2011 NCCN Colorectal Cancer Clinical Practice Guidelines Update Explained
Deng Hong, Department of Oncology, Guangdong Provincial Hospital of Traditional Chinese Medicine
Liu Yinhua, Peking University First Hospital Yao Hongwei, Peking University Third Hospital
In 2006, the National Comprehensive Cancer Network (NCCN) was introduced to China under the initiative of Academician Sun Yan, and the content is updated annually. Despite the differences between us and western countries in terms of ethnic characteristics and medical system, the NCCN guidelines still receive great attention in the process of clinical cancer diagnosis and treatment in China, and at the end of 2010, the first Chinese Code of Practice for the Diagnosis and Treatment of Colorectal Cancer published by the Ministry of Health also absorbed part of the NCCN guidelines as an important reference and recommendation. Based on the latest evidence-based medical evidence, the 2011 NCCN guidelines related to colon and rectal cancer (v1 and v2) have been released one after another. The following is a personal view on the hot issues of the updates, in order to throw light on them.
The main contents of the updated 2011 edition of the Guidelines
Based on the latest published high-level evidence-based medical evidence and the broad consensus reached by relevant expert teams as the basis for recommendations, the 2011 NCCN guidelines for colon and rectal cancer have 14 and 16 updates, respectively, covering multidisciplinary diagnosis and evaluation, surgery, adjuvant chemoradiotherapy, advanced relief therapy, targeted drug therapy, etc. Given the different embryologic development and anatomic locations of the colon and rectum, as well as the numerous differences between colon and rectal cancers in both pathogenesis and diagnostic and treatment concepts, the NCCN guidelines have always described the two separately, and the author has also categorized the changes separately (Tables 1 and 2). However, due to the lack of clinical trials on chemotherapy regimens for rectal cancer only to date, recommendations for chemotherapy regimens for rectal cancer are more extrapolated from the results of colon cancer studies, and therefore the chemotherapy regimens and their updates in the NCCN Clinical Practice Guidelines for Colon Cancer and the NCCN Clinical Practice Guidelines for Rectal Cancer are almost identical. We would like to bring this to the attention of our colleagues.
Some hot issues to watch in 2011
Multidisciplinary assessment remains a priority
Comprehensive evaluation of the overall condition of patients and their local tumor status, and organization of multidisciplinary experts including colorectal surgery, liver surgery, medical imaging, oncology chemoradiotherapy, pathology, gastroenterology, general internal medicine, etc. to complete a collaborative assessment model with independent and autonomous indication of opinions is the key to achieve individualized diagnosis and treatment of colorectal cancer. The image of surgeons who can treat tumors by performing exquisite surgeries or “bloodbath” is being questioned, and the traditional thinking and treatment mode of surgery + adjuvant chemoradiotherapy is a glorious history.
Today, colorectal cancer has entered the era of “norms and guidelines” under the guidance of evidence-based medicine. However, we must reiterate that the prerequisite for any guideline to guide clinical practice is a multidisciplinary assessment of the patient’s whole body and its local conditions, and it is not scientific to copy the guidelines without thinking about them. The treatment process recommended by guidelines should not become a constraint or shackle for clinical practice, which should be “individualized” based on a reasonable grasp of “evidence-based” medicine. Based on the 7th edition of the American Joint Committee on Cancer (AJCC) TNM staging system, which was introduced in 2010, the staging of colorectal cancer has become more refined, which is the basis for precise treatment. Obtain accurate TNM staging. This is especially important for rectal cancer. This year’s guidelines still do not recommend positron emission tomography (PET)-CT as a routine test and for monitoring the efficacy of neoadjuvant and palliative therapies due to the lack of sensitivity in differentiating inflammation from tumor and the absence of studies to demonstrate the significance of quantitative functional imaging values, including standardized uptake values (SUVs).
