National Health Commission guidelines for diagnosis and treatment of colorectal cancer in China (2025 edition, English version)

Abstract

The National Health Commission of the People’s Republic of China Guidelines for Diagnosis and Treatment of Colorectal Cancer (2025 edition), based on evidence-based medicine, integrates cutting-edge international advances with Chinese clinical practice, and supplements and completes the previous versions. This version of the guidelines, retains the core diagnostic and treatment framework, highlights new contents such as “Surgical treatment of anal canal cancer” and “New technologies and advances in diagnosis and treatment”, and systematically summarizes the core points in the surgical treatment, medical oncology treatment, radiation oncology treatment, imaging, and pathology treatment. It is designed to help clinicians quickly grasp the key points of the guidelines and promote the standardization, precision, and consistence of colorectal cancer diagnosis and treatment.

1. Introduction

The incidence and mortality of colorectal cancer in China continue to rise, with approximately 520,000 new cases and 240,000 deaths in 2022, posing a significant public health challenge (1). The National Health Commission of the People’s Republic of China Guidelines for Diagnosis and Treatment of Colorectal Cancer (2025 edition) (hereinafter referred to as “the Guidelines”) was revised by nearly one hundred multidisciplinary experts organized by the Chinese Medical Association Oncology Branch, which is entrusted by the Department of Medical Administration of the National Health Commission. Building on the core principle of “evidence-based medicine, combined with Chinese practice” since the first edition in 2013, the Guidelines add a chapter on “Surgical treatment of anal canal cancer” and a section on “New technologies and advances in diagnosis and treatment of colorectal cancer”. The Guidelines systematically incorporate cutting-edge technologies such as liquid biopsy, fluorescence laparoscopy, and fibroblast activation protein inhibitor (FAPI) imaging, and further strengthen the promotion of the multidisciplinary team (MDT) model.

This version, streamlining redundant details and highlighting core points and updated contents, aims to expand the dissemination of the guidelines and provides clinicians with authoritative and practical diagnostic and treatment references.

2. Overview

The incidence and mortality of colorectal cancer in China rank second and fourth among all malignant tumors, respectively. The incidence rate is significantly higher in urban areas than in rural areas, and the incidence rate of colon cancer shows a clear upward trend. Most patients are diagnosed at middle and late stages. Colorectal cancer screening is a key measure to reduce incidence and mortality. A screening program based on “risk assessment + fecal occult blood test” is recommended, and those with positive results should undergo further colonoscopy. For high-risk populations with poor compliance to colonoscopy, fecal DNA testing can be performed first, and colonoscopy is recommended after a positive result (2).

The diagnosis and treatment of colorectal cancer requires the integration of multiple approaches, including surgery, chemotherapy, radiotherapy, imaging evaluation, and pathological diagnosis. The MDT model can significantly improve the level of diagnosis and treatment. These guidelines aim to standardize diagnostic and treatment behaviors, improve patient prognosis, and ensure medical quality and safety.

3. Diagnosis

3.1. Clinical manifestations

Early colorectal cancer may have no obvious symptoms. As the disease progresses, changes in bowel habits, abnormal stool characteristics (thin stools, bloody stools, mucus stools), abdominal pain, abdominal masses, symptoms related to intestinal obstruction, and systemic symptoms such as anemia and weight loss may occur. In advanced stages, lower back pain, jaundice, ascites, and other metastasis-related manifestations may appear.

3.2. Medical history and family history

It is necessary to inquire in details about the patient’s history of ulcerative colitis, colorectal polyps, Crohn’s disease, schistosomiasis, and other conditions. Colorectal cancer has strong genetic correlations with 20%−30% of patients having a family history of cancer, and 6% having hereditary colorectal cancer. It is important to screen for family history of genetic-related diseases such as Lynch syndrome (LS) and familial adenomatous polyposis (FAP).

3.3. Physical examination

General assessment: Includes general condition, nutritional status, and examination of superficial lymph nodes (especially inguinal and supraclavicular lymph nodes).

Abdominal examination: Visual inspection for abdominal distension and intestinal patterns; palpation for masses; percussion and auscultation for assessing shifting dullness and bowel sounds.

Digital rectal examination (DRE): Suspected colorectal cancer must be preformed. Record tumor size, shape, consistency, distance from the anal verge, extent of invasion, etc., and check the glove for blood.

Tri-manual examination: Recommended for female patients with rectal cancer suspected of invading the vaginal wall to assess the relationship between the mass and the posterior vaginal wall.

3.4. Laboratory tests

Routine tests: Complete blood count (to assess anemia), urinalysis, stool routine, and fecal occult blood test (to screen for minor gastrointestinal bleeding).

Biochemical tests: Liver and kidney function, electrolytes, etc.

Tumor markers: Carcinoma embryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) must be measured before diagnosis and treatment, for efficacy evaluation, and during follow-up; Alpha fetoprotein (AFP) should be added for patients with liver metastasis; CA125 should be added for those suspected of peritoneal or ovarian metastasis.

