It is generally believed that the anatomical length of the rectum is 15-400 px, and traditional surgical segmentation divides the rectum into upper, middle and lower segments, and refers to the middle and lower rectal cancer as middle and low rectal cancer. Current studies have shown that there are significant differences between tumors within 300px from the anal verge and those above 300px in terms of surgical resection principles, comprehensive treatment strategies, and local recurrence rates. Therefore, the NCCN guidelines now define rectal cancer as cancerous lesions within 300px of the anal verge at rigid proctoscopy, which is the traditional definition of low- to intermediate-grade rectal cancer.
Surgical resection has long played the most important role in the treatment of rectal cancer. In recent years, with the emergence of new means and new concepts such as accurate preoperative staging, TME, minimally invasive laparoscopic treatment, neoadjuvant chemotherapy, targeted therapy and multidisciplinary comprehensive treatment, the treatment strategy of rectal cancer has been greatly changed. At this stage, China has made some achievements in the diagnosis and treatment of rectal cancer, but there is still a big gap from the international advanced level. On the one hand, it is related to the high proportion of patients with middle and late stage rectal cancer in China, but it is undeniable that the irregularity of diagnosis and treatment is also an important reason.
I. Preoperative staging
The prerequisite for standardized treatment is standardized preoperative diagnosis. The diagnosis of rectal cancer includes four aspects: characterization, localization, quantification and staging of lesions. At present, most domestic medical institutions can routinely carry out preoperative characterization and localization, but preoperative tumor TNM staging needs to be vigorously promoted in order to improve the standardization of treatment.
The main imaging methods for preoperative staging of rectal cancer are rectal endoscopic ultrasound, pelvic MRI and thoracoabdominopelvic CT scan, which should be selected to obtain the most accurate preoperative staging; the main examination methods for T-stage assessment are rectal endoscopic ultrasound and MRI; rectal endoscopic ultrasound is particularly accurate for T1 and T2 tumor staging, but there is often a problem of over-staging for T3 and T4 tumors. MRI is more accurate for the evaluation of T3 and T4 stage tumors, and it can also accurately display the structure of each layer of the rectal wall and the soft tissue structure of the rectal mesentery, making it the best choice for preoperative prediction of the circumferential margin for progressive rectal cancer. For the preoperative evaluation of N-stage, none of the 3 imaging has more significant advantages, and all 3 have similar roles in lymph node staging. The distant metastases of rectal cancer are most commonly liver and lung metastases. For the evaluation of distant metastases, NCCN guidelines recommend CT scans of the chest, abdomen and pelvis, while PET-CT examination is still not recommended as a routine examination.
II. Surgical treatment
1. Local excision
For patients with stage T1 rectal cancer that invades the mucosal layer and involves the submucosal layer but does not invade the muscular layer, local resection through the anus has become an important treatment option, and most of them can achieve radical results. the indications for local resection in the NCCN guidelines are as follows.
1. Tumor infiltration depth is stage T1;
2.Tumor diameter less than 75px or less than 1/3 circumference;
3. Within 200px from the anal verge;
4. Tumor differentiation grade is high or moderate, and there is no evidence of regional lymph node metastasis. Although stage T1 tumor is an indication for local resection, a considerable number of patients with preoperative diagnosis of stage T1 have tumor invasion beyond the submucosa, and the rate of lymph node metastasis varies significantly among different depths of submucosal involvement, therefore, local resection for early stage rectal cancer should be used with caution, and the imaging and pathology level of the primary unit should be correctly measured when performing such surgery. For patients with positive deep or circumferential margins after resection, or with vascular or lymphatic infiltration or nerve infiltration, standardized radical surgery should be performed; for patients who insist on anus preservation, standardized radiotherapy should be given.