Targeted therapies and related translational studies receive attention
The American Society of Clinical Oncology (ASCO), founded in 1964, is the world’s leading academic oncology organization, and the ASCO Annual Meeting is recognized as the world’s most important academic oncology meeting. Since 2005, ASCO has introduced an annual progress report to recognize the most important cancer research advances and achievements in the past year, and “only those studies that significantly change the way a cancer is treated or have a significant impact on patient care are selected. As of 2010, colorectal cancer-related projects selected for ASCO’s annual major research advances include: (1) postoperative chemotherapy reduces the recurrence rate of colorectal cancer (2005); (2) bevacizumab (anti-VEGF monoclonal antibody) improves survival in patients with colorectal cancer (2005); (3) adding cetuximab to the FOLFIRI regimen (5 fluorouracil + tetrahydrofolate + irinotecan) (anti-EGFR monoclonal antibody) to the FOLFIRI regimen (5 fluorouracil + tetrahydrofolate + irinotecan) improved the regression of colon cancer patients (2007); ④ cetuximab was selectively used in the treatment of KRAS gene wild-type colon cancer (2008); ⑤ adjuvant therapy with bevacizumab after surgery in colon cancer patients did not prevent recurrence (2009); and ⑥ BRAF gene mutation predicted poor prognosis in patients with metastatic colorectal cancer (2009).
Of the six major research advances mentioned above, five were related to targeted therapy. Therefore, colorectal cancer diagnosis and treatment has actually entered the era of “molecular typing” and “targeted therapy”, especially KRAS-BRAF gene testing has taken a pivotal role. 2009 NCCN Clinical Practice Guidelines for Colorectal Cancer In 2010, the NCCN Clinical Practice Guidelines for Colorectal Cancer recommended further testing for KRAS gene (V600E) mutation in patients with wild-type KRAS gene, and concluded that BRAF gene mutations do not appear to benefit from anti-EGFR monoclonal antibody therapy. Several retrospective studies have shown that anti-EGFR monoclonal antibodies in combination with effective chemotherapy appear to benefit patients in the first-line treatment of metastatic colorectal cancer, regardless of BRAF (V600E) mutation. However, in patients with metastatic colorectal cancer that has progressed after first-line treatment, there are insufficient studies to show that patients with BRAF(V600E) mutations are unresponsive to anti-EGFR monoclonal antibody therapy. Therefore, due to the lack of strong support from prospective studies, the 2011 edition of the NCCN Clinical Practice Guidelines for Colon/Rectal Cancer still recommends testing for KRAS-BRAF gene status, but has not yet made a recommendation to disable anti-EGFR monoclonal antibodies for patients with wild-type KRAS genes but mutated BRAF genes.
In recent years, although most of the KRAS-BRAF gene-related studies have completed the “magnificent transformation” from basic research to clinical application, and the translational studies have also achieved remarkable efficacy, as Academician Cheng Shujun has explained, tumor is a “molecular network disease”, and different targets and their conduction sites are the most important factors. However, as academician Cheng Shujun has explained, tumor is a “molecular network disease” and there are still many unknown aspects of different targets and their conduction pathways, so clinicians have reasons to continue to pay attention to the research progress of targeted therapy.
More detailed surgical treatment
Regarding the principles of surgical treatment, the updated points and concerns of the 2011 NCCN Clinical Practice Guidelines for Colon/Rectal Cancer are mainly focused on the following aspects: ① Minimally invasive techniques should be used rationally; ② Minimally invasive transanal endoscopic surgery is recommended for the first time for stage T1 rectal cancer; ③ Laparoscopic surgery is recommended for colon cancer with proven indications; ④ Laparoscopic rectal cancer surgery is still limited to clinical studies; ⑤ For local recurrent rectal cancer and The treatment of liver metastases is more aggressive and the status of surgery is further improved.
The indications for transanal surgery for rectal cancer are confirmed, and endoscopic minimally invasive techniques were recommended for the first time. 2009 NCCN Clinical Practice Guidelines for Rectal Cancer recommended that the indications for transanal surgery for rectal cancer are stage T1 and cautiously selected stage T2 cases, but the 2010 NCCN Clinical Practice Guidelines for Rectal Cancer strictly limited the indications to stage T1, and for cancers that meet the indications for transanal resection and can be adequately For cancers that are eligible for transanal resection and can be adequately visualized in the rectum, the recommended procedure in this guideline has been changed from “Minimally invasive transanal surgery may be considered” in 2010 to “Transanal endoscopic minimally invasive surgery (TEM) may be considered” in 2011. The advantages of TEM, which allows complete removal of the proximal rectal lesion, are incomparable to those of traditional open transanal surgery. In the author’s opinion, while it is important that the more minimally invasive TEM technique is recommended, it is even more important to use imaging methods to accurately evaluate and screen stage T1 rectal cancer before surgery, and even how to take further therapeutic measures when the postoperative pathological staging diagnosis confirms that the preoperative clinical stage is underestimated, which are also issues that need to be addressed through a multidisciplinary collaborative model.
