NCCN Clinical Practice Guidelines for Colorectal Cancer Update In recent years, the treatment of colorectal cancer has progressed very rapidly. In this article, the 2008 edition of the NCCN Clinical Practice Guidelines for Colorectal Cancer (hereinafter referred to as the Guidelines) is interpreted in the light of the current situation and hot spots of colorectal cancer treatment, hoping to provide some reference for the clinical work of medical practitioners. Pathological staging The 2008 edition of the Guidelines adopts the sixth edition of the American Joint Committee on Cancer (AJCC) tumor staging criteria. The most important feature of this staging is that stage II and III patients are divided into IIA (T3N0M0), IIB (T4N0M0) and IIIA (T1~2N1M0), IIIB (T3~4N1M0) and IIIC (TxN2M0) respectively, which makes the selection of treatment plan more targeted. According to the Surveillance, Epidemiology and End Results (SEER) database in the United States, among 119,363 colon cancer patients seen from 1991 to 2000, the 5-year survival rates for different stages were 93.2% (stage I), 84.7% (stage IIA), 72.2% (stage IIB), 83.4% (stage IIIA), 64.1% (stage IIIB), 44.3% (stage III The 2008 edition of the Guidelines takes a relatively conservative approach to laparoscopic resection of colon cancer, suggesting that it should be performed by experienced laparoscopists and considered for patients without significant intra-abdominal adhesions, acute bowel obstruction or perforation caused by tumor, and relatively early lesions. The Guidelines clearly state that laparoscopic resection of rectal cancer should only be used for clinical research and is not advocated for routine clinical practice. For low-stage rectal cancer (T1/T2), local resection (including transanal endoscopic resection) can be one of the curative methods. The Guidelines put forward more specific criteria for local resection: T1 or T2, tumor occupying <30% of the bowel circumference, tumor <3>3 mm, no clear lymph node metastasis in preoperative examination, tumor <8 cm from the anus, etc. Local resection of T2 tumor should be chosen with great caution because it has a high rate of local recurrence. Local resection can preserve anal function and reduce the occurrence of complications, but several studies have shown that its survival rate is lower than that of open surgery, so the Guidelines recommend that local resection should be chosen carefully after comprehensive consideration. Liver metastasis from colorectal cancer is one of the most vulnerable sites for colorectal cancer metastasis. Without resection of liver metastases, the 5-year survival rate is almost zero, and those who undergo resection of metastases have reported a maximum 5-year survival rate of 50%. Therefore, selecting suitable patients for resection of liver metastases is one of the most important measures to improve the outcome of stage IV colorectal cancer. The current emphasis on radical liver metastasectomy is to achieve negative margins as much as possible while preserving sufficient residual liver. The 2008 edition of the Guidelines does not recommend partial resection of metastases, nor does it recommend radiofrequency ablation for those who are suitable for surgical resection, and metastasectomy is not suitable for those with extrahepatic lesions, and hepatic artery embolization is only applicable in clinical trials. 3. chemotherapy Adjuvant chemotherapy The choice of treatment options for stage II colon cancer has been controversial. The 2008 edition of the guidelines recommends adjuvant chemotherapy after surgery for stage II colon cancer with high-risk factors (T4, obstruction, perforation, poor differentiation, negative margins, <12 sampled lymph nodes, or lymphovascular, vascular and nerve invasion). Stage II patients without high-risk factors can participate in clinical trials or be followed up only periodically after surgery. The Guidelines clearly state that adjuvant chemotherapy can improve the survival rate of patients with stage II colon cancer by <5%, and therefore the patient's wishes, adverse drug reactions and relevant socioeconomic factors should be taken into consideration when choosing adjuvant chemotherapy regimens. Although the number of lymph nodes to be sampled is related to the patient's age, gender, tumor site and histological grade, the Guidelines still recommend sampling at least 12 lymph nodes, and for cases with less than 12 lymph nodes, retesting is recommended to try to detect 12 lymph nodes. The 2008 edition of the Guidelines clearly recommends adjuvant chemotherapy for stage III colon cancer with positive lymph nodes. The FOLFOX regimen is recommended for stage III and stage II patients with high-risk factors; FLOX can be used as an alternative to FOLFOX, but studies have shown that the former has a higher incidence of 3rd to 4th degree diarrhea than the latter. Capecitabine