2.Total rectal mesenteric excision (TME)
In 1982, Professor Heald put forward the concept of TME, which is of great significance to reduce postoperative recurrence of rectal cancer and improve postoperative survival rate, and has become a surgical principle that must be followed in the radical surgery of low to medium rectal cancer. In the standardized surgery of rectal cancer in China, TME is still in the core position. TME emphasizes sharp separation under the view of the anterior sacral space to ensure the integrity of the pelvic fascia without breakage, and the resection of the distal rectal mesentery of the tumor should not be less than 125px; for middle rectal cancer, the distal 4-125px intestinal canal of the tumor should be resected, while for low rectal cancer less than 125px from the anal verge, intraoperative frozen pathology For low-grade rectal cancer less than 125px from the anal verge, the resection of 1-50px intestinal canal is acceptable if the margin is confirmed to be negative. The NCCN guidelines define a positive circumferential margin as a tumor less than 1 mm from the circumferential margin. on the premise of ensuring tumor eradication, the pelvic autonomic nerve should also be preserved to the maximum extent possible to reduce sexual function and urinary function of postoperative patients, especially male patients, and improve postoperative quality of life. The quality of life should be improved.
3.Anal preservation surgery
With the wide application of surgical anastomosis instruments, ultra-low anastomosis surgery has become simpler and the proportion of anus preservation has become higher and higher. However, whether anus preservation is possible for middle and low rectal cancer can no longer be based solely on the distance between the lower edge of the tumor and the anal edge. Anal preservation is not only a formal preservation of the anus, but also a comprehensive consideration of tumor eradication and functional aspects. In fact, it is very challenging to achieve tumor eradication while minimizing the impact on the patient’s quality of life. Before performing anal preservation surgery, we should consider the distance of the tumor from the anal margin, the stage and differentiation of the tumor, whether the distal margin is negative and whether the function of the anal levator muscle is intact, as well as the impact on the postoperative quality of life.
4.Laparoscopic surgery
Thanks to the results of the COST study, laparoscopic surgery for colon cancer has been recognized by the NCCN, but due to the lack of evidence support, the latest NCCN guidelines for laparoscopic rectal cancer surgery are still recommended to be limited to clinical studies. In fact, laparoscopic rectal cancer surgery has been widely performed in Asian countries such as Japan, Korea, and China, and the proportion of laparoscopic surgery in Japan and Korea is close to 50%. At present, laparoscopic surgery is considered to have the following advantages.
1.It truly achieves the principle of tumor non-contact;
2, with local magnification, clearer field of vision, exact identification of blood vessels and nerves, less bleeding, and lower incidence of complications of urinary and sexual functions;
3. Compared with open surgery, the operator can complete sharp freeing under direct vision, which is better to follow the principle of TME; 4. It has the advantage of video display, which is more conducive to the promotion of standardized surgical operation for rectal cancer. A large number of retrospective analyses also suggest that laparoscopic surgery is superior to open surgery in terms of patient recovery, while the effect of tumor radicalization is comparable to that of open surgery. It is believed that with the results of a series of well-designed multicenter randomized controlled studies, laparoscopic surgery is expected to become the standard procedure for low to medium rectal cancer.
5.Lateral lymph node dissection
Lateral lymph node dissection has been a hot topic of controversy among scholars in the East and West. Japanese scholars advocate lateral lymph node dissection, while European and American scholars are less likely to perform lateral dissection. A Meta-analysis of 20 clinical studies showed that patients with rectal cancer who underwent lateral lymph node dissection had no statistically significant differences in 5-year survival, disease-free survival, local recurrence and distant metastasis rates compared with those who underwent TME alone, but had a significantly higher risk of sexual and urinary dysfunction. In contrast, Japanese scholars organized the only multicenter randomized controlled study to date, and preliminary results showed that the lymph node positivity rate for combined lateral lymph node dissection was 7%, and increased in terms of operative time, intraoperative blood loss and complication rate compared to the TME alone group, while the results of local recurrence rate are inconclusive at present.
