1.Q: Hello, with the improvement of living standard and the increase of human life expectancy, the incidence rate and death rate of colorectal cancer are gradually increasing in China and even in the world, and there are more and more liver metastases of colorectal cancer. First of all, what is the current situation of colorectal cancer?
A: Colorectal cancer includes rectal cancer and colon cancer, which is one of the common malignant tumors. With the improvement of living standard, human life span and the increasing number of elderly patients, the incidence and death rate of colorectal cancer are gradually increasing in China and even in the world, and it is gradually ranking forward among malignant tumors. 2007, there were 1.2 million new cases and nearly 630,000 people died of colorectal cancer worldwide, and the incidence rate in China is 20.6/100,000, and the trend is increasing year by year. Colorectal cancer is the 3rd most prevalent tumor in the world and the 4th most common malignant tumor in China. The incidence rate is higher in economically developed areas, higher in urban than rural areas, and higher in large cities than in medium and small cities. It ranks 2nd in the incidence of malignant tumors in Shanghai.
2.Q: What is the current situation of liver metastasis of colorectal cancer?
A: Liver is the most metastatic part of colorectal cancer, and often the only metastatic part, about 10%-25% of patients have liver metastasis when diagnosed, and 20%-25% of patients have liver metastasis after surgery. If liver metastasis of colorectal cancer is not treated, the median survival period is only 8 months, and the 5-year survival rate is almost 0.
3.Q: What about the current treatment of liver metastasis of colorectal cancer?
A: There is no doubt that surgical radical resection is the best way to cure colorectal cancer liver metastasis, and the median survival of patients who can be resected is about 35 months, and the 5-year survival rate is about 30~50%. However, unfortunately, only 10%-20% of liver metastases can be completely resected at the time of initial diagnosis, and most of them are not completely resectable due to factors such as extrahepatic metastatic lesions, involvement of multiple large vessels and insufficient reserved functional liver, and the prognosis of patients with unresectable colorectal cancer liver metastases is very poor, and there are almost no reports of long-term survival. Therefore, patients with surgical conditions should actively strive for stage I or stage II surgical treatment, and patients with partial unresectable liver metastases should take active treatment measures to strive for converting unresectable liver metastases into resectable ones, so as to maximize the treatment effect. This is also the direction of our clinicians’ efforts. Among them, I think early diagnosis, standardized and integrated treatment with multidisciplinary teamwork is an effective way to improve the survival rate of patients with liver metastases from colorectal cancer.
4.Q: It seems that early diagnosis and early treatment of colorectal cancer liver metastasis are still crucial for patients’ prognosis and survival, so how to diagnose colorectal cancer liver metastasis early?
A: According to the international common classification method, liver metastasis of colorectal cancer is divided into simultaneous and heterochronic. Concurrent liver metastasis refers to liver metastasis found at the time of diagnosis of colorectal cancer or occurring within 6 months after radical resection of primary colorectal cancer; liver metastasis occurring after 6 months of radical resection of colorectal cancer is called heterochronic liver metastasis.
At present, colonoscopy + biopsy is the gold standard for diagnosis of colorectal cancer, and liver ultrasound is mandatory for every patient diagnosed with colorectal cancer, which has good screening effect on liver metastasis. patients suspected of liver metastasis by ultrasound should have serum AFP (alpha-fetoprotein) and enhanced CT examination of upper abdomen, and enhanced CT helps to determine the nature of lesions and shows structures such as hepatic veins, portal veins and bile ducts. MRI has a significant advantage in detecting lesions smaller than 1 cm, and the sensitivity of enhanced MRI examination of liver metastases is 80% to 90%. In addition, PET-CT examination has obvious advantages in sensitivity and specificity, and helps to detect extrahepatic metastases, which is the most accurate method for staging progressive colorectal cancer.
After radical colorectal cancer surgery, patients should be closely followed up. Serum CEA, CA199 and AFP should be tested every 3-6 months, as well as liver ultrasound and CT and MRI if necessary.
5.Q: For patients with liver metastases, whether the liver metastases can be surgically removed or not has a great impact on the prognosis and survival of the patients, so what kind of patients can have the primary foci and liver metastases surgically removed at the same time?
A: There are many international debates and different views on the management of liver metastases from colorectal cancer, but the general principle and trend in recent years is positive, as long as: (1) the patient can tolerate; (2) sufficient liver reserve (30-50% of residual liver volume) is guaranteed; (3) the surgical incision can be balanced; (4) there are no unresectable extrahepatic metastases and R0 resection (radical resection) is achieved, then we should strive for one-stage resection.
On 2010-6-19 at the 6th Shanghai International Colorectal Cancer Summit Forum, the 2010 edition of China’s Guidelines for the Treatment of Colorectal Cancer Liver Metastases was officially announced. This guideline will make the diagnosis and treatment of colorectal cancer liver metastasis more reasonable and standardized. It is clearly stated in the guideline that: if the primary colorectal foci can be radically resected; if the liver metastases are small and mostly located in the periphery of the liver or confined to the half liver, the liver resection volume is less than 50%; if there are no other inoperable hilar lymph nodes, abdominal or distant metastases; if the patient’s physical condition can tolerate the surgery; stage I resection is advocated. The emphasis is on R0 resection, which means that the margins are negative, i.e., no cancer remains, which is very important for the prognosis of the operated patient. Most experts believe that the cut margin of liver metastases should be at least 1 cm.
6.Q: If the patient’s physical condition does not allow the resection of colon tumor and liver at the same time, does the patient still have a chance to have a second operation to remove liver metastases?
