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

Abstract

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

Keywords

adjuvant / chemotherapy / Chinese Society of Clinical Oncology (CSCO) / colorectal cancer / diagnosis / immunotherapy / neoadjuvant / radiotherapy / surgery / targeted therapy

References

[1] Cai SR, Huang YQ, Zhang SZ, Li QR, Ma XY, Zheng S. Effects of subitems in the colorectal cancer screening protocol on the Chinese colorectal cancer screening program: an analysis based on natural community screening results. BMC Cancer. 2019; 19(1): 47.

[2] Chen H, Lu M, Liu C, Zou S, Du L, Liao X, et al. Comparative Evaluation of Participation and Diagnostic Yield of Colonoscopy vs Fecal Immunochemical Test vs Risk-Adapted Screening in Colorectal Cancer Screening: Interim Analysis of a Multicenter Randomized Controlled Trial (TARGET-C). Am J Gastroenterol. 2020; 115(8): 1264–74.

[3] Li QL, Ma XY, Yu LL, Xue F, Ma WL, Yao KY. [Age-specific detection rates of colorectal neoplasms by colonoscopic screening in high-incidence rural area]. Zhonghua Zhong Liu Za Zhi. 2013; 35(2): 154–7.

[4] Sung JJ, Ng SC, Chan FK, Chiu HM, Kim HS, Matsuda T, et al. An updated Asia Pacific Consensus Recommendations on colorectal cancer screening. Gut. 2015; 64(1): 121–32.

[5] Tao S, Hoffmeister M, Brenner H. Development and validation of a scoring system to identify individuals at high risk for advanced colorectal neoplasms who should undergo colonoscopy screening. Clin Gastroenterol Hepatol. 2014; 12(3): 478–85.

[6] Huang Y, Li Q, Ge W, Cai S, Zhang S, Zheng S. Predictive power of quantitative and qualitative fecal immunochemical tests for hemoglobin in population screening for colorectal neoplasm. Eur J Cancer Prev. 2014; 23(1): 27–34.

[7] Lee JK, Liles EG, Bent S, Levin TR, Corley DA. Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis. Ann Intern Med. 2014; 160(3): 171.

[8] Cai SR, Zhu HH, Huang YQ, Li QL, Ma XY, Zhang SZ, et al. Cost-Effectiveness between Double and Single Fecal Immunochemical Test(s) in a Mass Colorectal Cancer Screening. Biomed Res Int. 2016; 2016: 6830713.

[9] Chen WQ, Li N, Lan P, Chen HD, Du LB, Sun F, et al. China guideline for the screening, early detection and early treatment of colorectal cancer (2020, Beijing). China Cancer. 2021; 30(01): 1–28.

[10] Early Diagnosis and Early Treatment Group of the Oncology Branch of the Chinese Medical Association (CMA). Expert consensus on early diagnosis and treatment of colorectal cancer in China. Chin Med J (Engl). 2020; 100(22): 1691–8.

[11] National Clinical Research Center for Digestive Diseases, National Alliance for Early Diagnosis and Treatment of Digestive Tract Cancers, Digestive Endoscopy Society of Chinese Medical Association, Health Management Society of Chinese Medical Association, Digestive Endoscopy Professional Committee of the Endoscopy Physicians Branch of Chinese Medical Doctor Association, Endoscopic Health Management and Physical Examination Professional Committee of the Endoscopy Physicians Branch of Chinese Medical Doctor Association, et al. Expert consensus opinion on early colorectal cancer screening process in China (2019, Shanghai). Chin J Dig Endosc. 2019; 36(10): 709–19.

[12] Colorectal Cancer Professional Committee of the Chinese Anti-Cancer Association, Expert Committee for Consensus on Early Diagnosis and Screening for Colorectal Cancer in China. Expert consensus on early diagnosis and screening strategies for colorectal tumours in China. Chin J Gastrointest Surg. 2018; 21(10): 1081–6.

[13] Chinese Society Of Gastroenterology. Consensus opinion on colorectal tumour screening, early diagnosis and treatment and comprehensive prevention in China. J Gastroenterol Hepatol. 2011; 20(11): 979–95.

[14] Imperiale TF, Ransohoff DF, Itzkowitz SH, Levin TR, Lavin P, Lidgard GP, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014; 370(14): 1287–97.

[15] Lin JS, Piper MA, Perdue LA, Rutter CM, Webber EM, O'Connor E, et al. Screening for Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2016; 315(23): 2576–94.

[16] Gupta S, Lieberman D, Anderson JC, Burke CA, Dominitz JA, Kaltenbach T, et al. Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2020; 158(4): 1131–53 e5.

[17] Facciorusso A, Di Maso M, Serviddio G, Vendemiale G, Spada C, Costamagna G, et al. Factors Associated With Recurrence of Advanced Colorectal Adenoma After Endoscopic Resection. Clin Gastroenterol Hepatol. 2016; 14(8): 1148–54 e4.

[18] Cubiella J, Carballo F, Portillo I, Cruzado Quevedo J, Salas D, Binefa G, et al. Incidence of advanced neoplasia during surveillance in high- and intermediate-risk groups of the European colorectal cancer screening guidelines. Endoscopy. 2016; 48(11): 995–1002.

[19] Li J, Yuan Y, Yang F, Wang Y, Zhu X, Wang Z, et al. Expert consensus on multidisciplinary therapy of colorectal cancer with lung metastases (2019 edition). J Hematol Oncol. 2019; 12(1): 16.

[20] van ’t Sant I, Engbersen MP, Bhairosing PA, Lambregts DMJ, Beets-Tan RGH, van Driel WJ, et al. Diagnostic performance of imaging for the detection of peritoneal metastases: a meta-analysis. Eur Radiol. 2020; 30(6): 3101–12.

[21] Tsili AC, Alexiou G, Naka C, Argyropoulou MI. Imaging of colorectal cancer liver metastases using contrast-enhanced US, multidetector CT, MRI, and FDG PET/CT: a meta-analysis. Acta Radiol. 2021; 62(3): 302–12.

[22] Muaddi H, Silva S, Choi WJ, Coburn N, Hallet J, Law C, et al. When is a Ghost Really Gone? A Systematic Review and Meta-analysis of the Accuracy of Imaging Modalities to Predict Complete Pathological Response of Colorectal Cancer Liver Metastases After Chemotherapy. Ann Surg Oncol. 2021; 28(11): 6805–13.