3.5. Endoscopic examination

All suspected patients are recommended to undergo total colonoscopy (except in cases of intolerance, acute peritonitis, intestinal perforation, etc.). The endoscopy report should clearly specify the depth of insertion, tumor size, shape, distance from the anal verge, extent of invasion, and intestinal stenosis. Suspicious lesions must undergo biopsy. Colonic contraction may lead to errors in the distance of the tumor from the anal verge; it is recommended to confirm the lesion site in combination with computed tomography (CT), magnetic resonance imaging (MRI), or barium enema.

3.6. Imaging examinations

3.6.1. CT scan

Enhanced abdominal and pelvic CT scans are used for cTNM staging of colon cancer, assessment of non-regional lymph nodes and distant metastasis, and chest CT plain scan is used to screen for lung metastasis.

Enhanced chest, abdominal, and pelvic CT scans are used to determine local recurrence and distant metastasis during follow-up.

Enhanced CT can evaluate the efficacy of neoadjuvant/conversion therapy on primary and metastatic lesions.

For rectal cancer patients with MRI contraindications, CT can be used to assess cTNM staging, but its value in assessing extramural vascular invasion (EMVI), mesorectal fascia (MRF) status, and anal sphincter invasion is limited.

It is recommended to clean the colon and fill the intestine with 2.5% mannitol solution before performing axial thin-layer and sagittal and coronal reconstructions.

3.6.2. MRI scan

Pelvic MRI is the preferred method for rectal cancer staging, assessing cTNM staging, lateral lymph node status, EMVI, and MRF status.

Combined T2WI, diffusion-weighted imaging (DWI), and enhanced sequences are used to evaluate the efficacy of neoadjuvant/conversion therapy for locally advanced rectal cancer, and MRI tumor regression grade (mrTRG), fissure sign and other standards are used for evaluation.

Upper abdominal enhanced MRI (with liver-specific contrast agent if necessary) is used for liver metastases that cannot be confirmed by CT.

It is recommended to empty the bowels before pelvic MRI scans, and acquire high-resolution T2WI (sagittal, coronal, axial, and oblique axial), DWI, and enhanced sequences can be added.

3.6.3. Ultrasound examination

Endorectal ultrasound is used to evaluate early (T1−2 stage) rectal cancer, and CT/MRI assists in judging lymph node and distant metastasis.

After neoadjuvant therapy, patients with complete remission on MRI should be assessed for clinical complete response (cCR) in combination with endorectal ultrasound, digital rectal examination, and endoscopy.

Intraoperative contrast-enhanced ultrasound assists in the diagnosis of liver metastases not shown on CT/MRI.

3.6.4. Nuclear medicine examination

¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET)/CT can be used as an alternative means for clinical staging and efficacy evaluation, and it can help detect distant metastases missed by other imaging modalities; PET/MRI can evaluate the efficacy of local intrahepatic treatment and recurrence.

3.6.5. Structured reporting recommendations

Rectal cancer MRI should use structured reports for initial diagnosis and follow-up.

Colon cancer should use CT structured reports.

Liver metastasis should use CT/MRI structured reports.

3.7. Pathological histological examination

The pathology report is essential for guiding colorectal cancer treatment. Biopsy pathology showing high-grade intraepithelial neoplasia or intramucosal carcinoma requires endoscopic/imaging evaluation, and treatment strategy is made after MDT discussion; low rectal cancer biopsies need to note whether it is intramucosal carcinoma or adenocarcinoma.

Molecular testing: KRAS, NRAS, and BRAF gene mutations must be tested in patients with recurrence/metastasis.

All newly diagnosed patients should be tested for mismatch repair (MMR) protein expression or microsatellite instability (MSI) status for LS screening, prognostic stratification, and immunotherapy guidance.

MLH1-deficient MMR-deficient (dMMR) tumors require BRAF^V600E immunohistochemistry or gene mutation and MLH1 methylation testing.

Units where conditions permit can carry out genetic testings of HER2, NTRK, POLE/POLD1, RET, etc.

3.8. Open or laparoscopic exploratory surgery

This applies to: 1) Diagnosis is unclear but colorectal cancer is highly suspected; 2) Intestinal obstruction is ineffective with conservative treatment; 3) Suspected intestinal perforation; and 4) Lower gastrointestinal hemorrhage is ineffective with conservative treatment.

3.9. Diagnostic steps

After completing the above examinations, a clear diagnosis is made and cTNM staging is performed.

4. Specimen collection and pathological evaluation

4.1. Specimen fixation standards

Fixative: 4% neutral buffered formalin, avoid fixatives containing heavy metals.

Fixative volume: ≥5−10 times the specimen volume.

Fixation time: Biopsy specimens 6−48 h, endoscopic mucosal resection specimens 6−48 h, surgical specimens 12−48 h.

Fixation method: Biopsy specimens are adhered to filter paper and fixed; endoscopic resection of flat/depressed specimens should be marked with orientation and flattened for fixation; polyp specimens should be marked with the resection margin for fixation; surgical specimens should be incised along the opposite side of the tumor and spread out for fixation.

4.2. Sampling requirements

Biopsy specimens: Take all samples, with no more than 5 particles per wax block (preferably 3 particles).

Endoscopic resection specimens: Record the size of the specimen and tumor, and the distance from the resection margin; polyp specimens should be marked at the pedicle and basal resection margins, and sampled at regular intervals according to the specifications; endoscopic mucosal resection/dissection specimens should be marked with different pigments at the resection margins, and sampled in parallel at 2−3 mm intervals and embedded completely.

