Surgery For Colorectal Cancer Liver Metastases Research Articles

Risk of relapse and patient selection for metastatic colorectal cancer liver surgery.

96 Background: Previous data on surgery for colorectal cancer (CRC) liver metastases (CRLM) documented improvement in overall survival (OS) and low perioperative mortality, but patient (pt) selection requires complex multidisciplinary work. Predictive scores such as the Comprehensive Evaluation of Relapse Risk (CERR) estimate relapse risk after surgery and help in the pre-operative decision. Objectives: This study aims to evaluate OS and progression-free survival (PFS) in a population of pts who had surgery for CRLM, and to analyse survival outcomes by risk groups, according to the CERR score. We identified individual, anatomic and biological factors with potential prognostic impact. Methods: We retrospectively analysed the medical records of pts who had CRLM surgery between January 2012 and December 2021 in two Portuguese reference centres. Outcomes for CRLM surgery were analysed by risk groups according to the CERR score of each pt (based on nodal status, preoperative CEA/CA 19.9 values, KRAS/BRAF status, presence of extrahepatic disease and modified tumour burden score). Univariate and multivariate survival analyses were performed with the log-rank test and Cox proportional-hazards regression models. Results: A total of 174 pts were included: 66,1% (n=115) male, mean age at CRLM diagnosis 62,1 (±11,5) years, 80,5% (n=140) with isolated liver metastases. Thirty-three pts (19%) had a second surgery, independently of the CERR score (chi-square p = 0,60). Eighteen (10,3%) pts had a CERR score of 0-1 (low-risk, LR), 96 (55,2%) of 2-3 (medium-risk, MR) and 60 (34,5%) of 4-5 (high-risk, HiR). With a median (MED) follow-up of 85,1 (15,6-186,5) months (mo), 100 (57.5%) pts have died. MED OS was 88,0 mo (95% confidence interval [CI] 40,6-135,4) for LR, 46,4 mo (95% CI 38,7-54,1) for MR and 30,7 mo (95% CI 23,1-38,4) for HiR pts (p=0,02); ECOG performance status was an independent prognostic factor (p=0,002) for OS. Median PFS was 88,0 mo (95% CI 6,9-169,0) for LR, 12,9 mo (95% CI 9,1-16,7) for MR and 7,7 mo (95% CI 5,9-9,4) for HiR pts (p<0,001); positive resection margins and prior induction chemotherapy (CT) were additional independent negative prognostic factors for PFS (p<0,001). Conclusions: These results suggest a significant association between relapse risk after surgery for CRLM and both OS and PFS. The CERR score can be used to select potential candidates for CRLM surgery and improve the impact of this intervention in pts with CRC. The link between induction CT and worse survival may reflect selection bias as these pts possibly had a higher volume of disease and therefore received initial systemic therapy. Prospective studies are required to confirm these results.

Optimizing Adjuvant Therapy after Surgery for Colorectal Cancer Liver Metastases: A Systematic Review

The liver is the most common site of colorectal cancer metastatic spread. Although metastasectomy is the gold standard for fit patients with resectable colorectal cancer liver metastases (CRLMs), their management after surgical treatment remains controversial. The objective of this systematic review was to collate the currently available data of the agents used in the adjuvant setting in order to define the most optimal therapeutic strategy. A systematic review of the literature was conducted by searching PubMed/Medline and Cochrane library databases. We included studies that evaluated the efficacy, the tolerability and the safety profile of various chemotherapeutic agents that are used as adjuvant treatment after surgical resection of CRLMs. The outcomes of interest were regression-free survival (RFS), disease-free survival (DFS), overall survival (OS) and severe toxicities. From 543 initial articles, 29 publications with 7028 patients were finally included. In general, the results of the eligible studies indicated that adjuvant therapy after resection of CRLMs led to improved RFS/DFS rates, but this benefit did not contribute to a statistically significant prolongation of OS. Moreover, the choice of the therapeutic strategy, namely systematic or regional chemotherapy or the combination of both, did not seem to have a differential impact on patient outcomes. However, these results should be interpreted with caution since the majority of the chosen studies are of low or moderate quality. In this context, further high-quality clinical trials conducted on patient sub-populations with modern therapies are required in order to reduce in-study and between-study heterogeneity and determine which patients are expected to derive the maximum benefit from adjuvant therapy after surgery for CRLMs.

Impact of microscopic incomplete resection for colorectal liver metastases on surgical margin recurrence: R1-Contact vs R1

Several studies highlighted an inferior outcome of R1 resection for colorectal cancer liver metastases (CRLM); it is still unclear whether directly involved margins (R1-contact) are associated with a poorer outcome compared to R1<1mm. The aim of this study is to analyze the impact on surgical margin recurrence (SMR) of R1-contact vs R1<1mm patients. Patients who underwent surgery for CRLM between 2009-2018 with both R1 resections on final histology were included and compared in terms of recurrence and survival. Factors associated with SMR were assessed by univariate and multivariate analysis. Out of 477, 77 (17.2%) patients showed R1 resection (53 R1-Contact and 24 R1<1mm). Overall recurrence rate was 79.2% (R1<1mm = 70.8% vs R1-contact group = 83%, P=.222). Median disease-free survival (DFS) and disease-specific survival (DSS) were significantly higher in R1<1mm vs R1-contact group (93 vs 55months; P=.025 and 69 vs 46months; P=.038, respectively). The SMR rate was higher in R1-contact compared to R1<1mm group (30.2% vs 8.3%; P=.036). At univariate analysis, age, number of metastases, open surgical approach, RAS status, and R1-contact were associated with SMR. At multivariate analysis, R1-contact margin was the only factor independently associated with higher SMR (OR = 5.6; P=.046). R1-contact margin is independently associated with SMR after liver resection for CRLM. Patients with R1-contact margin will also experience poorer DFS and DSS.