[23] Moulton C-A, Gu C-S, Law CH, Tandan VR, Hart R, Quan D, et al. Effect of PET Before Liver Resection on Surgical Management for Colorectal Adenocarcinoma Metastases: A Randomized Clinical Trial. JAMA. 2014; 311(18): 1863–9.

[24] Fernandes MC, Gollub MJ, Brown G. The importance of MRI for rectal cancer evaluation. Surg Oncol. 2022; 43: 101739.

[25] O'Connell E, Galvin R, McNamara DA, Burke JP. The utility of preoperative radiological evaluation of early rectal neoplasia: a systematic review and meta-analysis. Colorectal Dis. 2020; 22(9): 1076–84.

[26] Roodbeen SX, de Lacy FB, van Dieren S, Penna M, Ris F, Moran B, et al. Predictive Factors and Risk Model for Positive Circumferential Resection Margin Rate After Transanal Total Mesorectal Excision in 2653 Patients With Rectal Cancer. Ann Surg. 2019; 270(5): 884–91.

[27] Lambregts DMJ, Bogveradze N, Blomqvist LK, Fokas E, Garcia-Aguilar J, Glimelius B, et al. Current controversies in TNM for the radiological staging of rectal cancer and how to deal with them: results of a global online survey and multidisciplinary expert consensus. Eur Radiol. 2022; 32(7): 4991–5003.

[28] Al-Sukhni E, Milot L, Fruitman M, Beyene J, Victor JC, Schmocker S, et al. Diagnostic accuracy of MRI for assessment of T category, lymph node metastases, and circumferential resection margin involvement in patients with rectal cancer: a systematic review and meta-analysis. Ann Surg Oncol. 2012; 19(7): 2212–23.

[29] Laparoscopic Surgery Committee of the Endoscopist Branch in the Chinese Medical Doctor Association (CMDA), Laparoscopic Surgery Committee of Colorectal Cancer Committee of Chinese Medical Doctor Association (CMDA), Colorectal Surgery Group of the Surgery Branch in the Chinese Medical Association (CMA), Chinese Anti-Cancer Association Colorectal Tumor Integrated Rehabilitation Committee, China International Exchange and Promotive Association for Medical and Health Care Colorectal Disease Branch, Zhou Zongguang, et al. Chinese expert consensus on the diagnosis and treatment for lateral lymph node metastasis of rectal cancer (2024 edition). Chin J Gastrointest Surg. 2024; 27(1): 1–14.

[30] Rooney S, Meyer J, Afzal Z, Ashcroft J, Cheow H, De Paepe KN, et al. The Role of Preoperative Imaging in the Detection of Lateral Lymph Node Metastases in Rectal Cancer: A Systematic Review and Diagnostic Test Meta-analysis. Dis Colon Rectum. 2022; 65(12): 1436–46.

[31] Rouleau Fournier F, Motamedi MAK, Brown CJ, Phang T, Raval MJ, Hague CJ, et al. Oncologic Outcomes Associated With MRI-detected Extramural Venous Invasion (mrEMVI) in Rectal Cancer: A Systematic Review and Meta-analysis. Ann Surg. 2022; 275(2): 303–14.

[32] Benson AB, Venook AP, Al-Hawary MM, Cederquist L, Chen YJ, Ciombor KK, et al. Rectal Cancer, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018; 16(7): 874–901.

[33] Hashiguchi Y, Muro K, Saito Y, Ito Y, Ajioka Y, Hamaguchi T, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2020; 25(1): 1–42.

[34] Lord AC, Corr A, Chandramohan A, Hodges N, Pring E, Airo-Farulla C, et al. Assessment of the 2020 NICE criteria for preoperative radiotherapy in patients with rectal cancer treated by surgery alone in comparison with proven MRI prognostic factors: a retrospective cohort study. Lancet Oncol. 2022; 23(6): 793–801.

[35] Battersby NJ, How P, Moran B, Stelzner S, West NP, Branagan G, et al. Prospective Validation of a Low Rectal Cancer Magnetic Resonance Imaging Staging System and Development of a Local Recurrence Risk Stratification Model: The MERCURY II Study. Ann Surg. 2016; 263(4): 751–60.

[36] Chen K, She HL, Wu T, Hu F, Li T, Luo LP. Comparison of percentage changes in quantitative diffusion parameters for assessing pathological complete response to neoadjuvant therapy in locally advanced rectal cancer: a meta-analysis. Abdom Radiol (NY). 2021; 46(3): 894–908.

[37] Feng L, Liu Z, Li C, Li Z, Lou X, Shao L, et al. Development and validation of a radiopathomics model to predict pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a multicentre observational study. Lancet Digit Health. 2022; 4(1): e8–e17.

[38] Du D, Su Z, Wang D, Liu W, Wei Z. Optimal Interval to Surgery After Neoadjuvant Chemoradiotherapy in Rectal Cancer: A Systematic Review and Meta-analysis. Clin Colorectal Cancer. 2018; 17(1): 13–24.

[39] Bates DDB, Homsi ME, Chang KJ, Lalwani N, Horvat N, Sheedy SP. MRI for Rectal Cancer: Staging, mrCRM, EMVI, Lymph Node Staging and Post-Treatment Response. Clin Colorectal Cancer. 2022; 21(1): 10–8.

[40] Chen S, Li N, Tang Y, Shi J, Zhao Y, Ma H, et al. The prognostic value of MRI-detected extramural vascular invasion (mrEMVI) for rectal cancer patients treated with neoadjuvant therapy: a meta-analysis. Eur Radiol. 2021; 31(12): 8827–37.

[41] Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, et al. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022; 386(25): 2363–76.

[42] Cooper HS. Pathology of the endoscopically removed malignant colorectal polyp. Current Diagnostic Pathol. 2007; 13(6): 423–37.

[43] Lee VWK, Chan KF. Tumor budding and poorly-differentiated cluster in prognostication in Stage II colon cancer. Pathol Res Pract. 2018; 214(3): 402–7.

