“Winning” with laparoscopic liver resection for colorectal cancer liver metastases (CRLM)

Laparoscopic liver resection (LLR) for liver tumors has increased dramatically in the past two decades with less complications, blood loss, packed red blood cell (pRBC) transfusions, and shorter length of stay (LOS) compared to open liver resection (OLR) (1-5). Specifically for colorectal cancer liver metastases (CRLM), multiple studies consisting of case-match series, propensity score analyses, and meta-analyses have shown clinical benefits with improved short-term outcomes and comparable long-term survival comparing LLR to OLR (6-15). Another benefit is that LLR for CRLM allows for quicker recovery with earlier initiation of adjuvant systemic chemotherapy compared to OLR (16-18).

Moreover, several randomized clinical trials have compared LLR to OLR for CRLM. In the landmark OSLO-COMET randomized clinical trial, Fretland et al. compared 133 patients undergoing parenchymal sparing LLR to 147 OLR for CRLM (19). The patients were well matched for number of tumors, tumor location, carcinoembryonic antigen (CEA) level, clinical risk score (CRS), and use of neoadjuvant chemotherapy. The LLR group had less postoperative complications (19% vs. 31%, P=0.02), and shorter LOS (2.2 vs. 4.0 days, P<0.001) compared to OLR. There were no differences in estimated blood loss (EBL), operating room (OR) time, R0 margins, or total costs. Quality of life (QOL) and quality-adjusted life years (QALYs) were better in the LLR group (P=0.001). At a median follow-up of 70 months, the 5-year OS was 54% in LLR vs. 55% in OLR, P=0.67 (20).

Likewise, in the LapOpHUVA randomized clinical trial, Robles-Campos et al. compared 96 patients undergoing LLR vs. 97 patients with OLR for CRLM (21). The patients were well-matched with lower global morbidity (12% vs. 24%, P=0.025), and shorter LOS (4 vs. 6 days, P<0.001) in the LLR vs. OLR group. There was no difference in OR time, EBL, transfusions, or R0 margins. Importantly, there was no difference in long-term 5-year OS: 49% LLR vs. 47% OLR.

Another important randomized clinical trial is the ORANGE-II PLUS study by Fichtinger et al. (22) which compared 332 patients undergoing hemihepatectomy to either LLR (n=166) or OLR (n=166). They found that laparoscopic hemihepatectomy was associated with a shorter time to functional recovery, and shorter hospital LOS. For QOL, both global health status and body image scored significantly higher in the LLR group. There was no difference in morbidity, 90-day mortality or R0 resection rates. Hence, the short-term clinical benefits of LLR in the observational studies were confirmed in randomized clinical trials.

In the recent publication, Dr. Paro and colleagues used the “win ratio” to compare LLR vs. OLR for CRLM (23). The “win ratio” is a composite outcome metric that assesses potential pairs of patients who have undergone two different treatment interventions (e.g., LLR vs. OLR) and scores wins vs. losses (or ties) for specific outcome measures. It is a novel and useful analysis technique because the win ratio method accounts for the proportion of patients who do better for an individual outcome component, and also accounts for the relative priority of the component outcomes.

They compared 962 patients undergoing hepatectomy for CRLM at five international hepatobiliary centers from 2001–2018. There were 130 LLR (14%) and 832 OLR (86%). The specific outcome measures selected for inclusion in this study to examine win/losses were surgical resection margin status, severity of postoperative complications, 90-day mortality, time to recurrence, and time to death. The patients were matched based on age, number of hepatic lesions, size of the largest lesion, primary tumor lymph node status, and receipt of neoadjuvant chemotherapy. The median number of hepatic lesions was 2 [interquartile range (IQR), 1–3], while the median size of the largest hepatic lesion was 3 cm (IQR, 1.9–4.5 cm). About 75% of patients were classified as having a medium tumor burden.

Among matched patient pairs, the odds of the patient undergoing LLR “winning” were 1.77 which means the LLR patients had 77% increased odds of “winning” compared to OLR. The win ratio favored LLR independent of tumor burden or presence of bilobar disease (win ratio: 4.57). The odds of “winning” were particularly pronounced relative to short-term outcomes including severity of postoperative complications (win ratio: 3.83) and 90-day mortality. Noteworthy, the laparoscopic liver resection approach had an advantage over OLR among patients regardless of age, sex, tumor burden, or tumor location. Importantly, LLR patients had fewer perioperative complications, and complications tended to be less severe. These findings are in agreement with many studies in the literature showing the short-term clinical benefits of LLR over OLR for CRLM (14). However, patients in the laparoscopic group had fewer hepatic lesions, smaller size, lesions, and therefore smaller tumor burden, and less frequent bilobar disease. This highlights the potential limitations of the laparoscopic approach or early hesitations in applying this approach to patients with high disease burden.

We think it is safe to say that most hepatobiliary surgeons are competitive and enjoy “winning”. Dr. Pawlik and his team should be congratulated for applying this “win ratio” methodology to the hot topic of minimally invasive vs. open hepatectomy for CRLM. Their findings reinforce the many clinical advantages of minimally invasive surgery (MIS) for resection of CRLM. Further studies will help determine which patients with CRLM are the most suitable candidates for MIS hepatectomy including laparoscopic or robotic liver resection based on tumor number and location. We hypothesize that robotic surgery can overcome some of the limitations of laparoscopic liver resection and expand the patient pool that receives the shown benefits of minimally invasive liver surgery.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, HepatoBiliary Surgery and Nutrition. The article did not undergo external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2024-704/coif). The 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/.

