Exploring the treatment strategy of rectal cancer from an individualized perspective
About 2/3 of colorectal cancer patients in China are rectal cancer patients. Although some progress has been made in the etiological study of rectal cancer and the comprehensive treatment based on surgical resection radiotherapy and chemotherapy, the treatment of rectal cancer still faces great challenges, and the overall 5-year survival rate of patients still needs to be further improved. Most doctors at home and abroad have started to pay attention to the standardized treatment of rectal cancer, but at the same time, we also found that there are individual differences in the treatment of rectal cancer, and the individual differences determine the different treatment effects, thus leading to the question of the relationship between standardized and individualized treatment of tumors.
I. Standardized and individualized treatment in the treatment of rectal cancer
At present, the treatment of rectal cancer basically has a systematic theoretical system and a set of relatively standard treatment principles and norms, and at the same time, every year various international professional societies issue updated clinical guidelines for rectal cancer, which are based on the standardized treatment of evidence-based medicine, and are obtained through statistics of large samples by using the incidence of clinical events, death rate and survival time per capita as the main efficacy observation indicators, It is a standardized guideline for the treatment of rectal cancer based on the overall assessment of the observed population.
However, the highest goal of medicine should be to achieve the best outcome for each patient. Therefore, standardized and individualized treatment of rectal cancer are two contradictory aspects, and standardization is the basis of tumor treatment, while individualized treatment in accordance with standardization is the higher level of rectal cancer treatment. The standardized treatment is the basis of tumor treatment, and the individualized treatment is the higher level of rectal cancer treatment.
In the development of individualized treatment plan for rectal cancer, doctors must first have a full understanding of the latest recognized evidence-based medical research results of rectal cancer, and carry out individualized treatment on the basis of standardization in order to reduce the blindness that exists to a greater or lesser extent in the development of individualized treatment plan, which is a necessary condition to improve the success rate of individualized treatment, and is based on the unification of standardization and individualized treatment on the basis of evidence-based medicine. This is a necessary condition to improve the success rate of individualized treatment, which is the experience of individualized treatment based on the unification of standardized and individualized treatment based on evidence-based medicine, and is the feedback to standardized treatment; it is both the evidence of new standardized treatment and the characteristics of individualized treatment plan, which is the supplement of individualized treatment to standardized treatment.
Preoperative clinical assessment is the basis of individualized treatment
Accurate determination of clinical stage of rectal cancer is crucial to the formulation of treatment plan, and is a prerequisite for the implementation of individualized surgical treatment. Clinical assessment of rectal cancer should include: (1) anal finger examination, which can help surgeons understand the location, size and activity of the tumor, and is sometimes the only criterion for surgeons to decide whether local resection is possible; (2) endoscopic examination, which can obtain a clear diagnosis of pathology, and can understand the morphology of the lesion and the presence of luminal stenosis or obstruction. (3) chest X-ray, abdominal B-mode ultrasound or CT examination for the presence of distant metastases; (4) transrectal intracavitary ultrasound or pelvic MRI examination to determine the size and extent of local lesion invasion and lymph node metastasis.
Our experience: the diagnostic compliance rate of rectal endoluminal ultrasound in diagnosing the depth of rectal cancer infiltration reached 79.3%, and the sensitivity of T1, T2, T3 and T4 stage diagnosis was 100% 58.8% 87.5% and 83.3%, respectively; while the sensitivity and accuracy of endoluminal ultrasound in diagnosing lymph node metastasis were 76.9% 75.0% and 75.9%, respectively; suggesting that endoluminal ultrasound has a positive effect on the depth of rectal cancer infiltration and peri-intestinal lymph node metastasis. It can be a good method for preoperative staging diagnosis of rectal cancer because of its high accuracy in diagnosing infiltration depth and peri-intestinal lymph node metastasis.
The most prominent advantage of MRI in rectal cancer staging is that it can clearly describe the relationship between the tumor and the encircling colorectal mesentery and fascia, therefore, the circumferential resection margin (CRM) determined during surgery can be judged from it, The accuracy of high-resolution MRI is 94%, which can accurately determine the degree of total rectal mesentery eradication, thus suggesting that the surgeon may have residual surgery and carry out individualized preoperative treatment.
Multidisciplinary treatment model is the driving force of individualized treatment
Which treatment modality should be used for a patient? Should neoadjuvant therapy be administered first? Is neoadjuvant therapy radiotherapy or radiochemotherapy? Duration? Dose of radiation? What type of surgery is used? The choice of stoma location and possible postoperative treatment strategies are individualized questions that cannot be fully answered by a single surgeon. Therefore, the driving force for individualized treatment is the multidisciplinary team (MDT).