[44] Romiti A, Roberto M, Marchetti P, Di Cerbo A, Falcone R, Campisi G, et al. Study of histopathologic parameters to define the prognosis of stage II colon cancer. Int J Colorectal Dis. 2019; 34(5): 905–13.

[45] Costas-Chavarri A, Nandakumar G, Temin S, Lopes G, Cervantes A, Cruz Correa M, et al. Treatment of Patients With Early-Stage Colorectal Cancer: ASCO Resource-Stratified Guideline. J Glob Oncol. 2019; 5: 1–19.

[46] Pai RK, Cheng YW, Jakubowski MA, Shadrach BL, Plesec TP, Pai RK. Colorectal carcinomas with submucosal invasion (pT1): analysis of histopathological and molecular factors predicting lymph node metastasis. Mod Pathol. 2017; 30(1): 113–22.

[47] Lugli A, Kirsch R, Ajioka Y, Bosman F, Cathomas G, Dawson H, et al. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Mod Pathol. 2017; 30(9): 1299–311.

[48] Benson AB, Venook AP, Al-Hawary MM, Azad N, Chen Y-J, Ciombor KK, et al. Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw. 2022; 20(10): 1139–67.

[49] Parfitt JR, Driman DK. The total mesorectal excision specimen for rectal cancer: a review of its pathological assessment. J Clin Pathol. 2007; 60(8): 849–55.

[50] WHO Classification of Tumours Editorial Board. WHO Classification of Tumours: Digestive System Tumours. 5th ed. 2019.

[51] Nagtegaal ID, Marijnen CAM, Kranenbarg EK, van de Velde CJH, van Krieken JHJM, Pathology Review C, et al. Circumferential margin involvement is still an important predictor of local recurrence in rectal carcinoma: not one millimeter but two millimeters is the limit. Am J Surg Pathol. 2002; 26(3): 350–7.

[52] Amin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK, et al. AJCC Cancer Staging Manual. 8 ed: Springer Cham; 2016; XVII: 1032.

[53] Sepulveda AR, Hamilton SR, Allegra CJ, Grody W, Cushman-Vokoun AM, Funkhouser WK, et al. Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017; 35(13): 1453–86.

[54] Qin S, Li J, Wang L, Xu J, Cheng Y, Bai Y, et al. Efficacy and Tolerability of First-Line Cetuximab Plus Leucovorin, Fluorouracil, and Oxaliplatin (FOLFOX-4) Versus FOLFOX-4 in Patients With RAS Wild-Type Metastatic Colorectal Cancer: The Open-Label, Randomized, Phase III TAILOR Trial. J Clin Oncol. 2018; 36(30): 3031–9.

[55] Kopetz S, Grothey A, Yaeger R, Cutsem EV, Desai J, Yoshino T, et al. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N Engl J Med. 2019; 381(17): 1632–43.

[56] Guo TA, Wu YC, Tan C, Jin YT, Sheng WQ, Cai SJ, et al. Clinicopathologic features and prognostic value of KRAS, NRAS and BRAF mutations and DNA mismatch repair status: A single-center retrospective study of 1,834 Chinese patients with Stage I-IV colorectal cancer. Int J Cancer. 2019; 145(6): 1625–34.

[57] Sinicrope FA, Shi Q, Smyrk TC, Thibodeau SN, Dienstmann R, Guinney J, et al. Molecular markers identify subtypes of stage III colon cancer associated with patient outcomes. Gastroenterology. 2015; 148(1): 88–99.

[58] Gavin PG, Colangelo LH, Fumagalli D, Tanaka N, Remillard MY, Yothers G, et al. Mutation profiling and microsatellite instability in stage II and III colon cancer: an assessment of their prognostic and oxaliplatin predictive value. Clin Cancer Res. 2012; 18(23): 6531–41.

[59] Benson AB, Venook AP, Al-Hawary MM, Arain MA, Chen Y-J, Ciombor KK, et al. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw. 2021; 19(3): 329–59.

[60] Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, et al. Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn. 2017; 19(1): 4–23.

[61] Panel Members of Expert Consensus on Molecular Testing for Colorectal Cancer. Expert consensus on molecular testing for colorectal cancer. Chinese Journal of Pathology. 2018; 47(4): 237–40.

[62] Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016; 17(6): 738–46.

[63] Hechtman JF, Benayed R, Hyman DM, Drilon A, Zehir A, Frosina D, et al. Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions. Am J Surg Pathol. 2017; 41(11): 1547–51.

[64] Solomon JP, Linkov I, Rosado A, Mullaney K, Rosen EY, Frosina D, et al. NTRK fusion detection across multiple assays and 33,997 cases: diagnostic implications and pitfalls. Mod Pathol. 2020; 33(1): 38–46.

[65] Forgo E, Gomez AJ, Steiner D, Zehnder J, Longacre TA. Morphological, immunophenotypical and molecular features of hypermutation in colorectal carcinomas with mutations in DNA polymerase epsilon (POLE). Histopathology. 2020; 76(3): 366–74.

[66] Ma X, Riaz N, Samstein RM, Lee M, Makarov V, Valero C, et al. Functional landscapes of POLE and POLD1 mutations in checkpoint blockade-dependent antitumor immunity. Nat Genet. 2022; 54(7): 996–1012.

[67] Kelly RJ, Bever K, Chao J, Ciombor KK, Eng C, Fakih M, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of gastrointestinal cancer. J Immunother Cancer. 2023; 11(6).

[68] Reinert T, Henriksen TV, Christensen E, Sharma S, Salari R, Sethi H, et al. Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer. JAMA Oncol. 2019; 5(8): 1124–31.

[69] Chen G, Peng J, Xiao Q, Wu HX, Wu X, Wang F, et al. Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer. J Hematol Oncol. 2021; 14(1): 80.

[70] Henriksen TV, Tarazona N, Frydendahl A, Reinert T, Gimeno-Valiente F, Carbonell-Asins JA, et al. Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences. Clin Cancer Res. 2022; 28(3): 507–17.

[71] Tie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S, et al. Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer. N Engl J Med. 2022; 386(24): 2261–72.

[72] Fujiya M, Tanaka K, Dokoshi T, Tominaga M, Ueno N, Inaba Y, et al. Efficacy and adverse events of EMR and endoscopic submucosal dissection for the treatment of colon neoplasms: a meta-analysis of studies comparing EMR and endoscopic submucosal dissection. Gastrointest Endosc. 2015; 81(3): 583–95.

[73] De Ceglie A, Hassan C, Mangiavillano B, Matsuda T, Saito Y, Ridola L, et al. Endoscopic mucosal resection and endoscopic submucosal dissection for colorectal lesions: A systematic review. Crit Rev Oncol Hematol. 2016; 104: 138–55.

[74] Ferlitsch M, Moss A, Hassan C, Bhandari P, Dumonceau JM, Paspatis G, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy. 2017; 49(3): 270–97.

[75] Ribeiro MS, Wallace MB. Endoscopic Treatment of Early Cancer of the Colon. Gastroenterol Hepatol (N Y). 2015; 11(7): 445–52.

[76] Tanaka S, Kashida H, Saito Y, Yahagi N, Yamano H, Saito S, et al. JGES guidelines for colorectal endoscopic submucosal dissection/endoscopic mucosal resection. Dig Endosc. 2015; 27(4): 417–34.

[77] Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, Saito Y, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol. 2018; 23(1): 1–34.

[78] Cooper HS, Deppisch LM, Gourley WK, Kahn EI, Lev R, Manley PN, et al. Endoscopically removed malignant colorectal polyps: clinicopathologic correlations. Gastroenterology. 1995; 108(6): 1657–65.

[79] Markowitz AJ, Winawer SJ. Management of colorectal polyps. CA Cancer J Clin. 1997; 47(2): 93–112.

[80] Yoshii S, Nojima M, Nosho K, Omori S, Kusumi T, Okuda H, et al. Factors associated with risk for colorectal cancer recurrence after endoscopic resection of T1 tumors. Clin Gastroenterol Hepatol. 2014; 12(2): 292–302 e3.

[81] Cooper HS. Surgical pathology of endoscopically removed malignant polyps of the colon and rectum. Am J Surg Pathol. 1983; 7(7): 613–23.

[82] Hassan C, Zullo A, Risio M, Rossini FP, Morini S. Histologic risk factors and clinical outcome in colorectal malignant polyp: a pooled-data analysis. Dis Colon Rectum. 2005; 48(8): 1588–96.

[83] Seitz U, Bohnacker S, Seewald S, Thonke F, Brand B, Bräutigam T, et al. Is Endoscopic Polypectomy an Adequate Therapy for Malignant Colorectal Adenomas? Presentation of 114 Patients and Review of the Literature. Diseases of the Colon & Rectum. 2004; 47(11): 1789–97.

[84] Volk EE, Goldblum JR, Petras RE, Carey WD, Fazio VW. Management and outcome of patients with invasive carcinoma arising in colorectal polyps. Gastroenterology. 1995; 109(6): 1801–7.

[85] Cranley JP, Petras RE, Carey WD, Paradis K, Sivak MV. When is endoscopic polypectomy adequate therapy for colonic polyps containing invasive carcinoma? Gastroenterology. 1986; 91(2): 419–27.

[86] Haggitt RC, Glotzbach RE, Soffer EE, Wruble LD. Prognostic factors in colorectal carcinomas arising in adenomas: implications for lesions removed by endoscopic polypectomy. Gastroenterology. 1985; 89(2): 328–36.

[87] Hu H, Kang L, Zhang J, Wu Z, Wang H, Huang M, et al. Neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, in mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer (PICC): a single-centre, parallel-group, non-comparative, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2022; 7(1): 38–48.

[88] Chalabi M, Verschoor YL, Tan PB, Balduzzi S, Van Lent AU, Grootscholten C, et al. Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer. N Engl J Med. 2024; 390(21): 1949–58.

[89] Cohen AM. Surgical considerations in patients with cancer of the colon and rectum. Semin Oncol. 1991; 18(4): 381–7.

[90] West NP, Hohenberger W, Weber K, Perrakis A, Finan PJ, Quirke P. Complete mesocolic excision with central vascular ligation produces an oncologically superior specimen compared with standard surgery for carcinoma of the colon. J Clin Oncol. 2010; 28(2): 272–8.

[91] Berger AC, Sigurdson ER, LeVoyer T, Hanlon A, Mayer RJ, Macdonald JS, et al. Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol. 2005; 23(34): 8706–12.

[92] Huang X, Lv B, Zhang S, Meng L. Preoperative colonic stents versus emergency surgery for acute left-sided malignant colonic obstruction: a meta-analysis. J Gastrointest Surg. 2014; 18(3): 584–91.

[93] Tournigand C, André T, Bonnetain F, Chibaudel B, Lledo G, Hickish T, et al. Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: subgroup analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer trial. J Clin Oncol. 2012; 30(27): 3353–60.

[94] Sargent DJ, Marsoni S, Monges G, Thibodeau SN, Labianca R, Hamilton SR, et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol. 2010; 28(20): 3219–26.

[95] Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, et al. Duration of Adjuvant Chemotherapy for Stage III Colon Cancer. N Engl J Med. 2018; 378(13): 1177–88.

[96] Iveson T, Sobrero AF, Yoshino T, Sougklakos I, Ou F-S, Meyers JP, et al. Prospective pooled analysis of four randomized trials investigating duration of adjuvant (adj) oxaliplatin-based therapy (3 vs 6 months {m}) for patients (pts) with high-risk stage II colorectal cancer (CC). J Clin Oncol. 2019; 37(15_suppl): 3501-.

[97] Chibaudel B, Tournigand C, Bonnetain F, Richa H, Benetkiewicz M, Andre T, et al. Therapeutic strategy in unresectable metastatic colorectal cancer: an updated review. Ther Adv Med Oncol. 2015; 7(3): 153–69.

[98] Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008; 26(12): 2013–19.

[99] Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014; 371(17): 1609–18.

[100] Tebbutt NC, Wilson K, Gebski VJ, Cummins MM, Zannino D, van Hazel GA, et al. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. J Clin Oncol. 2010; 28(19): 3191–8.

[101] Kabbinavar FF, Schulz J, McCleod M, Patel T, Hamm JT, Hecht JR, et al. Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol. 2005; 23(16): 3697–705.

[102] Hecht JR, Mitchell E, Chidiac T, Scroggin C, Hagenstad C, Spigel D, et al. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol. 2009; 27(5): 672–80.

[103] Tol J, Koopman M, Cats A, Rodenburg CJ, Creemers GJ, Schrama JG, et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med. 2009; 360(6): 563–72.

[104] Andre T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, et al. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020; 383(23): 2207–18.

[105] Yuan Y, Xiao W-W, Xie W-H, Cai P-Q, Wang Q-X, Chang H, et al. Neoadjuvant chemoradiotherapy for patients with unresectable radically locally advanced colon cancer: a potential improvement to overall survival and decrease to multivisceral resection. BMC Cancer. 2021; 21(1): 179.

[106] Lee JM, Byeon JS. Colorectal Stents: Current Status. Clin Endosc. 2015; 48(3): 194–200.

[107] Cetinkaya E, Dogrul AB, Tirnaksiz MB. Role of self expandable stents in management of colorectal cancers. World J Gastrointest Oncol. 2016; 8(1): 113–20.

[108] Hamady ZZ, Cameron IC, Wyatt J, Prasad RK, Toogood GJ, Lodge JP. Resection margin in patients undergoing hepatectomy for colorectal liver metastasis: a critical appraisal of the 1cm rule. Eur J Surg Oncol. 2006; 32(5): 557–63.

[109] Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999; 230(3): 309–18; discussion 18-21.

[110] Ayez N, van der Stok EP, Grunhagen DJ, Rothbarth J, van Meerten E, Eggermont AM, et al. The use of neo-adjuvant chemotherapy in patients with resectable colorectal liver metastases: Clinical risk score as possible discriminator. Eur J Surg Oncol. 2015; 41(7): 859–67.

[111] Liu W, Zhang W, Xu Y, Li YH, Xing BC. A Prognostic Scoring System to Predict Survival Outcome of Resectable Colorectal Liver Metastases in this Modern Era. Ann Surg Oncol. 2021; 28(12): 7709–18.

[112] Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016; 27(8): 1386–422.

[113] Wang Z-X, Yao Y-C, Mai Z-J, Lin W-H, Huang Y-S, Jin Y, et al. Temporal Change in Treatment Patterns of Metastatic Colorectal Cancer and Its Association with Patient Survival: A Retrospective Cohort Study Based on an Intelligent Big-Data Platform. Engineering. 2021; 7(4): 526–33.

[114] Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F, et al. Prognostic and Predictive Relevance of Primary Tumor Location in Patients With RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses of the CRYSTAL and FIRE-3 Trials. JAMA Oncol. 2017; 3(2): 194–201.

[115] Wang ZX, Wu HX, He MM, Wang YN, Luo HY, Ding PR, et al. Chemotherapy With or Without Anti-EGFR Agents in Left- and Right-Sided Metastatic Colorectal Cancer: An Updated Meta-Analysis. J Natl Compr Canc Netw. 2019; 17(7): 805–11.

[116] Benson AB, Venook AP, Adam M, Chang G, Chen YJ, Ciombor KK, et al. Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2024; 22(2 d): e240029.

[117] Overman MJ, Lenz H-J, Andre T, Aglietta M, Wong MK, Luppi G, et al. Nivolumab (NIVO) ± ipilimumab (IPI) in patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Five-year follow-up from CheckMate 142. J Clin Oncol. 2022; 40(16_suppl): 3510-.

[118] Masi G, Salvatore L, Boni L, Loupakis F, Cremolini C, Fornaro L, et al. Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: final results of the randomized BEBYP trial. Ann Oncol. 2015; 26(4): 724–30.

[119] Suenaga M, Mizunuma N, Matsusaka S, Shinozaki E, Ozaka M, Ogura M, et al. A phase I/II study of biweekly capecitabine and irinotecan plus bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer. Drug Des Devel Ther. 2015; 9: 1653–62.

[120] Xu RH, Muro K, Morita S, Iwasa S, Han SW, Wang W, et al. Modified XELIRI (capecitabine plus irinotecan) versus FOLFIRI (leucovorin, fluorouracil, and irinotecan), both either with or without bevacizumab, as second-line therapy for metastatic colorectal cancer (AXEPT): a multicentre, open-label, randomised, non-inferiority, phase 3 trial. Lancet Oncol. 2018; 19(5): 660–71.

[121] Kopetz S, Guthrie KA, Morris VK, Lenz HJ, Magliocco AM, Maru D, et al. Randomized Trial of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF-Mutant Metastatic Colorectal Cancer (SWOG S1406). J Clin Oncol. 2021; 39(4): 285–94.

[122] Li J, Qin S, Xu R, Yau TC, Ma B, Pan H, et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015; 16(6): 619–29.

[123] Bekaii-Saab TS, Ou F-S, Anderson DM, Ahn DH, Boland PM, Ciombor KK, et al. Regorafenib dose optimization study (ReDOS): Randomized phase II trial to evaluate dosing strategies for regorafenib in refractory metastatic colorectal cancer (mCRC): An ACCRU Network study. J Clin Oncol. 2018; 36(4_suppl): 611.

[124] Li J, Qin S, Xu RH, Shen L, Xu J, Bai Y, et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018; 319(24): 2486–96.

[125] Xu J, Kim TW, Shen L, Sriuranpong V, Pan H, Xu R, et al. Results of a Randomized, Double-Blind, Placebo-Controlled, Phase III Trial of Trifluridine/Tipiracil (TAS-102) Monotherapy in Asian Patients With Previously Treated Metastatic Colorectal Cancer: The TERRA Study. J Clin Oncol. 2018; 36(4): 350–8.

[126] Prager GW, Taieb J, Fakih M, Ciardiello F, Cutsem EV, Elez E, et al. Trifluridine–Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer. N Engl J Med. 2023; 388(18): 1657–67.

[127] Yoshino T, Di Bartolomeo M, Raghav K, Masuishi T, Loupakis F, Kawakami H, et al. Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun. 2023; 14(1): 3332.

[128] Alberts SR, Horvath WL, Sternfeld WC, Goldberg RM, Mahoney MR, Dakhil SR, et al. Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: a North Central Cancer Treatment Group phase II study. J Clin Oncol. 2005; 23(36): 9243–9.

[129] Bond MJG, Bolhuis K, Loosveld OJL, de Groot JWB, Droogendijk H, Helgason HH, et al. First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group. Lancet Oncol. 2023; 24(7): 757–71.