The status of laparoscopic colon cancer surgery is clear, while rectal cancer is still limited to clinical research The 2011 NCCN Clinical Practice Guidelines for Colon/Rectal Cancer has exactly the same recommendations for laparoscopic-assisted resection of colon and rectal cancer as previous versions. Based on the COST study, a joint statement issued by the American Society of Colorectal Surgeons (ASCRS) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) in 2005 stated that for curable colon cancer, laparoscopic colectomy performed by experienced surgeons achieves the same oncology-related survival rates as open surgery, and the COST study was also the basis for the 2006 The COST study is also the most important evidence that the NCCN Clinical Practice Guidelines on Colon Cancer first established the status of laparoscopic colon cancer resection surgery in 2006. To ensure the standardization of the surgery, the NCCN still continues to impose harsh restrictions on laparoscopic surgery until 2011: the surgery should be performed by surgeons skilled in laparoscopic techniques, the abdominal cavity should be fully explored during the surgery, there are no abdominal adhesions that seriously affect the surgery, there are no locally advanced tumors, there are no acute obstruction caused by tumors, and there are no tumors in the abdominal cavity. Preoperative marking can be considered for those with acute bowel obstruction or perforation caused by tumor and small tumor. Due to the lack of evidence-based medical evidence on survival associated with high-grade tumors, the 2006-2011 NCCN Clinical Practice Guidelines for Rectal Cancer have from the beginning recommended that laparoscopic rectal cancer surgery be limited to clinical studies. As a region where laparoscopic radical rectal cancer surgery was carried out earlier and with more mature technology in China, major cities such as Beijing, Shanghai and Guangzhou should take advantage of their advantages and carry out relevant multicenter prospective randomized controlled studies under the coordination of professional academic organizations in order to obtain evidence-based medical evidence suitable for the national population.
Treatment strategies for locally recurrent rectal cancer The popularity of standardized total mesorectal excision (TME) surgery for rectal cancer and the introduction of neoadjuvant treatment concepts have significantly reduced the rate of local recurrence of rectal cancer after surgery, from 20% to 50% in the 1980s and 1990s to 5% to 10% in this century. However, local recurrence after radical surgery is still a major problem. Despite the poor prognosis of patients with local recurrence, their overall prognosis has gradually improved, thanks in large part to the fact that some patients have undergone repeat radical resection. 2011 NCCN Clinical Practice Guidelines for Rectal Cancer fully recognize and positively recommend the value of surgery. The guidelines recommend that the first option is to evaluate whether the lesion is resectable. For isolated pelvic recurrence or anastomotic recurrence, if the patient has not received previous chemoradiotherapy, 5-fluorouracil (5-FU) continuous infusion chemotherapy combined with radiotherapy is recommended first; if the lesion is evaluated as resectable, surgery is chosen; if the lesion is potentially resectable, the following treatment strategies are recommended: (i) surgical resection followed by adjuvant chemoradiotherapy; (ii) preoperative chemoradiotherapy followed by surgery. In the author’s opinion, for locally recurrent rectal cancer, more aggressive surgical treatment is important, but what is more important is how to evaluate its resectability. Optimization of preoperative staging diagnosis and reasonable selection of imaging examinations such as pelvic CT, MRI, transrectal endoluminal ultrasound and PET-CT are indispensable parts of evaluating resectability of locally recurrent rectal cancer and the key to further improving the prognosis of patients with local recurrence.
In the 2011 NCCN Clinical Practice Guidelines for Colorectal Cancer, the position of “liver resection as one of the treatment options” was adjusted from 5th to 1st among all treatment strategies for resectable liver metastases. This is not simply a shift in position, but should be seen as a renewal of treatment philosophy and a declaration of the centrality of surgical resection to all treatment options. The guidelines reiterate that the size, number, and distribution of metastases are no longer key factors affecting the resectability of liver metastases from colorectal cancer.
