We appreciate the thoughtful commentary by Sun et al. regarding our study on clinical outcomes with a liver-first approach (LFA) to liver metastases from colon cancer (1,2). We applaud their emphasis on a multidisciplinary, evidence-based approach. Our study adds to early accumulating evidence of the benefits of the LFA in select patients. We observed that younger, less comorbid patients managed largely at academic institutions and preferentially treated with upfront chemotherapy, saw a survival benefit when treated with a LFA. Furthermore, patients treated with the LFA were more likely to have complete resection of primary and metastatic disease, which Sun et al. note concurs with previously reported Swiss data (3).
There is no clinical trial to guide optimal surgical oncology treatment strategy for patients presenting with synchronous resectable liver metastatic colon cancer. The RVERS trial, aimed to discern the optimal surgical approach in a randomized fashion, did not yield results applicable to clinical practice (4). In this void of trial data, the National Cancer Database (NCDB) is a rich resource, as it captures data on approximately 70% of cancer care in the United States and reflects national practice patterns and associated outcomes (5). Using this database, we show that most patients undergo either synchronous or staged resections, with the primary colon tumor resected first. Approximately 2% of patients in the United States are selected for the LFA. While the retrospective nature of NCDB based studies does not allow one to draw causal relationships, our survey of this database reveals the profile of patients selected for the LFA and demonstrates that this strategy provides survival benefit in select patients.
Colon cancer with synchronous, isolated liver metastasis is usually treated with systemic chemotherapy to eradicate micrometastatic disease and surgical resection to address gross disease. Though the overall survival benefit of adjuvant systemic therapy was called into question by the EORTC Intergroup trial 40983, most medical centers continue to employ a multimodality approach (6). In this context, Sun et al. correctly point out that in our study population the LFA was associated with a high rate of subsequent completion resection and chemotherapy utilization. Aggressive chemotherapy appears to be integral to the successful implementation of the LFA. The benefits of neoadjuvant chemotherapy for metastatic colorectal cancer are poorly understood, yet may have the added advantage of converting select patients with unresectable disease into candidates for metastasectomy, and thus completion resection.
The role of thermal ablation in the LFA has not been reported (7). Particularly in the context of increasing sophistication in interventional oncology radiology, there is much active interdisciplinary collaboration in the management of metastatic disease. Studies examining efficacy and timing of modalities such as microwave ablation will be beneficial. The results from the COLLISION RCT comparing surgery vs. thermal ablation for colorectal metastases are anticipated in 2023 and will enhance management strategies (8).
Given the pace of innovation in the machine learning and frequent examples of clinical applicability, Sun et al. correctly invite computer scientists to the interdisciplinary team. Indeed, novel predictive algorithms have potential to help guide treatment algorithms by forecasting tumor biology. However, such models are early in development and will require robust validation before wide incorporation into clinical practice.
Funding: This publication was made possible by CTSA Grant Number UL1 TR001863 from the National Center for Advancing Translational Science (NCATS), components of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH. This work was also supported by the Lampman Research Fund in Yale Surgical Oncology.
Provenance and Peer Review: This article was commissioned by the editorial office, Digestive Medicine Research. The article did not undergo external peer review.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/dmr-2020-25). Dr. SK reports grants from the National Institutes of Health, during the conduct of the study. The other authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
- Kurbatov V, Resio BJ, Cama CA, et al. Liver-first approach to stage IV colon cancer with synchronous isolated liver metastases. J Gastrointest Oncol 2020;11:76-83. [Crossref] [PubMed]
- Sun S, Maulat C, Eche T, et al. Controversies in the optimal surgical approach to colon cancer with isolated liver metastases. Dig Med Res 2020;3:95.
- Andres A, Toso C, Adam R, et al. A survival analysis of the liver-first reversed management of advanced simultaneous colorectal liver metastases: a LiverMetSurvey-based study. Ann Surg 2012;256:772-8; discussion 778-9. [Crossref] [PubMed]
- Siriwardena AK. Systemic chemotheRapy and the liVEr-fiRSt approach compared to index colorectal resection for colorectal cancer presenting with synchronous liver metastases. ISRCTN. 2013. Available online: https://doi.org/ [Crossref]
- Boffa DJ, Rosen JE, Mallin K, et al. Using the National Cancer Database for Outcomes Research: A Review. JAMA Oncol 2017;3:1722-8. [Crossref] [PubMed]
- Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet 2008;371:1007-16. [Crossref] [PubMed]
- Abdalla EK, Vauthey JN, Ellis LM, et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg 2004;239:818-25; discussion 825-7. [Crossref] [PubMed]
- Puijk RS, Ruarus AH, Vroomen LGPH, et al. Colorectal liver metastases: surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial. BMC Cancer 2018;18:821. [Crossref] [PubMed]
Cite this article as: Kurbatov V, Lu J, Khan S. A difficult balance of priorities when choosing management of colon cancer with synchronous isolated liver metastases. Dig Med Res 2020;3:117.