[130] Yalcin S, Uslu R, Dane F, Yilmaz U, Zengin N, Buyukunal E, et al. Bevacizumab + capecitabine as maintenance therapy after initial bevacizumab + XELOX treatment in previously untreated patients with metastatic colorectal cancer: phase III ‘Stop and Go’ study results–a Turkish Oncology Group Trial. Oncology. 2013; 85(6): 328–35.

[131] Esin E, Yalcin S. Maintenance strategy in metastatic colorectal cancer: A systematic review. Cancer Treat Rev. 2016; 42: 82–90.

[132] Tarantino I, Warschkow R, Guller U. Palliative Primary Tumor Resection in Patients With Metastatic Colorectal Cancer: For Whom and When? Ann Surg. 2017; 265(4): e59–e60.

[133] Hu CY, Bailey CE, You YN, Skibber JM, Rodriguez-Bigas MA, Feig BW, et al. Time trend analysis of primary tumor resection for stage IV colorectal cancer: less surgery, improved survival. JAMA Surg. 2015; 150(3): 245–51.

[134] Moritani K, Kanemitsu Y, Shida D, Shitara K, Mizusawa J, Katayama H, et al. A randomized controlled trial comparing primary tumour resection plus chemotherapy with chemotherapy alone in incurable stage IV colorectal cancer: JCOG1007 (iPACS study). Jpn J Clin Oncol. 2020; 50(1): 89–93.

[135] Fakih MG, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, et al. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023; 389(23): 2125–39.

[136] Rousseau B, Bieche I, Pasmant E, Hamzaoui N, Leulliot N, Michon L, et al. PD-1 Blockade in Solid Tumors with Defects in Polymerase Epsilon. Cancer Discov. 2022; 12(6): 1435–48.

[137] Wang F, Zhao Q, Wang Y-N, Jin Y, He M-M, Liu Z-X, et al. Evaluation of POLE and POLD1 Mutations as Biomarkers for Immunotherapy Outcomes Across Multiple Cancer Types. JAMA Oncol. 2019; 5(10): 1504–6.

[138] Chen YX, Wang ZX, Yuan SQ, Jiang TJ, Huang YS, Xu RH, et al. POLE/POLD1 mutation in non-exonuclease domain matters for predicting efficacy of immune-checkpoint-inhibitor therapy. Clin Transl Med. 2021; 11(9): e524.

[139] Jin Y, Huang R-J, Guan W-L, Wang Z-Q, Mai Z-J, Li Y-H, et al. A phase II clinical trial of toripalimab in advanced solid tumors with polymerase epsilon/polymerase delta (POLE/POLD1) mutation. Signal Transduct Targ Ther. 2024; 9(1): 227.

[140] Fukuoka S, Hara H, Takahashi N, Kojima T, Kawazoe A, Asayama M, et al. Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603). J Clin Oncol. 2020; 38(18): 2053–61.

[141] Wang F, He MM, Yao YC, Zhao X, Wang ZQ, Jin Y, et al. Regorafenib plus toripalimab in patients with metastatic colorectal cancer: a phase Ib/II clinical trial and gut microbiome analysis. Cell Rep Med. 2021; 2(9): 100383.

[142] Fakih M, Raghav KPS, Chang DZ, Larson T, Cohn AL, Huyck TK, et al. Regorafenib plus nivolumab in patients with mismatch repair-proficient/microsatellite stable metastatic colorectal cancer: a single-arm, open-label, multicentre phase 2 study. EClinicalMedicine. 2023; 58: 101917.

[143] Guo Y, Zhang W, Ying J, Zhang Y, Pan Y, Qiu W, et al. Phase 1b/2 trial of fruquintinib plus sintilimab in treating advanced solid tumours: The dose-escalation and metastatic colorectal cancer cohort in the dose-expansion phases. Eur J Cancer. 2023; 181: 26–37.

[144] Wang F, Jin Y, Wang M, Luo HY, Fang WJ, Wang YN, et al. Combined anti-PD-1, HDAC inhibitor and anti-VEGF for MSS/pMMR colorectal cancer: a randomized phase 2 trial. Nat Med. 2024; 30(4): 1035–43.

[145] Wang ZX, Peng J, Liang X, Cheng Y, Deng Y, Chen K, et al. First-line serplulimab in metastatic colorectal cancer: Phase 2 results of a randomized, double-blind, phase 2/3 trial. Med. 2024; 5(9): 1150–63.e3.

[146] Fang X, Zhu N, Zhong C, Wang L, Li J, Weng S, et al. Sintilimab plus bevacizumab, oxaliplatin and capecitabine as first-line therapy in RAS-mutant, microsatellite stable, unresectable metastatic colorectal cancer: an open-label, single-arm, phase II trial. EClinicalMedicine. 2023; 62: 102123.

[147] Rex DK, Kahi CJ, Levin B, Smith RA, Bond JH, Brooks D, et al. Guidelines for colonoscopy surveillance after cancer resection: a consensus update by the American Cancer Society and the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2006; 130(6): 1865–71.

[148] Tie J, Cohen JD, Wang Y, Christie M, Simons K, Lee M, et al. Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer. JAMA Oncol. 2019; 5(12): 1710–17.

[149] Al-Najami I, Rancinger CP, Larsen MK, Thomassen N, Buch N, Baatrup G. Transanal endoscopic microsurgery for advanced polyps and early cancers in the rectum-Long-term outcome: A STROBE compliant observational study. Medicine (Baltimore). 2016; 95(36): e4732.

[150] Heald RJ, Husband EM, Ryall RD. The mesorectum in rectal cancer surgery–the clue to pelvic recurrence? Br J Surg. 1982; 69(10): 613–6.

[151] Serra-Aracil X, Pericay C, Badia-Closa J, Golda T, Biondo S, Hernandez P, et al. Short-term outcomes of chemoradiotherapy and local excision versus total mesorectal excision in T2-T3ab,N0,M0 rectal cancer: a multicentre randomised, controlled, phase III trial (the TAU-TEM study). Ann Oncol. 2023; 34(1): 78–90.

[152] Gerard JP, Myint AS, Barbet N, Dejean C, Thamphya B, Gal J, et al. Targeted Radiotherapy Using Contact X-ray Brachytherapy 50 kV. Cancers (Basel). 2022; 14(5).