Surgical specimens: Record tumor size, gross type, depth of invasion, distance from resection margin, mesentery integrity. Take samples from the deepest part of the tumor invasion, and take remote, proximal and mesentery/circumferential resection margins. Specimens containing the ileocecal region or anal canal need to be sampled from the corresponding parts, and the appendix is routinely sampled. The integrity of the mesentery must be evaluated for total mesorectal excision (TME) specimens. Embed all detected lymph nodes, and at least 12 lymph nodes should be detected in radical resection specimens that have not undergone neoadjuvant therapy. The original tumor site should be observed for specimens after neoadjuvant therapy, and all original tumor ranges should be sampled when there is no obvious tumor.

4.3. Pathological type and grading

Staging definition: pT1 is defined as cancer cells infiltrating the submucosa without involving the muscularis propria; intramucosal carcinoma is defined as pTis.

Gross type: Advanced colorectal cancer is divided into protruding, ulcerative, and infiltrative types.

Histological type: Refer to the 2019 WHO classification, including adenocarcinoma (not otherwise specified), serrated adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma, etc. The proportion needs to be noted when special types are included (3).

Histological grade: Divided into low grade (high-moderate differentiation) and high grade (low differentiation), determined based on the worst differentiation component.

Tumor budding: Recommended to report grading: 0−4 in the hotspot area under 20× field is low degree; 5−9 is moderate degree; ≥10 is high degree.

4.4. Pathological report content

Biopsy specimens: Contains patient information, intraepithelial neoplasia grading, invasive carcinoma histological type, and molecular test results.

Endoscopic resection specimens: Includes specimens and tumor size, grading of tumor lesion, depth of invasion, vascular/nerve invasion, resection margin status, tumor budding, and molecular test results.

Surgical specimens: Includes gross conditions, histological typing and grading, pT/pN/pM staging, tumor budding, lymph node metastasis, resection margin status, TRG score, vascular/nerve invasion, molecular test results, etc.

4.5. Colorectal cancer TNM staging

The American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) 8th edition staging system is used, which is divided into three dimensions: T (primary tumor), N (regional lymph nodes), and M (distant metastasis). Pathological staging is pTNM, staging after neoadjuvant therapy is ypTNM, and staging after recurrence is rTNM (4).

5. Surgical treatment

5.1. Surgical treatment of colon cancer

5.1.1. Surgical principles

Thoroughly explore the abdominal cavity and assess metastasis from distal to proximal; Resect sufficient bowel (≥5 cm from the tumor), clear regional lymph nodes (at least two stations), and resect en bloc; Follow tumor-free and sterile principles; For those who cannot be resected radically, consider whether to resect the primary lesion after MDT evaluation when there are no symptoms such as bleeding or obstruction; If malignancy is highly suspected but not confirmed by pathology, exploration is recommended if tolerated.

5.1.2. Treatment for different stages

cT1N0M0: Endoscopic resection [endoscopic mucosal resection/endoscopic submucosal dissection (EMR/ESD)], local resection, or bowel segment resection can be selected. SM1 shallowly invasive carcinoma can be considered for endoscopic resection; if postoperative pathology suggests poor differentiation, vascular invasion, positive margins and other high-risk factors, additional bowel segment resection + lymph node dissection should be added.

cT2−4N0−2M0: Bowel segment resection + regional lymph node dissection is preferred; total colectomy is recommended for FAP; for patients with LS, total colectomy or segmental resection + colonoscopy follow-up should be selected according to the site of canceration and age; for cT4 stage patients, after MDT evaluation, neoadjuvant therapy followed by surgery can be considered for those who cannot be radically resected; open, laparoscopic or robot-assisted surgery can be selected, and natural orifice specimen extraction surgery (NOSES) surgery can be considered when the indications are strictly followed.

Obstructed patients: One-stage resection and anastomosis, one-stage resection + ostomy, or two-stage resection are recommended for those who can be resected; palliative ostomy, stent implantation, etc. are performed for those who cannot be resected.

5.2. Surgical treatment of rectal cancer

5.2.1. Surgical principles

Abdominal exploration is the same as colon cancer; MDT is required to evaluate whether neoadjuvant therapy is needed for middle and low rectal cancer, and to preserve anal sphincter function as much as possible; follow the principles of TME to ensure negative circumferential resection margins; the distal intestinal margin is ≥1−2 cm from the tumor, and the distal mesorectal margin is ≥5 cm.

5.2.2. Treatment for different stages

cT1N0M0: The principle of treatment is the same as for early colon cancer. Transanal local resection needs to meet the conditions of tumor <3 cm, invasion of intestinal circumference <30%, resection margin distance from the tumor >3 mm, distance from the anal margin <8 cm and high-moderate differentiation, etc. Transanal endoscopic microsurgery/transanal minimally invasive surgery (TEM/TAMIS) technology can expand the applicable range from the anal margin.

cT2−4N0−2M0: Radical surgery is recommended, and the upper rectal cancer is resected according to the principles of colon cancer; patients with preoperative cT3−4 or N+ in middle and low rectal cancer are advised to have neoadjuvant therapy (radiochemotherapy, immunotherapy, etc.); for patients with tumors invading surrounding organs, neoadjuvant/conversion therapy should be performed to strive for combined organ resection; the treatment of obstructed patients is the same as that of colon cancer; laparoscopic and robot-assisted surgery can be selected, and TAMIS, NOSES and other surgical methods can be performed when the indications are strictly followed; for those with cCR after neoadjuvant therapy, the “Watch & Wait” strategy can be considered after MDT evaluation.

