Laparoscopy-assisted versus open surgery for low rectal cancer (LASRE): 3-year survival outcomes of a multicentre, randomised, controlled, non-inferiority trial

Background: Laparoscopic surgery is increasingly used for rectal cancer, but the long-term oncological outcomes for low rectal cancer have not been fully established. We aimed to evaluate the 3-year survival outcomes of laparoscopic surgery versus open surgery in the treatment of low rectal cancer.

Methods: This multicentre, randomised, controlled, non-inferiority trial was conducted at 22 tertiary hospitals in China. Individuals aged 18-75 years with histologically confirmed cT1-2N0, cT3-4aN0, or cT1-4aN1-2 rectal adenocarcinoma within 5 cm from the dentate line were eligible for inclusion. Participants were randomly assigned (2:1) to undergo laparoscopic surgery or open surgery. Central randomisation was conducted using a web response system, and was stratified by clinical stage, age, sex, BMI, and American Society of Anesthesiologists classification. Investigators, patients and statisticians were not masked to group allocation. The primary outcome was 3-year disease-free survival, defined as the time from the date of surgery to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first. Non-inferiority was defined as a lower limit of one-sided 97·5% CI for group difference (laparoscopic surgery group minus open surgery group) of greater than -10%. The primary analyses were performed in the modified intention-to-treat population, which excluded patients with distant metastasis discovered during surgery and those who did not undergo surgery or underwent local resection only. The trial is registered with ClinicalTrials.gov, NCT01899547, and has been completed.

Findings: Between Nov 12, 2013, and June 6, 2018, 1070 patients were enrolled and randomly assigned to treatment. 1039 patients (685 in the laparoscopic surgery group and 354 in the open surgery group; median age 57 years, IQR 50 to 64; 620 [60%] male and 419 [40%] women) were included in the modified intention-to-treat analysis. 3-year disease-free survival was 81·4% (95% CI 78·2 to 84·1) in the laparoscopic surgery group and 79·8% (75·2 to 83·6) in the open surgery group (hazard ratio [HR] 0·92, 95% CI 0·69 to 1·23; p=0·56). The difference between groups was 1·60% (one-sided 97·5% CI -3·34 to ∞, p<0·0001 for non-inferiority). 3-year overall survival was 91·7% (95% CI 89·3 to 93·5) in the laparoscopic surgery group and 93·7% (90·6 to 95·8) in the open surgery group (HR 1·34, 95% CI 0·82 to 2·19; p=0·24). 3-year locoregional recurrence was 3·7% (95% CI 2·5 to 5·3) and 2·3% (1·1 to 4·3), respectively (HR 1·64, 95% CI 0·74 to 3·63; p=0·22). 5-year overall survival was 84·6% (95% CI 81·5 to 87·1) and 86·6% (82·5 to 89·8) in the open group (HR 1·16, 95% CI 0·82 to 1·64; p=0·41).

Interpretation: Laparoscopic surgery performed by experienced surgeons is non-inferior to open surgery for 3-year disease-free survival among patients with low rectal cancer. These results support the use of laparoscopic surgery for low rectal cancer.

Funding: The Key Clinical Specialty Discipline Construction Program of the National Health and Family Planning Commission of China; Minimally Invasive Medical Center Construction Program, Fujian Province, China; and Joint Funds for the Innovation of Science and Technology, Fujian Province, China.