III. Neoadjuvant therapy
The risk of local recurrence after rectal cancer surgery is high, therefore, the purpose of adjuvant therapy is to control local recurrence, therefore, radiotherapy plays an important role in the treatment of rectal cancer. It has been confirmed that for patients with surgically resectable rectal cancer, preoperative simultaneous radiotherapy compared with preoperative radiotherapy alone can significantly improve the pathological complete remission rate and reduce the risk of recurrence of seizure and pathological stage, although there is no significant improvement in the long-term survival rate of patients. Some experts compared the group of patients with surgically resectable stage II and III rectal cancer who received preoperative concurrent radiotherapy with the group who received postoperative concurrent radiotherapy, and the results showed that the two groups were similar in terms of long-term survival rate, but the preoperative concurrent radiotherapy group had significant advantages in terms of local recurrence and preservation of the anus. Based on this, for surgically resectable stage II and III rectal cancer, the multidisciplinary combination of preoperative simultaneous radiotherapy, TME, and postoperative adjuvant chemotherapy has become the best treatment mode and has been recommended by NCCN guidelines. Surgery should not be preferred unless patients have complications such as bleeding, obstruction, or contraindications to neoadjuvant therapy.
Preoperative simultaneous radiotherapy has the following advantages.
1. Preoperative tumor tissue is rich in blood supply, which is more sensitive to radiotherapy and has more accurate efficacy;
2.It can reduce the tumor stage and improve the radical resection rate and anus preservation rate;
3.It can avoid the damage of small intestine caused by postoperative radiotherapy;
4.It can reduce the local recurrence rate after surgery. For preoperative radiotherapy, most scholars advocate controlling the pelvic dose at 45.0 Gy or 50.4 Gy with 25 or 28 consecutive radiotherapy sessions, and then proceeding to surgery after 5-10 weeks interval after the completion of 5.5 weeks of radiotherapy and chemotherapy. In contrast, European scholars prefer a short course of radiotherapy (25 Gy/5d) with surgery 1 week after the completion of radiotherapy. Compared with conventional radiotherapy, short-course radiotherapy seems to be more effective for local control, while it is not significant for tumor downstaging. Therefore, short-course radiotherapy may be more suitable for patients with resectable tumors.
The NCCN guidelines recommend both capecitabine and fluorouracil (5-FU) infusion radiotherapy as Class I and preferably for patients with stage II and III rectal cancer. The two-drug regimen of oxaliplatin plus capecitabine or 5-FU in concurrent radiotherapy did not show significant advantages compared with the single-drug regimen of capecitabine or 5-FU, and the adverse effects were significantly increased. Therefore, single-agent regimens of capecitabine or 5-FU remain the current standard chemotherapy regimen for preoperative concurrent radiotherapy of rectal cancer. For patients with combined resectable distant metastases, there is an obvious risk of insufficient therapeutic intensity in single-agent-based concurrent radiotherapy regimens, and concurrent radiotherapy with oxaliplatin plus capecitabine or 5-FU still has greater clinical value.
Of course, there are certain problems in the implementation of neoadjuvant radiotherapy. First of all, preoperative neoadjuvant radiotherapy requires high cost and good patient compliance, and it is still doubtful whether many patients in China will accept neoadjuvant radiotherapy because of economic factors, and about 1/3 of patients are not sensitive to neoadjuvant radiotherapy, which causes waste of medical resources and also delays the best treatment time. This also suggests that the research on the sensitivity of neoadjuvant radiotherapy is of great significance.
IV. Multidisciplinary integrated treatment
In recent years, MDT (multidisciplinary treatment model) has been a major change in the treatment concept of rectal cancer. In some European and American countries, MDT has become a fixed mode of rectal cancer treatment. In China, some large tertiary hospitals and oncology hospitals in Beijing, Shanghai and Guangzhou also routinely carry out MDT treatment model and achieve good results. However, we still need to see several shortcomings clearly.
The proportion of medical centers that routinely carry out MDT is still too low, and there are few doctors who carry out treatment according to the traditional concept in the majority of primary hospitals, and many doctors’ treatment paths are not standardized enough, and even the phenomenon of turning individualized treatment into random treatment;
2. How to face up to the current situation and popularize the MDT concept and the way it is carried out in more medical centers in China so that more patients can benefit from it?
We believe that with the development of domestic multicenter randomized controlled studies and the continuous publication of data in the future, the diagnosis and treatment level of rectal cancer in China will be promoted and standardized treatment plan for rectal cancer will be produced in accordance with the national conditions of China, which will ultimately benefit the patients.