5.3. Surgical treatment of anal canal cancer (New chapter)

Surgical treatment of anal canal adenocarcinoma refers to the treatment principles of low rectal cancer; anal canal squamous cell carcinoma is not within the scope of this guideline. The surgery needs to be combined with the location of the tumor, the depth of invasion, and the patient’s condition to choose local resection, abdominoperineal resection, or combined organ resection, and preoperative or postoperative radiochemotherapy is necessary.

6. Medical oncology treatment

6.1. General principles of treatment

Clarify the purpose of treatment (neoadjuvant, adjuvant, palliative treatment); complete baseline imaging evaluation and molecular marker detection before treatment; evaluate efficacy and adverse reactions in time during treatment, and adjust the plan under MDT guidance; pay attention to improving quality of life and treating complications.

6.2. Neoadjuvant therapy

6.2.1. Neoadjuvant therapy for rectal cancer

dMMR/MSI-H rectal cancer: Neoadjuvant immune checkpoint inhibitor therapy can be considered under MDT guidance. The decision to proceed with radiochemotherapy and/or surgery should be based on the response to immunotherapy (5).

Proficient MMR/microsatellite stable (pMMR/MSS) rectal cancer: Direct surgery is performed for T1−2N0M0 or those with contraindications to radiochemotherapy; for those with difficulty in preserving the anus and a strong desire to preserve the anus, evaluate whether surgery is needed after radiochemotherapy; for those with T3 and/or N+, recurrence risk is evaluated by MDT, and high-risk patients should undergo neoadjuvant therapy; for T4 stage or unresectable patients, neoadjuvant radiochemotherapy should be performed before evaluating surgical feasibility.

Chemotherapy regimen: includes long-term radiotherapy with concurrent capecitabine monotherapy, 5-fluorouracil (5-FU) continuous infusion, etc.; those who are not suitable for radiotherapy should undergo simple neoadjuvant chemotherapy.

6.2.2. Neoadjuvant therapy for T4b colon cancer

Locally unresectable patients: pMMR/MSS patients should receive chemotherapy or chemotherapy combined with targeted therapy, and local radiotherapy should be added if necessary. dMMR/MSI-H patients can consider immune checkpoint inhibitors under the guidance of MDT.

Initially resectable patients: Patients can choose direct surgery or neoadjuvant therapy followed by surgery after evaluated by MDT.

6.2.3. Neoadjuvant therapy for liver/lung metastasis of colorectal cancer

Radically resectable metastasis: Neoadjuvant therapy can be performed under MDT guidance, PD-1±CTLA-4 monoclonal antibody for dMMR/MSI-H patients, and chemotherapy ± targeted therapy for pMMR/MSS patients, with a treatment duration of 2−3 months.

Unresectable metastasis: Managed according to palliative treatment, and evaluate whether it can be transformed into resectable metastasis every 6−8 weeks. Those who are successfully transformed should undergo radical local treatment.

6.3. Adjuvant therapy

Stage I colorectal cancer (T1−2N0M0): Adjuvant therapy is not recommended.

Stage II colon cancer:

No high-risk factors: Follow-up observation or single-agent fluoropyrimidine chemotherapy is performed.

With high-risk factors (poor differentiation and pMMR or MSS, T4 stage, vascular/nerve invasion/high-grade budding, preoperative intestinal obstruction/perforation, less than 12 lymph nodes detected, positive or unassessable margins): Adjuvant chemotherapy is recommended, the regimen is CapeOx, FOLFOX or single-agent 5-FU/LV, capecitabine, with a course of 3−6 months.

dMMR/MSI-H patients: Adjuvant chemotherapy is not recommended.

Microscopic residual tumor detection can be considered to appropriately adjust adjuvant treatment decisions.

Stage II rectal cancer: See the Radiotherapy chapter for adjuvant radiotherapy.

Stage III colorectal cancer: Adjuvant chemotherapy is recommended, the regimen is CapeOx, FOLFOX or single-agent capecitabine, 5-FU/LV; low-risk patients (T1−3N1) can consider a 3-month CapeOx regimen.

Adjuvant radiochemotherapy for rectal cancer: For those who have not undergone neoadjuvant radiotherapy before surgery, adjuvant radiochemotherapy can be performed for postoperative pathological stage II−III, and chemotherapy is based on fluoropyrimidines.

6.4. Systemic therapy for recurrent/metastatic colorectal cancer

dMMR/MSI-H patients: Those who have not received immune checkpoint inhibitors are recommended to receive PD-1±CTLA-4 monoclonal antibody therapy.

pMMR/MSS patients:

First- and second-line treatment: Patients who can tolerate chemotherapy can receive combination chemotherapy ± targeted therapy, such as FOLFOX/FOLFIRI + cetuximab (RAS/NRAS/BRAF wild-type), FOLFIRI + cetuximab β (RAS/NRAS/BRAF wild-type) and CapeOx/FOLFOX/FOLFIRI + bevacizumab. FOLFOXIRI ± targeted therapy can also be considered.