Histopathological Growth Patterns and Survival After Resection of Colorectal Liver Metastasis: An External Validation Study.

BackgroundAfter resection of colorectal cancer liver metastases (CRLM), 2 main histopathological growth patterns can be observed: a desmoplastic and a nondesmoplastic subtype. The desmoplastic subtype has been associated with superior survival. These findings require external validation.MethodsAn international multicenter retrospective cohort study was conducted in patients treated surgically for CRLM at 3 tertiary hospitals in the United States and the Netherlands. Determination of histopathological growth patterns was performed on hematoxylin and eosin–stained sections of resected CRLM according to international guidelines. Patients displaying a desmoplastic histopathological phenotype (only desmoplastic growth observed) were compared with patients with a nondesmoplastic phenotype (any nondesmoplastic growth observed). Cutoff analyses on the extent of nondesmoplastic growth were performed. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan-Meier and multivariable Cox analysis. All statistical tests were 2-sided.ResultsIn total 780 patients were eligible. A desmoplastic phenotype was observed in 19.1% and was associated with microsatellite instability (14.6% vs 3.6%, P = .01). Desmoplastic patients had superior 5-year OS (73.4%, 95% confidence interval [CI] = 64.1% to 84.0% vs 44.2%, 95% CI = 38.9% to 50.2%, P < .001) and DFS (32.0%, 95% CI = 22.9% to 44.7% vs 14.7%, 95% CI = 11.7% to 18.6%, P < .001) compared with their nondesmoplastic counterparts. A desmoplastic phenotype was associated with an adjusted hazard ratio for death of 0.36 (95% CI = 0.23 to 0.58) and 0.50 (95% CI = 0.37 to 0.66) for cancer recurrence. Prognosis was independent of KRAS and BRAF status. The cutoff analyses found no prognostic relationship between either OS or DFS and the extent of nondesmoplastic growth observed (all P > .1).ConclusionsThis external validation study confirms the remarkably good prognosis after surgery for CRLM in patients with a desmoplastic phenotype. The extent of nondesmoplastic growth does not affect prognosis.

Advances in the surgical treatment of colorectal cancer liver metastases through ultrasound

Surgery remains the gold standard of treatment for colorectal cancer liver metastases (CLM). The only limitation of surgery for CLM is its technical feasibility, the key point being to leave enough remnant liver to ensure patient survival. This report describes a surgical procedure based extensively on ultrasound guidance, which allows for curative resection in one stage and also for multiple bilobar CLM. This strategy minimizes the need for two-stage hepatectomy and may thus overcome many of the limitations and consequences of a two-stage approach, such as the impossibility to complete the treatment approach in 20%-25% of patients and the amputation of major vascular structures, which can result in less technical solutions for CLM relapse.

Preoperative Bevacizumab Does Not Significantly Increase Postoperative Complication Rates in Patients Undergoing Hepatic Surgery for Colorectal Cancer Liver Metastases

Although bevacizumab (BV) increases survival rates when used with chemotherapy (CTX) in patients who have metastatic colorectal cancer (CRC), an increase in wound complications has been observed in patients who undergo surgery while receiving BV. We therefore evaluated whether neoadjuvant BV is associated with an increase in postoperative complications in patients undergoing surgery for CRC liver metastases. Two subgroups of patients who received neoadjuvant CTX + BV (n = 81) or CTX alone (n = 44) were identified from a database of patients who underwent surgery for CRC liver metastases. Univariate and multivariate logistic regression models were used to evaluate the association of patient and tumor characteristics, neoadjuvant therapy, and operative factors with postoperative complications. Postoperative complications developed in 40 patients (49%) who received CTX + BV and 19 patients (43%) who received CTX. The median time from BV discontinuation to surgery was 58 days (range, 31 to 117 days). No significant associations were identified between BV use and timing of BV discontinuation and postoperative complications. On multivariate analysis, lower serum albumin and concomitant surgical procedures were associated with an increased risk of developing any complication (P = .035 and .023, respectively), and lower serum albumin was associated with hepatobiliary complications (P = .016). Neither the use of BV nor timing of BV administration was associated with an increase in complication rates. These data suggest that the combination of BV with neoadjuvant CTX in patients who have CRC liver metastases does not increase surgical complications. To determine the optimal timing of surgery in patients receiving neoadjuvant BV, confirmatory prospective studies are required.

Contrast-Enhanced Intraoperative Ultrasonography During Hepatectomies for Colorectal Cancer Liver Metastases

Preliminary reports showed that contrast-enhanced intraoperative ultrasonography (CEIOUS) provides information on primary or metastatic tumors of the liver that is not obtainable with conventional intraoperative ultrasonography (IOUS). This study validates the impact of CEIOUS, focusing on resective surgery for colorectal cancer (CRC) liver metastases. Twenty-four consecutive patients underwent liver resection using IOUS and CEIOUS for CRC liver metastases. CEIOUS was accomplished with intravenous injection of 4.8 mL of sulphur-hexafluoride microbubbles. CEIOUS found lesions missed at preoperative imaging and at IOUS in four patients and confirmed all of the new findings of IOUS in four patients. In addition, CEIOUS helped to define the tumor margins of the main lesion in 29% of patients with CRC liver metastases. No adverse effects were observed in relation with CEIOUS. In conclusion, CEIOUS improves IOUS accuracy with a significant impact on surgical strategy and radicality in patients who undergo surgery for CRC liver metastases.