (Category 3) ∙ Irinotecan ± Bevacizumabc ∙ Other local treatments (Category 2A) ∙ Irinotecan + Raltitrexed (Fluorouracil intolerable) (Category 2A) ∙ Irinotecan + Capecitabine ± Bevacizumabd (Category 1B) (Category 3) ∙ Irinotecan + Cetuximab + Vemurafenib (RAS wild-type/BRAF V600E mutation)e (Category 2B) ∙ BRAF inhibitor + Cetuximab ± MEK inhibitor (RAS wild-type/BRAF V600E mutation)e (Category 2B) ∙ Other local treatments (Category 3) ∙ BRAF inhibitor + Cetuximab ± MEK inhibitor (RAS wild-type/BRAF V600E mutation)e (Category…

  The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update · 2024 · DOI

• Other local treatments (Category 2B) Right-sided tumorsa ∙ FOLFOX/CAPEOX/FOLFIRI + Bevacizumab (Category 2A) ∙ FOLFOXIRI ± Bevacizumab ∙ CAPEOX (Category 2A) ∙ FOLFOX/FOLFIRI ± Cetuximaba (Category…

  The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update · 2024 · DOI

• ∙ Neoadjuvant chemotherapyc after primary lesion relief + colon resection + simultaneous or staged resectionb, radiofrequency ablation (RFA) and other local treatmentsd to treat metastatic lesions + postoperative adjuvant chemotherapy ∙ Colon resection + neoadjuvant chemotherapyc + metastasis resection, /RFA and other local treatmentsd + postoperative adjuvant…

  The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update · 2024 · DOI

• Contrast-enhanced upper abdominal ultrasoundj Abbreviations: CA199, carbohydrate antigen 199; CEA, carcinoembryonic antigen; CT, computed tomography; MRI, magnetic resonance imaging; US, ultrasound. aColonoscopy is generally prohibited in patients with clinically evident intestinal obstruction, as bowel preparation before the examination may exacerbate the obstruction or cause perforation. bAlthough it cannot serve as diagnostic evidence, it’s emphasized that clinicians should perform digital rectal exams on all patients with suspected rectal cancer. cFor patients who are not eligible, who refuse a full colonoscopy, or whose colonoscopy cannot examine the entire colon, it is recommended to perform a contrastenhanced abdominal/pelvic CT scan after bowel cleansing. dHigh-resolution pelvic MRI is the optimal imaging method for diagnosing rectal cancer with cT3 and higher stages, cN stages, mesorectal fascia, extramural vascular invasion, and anal canal structures. Both rectal endoscopic ultrasound and MRI are superior to CT for cT staging of rectal cancer, and rectal endoscopic ultrasound is better than MRI in the diagnosis of cT2 and lower-stage disease. eWhen patients have contraindications for MRI scanning, non-contrast and contrast-enhanced pelvic CT is recommended. fContrast-enhanced chest CT is recommended for diagnosis and differential diagnosis of metastatic lymph nodes. Continuous thin-section axial, coronal, and sagittal reconstructed images are recommended for diagnosis and differential diagnosis of pulmonary metastases from colorectal cancer wherever possible. Enhanced abdominal and pelvic CT is recommended for diagnosis of ovarian metastases and peritoneal metastases. gFor patients with contraindications to venous contrast, it is recommended to perform contrast-enhanced abdominal/pelvic MRI plus non-contrast-enhanced chest CT. hWhen the diagnosis of ovarian metastasis cannot be confirmed by CT, pelvic MRI or gynecologic ultrasound is recommended to support the diagnosis, and MRI is recommended to include T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and multi-phase T1-weighted enhanced imaging sequences. iWhen the diagnosis of liver metastases cannot be confirmed by CT or when treatment decisions for liver metastases need to be changed, liver MRI including T2WI, DWI, and multi-phase T1-weighted enhanced imaging sequences is recommended to determine the number, size, and distribution of liver metastases. Eligible patients may directly choose liver-specific contrast agent-enhanced MRI, which is more helpful in detecting lesions smaller than 1 cm, especially metastases that cannot be visualized by CT after chemotherapy [21, 22]. jFor eligible patients, contrast-enhanced liver ultrasound or contrast-enhanced intraoperative ultrasound can be performed to further clarify the diagnosis of liver metastases, especially metastases that cannot be visualized by CT after chemotherapy. PET/CT can be used to detect potential metastases when there is clinical suspicion of metastasis that cannot be confirmed by other imaging examinations, or before major treatment decisions are made (e.g., when there is a possibility of curative treatment in recurrent metastatic patients), thus helping to avoid overtreatment. However, PET/CT is not recommended as a routine test for the diagnosis of colorectal cancer. 2.2.3. Diagnosis methods for rectal-anal cancer 2.2.3.1.