Maintenance treatment: Patients with stable disease after 4−6 months of palliative treatment can receive 5-FU/LV or capecitabine ± targeted therapy or suspend treatment.

Third-line and above treatment (or drugs that are resistant to fluoropyrimidines, oxaliplatin, and irinotecan): Regorafenib, fruquintinib, and trifluridine tipiracil can be selected, and cetuximab + irinotecan can be considered for RAS/NRAS/BRAF wild-type patients (6).

NTRK-fusion patients: NTRK inhibitors are given after standard treatment fails.

Local recurrence: MDT evaluates whether to resect again, radiotherapy and other local treatments, and those who are only suitable for systemic treatment are treated according to the principles of advanced patients.

6.5. Best supportive care

Best supportive care includes pain management (three-step treatment), nutritional support (priority for enteral nutrition), mental and psychological intervention, etc., throughout the entire treatment process.

7. Radiotherapy

7.1. Indications for radiotherapy

Rectal cancer radiotherapy/radiochemotherapy mainly includes neoadjuvant/adjuvant therapy, radical therapy, conversion therapy and palliative therapy.

Stage I rectal cancer: For those with difficulty in preserving the anus and a strong desire to preserve the anus, radiochemotherapy followed by “Watch & Wait” or surgery can be considered; for those with high-risk factors after local resection and surgery is impossible, concurrent radiochemotherapy + “Watch & Wait” can be performed.

Stage II−III rectal cancer neoadjuvant radiochemotherapy: This is mainly applied to middle and low rectal cancer (tumor lower edge distance from the anal margin ≤10 cm). Treatment is stratified according to MMR/MSI status and recurrence risk, and total neoadjuvant therapy (TNT) model or combined immune checkpoint inhibitors can be used for high-risk recurrent patients (7).

Neoadjuvant immunotherapy: Immune checkpoint inhibitors are recommended for dMMR/MSI-H patients; pMMR/MSS patients can undergo radiochemotherapy + PD-1/PD-L1 monoclonal antibody or participate in clinical studies after complete communication.

Adjuvant radiochemotherapy: For stage II−III rectal cancer that has not undergone neoadjuvant radiotherapy before surgery, treatment is stratified according to recurrence risk.

“Watch & Wait” strategy: For low rectal cancer patients who achieve cCR (digital rectal examination, endoscopy, pelvic MRI are all up to standard) 8−12 weeks after radiochemotherapy, “Watch & Wait” strategy can be performed, and follow-up every 2−3 months for the first 2 years.

Stage IV rectal cancer: MDT evaluates the order of local and systemic treatment for synchronous metastasis; local destructive treatment or palliative symptom-reducing radiotherapy can be considered for metachronous metastasis.

Local regional recurrent rectal cancer: Preoperative radiochemotherapy followed by surgery can be performed for those who have not received radiotherapy in the past; the risk of second-course radiotherapy should be carefully evaluated for those who have received radiotherapy in the past.

7.2. Radiotherapy specifications

7.2.1. Radiotherapy technology

Intensity-modulated radiotherapy is recommended, and volumetric modulated arc therapy can be performed for those with conditions permit; 3D image-guided radiotherapy is used, and routine radioactive particle implantation is not recommended.

7.2.2. Target area definition

Gross tumor volume (GTV): Includes rectal primary tumor, EMVI-positive areas and positive lymph nodes.

Clinical tumor volume (CTV): GTV + high-risk recurrence area of the primary tumor (tumor/tumor bed, mesorectal area, presacral area) + regional lymph drainage area (mesorectal area, internal iliac, obturator area).

Planning tumor volume (PTV): Formed by expanding the CTV, covering organ movement and positioning errors.

Organs at risk: Small intestine, colon, bladder, femoral head, external genitalia, etc., need to limit the radiation dose.

7.2.3. Radiotherapy dose and fractionation mode

Short-term radiotherapy: 5 Gy × 5 times, surgery can be performed within 1 week or sequential chemotherapy after surgery.

Long-term radiochemotherapy: DT 45.0−50.4 Gy, 1.8−2.0 Gy each time, 25−28 times in total, concurrent chemotherapy with fluoropyrimidine single agent or capecitabine + irinotecan.

Postoperative adjuvant radiotherapy: DT 45.0−50.4 Gy, 1.8−2.0 Gy each time, 25−28 times in total, concurrent fluoropyrimidine chemotherapy; local boost 10.0−15.0 Gy can be performed for positive margins.

Re-irradiation: Super-fractionated or conventional fractionation is used, with a total dose of 30.0−40.0 Gy, for the purpose of palliative symptom reduction or increasing the resection rate.

7.2.4. Radiotherapy and surgical interval

Surgery is performed within 1 week after short-term radiotherapy or sequential chemotherapy; 5−12 weeks after long-term radiochemotherapy; the interval can be extended to 16−24 weeks for high-risk recurrent patients or those who need to preserve the anus.

