Prevalence of Lung Metastases among 19,321 Metastatic Colorectal Cancer Patients in Eight Countries of Europe and Asia

Background: Colorectal cancer is one of the most common malignancies in the Western world, and is responsible for about 10% of annual cancer-related deaths. Especially for UICC stage IV, the probability of survival is significantly reduced. Little is known about risk factors for specific metastatic patterns of colorectal cancer that may also influence patients’ overall survival. Methods: We used data from the IQVIA oncology dynamics (OD) database to determine the prevalence of pulmonary metastases in 19,321 patients with UICC stage IV colorectal cancer in eight European and Asian countries. Results: In total, 6132 of 19,321 (31.7%) study patients had lung metastases, with a higher prevalence among patients with rectal (37.5%) than colon (30.1%) cancer. When compared to China as the country with the lowest lung metastases prevalence, the odds for lung metastases were highest in UK (OR: 2.02, 95%CI: 1.80–2.28), followed by Italy (OR: 1.86, 95%CI: 1.52–2.27), Spain (OR: 1.85, 95%CI: 1.64–2.09), and Germany (OR: 1.47, 95%CI: 1.26–1.71). Conclusion: The prevalence of pulmonary metastases in UICC stage IV colorectal cancer varies widely among the different analyzed countries. Although the present data are purely descriptive, a possible combination of ethnic, environmental, and health care system-associated differences could be discussed as the underlying cause. Further studies are needed to investigate the reasons for differences in the prevalence of lung metastases.

Impact of Metformin Use on Survival in Patients Undergoing Liver Resection for Colorectal Cancer Metastases

Introduction Resection of colorectal liver metastases provides the best chance for survival in patients with Stage IV colorectal cancer; however, hepatic recurrence is frequent and the main cause of death. Multiple epidemiological studies have documented an association between metformin and anti-neoplastic effects in a variety of cancers. Given the vast literature, we evaluated the incidence on recurrence and survival of patients on metformin who undergo surgery for colorectal liver metastasis (CRLM). Methods We selected 270 consecutive patients with known CRLM who underwent hepatic metastases resection at our institution between January 1st 2012 and December 31st 2019. Patients were divided based on their use of metformin (n = 62) or no metformin (n = 208). Adjusted analysis of recurrence-free (RFS) and overall survival (OS) was performed. Results Patients on metformin had significantly longer RFS (HR: .44, 95% CI: .26-.75, P < .002; Median RFS: 49 months vs 33 months) and OS (HR .60, 95% CI .31-.97, P < .048, Median OS: 72 months vs 60 months). Additional factors associated with shorter RFS on univariate analysis included the following: CEA > 200 ng/ml (HR: 2.23, 95% CI 1.21-4.03, P < .010), positive liver margin (HR: 3.70, 95% CI 2.27-6.03, P < .001), and >1 tumor (HR: 1.98, 95% CI 1.26-3.09, P < .003). Liver margin remained a significant factor for predicting shorter OS (HR: 4.99, 95% CI 2.49-10.0, P < .001). Conclusion In this study, we found that patients with CRLM on metformin have prolonged RFS and OS postliver resection. Further prospective randomized trials need to be carried out to evaluate the anti-neoplastic effect of metformin in diabetic and non-diabetic cancer patients.

Perspectives on Hepatic Metastases and the Minimally Invasive Approach to Resection

Surgical resection is the most effective treatment approach in colorectal liver metastases. The improved survival in Stage IV colorectal cancer is associated with a better diagnosis and evaluation, proper decision-making, improved chemotherapy, and the adoption of parenchymal-sparing hepatic resections. Liver surgery was one of the last frontiers reached by minimally invasive surgery. Surgical techniques and specialised equipment evolved to overcome the technical limitations, making laparoscopic liver resections safe and feasible. The aetiology and pathophysiology of hepatic metastases are discussed along with the rationale for and efficacy of minimally invasive surgery for colorectal liver metastases. Improved imaging techniques, identification of genomic markers, advances in chemotherapy, and personalised therapy will further improve the outcome of minimally invasive surgery in the management of Stage IV colorectal cancer.

Primary Tumor Resection With Or Without Metastasectomy For Left- And Right-Sided Stage IV Colorectal Cancer: An Instrumental Variable Analysis

Background Whether primary tumor location (PTL) is predictive of survival benefits following primary tumor resection plus metastasectomy (PMTR) and primary tumor resection (PTR) alone in stage IV colorectal cancer patients is not known. We sought to address this issue by employing instrumental variable analysis to evaluate the efficacy of PMTR and PTR with stratification for primary tumor location in stage IV colorectal cancer patients.Patients and Methods Stage IV colorectal cancer patients diagnosed between January 1, 2005 and December 31, 2015 were identified from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. To account for both measured and unmeasured confounders, the efficacy of PMTR and PTR in the left- and right-sided subgroups was evaluated using instrumental variable analysis, with the health service area as the instrument variable. Overall survival (OS) was the primary outcome of interest.Results A total of 50333 eligible patients were analyzed (left-sided, n=29402 and right-sided, n=20931). OS was significantly better with PMTR than with other treatments (PTR, metastasectomy only, or no surgery) in patients with left-sided tumors (hazard ratio [HR]=0.37 [95% CI, 0.24-0.58], P<0.001), but not in patients with right-sided tumors (HR=0.98 [95% CI, 0.65-1.47], P = 0.910; interaction test P<0.001). OS was comparable in patients treated with PTR and those treated with no surgery in both the left-sided (HR=1.11 [95% CI, 0.68-1.81], P=0.690) and right-sided (HR=0.85 [95% CI, 0.50-1.43], P=0.530; interaction test P=0.466) subgroups.Conclusions PMTR appears to only benefit patients with left-sided stage IV colorectal cancer but not those with right-sided tumors. PTR does not improve OS, regardless of primary tumor location. When selecting patients for PMTR, primary tumor location should be considered. Overuse of PTR should be avoided.