References

1. Nguyen KT, Gamblin TC, Geller DA. World review of laparoscopic liver resection-2,804 patients. Ann Surg 2009;250:831-41. [Crossref] [PubMed]
2. Nguyen KT, Marsh JW, Tsung A, et al. Comparative benefits of laparoscopic vs open hepatic resection: a critical appraisal. Arch Surg 2011;146:348-56. [Crossref] [PubMed]
3. Wakabayashi G, Cherqui D, Geller DA, et al. Recommendations for laparoscopic liver resection: a report from the second international consensus conference held in Morioka. Ann Surg 2015;261:619-29. [PubMed]
4. Bagante F, Spolverato G, Strasberg SM, et al. Minimally Invasive vs. Open Hepatectomy: a Comparative Analysis of the National Surgical Quality Improvement Program Database. J Gastrointest Surg 2016;20:1608-17. [Crossref] [PubMed]
5. Ciria R, Cherqui D, Geller DA, et al. Comparative Short-term Benefits of Laparoscopic Liver Resection: 9000 Cases and Climbing. Ann Surg 2016;263:761-77. [Crossref] [PubMed]
6. Castaing D, Vibert E, Ricca L, et al. Oncologic results of laparoscopic versus open hepatectomy for colorectal liver metastases in two specialized centers. Ann Surg 2009;250:849-55. [Crossref] [PubMed]
7. Nguyen KT, Laurent A, Dagher I, et al. Minimally invasive liver resection for metastatic colorectal cancer: a multi-institutional, international report of safety, feasibility, and early outcomes. Ann Surg 2009;250:842-8. [Crossref] [PubMed]
8. Montalti R, Berardi G, Laurent S, et al. Laparoscopic liver resection compared to open approach in patients with colorectal liver metastases improves further resectability: Oncological outcomes of a case-control matched-pairs analysis. Eur J Surg Oncol 2014;40:536-44. [Crossref] [PubMed]
9. Schiffman SC, Kim KH, Tsung A, et al. Laparoscopic versus open liver resection for metastatic colorectal cancer: a metaanalysis of 610 patients. Surgery 2015;157:211-22. [Crossref] [PubMed]
10. Beppu T, Wakabayashi G, Hasegawa K, et al. Long-term and perioperative outcomes of laparoscopic versus open liver resection for colorectal liver metastases with propensity score matching: a multi-institutional Japanese study. J Hepatobiliary Pancreat Sci 2015;22:711-20. [Crossref] [PubMed]
11. Allard MA, Cunha AS, Gayet B, et al. Early and Long-term Oncological Outcomes After Laparoscopic Resection for Colorectal Liver Metastases: A Propensity Score-based Analysis. Ann Surg 2015;262:794-802. [Crossref] [PubMed]
12. Cipriani F, Rawashdeh M, Stanton L, et al. Propensity score-based analysis of outcomes of laparoscopic versus open liver resection for colorectal metastases. Br J Surg 2016;103:1504-12. [Crossref] [PubMed]
13. Lewin JW, O'Rourke NA, Chiow AKH, et al. Long-term survival in laparoscopic vs open resection for colorectal liver metastases: inverse probability of treatment weighting using propensity scores. HPB (Oxford) 2016;18:183-91. [Crossref] [PubMed]
14. Ciria R, Ocaña S, Gomez-Luque I, et al. A systematic review and meta-analysis comparing the short- and long-term outcomes for laparoscopic and open liver resections for liver metastases from colorectal cancer. Surg Endosc 2020;34:349-60. [Crossref] [PubMed]
15. Beard RE, Khan S, Troisi RI, et al. Long-Term and Oncologic Outcomes of Robotic Versus Laparoscopic Liver Resection for Metastatic Colorectal Cancer: A Multicenter, Propensity Score Matching Analysis. World J Surg 2020;44:887-95. [Crossref] [PubMed]
16. Tohme S, Goswami J, Han K, et al. Minimally Invasive Resection of Colorectal Cancer Liver Metastases Leads to an Earlier Initiation of Chemotherapy Compared to Open Surgery. J Gastrointest Surg 2015;19:2199-206. [Crossref] [PubMed]
17. Mbah N, Agle SC, Philips P, et al. Laparoscopic hepatectomy significantly shortens the time to postoperative chemotherapy in patients undergoing major hepatectomies. Am J Surg 2017;213:1060-4. [Crossref] [PubMed]
18. Kawai T, Goumard C, Jeune F, et al. Laparoscopic liver resection for colorectal liver metastasis patients allows patients to start adjuvant chemotherapy without delay: a propensity score analysis. Surg Endosc 2018;32:3273-81. [Crossref] [PubMed]
19. Fretland ÅA, Dagenborg VJ, Bjørnelv GMW, et al. Laparoscopic Versus Open Resection for Colorectal Liver Metastases: The OSLO-COMET Randomized Controlled Trial. Ann Surg 2018;267:199-207. [Crossref] [PubMed]
20. Aghayan DL, Kazaryan AM, Dagenborg VJ, et al. Long-Term Oncologic Outcomes After Laparoscopic Versus Open Resection for Colorectal Liver Metastases : A Randomized Trial. Ann Intern Med 2021;174:175-82. [Crossref] [PubMed]
21. Robles-Campos R, Lopez-Lopez V, Brusadin R, et al. Open versus minimally invasive liver surgery for colorectal liver metastases (LapOpHuva): a prospective randomized controlled trial. Surg Endosc 2019;33:3926-36. [Crossref] [PubMed]
22. Fichtinger RS, Aldrighetti LA, Abu Hilal M, et al. Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial. J Clin Oncol 2024;42:1799-809. [Crossref] [PubMed]
23. Paro A, Hyer JM, Avery BS, et al. Using the win ratio to compare laparoscopic versus open liver resection for colorectal cancer liver metastases. Hepatobiliary Surg Nutr 2023;12:692-703. [Crossref] [PubMed]