7.3. Principles of radiochemotherapy combination

Concurrent chemotherapy regimen: Long-term radiotherapy with concurrent capecitabine monotherapy, 5-FU continuous infusion, etc., or capecitabine + irinotecan (UGT1A1 gene typing guides the dose); concurrent chemotherapy or targeted therapy is not recommended for short-term radiotherapy; bevacizumab, cetuximab, etc. are not recommended to be added to preoperative concurrent radiochemotherapy.

Interval chemotherapy: Sequential chemotherapy ± PD-1/PD-L1 monoclonal antibody after long-term radiochemotherapy or short-term radiotherapy, the regimen is FOLFOX, CapeOx, etc., with a course of 2−6 cycles.

Order of postoperative adjuvant radiochemotherapy: Concurrent radiochemotherapy followed by adjuvant chemotherapy or “sandwich” mode (1−2 cycles of adjuvant chemotherapy + concurrent radiochemotherapy + adjuvant chemotherapy) is recommended.

7.4. Radiotherapy for metastatic lesions

MDT is required for radiotherapy of colorectal cancer metastatic lesions; stereotactic body radiation therapy (SBRT) (BED>100 Gy) can be used for radical treatment of liver, lung and other metastatic lesions, and has the advantages of non-invasive and high safety; palliative radiotherapy can relieve bone metastasis pain and intracranial pressure and other symptoms caused by brain metastasis.

8. Treatment of metastatic lesions

8.1. Treatment of liver metastasis

8.1.1. Initially radically resectable lesions

Neoadjuvant therapy: Recommended for those with no emergency in the primary lesion but with difficult resection of liver metastatic lesions or those with high-risk factors for recurrence.The regimen is the same as medical oncology treatment.

Local treatment: Includes surgical resection (sufficient liver function needs to be preserved, resection margin ≥1 mm), radiofrequency/microwave ablation (metastatic lesions <3 cm, ≤3 lesions at a time) and SBRT (BED>100 Gy). Liver transplantation can be performed for those with conditions permit.

8.1.2. Potentially resectable lesions

MDT formulates regimens of chemotherapy + targeted therapy regimen, and evaluates after treatment. Those who are transformed into resectable ones are treated according to the above regimen, and those who are still unresectable are treated palliatively.

8.1.3. Unresectable lesions

No emergency in the primary lesion: Perform systemic therapy, or resect the primary lesion first and then deal with the metastatic lesions.

Emergency in the primary lesion: Resect the primary lesion first, and then perfoem systemic chemotherapy.

Local treatment: Includes blation therapy, radiotherapy, hepatic arterial infusion (HAI), transarterial chemoembolisation (TACE), etc.

8.2. Treatment of lung metastasis

8.2.1. Resectable lesions

Neoadjuvant/adjuvant therapy: Refer to the liver metastasis guidelines.

Local treatment: Includes surgical resection (wedge resection, pulmonary segment/lobectomy, etc., minimally invasive preferred), radiofrequency ablation (metastatic lesions <3 cm, far from large blood vessels) and SBRT (BED>100 Gy).

Recurrent metastatic lesions: Secondary or multiple resections can be performed when conditions permit.

8.2.2. Unresectable lesions

Refer to the treatment principles of unresectable liver metastasis, with systemic therapy as the mainstay, and combined with local palliative treatment if necessary.

8.3. Other metastasis treatment

Peritoneal metastasis: Systemic therapy + local treatment (CRS+HIPEC) needs to be evaluated and implemented by MDT in experienced centers.

Ovarian metastasis: Surgical resection of bilateral ovaries is preferred, followed by systemic therapy; CRS+HIPEC can be performed for those with other metastases.

Brain metastasis: Surgical resection + whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) is recommended for single metastasis; surgical resection of lesions with obvious occupying effects + WBRT can be considered for multiple metastases; glucocorticoids are recommended to relieve cerebral edema, and antiepileptic treatment is performed for patients with epilepsy.

Bone metastasis: Comprehensive treatment, including surgery (prevention/treatment of pathological fractures and nerve compression), radiotherapy (relieving pain), bisphosphonates/denosumab, systemic therapy, etc. is selected.

9. Treatment of local recurrent rectal cancer

9.1. Typing

It is divided into central type, anterior type (involving the genitourinary system), posterior type (involving the sacrum and presacral fascia), and lateral type (involving the pelvic wall soft tissue or bony pelvis).

9.2. Treatment principles

Comprehensive evaluation of MDT is needed. Initially resectable patients are mainly treated with surgery combined with perioperative radiochemotherapy; initially unresectable patients undergo radiochemotherapy and/or systemic treatment before re-evaluating resectability.

9.3. Surgical treatment

Resectability evaluation: Preoperative evaluation of the possibility of radical resection, intraoperative verification, and frozen pathology examination if necessary.

Surgical principles: En bloc resection, R0 resection should be achieved as much as possible; a plan in conjunction with urology, orthopedics and other MDTs should be made; protect the ureter and urethra.

Surgical methods: Abdominoperineal resection (APR), low anterior resection (LAR), pelvic exenteration (PE), etc. are selected according to the type, and PE can be performed for those who invade multiple organs.

