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‘Intriguing and unexpected’ survival benefit with laparoscopic resection for colorectal liver metastases
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Laparoscopic resection conferred a long-term survival advantage compared with open hepatectomy for patients with liver metastases from colorectal cancer, according to findings from a patient-level meta-analysis published in Annals of Surgery.
The results — which researchers characterized as “intriguing and unexpected” — showed laparoscopic hepatectomy reduced risk for death by 12% to 20% depending on the statistical model used.
“The pooled data suggests that there is a statistically significant survival advantage associated with laparoscopy, but ... we prefer to take a more conservative stance and interpret our result as showing that laparoscopy is at least noninferior to open resection in terms of long-term survival,” Tousif Kabir, MBBS, MMed, FRCS, consultant on the hepatopancreatobiliary service in the department of general surgery at Sengkang General Hospital in Singapore, told HemOnc Today. “[Still], our results should allay the long-held concern among many hepatobiliary surgeons that a laparoscopic approach may compromise oncological adequacy and be associated with worse long-term survival.”
Advances in diagnostic imaging and surgical techniques — along with the expanded role and use of neoadjuvant chemotherapy — have improved outcomes considerably for patients with colorectal liver metastases over the past few decades.
Few randomized comparisons of laparoscopic and open liver resection have been performed.
Results of the randomized OSLO-COMET trial — presented in June at ASCO Annual Meeting — showed no survival difference in this population between laparoscopic surgery and open resection based on 3 years of follow-up. Prior to that presentation, no long-term data existed on the impact of the minimally invasive approach on long-term oncological outcomes — particularly OS.
“Our meta-analysis was done to address this very clinically important question, which has largely remained unanswered,” Kabir said.
Kabir and colleagues conducted an individual patient data meta-analysis of randomized trials and propensity score-matched studies that compared laparoscopic resection with open hepatectomy for patients with colorectal liver metastases.
Investigators used published Kaplan-Meier curves — with the help of a computer vision program — to reconstruct survival information for individual patients. They used frequentist and Bayesian survival models that accounted for random effects and nonproportional hazards to compare OS based on surgical approach.
The analysis included data on 3,148 participants in two randomized trials and 13 propensity score-matched studies. A higher percentage of patients underwent open surgery (59.5%; n = 1,873) than laparoscopy (40.5%; n = 1,275).
Patients who underwent laparoscopic resection demonstrated a reduced risk for death (stratified HR = 0.85; 95% CI, 0.75-0.96). Results also showed evidence of time-varying effects in which the magnitude of HRs increased over time (P = .0324).
Analysis of reconstructed individual patient data showed restricted mean survival time (RMST) in the laparoscopy group was 8.6 months longer at 10-year follow-up and 30 months longer at 15-year follow-up. This translated to a 12.1% increase in relative life expectancy at 10 years and a 38.6% increase at 15 years (P < .0001 for all).
Kaplan-Meier plots for both patient groups reached plateaus at approximately 9 years, an observation consistent with other long-term studies that suggested patients who lived 5 to 10 years after surgery are effectively cured.
Researchers used cure models to calculate estimated fractional cure rates. Results showed the percentage of long-term cancer survivors in the laparoscopy group was more than twice as high as in the open surgery group (47.4% vs. 18%).
“Traditionally, when surgical oncologists assess the oncological outcomes of cancer surgery, they look to a surrogate short-term endpoint — resection margins,” Kabir told HemOnc Today. “Along this conventional line of thinking, given that laparoscopy offers R0 resection rates that are merely comparable — if not worse — than open surgery, long-term survival should not be expected to be better for patients treated by laparoscopy.”
However, results from studies of hepatectomy for colorectal liver metastases have called into question the utility of resection margins as a surrogate endpoint for OS, given so many other factors — including postoperative complications — affect survival, Kabir said.
In addition, another meta-analysis published in Annals of Surgery showed minimally invasive esophagectomy for esophageal cancer appeared associated with longer survival than the open approach (HR = 0.82; 95% CI, 0.76-0.88).
“So, perhaps our finding — albeit in a different oncological setting — is not that surprising after all,” Kabir said.
Researchers conducted a subgroup analyses based on two studies that exclusively enrolled older individuals (n = 608); one included patients aged 65 years or older, and another included those aged 70 years or older.
Results showed longer median OS among those who underwent laparoscopy (53.1 months vs. 44.9 months), as well as a longer 3-year RMST (RMST ratio = 1.06; 95% CI, 1.01-1.11).
Nearly half (46.1%) of older patients who underwent laparoscopy survived at least 5 years, a milestone that researchers suggested translates to apparent cure.
Kabir and colleagues identified several potential explanations for why laparoscopic resection could improve survival. These include earlier resumption of chemotherapy after laparoscopic resection than open surgery, reduced incidence of postoperative complications and greater amenability to repeat hepatectomy. Other biological mechanisms also may play a role.
Adequately powered studies are necessary to determine whether the treatment effect observed in this meta-analysis varies across key subgroups, Kabir said. These include minor hepatectomies vs. major hepatectomies; synchronous vs. staged resection of the colorectal primary tumor and liver metastases; elderly vs. nonelderly patients; and different types of minimally invasive procedures, such as robotic hepatectomy, standard four-port laparoscopic surgery, single-incision laparoscopic surgery or laparoscopic-assisted hepatectomy.
Given the findings, a well-designed prospective randomized trial to compare laparoscopic resection with open hepatectomy is “certainly” needed, Kabir said.
“The numerous propensity score-matched studies we included in our meta-analysis are no substitute for randomized controlled trials,” Kabir told HemOnc Today. “Considering the large amount of safety data supporting a laparoscopic approach, there is arguably sufficient equipoise to do more randomized controlled trials in this field.” – by Mark Leiser
For more information:
Tousif Kabir, MBBS, MMed, FRCS, can be reached at tousif.kabir@singhealth.com.sg.
Disclosures: Kabir reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Syn NL, et al. Ann Surg. 2019;doi:10.1097/SLA.0000000000003672.
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