MDT usually refers to a clinical treatment model in which specialists from two or more related disciplines, usually including multiple disciplines, form a relatively fixed group of experts to provide treatment opinions for a particular organ or systemic disease through regular meetings at regular intervals. In the UK, the NHS Cancer Plan has included MDT in the treatment model for rectal cancer.
Sharma et al. followed up 253 colorectal surgeons and evaluated MDT using a questionnaire. 96.5% of the surgeons considered MDT beneficial for the treatment of rectal cancer patients. Our study showed that MDT significantly improved the rate of anus preservation (P=0.041) and local recurrence (P=0.042) in patients with low-grade rectal cancer (tumor lower margin <5 cm from the anal margin), which significantly improved the 5-year survival rate (77.20% vs. 69.80%, P=0.049).
IV. Surgery is an important part of individualized treatment
According to the pre-surgical evaluation, different surgical methods are used to treat rectal segments, which is important for the selection of rectal cancer surgery. This classification is clinically important.
In terms of treatment strategy, standard total mesorectal excision (TME) is required for middle and lower rectal cancer, but TME is not necessary for upper rectal cancer. Direct surgery.
The blood supply to the rectum mainly comes from the inferior mesenteric artery, which is a branch of the internal iliac artery, called the middle rectal artery, and the branch of the internal pubic artery or the anterior trunk of the internal iliac artery, called the inferior rectal artery, which innervates the upper and lower dentate line and the anal canal. In most surgeons’ conceptions, surgery for rectal cancer should be performed with a high ligation.
Traditionally, it was believed that high ligation would ensure the extent of surgical resection and complete lymph node dissection; however, in recent years, there has been increasing evidence that high ligation does not improve patient survival and prognosis, but rather increases the complications of surgery. Therefore, neither the NCCN nor the ASCRS guidelines recommend high ligation as the recommended procedure, while low ligation, i.e., ligation at the level of the superior rectal artery origin, is widely accepted.
At present, radical surgical resection of rectal cancer places more emphasis on the integrity of the rectal mesentery and emphasizes the CRM negative rate, because a positive CRM is a recognized high-risk factor for postoperative recurrence. Therefore, no matter which surgical approach is used for individualized treatment, eradication is the primary goal and standard, and individualized surgery must obey this standard and preserve normal physiological functions as much as possible on the basis of eradication.
V. Genetic testing is the basis of individualized targeted therapy
Molecular targeted therapy is to target certain iconic molecules overexpressed by tumor cells and select targeted blocking agents, which can effectively interfere with the signaling pathways regulated by the iconic molecules and closely related to tumorigenesis, so as to achieve the effect of inhibiting tumor growth and progression and metastasis, The emergence of a-directed drugs has brought rectal cancer treatment to a new stage, and the in-depth study of the mechanism of action of targeted drugs has advanced the process of individualized treatment of rectal cancer.
Epidermal growth factor receptor (EGFR) is a member of the ErbB receptor family, and its expression or upregulation is seen in 60%-80% of colorectal cancers; its ligand (EGF or TGF-α) binds to the extracellular segment of EGFR and dimerizes it, which leads to the activation of tyrosine kinase in the intracellular segment and a series of signal transduction cascades, promoting cell proliferation and angiogenesis. Cetuximab is a human-mouse chimeric IgG1 monoclonal antibody that acts on the EGFR signaling pathway and has a much higher affinity for EGFR than its natural ligand.
Therefore, the K-ras gene became the first biomarker that can be used to select targeted therapeutic agents for rectal cancer. Currently, the detection of K-ras gene mutations is mainly focused on the detection of codons 12 and 13.
Therefore, K-ras gene testing can not only help doctors understand whether there is a mutation in the K-ras gene, but more importantly, it can help screen people who are suitable for cetuximab treatment and achieve individualized treatment for rectal cancer, so as to achieve a good prognosis while significantly reducing unnecessary treatment costs and adverse effects
It is believed that with the emergence of more and more targeted drugs, genetic testing will provide more and more important basis for individualized treatment under the concept of standardized treatment.
Just as the wheel of history is moving forward through the creation and resolution of contradictions, so is the process of medical development. These norms are the guarantee of individualized treatment and can guide individualized treatment. The two are transformed into each other through continuous practice and observation, and develop together.