9.4. Principles of radiotherapy and medical oncology treatment

Preoperative concurrent radiochemotherapy followed by surgery is recommended for those who have not received radiotherapy in the past; routine radiotherapy is not recommended for those who have received radiotherapy in the past, and individualized regimens are made after MDT evaluation; the perioperative drug treatment is determined according to the previous treatment history for initially resectable patients; MDT decides the regimen of radiochemotherapy and/or systemic treatment for initially unresectable patients.

10. Ostomy rehabilitation treatment

10.1. Personnel and structure

Hospitals with conditions permit are equipped with full-time ostomy therapists who are responsible for ostomy care, wound treatment, and patient education.

10.2. Preoperative care

Psychological treatment: Explain the condition, surgery and nursing knowledge to patients and their families to relieve anxiety.

Ostomy positioning: Positioning is chosen together by physicians, ostomy therapists, patients and their families, ensuring patients to be able to observe by themselves, have enough paste area, and have no discomfort.

10.3. Postoperative care

The blood transport and retraction of the ostomy is closely observed; lightweight, deodorant, and leak-proof ostomy products are chosen; keep the skin around the ostomy clean and dry; and be alert to fungal infections for those who use immunosuppressants and other drugs for a long time.

11. Follow-up

History, physical examination, and tumor markers (CEA, CA19-9) testing: Check once every 3 months for 2 years; once every 6 months for 5 years; once a year after 5 years.

Imaging examination: Chest, abdomen, and pelvic CT or MRI performed every half year for 2 years; once a year for 5 years; rectal MRI is preferred for follow-up after rectal cancer surgery.

Colonoscopy: Check within 1 year after surgery, and recheck within 1 year for abnormalities; recheck within 3 years for those without polyps; then once every 5 years, and all adenomas need to be removed once found; if the total colonoscopy has not been completed before surgery, it should be checked within 3−6 months after surgery.

PET/CT: Not routinely recommended, can be considered when recurrence or distant metastasis is suspected.

12. New technologies and advances in diagnosis and treatment of colorectal cancer (New section)

12.1. Liquid biopsy circulating tumor DNA (ctDNA) detection

ctDNA detection runs through the entire diagnosis and treatment process, and is divided into the tumor-unknown method (simple process) and the tumor-prior method (high sensitivity). Postoperative ctDNA positivity suggests an increased risk of recurrence and can guide adjuvant therapy; in metastatic patients, it can be used for RAS/BRAF typing and drug resistance monitoring to provide a basis for precision treatment (8).

12.2. Fluorescence laparoscopic technology

Based on indocyanine green (ICG) near-infrared imaging, it is used for lymphatic navigation, intestinal perfusion assessment and liver metastasis detection in colorectal cancer surgery, which can optimize lymph node dissection and resection margin selection, and reduce the risk of anastomotic leakage. At present, it is necessary to solve the problems of imaging stability and standardization (9).

12.3. FAPI imaging diagnosis

FAPI targets and binds to tumor-associated fibroblasts. It has significant imaging advantages in mucinous adenocarcinoma, peritoneal metastasis, etc. Compared with FDG, it has lower background and higher tumor/normal tissue ratio, which can accurately detect metastatic lesions, clarify tumor boundaries, and optimize radiotherapy target area delineation (10).

12.4. Pressurized intraperitoneal aerosol chemotherapy (PIPAC)

PIPAC drives atomized chemotherapy drugs through CO₂ pneumoperitoneum, which improves distribution uniformity and peritoneal penetration depth. The drug dose is only 10%−30% of that of HIPEC. Domestic high-pressure atomization systems have been independently developed, but their safety and effectiveness need to be verified by large-sample randomized controlled trials (RCTs).

12.5. One-stop radiotherapy and adaptive radiotherapy (ART)

One-stop radiotherapy, combining artificial intelligence (AI) algorithms, can complete scanning, delineation, and plan formulation within 30 min; ART dynamically optimizes target areas and doses based on real-time images to reduce irradiation to normal tissues. The two work together to improve the accuracy and timeliness of rectal cancer radiotherapy.

12.6. Application of SBRT in metastatic tumors

SBRT delivers high-dose irradiation to unresectable liver and lung metastases, with high local control rates. It can treat multiple sites of metastasis synchronously, and its efficacy is superior to thermal ablation for tumors adjacent to key structures, and toxicity is controllable.

12.7. Advances in precision drug therapy

dMMR/MSI-H stage III colon cancer: Chemotherapy combined with PD-L1 monoclonal antibody adjuvant therapy can be considered.

BRAF^V600E mutation patients: BRAF inhibitor + anti-EGFR monoclonal antibody ± MEK inhibitor is recommended.

HER2-high expression patients: Dual-target anti-HER2 therapy or antibody-drug conjugates can be selected.

KRAS^G12C mutation patients: G12C inhibitor ± anti-EGFR monoclonal antibody can be considered.

NTRK fusion, RET fusion, POLE/POLD1 mutation patients: Corresponding targeted drugs or immunotherapy can be selected.

13. Summary of five core modules

13.1. Surgical treatment

Taking radical resection as the core, surgical treatment emphasizes the TME principle and negative margins and promotes minimally invasive techniques such as laparoscopy and robots and NOSES procedures. A chapter on surgical treatment of anal canal cancer is added, optimizing the indications for local resection of early tumors and the combined surgical strategy of neoadjuvant therapy for advanced tumors, and the “Watch & Wait” strategy provides a possibility for organ preservation for some patients.