[153] Jensen LH, Risum S, Nielsen JD, Mynster T, Ploeen J, Rahr HB, et al. Curative chemoradiation for low rectal cancer: Primary clinical outcomes from a multicenter phase II trial. Am Soc Clin Oncol. 2022: LBA3514.

[154] Gerard J-P, Barbet NN, Pacé-Loscos T, Magné N, Serrand J, Mineur L, et al. Contact x-ray brachytherapy (Papillon) in addition to chemoradiotherapy to improve organ preservation in early cT2-T3 rectal adenocarcinoma: The 3-year results of OPERA randomized trial (NCT02505750). J Clin Oncol. 2022; 40(16_suppl): 3512-.

[155] Chen G, Jin Y, Guan WL, Zhang RX, Xiao WW, Cai PQ, et al. Neoadjuvant PD-1 blockade with sintilimab in mismatch-repair deficient, locally advanced rectal cancer: an open-label, single-centre phase 2 study. Lancet Gastroenterol Hepatol. 2023; 8(5): 422–31.

[156] Fokas E, Appelt A, Glynne-Jones R, Beets G, Perez R, Garcia-Aguilar J, et al. International consensus recommendations on key outcome measures for organ preservation after (chemo)radiotherapy in patients with rectal cancer. Nat Rev Clin Oncol. 2021; 18(12): 805–16.

[157] Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative Versus Postoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: Results of the German CAO/ARO/AIO-94 Randomized Phase III Trial After a Median Follow-Up of 11 Years. J Clin Oncol. 2012; 30(16): 1926–33.

[158] Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006; 24(28): 4620–5.

[159] Bosset JF, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, et al. Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results–EORTC 22921. J Clin Oncol. 2005; 23(24): 5620–7.

[160] Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012; 13(6): 579–88.

[161] Zhu J, Liu A, Sun X, Liu L, Zhu Y, Zhang T, et al. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer. J Clin Oncol. 2020; 38(36): 4231–9.

[162] Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, et al. Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. J Clin Oncol. 2019; 37(34): 3223–33.

[163] Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, et al. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015; 16(8): 957–66.

[164] Cercek A, Roxburgh CSD, Strombom P, Smith JJ, Temple LKF, Nash GM, et al. Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer. JAMA Oncol. 2018; 4(6): e180071.

[165] Garcia-Aguilar J, Patil S, Gollub MJ, Kim JK, Yuval JB, Thompson HM, et al. Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy. J Clin Oncol. 2022; 40(23): 2546–56.

[166] Gay HA, Barthold HJ, O'Meara E, Bosch WR, El Naqa I, Al-Lozi R, et al. Pelvic normal tissue contouring guidelines for radiation therapy: a Radiation Therapy Oncology Group consensus panel atlas. Int J Radiat Oncol Biol Phys. 2012; 83(3): e353–62.

[167] André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer. N Engl J Med. 2004; 350(23): 2343–51.

[168] Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, et al. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2014; 15(11): 1245–53.

[169] Swedish Rectal Cancer T, Cedermark B, Dahlberg M, Glimelius B, Pahlman L, Rutqvist LE, et al. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997; 336(14): 980–7.

[170] van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011; 12(6): 575–82.

[171] Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006; 93(10): 1215–23.

[172] Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, et al. Randomized Trial of Short-Course Radiotherapy Versus Long-Course Chemoradiation Comparing Rates of Local Recurrence in Patients With T3 Rectal Cancer: Trans-Tasman Radiation Oncology Group Trial 01.04. J Clin Oncol. 2012; 30(31): 3827–33.

[173] Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM-K, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021; 22(1): 29–42.

[174] Schrag D, Shi Q, Weiser MR, Gollub MJ, Saltz LB, Musher BL, et al. Preoperative Treatment of Locally Advanced Rectal Cancer. N Engl J Med. 2023; 389(4): 322–34.

[175] Lai LL, Fuller CD, Kachnic LA, Thomas CR,. Can pelvic radiotherapy be omitted in select patients with rectal cancer? Semin Oncol. 2006; 33(6 Suppl 11): S70–4.

[176] Gunderson LL, Sargent DJ, Tepper JE, Wolmark N, O'Connell MJ, Begovic M, et al. Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis. J Clin Oncol. 2004; 22(10): 1785–96.

[177] Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB,, Cummings B, et al. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control–final report of intergroup 0114. J Clin Oncol. 2002; 20(7): 1744–50.

[178] Conroy T, Bosset JF, Etienne PL, Rio E, Francois E, Mesgouez-Nebout N, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021; 22(5): 702–15.

[179] Verheij FS, Omer DM, Williams H, Lin ST, Qin LX, Buckley JT, et al. Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial. J Clin Oncol. 2024; 42(5): 500–6.

[180] Tamberi S, Grassi E, Zingaretti C, Papiani G, Pini S, Corbelli J, et al. A phase II study of capecitabine plus concomitant radiation therapy followed by durvalumab (MEDI4736) as preoperative treatment in rectal cancer: PANDORA study final results. J Clin Oncol. 2022; 40: LBA3513–LBA.

[181] WU A, Li Y, Ji D, Zhang L, Zhang X, Cai Y, et al. Total neoadjuvant chemoradiation combined with neoadjuvant PD-1 blockade for patients with pMMR, high-risk, and locally advanced middle to low rectal cancer. J Clin Oncol. 2022; 40(16_suppl): 3611.

[182] Salvatore L, Bensi M, Corallo S, Bergamo F, Pellegrini I, Rasola C, et al. Phase II study of preoperative (PREOP) chemoradiotherapy (CTRT) plus avelumab (AVE) in patients (PTS) with locally advanced rectal cancer (LARC): The AVANA study. J Clin Oncol. 2021; 39(15_suppl): 3511.

[183] George TJ, Yothers G, Jacobs SA, Finley GG, Wade JL, Rocha Lima CMSP, et al. Phase II study of durvalumab following neoadjuvant chemoRT in operable rectal cancer: NSABP FR-2. J Clin Oncol. 2022; 40(4_suppl): 99–9.

[184] Lin Z, Cai M, Zhang P, Li G, Liu T, Li X, et al. Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer. J Immunother Cancer. 2021; 9(11).