The indications for surgery for colorectal cancer liver metastases are as follows: (i) to ensure adequate postoperative residual liver function; and (ii) to enable resection of all lesions to achieve R0 resection. In contrast, the contraindications to surgery for liver metastases from colorectal cancer are: (i) insufficient postoperative liver remnants; (ii) inability to obtain R0 resection; and (iii) the presence of unresectable extrahepatic lesions. Similar to the pattern of diagnosis and treatment of locally recurrent rectal cancer, multidisciplinary evaluation of the resectability of liver lesions remains a prerequisite and basis for all local therapeutic approaches, including surgical resection. Supported by the results of numerous clinical studies based on evidence-based medicine, R0 surgical resection of liver metastases has become the norm, and its irreplaceability is becoming increasingly evident. Of course, at present, radiofrequency ablation, hepatic artery interventional embolization therapy and conformal external radiation radiotherapy should not be excluded for certain carefully selected cases of resectable liver metastases.
Diagram of colon cancer surgery
Preoperative clinical staging diagnosis based on imaging examination is the key to scientifically formulate the initial treatment decision of colorectal cancer, while pathological staging diagnosis based on postoperative histological examination becomes the basis for evaluating the efficacy, perfecting adjuvant therapy and even judging the prognosis. During my study in Japan in the early 1990s, I deeply felt that Japanese surgeons attached great importance to tumor pathological data. Back then, D4 debridement as one of the standardized gastric cancer procedures took about 4 hours, which was recognized by surgeons in China, but the pathology reading sessions, which also took 4 hours for clinical surgeons to examine the surgical resection specimens and were packed once a week, might be of less concern. Thus, it is not surprising that 100 lymph nodes can be detected in Japanese D2 surgery. Similarly, the 2009 AJCC 7th edition TNM staging update is not a fabrication, but is derived from the complete pathology data of the US National Cancer Data Center. Compared with advanced countries, there is no unified cancer database in China now, which is undoubtedly a great shortcoming.
The revision of the NCCN Clinical Practice Guidelines for Colorectal Cancer 2011 on the content of pathological examination reports of colorectal cancer specimens is regarded as one of the most important updates in this edition of the guidelines, which has further improved the standardization of pathological examination of colorectal cancer. 2010 guidelines require the content of pathological reports to include the degree of tumor differentiation, depth of tumor infiltration (T stage), number of detected lymph nodes and positive lymph nodes. In addition to the definition of positive circumferential margin as “tumor ≤1 mm from circumferential margin”, the 2011 guidelines also require the report to include In addition to the definition of positive circumferential margin as “tumor ≤1 mm from circumferential margin”, the 2011 guideline also requires the report to include “circumferential margin, evaluation of response to neoadjuvant therapy, vascular infiltration, perineural infiltration, and extra-lymph node tumor deposits”. In 2011, prognostic and predictive indicators were introduced as a basis for determining the likelihood of tumor recurrence after surgery and predicting the effectiveness of treatment. For example, positive circumferential margins, vascular infiltration, perineural infiltration and extra-lymph node tumor deposits are considered as indicators of high recurrence rate and poor prognosis, and these indicators also indicate the need for more aggressive and comprehensive adjuvant therapy after surgery, and the evaluation of neoadjuvant response can be an important reference for the selection of adjuvant therapy. Therefore, it is easy to see that a standardized pathology report plays a central role in the multidisciplinary diagnosis and treatment of colorectal cancer, which can judge the effectiveness of previous neoadjuvant and surgical treatments, guide the subsequent adjuvant and targeted treatments, and even predict the risk of recurrence and prognosis.
Outlook
Since the 21st century, the concept of colorectal cancer diagnosis and treatment has changed dramatically, and the NCCN guidelines, RECIST criteria and TNM staging have been updated one after another. The concept of neoadjuvant therapy and targeted therapy has been popularized, and genetic diagnosis and molecular pathology diagnosis have been transformed from laboratory research to clinical practice, and we have entered the era of “evidence-based medicine” from “empirical medicine”. As the backbone of colorectal cancer diagnosis and treatment, surgeons not only need to pursue the perfection of surgical skills, but also keep pace with scientific progress.
The recommendations of NCCN guidelines are derived from high-level evidence based on the population, and are the guideposts for diagnosis and treatment of colorectal cancer at various stages and with different disease characteristics, but no guidelines and norms can guide objective individuals, and many medical disputes are caused by the lack of comprehensive knowledge of the disease or the stereotypical copying of guidelines. Therefore, the true meaning of scientific understanding and application of guidelines is to follow the group “evidence-based” basis and reasonably guide the individual “cause-based” clinical practice activities.
This article is retrieved from: http://www.caca.org.cn/system/2011/07/13/010083075.shtml