SECURE: Restrictive Cholecystectomy Strategy Shows No Benefit for Pain-Free Outcomes

Philip de Reuver, MD, PhD

Credit: Radboud University Medical Center

Long-term findings from the Scrutinizing (In)efficient Use of Cholecystectomy, A Randomized Trial Concerning Variation in Practice (SECURE) trial suggest a restrictive strategy for managing symptomatic cholelithiasis may lead to fewer cholecystectomies without increasing complications but does not improve the likelihood of patients achieving a pain-free state compared to usual care.¹

The study was published in JAMA Surgery and builds upon previous 1-year findings from SECURE demonstrating a 7.7% reduction in cholecystectomies with a restrictive strategy but a lack of significant impact on persistent pain. Findings through 5 years of follow-up again failed to demonstrate noninferiority versus usual care for achieving a pain-free state, although an 8.3% reduction in operation rate was observed with the restrictive strategy without an increase in biliary or surgical complications.^1,2

“The initial follow-up period of 1 year in the SECURE trial was pragmatic but may have been too short to yield the true outcomes in the long run. Patient crossover from conservative to surgical treatment and the occurrence of late biliary complications impair outcomes of a restrictive strategy,” Philip de Reuver, MD, PhD, a gastrointestinal surgeon and hepatobiliary pancreatic surgeon at Radboud University Medical Center in the Netherlands, and colleagues wrote.¹ “To ascertain the long-term consequences of a restrictive strategy in patients with gallstones, there is a need for long-term data.”

A multicenter, parallel-arm, noninferiority, prospective randomized clinical trial, SECURE was conducted at 24 academic and nonacademic centers in the Netherlands between February 2014 and April 2017. It enrolled patients aged 18 to 95 years with symptomatic, uncomplicated cholelithiasis who were referred to a surgical outpatient clinic to discuss cholecystectomy.¹

Patients were randomly assigned in a 1:1 ratio to receive usual care or a restrictive strategy with stepwise selection for cholecystectomy before their first visit at the surgical outpatient clinic. Patients assigned to the usual care arm received the standard care given in the participating centers, and selection for cholecystectomy was left to the discretion of the surgeon in a shared decision with the patient. In the restrictive strategy arm, advice to perform a laparoscopic cholecystectomy was displayed by the triage instrument for patients who fulfilled prespecified criteria for symptomatic cholelithiasis.¹

The primary endpoint of the SECURE trial was the number of patients who were pain-free at 1-year follow-up, defined as an Izbicki pain score (IPS) ≤ 10 with a visual analog scale (VAS) pain score ≤ 4. For the 5-year follow-up, achieving a pain-free status was redefined as a VAS pain score ≤ 4. Secondary endpoints included cholecystectomy rates, biliary and surgical complications, and patient satisfaction.¹

Between July 11, 2019, and September 23, 2023, investigators contacted 1067 SECURE participants who passed the 5-year follow-up by telephone. Their median age was 49.0 (Interquartile range, 38 to 59) years and the majority (73.7%) of patients were female. In total, 970 patients completed the telephone survey, including 91.4% of the usual care group and 90.4% of the restrictive strategy group.¹

At the 5-year follow-up, investigators noted 62.8% of patients were pain-free in the usual care group compared with 61.2% of patients in the restrictive strategy group (difference, 1.6%; 1-sided 95% lower confidence limit [CL], −7.6%; noninferiority P = .18). After cholecystectomy, 63.6% of patients in the usual care group and 63.0% in the restrictive strategy group were pain-free, respectively (P = .88). A VAS pain score ≤ 4 was reported in 80.9% (95% CI, 77.4% to 84.3%) of patients in the usual care group versus 79.3% (95% CI, 75.7% to 82.9%) of those in the restrictive strategy group (difference, 1.6%; 1-sided 95% lower CL, −5.7%; noninferiority P = .09).¹

The restrictive strategy resulted in 8.3% fewer cholecystectomies compared with usual care (73.2% vs 81.5%, respectively; P = .001). Investigators did not observe any significant differences in surgery- or cholelithiasis-related complications. Additionally, they pointed out patient-reported outcomes for biliary and functional gastrointestinal symptoms were similar, and there was no significant difference in patient-reported satisfaction between the 2 groups (median rating, 9.0 vs 8.9; P = .38).¹

Investigators acknowledged multiple limitations to these findings, including protocol deviations in the restrictive strategy group; additional factors influencing the decision for cholecystectomy; and the loss of participants to follow-up.¹

“Regardless of the strategy, only two-thirds of patients achieved a pain-free state after cholecystectomy,” investigators concluded.¹ “The results of this long-term analysis may suggest that, in the future, a more restrictive approach could be adopted to avoid unnecessary cholecystectomies, and improving the selection of patients who actually benefit from cholecystectomy needs to be the focus of care.”

References

1. ^{Comes DJ, Wennmacker SZ, Latenstein CSS, et al. Restrictive Strategy vs Usual Care for Cholecystectomy in Patients With Abdominal Pain and Gallstones: 5-Year Follow-Up of the SECURE Randomized Clinical Trial. JAMA Surg. doi:10.1001/jamasurg.2024.3080}
2. ^{van Dijk AH, Wennmacker SZ, de Reuver PR, et al. Restrictive strategy versus usual care for cholecystectomy in patients with gallstones and abdominal pain (SECURE): a multicentre, randomised, parallel-arm, non-inferiority trial. The Lancet. 10.1016/S0140-6736(19)30941-9}