[185] Zhang T, Tao K, Lin Z, Zhang P, Yin Y, Chi P, et al. LBA25 Neoadjuvant short-course radiotherapy followed by camrelizumab plus chemotherapy versus long-course chemoradiotherapy followed by chemotherapy in locally advanced rectal cancer: A randomized phase III trial (UNION). Ann Oncol. 2023; 34: S1266–7.

[186] Boyle KM, Sagar PM, Chalmers AG, Sebag-Montefiore D, Cairns A, Eardley I. Surgery for locally recurrent rectal cancer. Dis Colon Rectum. 2005; 48(5): 929–37.

[187] Hahnloser D, Nelson H, Gunderson LL, Hassan I, Haddock MG, O'Connell MJ, et al. Curative potential of multimodality therapy for locally recurrent rectal cancer. Ann Surg. 2003; 237(4): 502–8.

[188] Moore HG, Shoup M, Riedel E, Minsky BD, Alektiar KM, Ercolani M, et al. Colorectal cancer pelvic recurrences: determinants of resectability. Dis Colon Rectum. 2004; 47(10): 1599–606.

[189] Heriot AG, Byrne CM, Lee P, Dobbs B, Tilney H, Solomon MJ, et al. Extended radical resection: the choice for locally recurrent rectal cancer. Dis Colon Rectum. 2008; 51(3): 284–91.

[190] Yamada K, Ishizawa T, Niwa K, Chuman Y, Aikou T. Pelvic exenteration and sacral resection for locally advanced primary and recurrent rectal cancer. Dis Colon Rectum. 2002; 45(8): 1078–84.

[191] Bouchard P, Efron J. Management of recurrent rectal cancer. Ann Surg Oncol. 2010; 17(5): 1343–56.

[192] Mirnezami AH, Sagar PM, Kavanagh D, Witherspoon P, Lee P, Winter D. Clinical algorithms for the surgical management of locally recurrent rectal cancer. Dis Colon Rectum. 2010; 53(9): 1248–57.

[193] Lynch HT, Shaw TG. Practical genetics of colorectal cancer. Chin Clin Oncol. 2013; 2(2): 12.

[194] Grover S, Kastrinos F, Steyerberg EW, Cook EF, Dewanwala A, Burbidge LA, et al. Prevalence and phenotypes of APC and MUTYH mutations in patients with multiple colorectal adenomas. JAMA. 2012; 308(5): 485–92.

[195] Yang S, Cai S, Zhang S. Clinical and genetic phenotype of familial adenomatous polyposis and its subtypes. J Pract Oncol. 2007; 22(3): 270–73.

[196] Nieuwenhuis MH, Vasen HF. Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): a review of the literature. Crit Rev Oncol Hematol. 2007; 61(2): 153–61.

[197] Yan D, Yu X, Xiao-Dong X. Research on the fundus fluorescein angiography in congenital hypertrophy of the retinal pigment epithelium in patients with familial adenomatous polyposis. International Eye Science. 2020; 10(6): 1157–9.

[198] Cao HL, Wang BM, Cao XC. Clinical features of Gardner syndrome and Turcot syndrome in Chinese population:an analysis of 93 cases. World Chinese J Digestol. 2010; 18(36): 3922–5.

[199] Lou Z, Yu ED, Meng RG. Familial adenomatous polyposis-associated desmoid tumors. Acad J Second Mil Med Univ. 2006; 27(5): 541–3.

[200] Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, et al. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med. 2003; 348(9): 791–9.

[201] Lindor NM, Rabe K, Petersen GM, Haile R, Casey G, Baron J, et al. Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA. 2005; 293(16): 1979–85.

[202] Li XF, Yuan Y. Research progress of Lynch syndrome in China. Chinese J Colorect Dis (Electronic Edition). 2015(3): 21–6.

[203] Moreira L, Balaguer F, Lindor N, de la Chapelle A, Hampel H, Aaltonen LA, et al. Identification of Lynch syndrome among patients with colorectal cancer. JAMA. 2012; 308(15): 1555–65.

[204] National Collaborative Group on Hereditary Colorectal Cancer. Implementation of screening standards for hereditary colorectal cancer in the Chinese population. Chinese J Oncol. 2004; 26(3): 191–2.

[205] Ligtenberg MJ, Kuiper RP, Chan TL, Goossens M, Hebeda KM, Voorendt M, et al. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1. Nat Genet. 2009; 41(1): 112–7.

[206] Senter L, Clendenning M, Sotamaa K, Hampel H, Green J, Potter JD, et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology. 2008; 135(2): 419–28.

[207] Yuan Y, Cao WM, Cai SR, Zhang SZ. Clinical phenotype of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families. Chinese J Oncol. 2006; 28(1): 36–8.

[208] Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med. 2005; 352(18): 1851–60.

[209] Wang SL, Da JP, Gu GL. Research Advance of Muir-Torre Syndrome. Chinese J Bases & Clinics Gen Surg. 2005; 12(2): 192–4.

[210] Xicola RM, Llor X, Pons E, Castells A, Alenda C, Pinol V, et al. Performance of different microsatellite marker panels for detection of mismatch repair-deficient colorectal tumors. J Natl Cancer Inst. 2007; 99(3): 244–52.

[211] Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998; 58(22): 5248–57.

[212] Zhu M, Liu XR, Huang YQ, Yuan Y, Li JT, Zhang XM, et al. The analysis for identifying large DNA fragment aberrations of MSH2 and MLH1 genes from familial colorectal cancer in China. Chinese J Med Genet. 2005; 22(6): 603–6.

[213] Dai YC, Xie JP, Zeng W, Fu YK, Chen ZX. Clinical meta-analysis of melanotic polyp syndrome in mainland China. J Clin Intern Med. 2008(08): 526–7.

[214] Kang LC, Zhao XR, Zhou YS, Jia YX, Kang SH, Chen Z, et al. Mutational analysis of the STK11 gene in a family line with Peutz-Jeghers syndrome. Science Bulletin. 2002; 47(21): 1639–43.

[215] Genetics Group of the Colorectal Cancer Professional Committee of the Chinese Anti-Cancer Association. Consensus on clinical diagnosis, treatment and pedigree management of hereditary colorectal cancer in China. Chinese J Oncol. 2018; 40(1): 64–77.

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