The liver-first approach for synchronous colorectal liver metastases: A systematic review and meta-analysis of completion rates and effects on survival

Background: Patients presenting with synchronous colorectal liver metastases are increasingly being considered for a curative treatment, and the liver-first approach is gaining popularity in this context. However, little is known about the completion rates of the liver-first approach and its effects on survival. Methods: A systematic review and meta-analysis of liver-first strategy for colorectal liver metastasis. The primary outcome was an assessment of the completion rates of the liver-first approach. Secondary outcomes included overall survival, causes of non-completion, and clinicopathologic data. Results: Seventeen articles were amenable for inclusion and the total study population was 1041. The median completion rate for the total population was 80% (range 20–100). The median overall survival for the completion and non-completion groups was 45 (range 12–69) months and 13 (range 10.5–25) months, respectively. Metadata showed a significant survival benefit for the completion group, with a univariate hazard ratio of 12.0 (95% confidence interval, range 5.7–24.4). The major cause of non-completion (76%) was liver disease progression before resection of the primary tumor. Pearson tests showed significant negative correlation between median number of lesions and median size of the largest metastasis and completion rate. Conclusions: The liver-first approach offers a complete resection to most patients enrolled, with an overall survival benefit when completion can be assured. One-fifth fails to return to intended oncologic therapy and the major cause is interim metastatic progression, most often in the liver. Risk of non-completion is related to a higher number of lesions and large metastases. The majority of studies stem from primary rectal cancers, which may influence on the return to intended oncologic therapy as well. PROSPERO id no: 170459

The prognostic significance of a histological response to preoperative chemotherapy in patients with synchronous colorectal liver metastases

Objective: Preoperative chemotherapy (PC) for colorectal liver metastasis (CRLM) is widely used to improve prognosis, but its clinical benefit has not been fully established. This study aimed to assess the effectiveness of PC for synchronous CRLM and the correlation between the histological response to PC and survival. Summary of Background Data: We enrolled 69 patients who underwent initial hepatectomy for synchronous CRLM between 2004 and 2018 at Gifu University Hospital. Methods: We retrospectively analyzed the clinicopathological factors and outcomes of 69 patients who underwent hepatectomy after receiving PC (PC group: n = 43) or who underwent upfront hepatectomy (non-PC group: n = 26). In the PC group, the patients were divided into the Grade 1 (n = 27) and Grade 2/3 (n = 16) groups according to their histological responses to PC. Results: The median survival and 5-year overall survival (OS) rates were 80.9 months and 61.5%, respectively, in the PC group and 71.7 months and 61.5%, respectively, in the non-PC group ( P = 0.867). Regarding recurrence-free survival (RFS) and remnant liver-RFS, there were no significant differences between the two groups ( P = 0.087 and 0.291). However, in a subgroup analysis, the median 5-year OS, RFS, and remnant liver RFS were significantly longer in the Grade 2/3 than Grade 1 group ( P = 0.008, P = 0.002, and P < 0.001, respectively). Conclusions: Some patients benefit from PC, and the histological response to PC had prognostic significance for patients with synchronous CRLM.

Open Resection Compared to Mini-Invasive in Colorectal Cancer and Liver Metastases: A Meta-Analysis

Background: We performed a meta-analysis to evaluate the outcomes of minimally invasive surgery and open surgery in the simultaneous resection of colorectal cancer and synchronous colorectal liver metastases.Methods: A systematic literature search up to April 2021 was done and 13 studies included 1,181 subjects with colorectal cancer and synchronous colorectal liver metastases at the start of the study; 425 of them were using minimally invasive surgery and 756 were open surgery. They were reporting relationships between the outcomes of minimally invasive surgery and open surgery in the simultaneous resection of colorectal cancer and synchronous colorectal liver metastases. We calculated the odds ratio (OR) or the mean difference (MD) with 95% CIs to assess the outcomes of minimally invasive surgery and open surgery in the simultaneous resection of colorectal cancer and synchronous colorectal liver metastases using the dichotomous or continuous method with a random or fixed-effect model.Results: Minimally invasive surgery in subjects with colorectal cancer and synchronous colorectal liver metastases was significantly related to longer operation time (MD, 35.61; 95% CI, 7.36–63.87, p = 0.01), less blood loss (MD, −151.62; 95% CI, −228.84 to −74.40, p < 0.001), less blood transfusion needs (OR, 0.61; 95% CI, 0.42–0.89, p = 0.01), shorter length of hospital stay (MD, −3.26; 95% CI, −3.67 to −2.86, p < 0.001), lower overall complications (OR, 0.59; 95% CI, 0.45–0.79, p < 0.001), higher overall survival (OR, 1.66; 95% CI, 1.21–2.29, p = 0.002), and higher disease-free survival (OR, 1.49; 95% CI, 1.13–1.97, p = 0.005) compared to open surgery.Conclusions: Minimally invasive surgery in subjects with colorectal cancer and synchronous colorectal liver metastases may have less blood loss, less blood transfusion needs, shorter length of hospital stay, lower overall complications, higher overall survival, and higher disease-free survival with longer operation time compared with the open surgery. Furthers studies are required to validate these findings.

Clinical Impact of Operative Order in Laparoscopic Simultaneous Resection for Synchronous Colorectal Liver Metastases

Background: Curative resection for colorectal cancer and their synchronous liver metastases are increasingly performed. However, it is still unclear whether the operative order affects the surgical outcome in laparoscopic simultaneous resection of primary and liver metastatic lesions. Patients and Methods: A total of 27 patients underwent laparoscopic simultaneous resection of primary colorectal cancer and liver metastases at Kumamoto University Hospital. They were divided into two groups based on the order of resection: Colon-first (n=11) and liver-first (n=16) groups. The surgical outcomes between the two groups were retrospectively compared. Results: There was no significant difference in the perioperative surgical outcomes between the two groups except for operative blood loss, which was significantly less in the liver-first group [164 (range=5-820) versus 560 (range=95-2,016) ml, respectively] (p=0.0299). Conclusion: In the simultaneous resection of primary and liver metastatic lesions, the operative order does not affect the short-term surgical outcomes except for operative blood loss.

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry

Background The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach. Methods Patients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis. Results Overall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003). Conclusion In patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard.