Zullo 2009.

Methods	Multicentre randomised controlled trial Study dates: March 2001 to December 2003 (33 months)
Participants	84 women randomised 42 in laparoscopy group, mean age 62.1 years (SD 14.5), BMI 29.9 (SD 7.5). 42 in laparotomy group, mean age 61.5 years (SD 13.3), BMI31.8 (SD 8.5). Inclusion criteria: early stage EC. Exclusion criteria: advanced stage EC; other pre malignancies or malignancies; major medical conditions; psychiatric disorders; current or history of acute or chronic physical illness; premenstrual syndrome; current or past (within 6 months from study enrolment) use of drugs influencing cognition.
Interventions	Intervention: LAVH, bilateral salpingo‐oophorectomy, peritoneal washings, + pelvic lymph node dissection, ± para‐aortic lymph node dissection, "uterus cannulated with minimal manipulation". Control: laparotomy, vertical midline skin incision, TAH, bilateral salpingo‐oophorectomy, peritoneal washings, pelvic lymph node dissection, ± para‐aortic lymph node dissection. Decision for para‐aortic lymph node dissection based on intraoperative frozen section of pelvic nodes and if frozen section positive, proceed to para‐aortic lymph node dissection. For serous papillary carcinoma, proceeded to omentectomy and appendicectomy. Surgeons: 1 surgeon performed all procedures.
Outcomes	Primary outcomes: OS DFS Secondary outcomes: Moderate and major adverse events including intraoperative blood loss Postoperative pain Hospital stay QoL measures: SF‐36 and Kupperman Index assessed at baseline; 1, 3 and 6 months postsurgery SF‐36 scores annually for 7 years Follow‐up: every 3 months for 2 years, every 6 months for 3 years, yearly thereafter; vaginal and abdominal examination, ultrasound, bloods for haematology, CA125 if initially elevated, assessed QoL and climacteric symptoms with Italian Short‐Form Health Survey SF‐36 and Kupperman Index at each visit, vaginal smears every 6 months for first 2 years and yearly thereafter, chest X‐ray yearly.
Notes	Duration of follow‐up: 78 months (range 19–84), loss to follow‐up documented for entire study for intervention vs control: non‐attenders after 3 months (2 in laparoscopy group vs 4 in laparotomy group), non‐compliance with protocol following surgery documented (3 in laparoscopy group vs 2 in laparotomy group). Definition of disease failure: locoregional (vaginal or pelvic recurrence, or both) or distant (para‐aortic node metastases, abdominal, liver, lung, bone and diffuse metastatic disease). Follow‐up data: 7 years available. Women who had not participated in the first follow‐up visit after randomisation were excluded from the final analysis. Postoperative complications: within 30 days from surgery. Adjuvant therapy: "Patients with advanced stage surgical cancer (stage I) were treated according Network 2008 guidelines. Combined chemotherapy/brachytherapy regimen was prescribed for patients with aggressive non endometrioid cancers (i.e., uterine papillary serous carcinoma and uterine clear cell carcinoma)". Pelvic radiotherapy: 46 Gy, with 2 Gy daily fractions for 5 days per week. Brachytherapy: 22 Gy, with 5.5 Gy, twice weekly, 4 doses. Chemotherapy: 6 cycles of paclitaxel and cisplatin/carboplatin or doxorubicin. Adjuvant treatment received: 23 (57.5%) in laparoscopy group,19 (50%) in laparotomy group; P = 0.507. No differences in percentage of moderate/major adverse events were recorded throughout the study (4 (10.0%) participants in laparoscopy group vs 6 (15.7%) participants in laparotomy group; P = 0.445).  Number of lymph nodules were similar between groups (pelvic: 11.5 (SD 4.6) in laparoscopy group vs 10.7 (SD 5.5) in laparotomy group: para‐aortic: 5.8 (SD 4.2) in laparoscopy group vs 4.9 (SD 3.9) in laparotomy group). Postoperative pain: no difference between groups during first 48 hours from surgery, whereas at hospital discharge VAS score was significantly lower in laparoscopic group (P < 0.05). Mean hospital stay and length time needed to return to full activity or work (or both) were significantly (P < 0.05) lower in laparoscopy group (hospital stay: 3.0 (SD 1.4) in laparoscopy group vs 6.9 (SD 2.6) in laparotomy group); time needed to return to full activity or work: 28.2 (SD 12.8) in laparoscopy group vs 47.8 (SD 24.7) in laparotomy group). Missing data: women who missed first follow‐up excluded from final analysis.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Single blocks, computer generated lists.
Allocation concealment (selection bias)	Low risk	Yes. All eligible participants were assigned randomly in single blocks in 2 surgical treatment groups with the use of a computer generated randomisation list.
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	78/84 (93%) participants analysed Participants who had not participated in the first follow‐up visit after randomisation were excluded from final analysis.
Selective reporting (reporting bias)	Low risk	All data analysed by ITT method on basis of treatment assignment and not on treatment receipt; only those participants who had not participated in the first follow‐up visit after randomisation were excluded from final analysis.
Other bias	Unclear risk	Insufficient information to assess whether any additional bias was present.

AP: BMI: body mass index; BPI: Brief Pain Inventory; D&C: dilation and curettage; DFS: disease free survival; DVT: deep vein thrombosis; EC: endometrial cancer; ECOG: Eastern Cooperative Oncology Group; EnWB; EWB: ; FACT‐G: Functional Assessment of Cancer Therapy scale – General; FIGO: International Federation of Gynaecology and Obstetrics; FWB: ; GOG: Gynecologic Oncology Group; IQR: interquartile range; ITT: intention to treat; LAVH: laparoscopically assisted vaginal hysterectomy; LPS: laparoscopic hysterectomy; LPT: abdominal hysterectomy; min: minute; OS: overall survival; PE: pulmonary embolism; PS: performance status; PWB: ; QoL: quality of life; SAQ: Sexual Activity Questionnaire; SD: standard deviation; SF‐36: 36‐item Short‐Form Healthy Survey; SGOT: serum glutamic oxaloacetic transaminase (enzyme); SWB: ; TAH: total abdominal hysterectomy; TLH: total laparoscopic hysterectomy; VAS: visual analogue scale.