13.2. Medical oncology treatment

Molecular markers guiding individualized treatment is the core. The status of immunotherapy for dMMR/MSI-H patients is improved, and the combined regimens of targeted drugs (anti-EGFR, anti-VEGF monoclonal antibodies, etc.) and chemotherapy are continuously optimized. New third-line treatment drugs such as regorafenib and fruquintinib are added to expand the treatment options for rare targets such as NTRK inhibitors, and the concept of whole-course treatment runs through the whole process.

13.3. Radiotherapy

The concept of stratified treatment is further strengthened, and individualized programs are formulated according to tumor stage, recurrence risk, and MMR/MSI status. TNT regimens, chemoradiotherapy combined with immunotherapy, and other programs improve tumor regression rate and sphincter preservation rate. SBRT technology has expanded its application in the treatment of metastatic lesions, and the standardized implementation of the “Watch & Wait” strategy provides a new path for organ preservation.

13.4. Imaging diagnosis

The promotion of structured reports improves the degree of diagnostic standardization, and the core position of MRI in rectal cancer staging and efficacy evaluation is further consolidated. New technologies such as FAPI imaging and fluorescence laparoscopy supplement the shortcomings of traditional imaging, and PET/CT and PET/MRI provide more accurate means for detecting recurrence and metastasis, and the integration of imaging technology and clinical treatment is closer.

13.5. Pathological diagnosis

The scope of molecular detection is further expanded, MMR/MSI, KRAS, NRAS, and BRAF have become routine detection items, and HER2, NTRK and other target detection is gradually promoted; indicators such as tumor budding grading and TRG scores are included in the pathology report to provide more basis for prognosis evaluation and treatment decision-making; sample fixation and sampling standards are continuously standardized, and structured pathology reports improve the efficiency of diagnosis and treatment information transmission.

Expert group list

General consultant: Yan Sun

Consultant: Shu Zheng, Desen Wan

Leader: Jin Gu, Jianping Wang, Lin Shen, Ruihua Xu

Surgical group (listed alphabetically by last name)

Group leader: Sanjun Cai, Jin Gu, Jianping Wang, Xishan Wang, Suzhan Zhang

Members: Gong Chen, Kefeng Ding, Peirong Ding, Xuedong Fang, Baoqing Jia, Dalu Kong, Ping Lan, Qian Liu, Zhizhong Pan, Haiping Pei, Li Ren, Guiying Wang, Zhenning Wang, Ziqiang Wang, Xiaojian Wu, Yi Xiao, Baocai Xing, Jianmin Xu, Zhongfa Xu, Jin Yan, Yingjiang Ye, Zhongtao Zhang, Ren Zhao

Secretary: Ruoxu Dou, Yanxin Luo, Yifan Peng

Medicine group (listed alphabetically by last name)

Group leader: Jin Li, Lin Shen, Ruihua Xu

Members: Yi Ba, Chunmei Bai, Li Bai, Yanhong Deng, Tianshu Liu, Yunpeng Liu, Meng Qiu, Hongming Pan, Jia Wei, Jianming Xu, Xianglin Yuan, Ying Yuan, Yanqiao Zhang, Aiping Zhou, Jun Zhou

Secretary: Jian Li, Feng Wang, Xicheng Wang, Zhenghang Wang

Radiotherapy group (listed alphabetically by last name)

Group leader: Jing Jin, Zhen Zhang

Members: Yong Cai, Yuanhong Gao, Ning Li, Yongheng Li, Shixin Liu, Yuan Tang, Xiangbo Wan, Weihu Wang, Junxin Wu, Jinbo Yue, Hongyan Zhang, Ji Zhu, Li Zhu, Yuan Zhu

Secretary: Fan Xia, Yongjing Yang

Pathology group (listed alphabetically by last name)

Group leader: Zhiyong Liang

Members: Mulan Jin, Li Liang, Weiqi Sheng, Yan Sun, Weicheng Xue, Shuangmei Zou

Secretary: Weixun Zhou

Imaging group (listed alphabetically by last name)

Group leader: Yingshi Sun

Members: Zhenhui Li, Xiaochun Meng, Tong Tong, Juan Wang, Yi Wang, Tao Yu, Jianxin Zhang, Xiaoyan Zhang, Zhiyang Zhou

Secretary: Zhen Guan, Ruijia Sun

Secretary group (listed alphabetically by last name)

Group leader: Yanxin Luo, Yifan Peng

Members: Ruoxu Dou, Zhen Guan, Jian Li, Ruijia Sun, Feng Wang, Xicheng Wang, Zhenghang Wang, Fan Xia, Yongjing Yang, Weixun Zhou

Translation group: Jin Gu, Yong Yang

Correspondence to: Jin Gu. Peking University Cancer Hospital, No. 52 Fucheng Road, Beijing 100142, China. Email: zlguj@bjmu.edu.cn; Jianping Wang. The Sixth Affiliated Hospital, Sun Yat-sen University, No. 26 Yuan Cun Er Heng Road, Guangzhou 510655, China. Email: wjp@mail.sysu.edu.cn.

Conflicts of Interest: The expert group members have no conflicts of interest to decare.