alone has comparable efficacy to the 5-FU/CF regimen in stage III colon cancer and may be an option. The Guidelines do not recommend the FOLFIRI regimen for use in the adjuvant chemotherapy of stage III colon cancer. There is also insufficient evidence to confirm the efficacy of a multi-drug combination regimen containing capecitabine in adjuvant chemotherapy for stage III colon cancer. Neoadjuvant chemotherapy is increasingly being used for metastatic colorectal cancer, especially for hepatic metastases from colorectal cancer. However, recent studies have confirmed that after neoadjuvant chemotherapy for colorectal cancer with liver metastases, a significant proportion of patients in complete remission on CT still do not achieve pathologic complete remission, and therefore the 2008 edition of the Guidelines recommends that the effect of neoadjuvant chemotherapy should be evaluated more frequently to facilitate early surgical resection. The neoadjuvant chemotherapy regimens recommended in the Guidelines for metastatic colorectal cancer include FOLFIRI, FOLFOX, and CapeOX (capecitabine + oxaliplatin). Because the safety of bevacizumab in neoadjuvant chemotherapy has not been proven and can affect wound healing, the Guidelines recommend that surgery should be started at least 6 weeks after bevacizumab is discontinued. The 2008 edition of the Guidelines still recommends bevacizumab in combination with FOLFOX, FOLFIRI, CapeOX and 5-Fu/CF as first-line chemotherapy for metastatic colorectal cancer. For metastatic colorectal cancer that has progressed after first-line treatment without bevacizumab, there are studies in Europe that support bevacizumab in combination with FOLFOX as a second-line treatment option. The Guidelines do not recommend bevacizumab monotherapy. In the 2008 edition of the Guidelines, there is more scope for cetuximab. The Guidelines recommend cetuximab + irinotecan for second-line treatment of progression after first-line treatment with bevacizumab + FOLFOX or bevacizumab + FOLFIRI, with cetuximab monotherapy as an option if second-line treatment fails. The use of panitumumab in metastatic colorectal cancer is just beginning, and currently the Guidelines only recommend its use as a single agent, but the NCCN panel allows its use as an alternative to cetuximab monotherapy in second- or third-line treatment of metastatic colorectal cancer. 5. radiotherapy and radiochemotherapy Radiotherapy and/or radiochemotherapy play an important role in the treatment of rectal cancer, and preoperative neoadjuvant radiotherapy or radiochemotherapy is increasingly used in locally advanced rectal cancer. The 2008 edition of the Guidelines recommends the use of radiotherapy in neoadjuvant and adjuvant treatment, rather than radiotherapy alone. For T3-4 locally advanced rectal cancer, the Guidelines recommend preoperative neoadjuvant radiotherapy as the standard of care when conditions permit. For T3N0 and TxN1~2 rectal cancer, direct surgery is only considered when there is a contraindication to preoperative multidisciplinary treatment. Since the use of radiotherapy will significantly increase the adverse effects, the Guidelines also cautiously state in the Supplementary Note that surgery combined with postoperative adjuvant chemotherapy may be an option for high-grade T3N0M0 rectal cancer with low risk of recurrence. For stage T4 and locally unresectable rectal cancer, the Guidelines suggest that surgical resection should be considered after neoadjuvant radiotherapy if possible, and postoperative adjuvant chemotherapy should be administered for 6 months regardless of the pathological results. The widespread implementation of neoadjuvant chemotherapy for rectal cancer is mainly due to the advancement of imaging technology. The Guidelines emphasize the integrated use of multiple preoperative imaging tests (e.g., endoluminal ultrasound, rectal MRI and CT) to obtain the most accurate preoperative staging so that oncologists can select different treatment plans for different stages. Endorectal ultrasound is currently considered to be the most accurate means to determine T and N stages, and rectal MRI has the best value for rectal cancer invading the rectal mesentery, so the guideline recommends physicians to consider all aspects when choosing. Regarding postoperative follow-up, the 2008 edition of the Guidelines is basically similar to the 2007 edition, especially PET is still not recommended as a routine postoperative follow-up. During postoperative follow-up, PET may be considered to clarify the presence or absence of metastases if the carcinoembryonic antigen (CEA) is persistently elevated but no obvious metastases are detected by conventional imaging. For colorectal cancer with simultaneous metastases, if complete resection of metastases is initially evaluated, PET examination can be considered to exclude metastases from other sites.