  The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update · 2024 · DOI

• Contrast-enhanced upper abdominal USh Abbreviations: CA199, carbohydrate antigen 199; CEA, carcinoembryonic antigen; CT, computed tomography; MRI, magnetic resonance imaging; US, ultrasound. aColonoscopy is generally prohibited in patients with clinically evident intestinal obstruction, as bowel preparation before the examination may exacerbate the obstruction or cause perforation. bA digital rectal exam can provide specific clinical signs of whether there are tumor lesions in the pelvic floor, which is a specific clinical sign of peritoneal metastasis. cFor patients who are not eligible, who refuse a full colonoscopy, or whose colonoscopy cannot examine the entire colon, it is recommended to perform a contrastenhanced abdominal/pelvic CT scan after bowel cleansing. dContrast-enhanced chest CT is recommended for diagnosis and differential diagnosis of metastatic lymph nodes. Continuous thin-section axial, coronal, and sagittal reconstructed images are recommended for diagnosis and differential diagnosis of pulmonary metastases from colorectal cancer wherever possible. Enhanced abdominal and pelvic CT is recommended for diagnosis of ovarian metastases and peritoneal metastases. eFor patients with contraindications to venous contrast, it is recommended to perform contrast-enhanced abdominal/pelvic MRI plus non-contrast-enhanced chest CT. fWhen the diagnosis of ovarian metastasis cannot be confirmed by CT, pelvic MRI or gynecologic ultrasound is recommended to support the diagnosis, and MRI is recommended to include T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and multi-phase T1-weighted enhanced imaging sequences. gWhen the diagnosis of liver metastases cannot be confirmed by CT or when treatment decisions for liver metastases need to be changed, liver MRI including T2WI, DWI, and multi-phase T1-weighted enhanced imaging sequences is recommended to determine the number, size, and distribution of liver metastases. Eligible patients may directly choose Hepatocyte-specific contrast-enhanced liver MRI, which is more helpful in detecting lesions smaller than 1 cm, especially metastases that cannot be visualized by CT after chemotherapy [21, 22]. hFor eligible patients, contrast-enhanced liver ultrasound or contrast-enhanced intraoperative ultrasound can be performed to further clarify the diagnosis of liver metastases, especially metastases that cannot be visualized by CT after chemotherapy. PET/CT can be used to detect potential metastases when there is clinical suspicion of metastasis that cannot be confirmed by other imaging examinations, or before major treatment decisions are made (e.g., when there is a possibility of curative treatment in recurrent metastatic patients), thus helping to avoid overtreatment. However, PET/CT is not recommended as a routine test for the diagnosis of colorectal cancer. 2.2.2.

  The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update · 2024 · DOI

• ∙ Contrast-enhanced abdominal/pelvic CTc ∙ Surgical exploration ∙ Non-contrast chest CT and contrast-enhanced abdominal/pelvic MRIe,f ∙ Serum CEA ∙…

  The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update · 2024 · DOI

• Organ-preserving strategies combining chemoradiotherapy with local excision may improve functional outcomes, yet long-term patient-reported data remain limited.

  Bowel dysfunction (LARS) and quality of life after chemoradiotherapy and local excision versus total mesorectal excision in T2–T3ab, N0, M0 rectal cancer: the TAUTEM randomized clinical trial · 2026 · DOI

• However, the relationship between recurrence timing and long-term survival outcomes remains inadequately characterized, particularly in Chinese populations, limiting risk stratification and individualized treatment strategies.

  Relationship between postoperative tumor recurrence time and long-term survival in colorectal cancer patients · 2026 · DOI

• from of Gastrointestinal Importantly, contrast administration did not substantially improve primary tumour detection beyond T2W imaging alone.