A: You are talking about the second-stage resection of liver metastases. For those who cannot be resected simultaneously in one stage in preoperative evaluation, performing second stage resection 4-6 weeks after radical colorectal cancer surgery reduces the risk of surgery and can also provide better treatment effect. It has been confirmed that 3-6 cycles of chemotherapy prior to metastasectomy does not affect the resection rate of liver metastases and can prolong disease-free survival, which is not a better option. The prerequisites for second-stage resection are also that the liver metastases can be radically resected and sufficient amount of residual liver is guaranteed; there are no other inoperable hilar lymph nodes, abdominal or distant metastases; the primary colorectal foci have been radically resected and are not accompanied by recurrence of the primary foci; and the patient can tolerate surgical treatment.
7.Q: What about those patients who cannot be resected?
A: This requires specific treatment for specific conditions. For patients with colorectal cancer without obstruction, bleeding or perforation, neoadjuvant chemotherapy + local radiotherapy is currently advocated, and active measures can be taken as much as possible to turn 10% of unresectable lesions into resectable ones, and their survival is comparable to that of patients with resectable liver metastases at the time of initial diagnosis.
8.Q: So what is neoadjuvant chemotherapy? What is the significance of neoadjuvant chemotherapy for patients with rectal cancer liver metastases?
A: Neoadjuvant chemotherapy refers to systemic chemotherapy applied before local surgery or radiotherapy for malignant tumors. Its clinical significance includes: (1) to make the originally unresectable liver metastases resectable, to shrink the originally resectable lesions and to ensure sufficient cutting edge; (2) to reduce the resection of liver parenchyma and to preserve liver function to the maximum extent; (3) to remove proliferating cancer cells prone to metastasis and to eliminate micro-metastases in the liver; (4) preoperative chemotherapy is a reliable drug-sensitive screening test, and by evaluating the radiology and pathology of the lesions after chemotherapy (4) preoperative chemotherapy is a reliable drug sensitivity screening test, and through radiological and pathological evaluation of lesions after chemotherapy, an effective regimen is selected as the first choice for postoperative chemotherapy.
9.Q: Since neoadjuvant chemotherapy has so many advantages, should all patients have current neoadjuvant chemotherapy?
A: Not necessarily, neoadjuvant chemotherapy also has disadvantages and shortcomings, which may damage the liver and affect liver regeneration, especially after resection of a large portion of the liver (>70%), which is an important issue related to the safety of surgery. In some patients, the disease may progress rapidly during neoadjuvant therapy, and that patient may not benefit from resection. How to get the maximum benefit after neoadjuvant chemotherapy, minimize liver damage, and get the best surgical timing for R0 surgery, in addition to choosing the appropriate number of chemotherapy cycles and chemotherapy regimen, it requires a group of experts from multiple disciplines, including surgery, internal medicine, oncology and pathology, to discuss together and develop a reasonable treatment plan.
10.Q: Should all patients with liver metastasis from colorectal cancer need postoperative chemotherapy, right?
A: Yes, because all patients with metastasis are stage IV or above, and they should have at least 6 cycles of chemotherapy after surgery. Currently, the combination of FOLFOX and FOLFIRI based on oxaliplatin and irinotecan is the standard regimen for first-line treatment.
11.Q: Besides the above two chemotherapy regimens, are there any new drugs for patients with liver metastases from colorectal cancer?
A: In recent years, with the emergence of molecularly targeted drugs, such as anti-VEGF monoclonal antibody (bevacizumab) and anti-EGFR monoclonal antibody (cetuximab) combined with traditional chemotherapy drugs, the efficiency and median survival of metastatic colorectal cancer have been further improved.
The NCCN clinical practice guidelines (2009) clearly indicate the use of cetuximab for first-line treatment of metastatic colorectal cancer. Bevacizumab has also shown more promising results in the treatment of metastatic colorectal cancer. In combination with 5-FU, LV and irinotecan, the overall effectiveness of first-line therapy ranged from 45% to 70%. cetuximab added to FOLFOX in patients with K-RAS wild type achieved good results, while no benefit was seen in patients with mutant type. Currently, chemotherapy combined with molecularly targeted drugs is considered the most promising treatment to improve the resection rate of liver metastases.
12.Q: Are there any non-surgical treatments for liver metastases that cannot be surgically resected?
A: There are many methods. For example, radiofrequency ablation (RFA) for liver metastases is a classical and practical method. Its advantages are: simple operation, small trauma, few complications, easy to be tolerated by patients and repeatable, especially for those who cannot tolerate surgery; it is effective for tumors below 3cm. Because of the effective radius of ablation, local ablation therapy is mostly used as palliative or adjuvant treatment when the liver metastases are too large. There are also: local hepatic artery infusion chemotherapy, embolization, stereotactic radiotherapy, anhydrous alcohol injection, cryoablation, high-intensity ultrasound therapy, radioactive iodine ion implantation, etc. However, each method has certain advantages and shortcomings, and it is only used as part of the comprehensive treatment, which may lose its therapeutic significance alone.
13.Q: Besides liver metastasis, will there be metastasis of other organs in colorectal cancer?
A: Yes, extrahepatic metastasis of colorectal cancer is more common in lung, brain, ovary, bone and adrenal gland. Extrahepatic lesions used to be considered an absolute contraindication to resection of liver metastases from colorectal cancer, but with the application of new chemotherapeutic agents and advances in perioperative treatment, many surgeons have revised this view.
14.Q: What are the factors of poor prognosis of liver metastasis from colorectal cancer?
A: The 10 factors of liver metastasis site, number of liver metastases, size of maximum liver metastases, pathological type of primary tumor, degree of differentiation of primary tumor, depth of primary tumor infiltration, regional lymph node metastasis, presence or absence of abdominal implantation, presence or absence of extrahepatic metastases and treatment for liver metastases have an impact on the prognosis of patients with liver metastases from colorectal cancer.