Walker 2012.

Methods	Multicentre randomised controlled trial with 2:1 intervention:control randomisation Study dates: May 1996 to September 2005 (112 months)
Participants	2616 women randomised, 1696 in laparoscopy group, 920 in laparotomy group. 1630 women included in analysis in laparoscopy group: median age 63 (IQR 55–‐72), median BMI 28 (IQR 24–34), stage I/IIA disease 1287/1630 (76.5%). 886 women included in analysis in laparotomy group: median age 63 (IQR 55–71), median BMI 29 (IQR 24–34), stage I/IIA disease 700/886 (77%). Inclusion criteria: stage I to IIA uterine cancer (FIGO 1988); adenocarcinoma or uterine sarcoma; aged > 18 years; no contraindication to laparoscopy; no clinical or chest X‐ray evidence of metastases beyond the uterus or macroscopic involvement of cervix; PS GOG 0–3; white cell count > 3000/mm³; platelet count > 100 000/mm³; bilirubin ≤ 1.5 times normal; SGOT ≤ 3 times normal; creatinine ≤ 2 mg/dL; prior malignancy allowed if no current evidence of disease. Exclusion criteria: prior pelvic or abdominal radiotherapy; no prior retroperitoneal surgery; pregnancy.
Interventions	Intervention: LPS included laparoscopic assisted techniques, total laparoscopic approaches, and rarely robotics. Washings, extrafascial hysterectomy and bilateral salpingo‐oophorectomy, + pelvic lymph node sampling + para‐aortic lymph node sampling. Control: laparotomy, washings, extrafascial hysterectomy and bilateral salpingo‐oophorectomy, + pelvic lymph node sampling + para‐aortic lymph node sampling.
Outcomes	OS and recurrence free survival Severe postoperative adverse events Intraoperative complications Operative time Hospitalisation > 2 days
Notes	Conversion from laparoscopy to laparotomy was secondary to poor visibility in 246 (14.6%) participants, metastatic cancer in 69 (4.1%) participants, bleeding in 49 (2.9%) participants and other cause in 70 (4.2%) participants. Original protocol Primary outcomes: conversion to laparotomy rate, operative time, duration of hospital stay, blood transfusion, death in 6 weeks, readmission, reoperation rate, postoperative complications for 6 weeks postoperative, pathological stage by nodal status, pathological stage by pelvic washing, node positivity rate, first site of recurrence after 5 years, progression free survival every 3 months for 2 years, and every 6 months for 5 years. Secondary outcomes: QoL assessed by FACT‐G; body image; sexual function; SF‐36; BPI: personal appearance; return to work before surgery; and 1 week, 6 weeks and 1 year. QoL measures: FACT‐G; additional treatment related symptoms (AP); resumption of normal activities; BPI; fear of recurrence; body image; return to work at baseline, 1 week, 3 weeks, 6 weeks and 6 months postsurgery. Amended protocol Primary outcomes: recurrence free survival Protocol amendment: trial was originally designed to accrue 800 participants over 3‐year period to evaluate surgical complications, adverse events, length of hospital stay and improving QoL. In 2001, protocol was amended, and sample size increased to 2550 to assess whether laparoscopy could be considered not inferior to open laparotomy with regard to recurrence free survival. Secondary outcomes: perioperative adverse events, laparoscopy conversion to laparotomy, length of hospital stay after surgery, operative time, QoL, sites of recurrence, survival. Reported to date: 2009 6‐week morbidity and mortality, hospital length of stay, conversion from laparoscopy to laparotomy, recurrence free survival, site of recurrence and participant reported QoL outcomes. Follow‐up: protocol: 6 weeks, every 3 months for 2 years, every 6 months for 3 years Drop‐out rate: not documented Final stage and histopathological characteristics: "Final FIGO staging results were the same by the randomisation arm". Not yet reported: survival and long‐term outcome Laparoscopy had fewer moderate to severe postoperative adverse events than laparotomy (14% in laparoscopy group vs 21% in laparotomy group; P < 0.0001) but similar rates of intraoperative complications, despite having a significantly longer operative time (median: 204 min in laparoscopy group vs 130 min in laparotomy group; P < 0.001). Hospitalisation > 2 days was significantly lower with laparoscopy (52% in laparoscopy group vs 94% in laparotomy group; P < 0.0001). Pelvic and para‐aortic nodes were not removed in 8% of participants in laparoscopy group and 4% of participants in laparotomy group (P < 0.0001). No difference in overall detection of advanced stage (stage IIIA, IIIC or IVB) (17% in laparoscopy group vs 17% in laparotomy group; P < 0.841). Median follow‐up time of 59.3 months for both groups, 350 participants (13.5%) died (229 (13.6%) in laparoscopy group vs 121 (13.3%) in laparotomy group), of which 224 deaths resulted from disease (152 in laparoscopy group vs 72 in laparotomy group). 309 (11.9%) participants had recurrent disease (210 (12.5%) in laparoscopy group vs 99 (10.9%) in laparotomy group). Hazard ratio for recurrence free survival for laparoscopy relative to laparotomy: 1.14. Sites of recurrence were similar between groups (P = 0.470). Postoperative adjuvant therapy was similar between groups (P = 0.607). Estimated 5‐year OS: 89.9% in laparoscopy group vs 89.9% in laparotomy group.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random assignment using permuted block design such that approximately twice as many registered participants underwent laparoscopy compared with laparotomy.
Allocation concealment (selection bias)	Low risk	Central allocation
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	Excluded (surgery refused or contraindicated): 11 in laparoscopy group, 14 in laparotomy group. Used for surgical analysis: 1682 in laparoscopy group, 909 in laparotomy group. Underwent assigned procedure: 1682 in laparoscopy group, 901 in laparotomy group. Excluded following pathology review: 52 in laparoscopy group, 23 in laparotomy group. Participants included in analysis of pathology: 1630 in laparoscopy group, 886 in laparotomy group.
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement. Results of long‐term follow‐up awaited.
Other bias	Unclear risk	Insufficient information to assess whether any additional bias was present.