  MRI Staging of Carcinoma Rectum with Peroperative and Pathological Correlation · 2026 · DOI

• The relationship between degree of therapeutic pathomorphosis severity and clinical outcomes such as anastomotic leak rates, margin status, and disease-free survival requires further correlation analysis.

  RESULTS OF THE STUDY OF THERAPEUTIC PATHOMORPHOSIS OF MALIGNANT EPITHELIAL TUMORS IN PATIENTS WITH LOCALLY ADVANCED RESECTABLE COLON TUMORS UNDER PREOPERATIVE CHEMORADIATION INDUCTION · 2026 · DOI

• The follow-up strategy for early colorectal cancer after non-curative endoscopic resection followed by additional surgery is based on alignment with standard postoperative follow-up protocols, but lacks specific evidence for this particular patient population.

  Chinese expert consensus on additional surgery following endoscopic resection for early colorectal cancer (2025 edition) · 2026 · DOI

• Concurrent chemoradiotherapyd for patients with a strong desire of sphincter preservation, if ∙ cCRe – watch and waitf ∙ ycT1 – transanal local…

  The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update · 2024 · DOI

Most-cited papers in Colorectal Cancer Surgical Treatments

• Effect of Robotic-Assisted vs Conventional Laparoscopic Surgery on Risk of Conversion to Open Laparotomy Among Patients Undergoing Resection for Rectal Cancer · JAMA · 2017 · 1,281 citations
• NCCN Guidelines® Insights: Rectal Cancer, Version 3.2024 · Journal of the National Comprehensive Cancer Network · 2024 · 214 citations
• Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial · Annals of Oncology · 2024 · 175 citations
• Organ Preservation and Survival by Clinical Response Grade in Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy · JAMA Network Open · 2024 · 122 citations
• Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH) · Journal of Clinical Oncology · 2024 · 101 citations
• Indocyanine green near-infrared fluorescence bowel perfusion assessment to prevent anastomotic leakage in minimally invasive colorectal surgery (AVOID): a multicentre, randomised, controlled, phase 3 trial · ˜The œLancet. Gastroenterology & hepatology · 2024 · 88 citations
• Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial · Cancer Cell · 2024 · 82 citations
• The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update · Cancer Communications · 2024 · 57 citations
• Mass Legal Executions in America through 1865 · Crime Histoire et Sociétés · 2004 · 27 citations
• Multimodal treatment of rectal cancer · Deutsches Ärzteblatt international · 2022 · 18 citations

Most recent work

• Stratified Procedural Risk Assessment in Colorectal Surgery: A Comparative Analysis of Statistical and Machine Learning Approaches Using Combined Surgical Approach and Operative Duration Categories · Surgeries · 2026
• <scp>MRI</scp> Habitat Analysis for Preoperative Prediction of Perineural Invasion and Prognostic Stratification in Rectal Cancer · Journal of Magnetic Resonance Imaging · 2026
• Rectal location and recurrence after resection of high-risk T1 colorectal cancer · Gastrointestinal Endoscopy · 2026
• Chinese expert consensus on additional surgery following endoscopic resection for early colorectal cancer (2025 edition) · Cancer Biology & Medicine · 2026
• RESULTS OF THE STUDY OF THERAPEUTIC PATHOMORPHOSIS OF MALIGNANT EPITHELIAL TUMORS IN PATIENTS WITH LOCALLY ADVANCED RESECTABLE COLON TUMORS UNDER PREOPERATIVE CHEMORADIATION INDUCTION · Art of Medicine · 2026
• Neoadjuvant FOLFOXIRI chemotherapy with or without camrelizumab in the treatment of locally advanced rectal cancer: a retrospective cohort study · npj Precision Oncology · 2026
• Textbook outcome in cancer surgery and its prognostic value: a systematic review and meta-analysis. · European Journal of Cancer Prevention · 2026
• Balancing benefit and burden: a critical appraisal of prophylactic ileostomy in laparoscopic low anterior resection · Annals of Medicine & Surgery · 2026
• Histopathological characteristics of screen-detected colorectal cancers · Virchows Archiv · 2026
• Robotic total pelvic exenteration using a transanal-first approach for locally advanced rectal cancer occupying the pelvis: a video vignette · Techniques in Coloproctology · 2026

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