Liver metastases are often clinically classified as resectable, potentially resectable, or unresectable, and the treatment methods adopted are different. For resectable liver metastases, if the primary foci can also be resected, the primary and metastatic foci can be removed in stages or at the same time; for those with high risk factors of recurrence, neoadjuvant chemotherapy can be considered. For unresectable primary foci, resected when the tumor regresses and transforms to resectable after active treatment; for primary foci still unresectable or progressive liver metastases, treatment is aimed at prolonging survival and improving quality of life (reduced-status surgery). NCCN guidelines The National Comprehensive Cancer Network (NCCN) guidelines suggest that in unresectable cases with only liver and/or lung metastases, primary resection should be considered only if there is an imminent risk of obstruction or significant bleeding, but otherwise systemic chemotherapy should be administered first. Therefore, the current consensus is that the value and purpose of primary resection includes the following 2 main aspects. Symptom control. If symptoms of the primary site are present: obstruction, bleeding, perforation, severe anemia, etc.; survival benefit. For those with resectable metastases, if the primary tumor + metastases are resected together, the maximum survival benefit can be achieved. However, there is also some controversy regarding the treatment of mCRC with asymptomatic primary foci or unresectable metastases, i.e., what is the value of resecting the primary tumor? To date, however, there have been no prospective randomized controlled studies addressing this question. Therefore, studies are needed to address the following aspects. Does the presence of the primary tumor affect the development of systemic therapy? Does it cause intestinal complications after systemic therapy? How many patients require follow-up emergency and surgical interventions? Does resection of the primary tumor provide additional survival benefit to the patient? Is there any clinical value in managing mCRC primary tumors? I. Does the presence of a primary tumor affect the safety of treatment? The NSABP C-10 study investigated whether the presence of asymptomatic primary tumors in patients with mCRC affects the safety of bevacizumab-containing systemic chemotherapy. All 86 mCRC patients enrolled received initial treatment with the mFOLFOX6 (oxaliplatin + calcium folinate + 5-fluorouracil) regimen + bevacizumab. The results showed that only 12 patients (14%) had a primary endpoint event, with a cumulative primary endpoint event rate of 16.3% at 24 months. While 28 patients (32.6%) were also free of primary tumor events by the time of death, 35 patients (40.7%) survived with primary tumor and without events at the final follow-up, and another 14 patients (16.3%) had minor complications of primary tumor. It can be seen that mFOLFOX6 chemotherapy combined with bevacizumab treatment did not increase the incidence of primary tumor-related events such as obstruction, perforation, bleeding, or death. In another single-center prospective study from Katherine Memorial Cancer Hospital in Sloan, New York, USA, data from 233 asymptomatic mCRC patients enrolled between 2000 and 2006 showed that 217 (93%) patients did not require surgical intervention for the primary tumor at the end, and only 16 (7%) patients underwent emergency surgery to manage primary tumor perforation and obstruction. Similarly, data from the Royal Marsden Hospital showed that most initial chemotherapy for mCRC was safe and did not increase serious complications of the bowel compared to initial resection of the primary tumor. Data from the Fox Chase Cancer Center also showed that only 9.8% of patients required surgical intervention for primary tumor-related complications, and the chance of requiring subsequent surgical intervention for primary tumor-related complications was low. This suggests that most asymptomatic mCRC initial chemotherapy is safe or may eliminate the need for prophylactic or non-radical primary resection. The impact of primary tumor resection on patient prognosis With regard to the impact of resection of unresectable mCRC primary foci on survival, the results of several retrospective studies have shown that patients with resected primary foci have a 6- to 8-month longer survival than those without resection. However, these data were retrospective and did not reach the mean median survival in the control group, suggesting some selection bias in material and treatment choice. By the American Society of Clinical Oncology (ASCO) in 2012, a French study that included four randomized controlled studies related to mCRC drug therapy from 1997 to 2008 showed an absolute 2-year overall survival (OS) benefit of 10% to 22% in patients with resection of the primary site, with a benefit in OS achieved in patients with resection of the primary site. Subsequently, the results of a retrospective analysis of the largest population based on the SEER database, published in 2014 in the journal Annals of Surgery (Ann Surg), showed that 23,004 of 37,793 patients (60.9%) underwent resection of the primary focus. The results showed that patients who had their primary foci resected would have a benefit in OS [risk ratio (HR) of 0.40, P<0.001] and a benefit in tumor-related survival (HR of 0.39, P<0.001). Both demonstrated that resection of the primary tumor can provide a survival benefit to patients. However, in a 2015 study published in JAMA? Surg (JAMA Surg), another bulk case-review analysis study, based on the above SEER database data and also incorporating NCI database data, showed a decreasing trend in primary tumor resection but improved patient OS, suggesting that the survival benefit may not come exclusively from primary tumor resection and that there may be over-resection. A contradiction with the previous study results was observed. [Summary] Together, the results of the above studies can tentatively answer the questions raised in the above paper. In asymptomatic, unresectable mCRC with metastases, the presence of the primary tumor did not affect the development of systemic therapy or the occurrence of intestinal complications after systemic therapy. And as to whether there is a survival benefit? Only the possibility exists and has not been answered with complete certainty. What is certain is that there must be a group of patients who would benefit from resection of the primary tumor, and therefore we need to determine this by the biological behavior of the patients, etc., to select a population of patients who would benefit. Two studies comparing chemotherapy after initial primary tumor resection with direct chemotherapy are underway worldwide, namely the SYNCHRONOUS study in Germany (patients recruited since January 2011) and the CAIRO4 study in the Netherlands (patients recruited since May 2012); meanwhile, the 308 project at the Center for Oncology Control of Sun Yat-sen University, in which 20 centers in China are participating, is also underway. We hope that more randomized controlled clinical studies will provide more evidence-based medical evidence on the controversial topic of whether to remove mCRC primary tumors, so let's wait and see!