Kitchener 2009.

Methods	Multi‐centre RCT randomly assigning participants from 85 centres in 4 countries (UK, South Africa, Poland, and New Zealand)
Participants	1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus Median age at the time of randomisation was 63 years (range 36 to 89) for standard surgery and 63 years (range 34 to 93) for lymphadenectomy Time from diagnosis to random assignment was ≤ 6 weeks for 576 (82%) women in the standard surgery group vs 588 (84%) in the lymphadenectomy arm and > 6 weeks for 128 (18%) women in the standard surgery group vs 116 (16%) in the lymphadenectomy arm 1057 participants (75%) had WHO performance status 0; 295 (21%) had status 1; 45 (3%) status 2; 9 (1%) status 3; and 2 (0%) status 4, similarly spread between the 2 groups 650 (92%) women underwent open surgery and 54 (8%) underwent laparoscopic surgery in the standard surgery group vs 659 (94%) open and 45 (6%) laparoscopic in the lymphadenectomy group Baseline characteristics below excluded participants whose pathology details did not confirm endometrial cancer: 39 women (21 standard surgery group, 18 lymphadenectomy group) who had no other tumour in the surgical specimen; atypical hyperplasia; or cervical, ovarian, or colorectal cancer Tumour was confined to the corpus uteri in 1091 (80%) women and spread beyond the corpus in 274 (20%) women: 553 (81%) standard surgery; 538 (79%) lymphadenectomy Depth of invasion was as follows for standard surgery: endometrium only 96 (14%); inner half of myometrium 369 (55%); outer half of myometrium 212 (31%): unknown 6 (0.9%) Depth of invasion was as follows for lymphadenectomy: endometrium only 89 (13%); inner half of myometrium 310 (46%); outer half of myometrium 274 (41%): unknown 13 (1.9%) FIGO staging (pre‐2009): Stage IIIC was not included, and women with positive lymph nodes were classified irrespective of nodal status. In the standard surgery group, 553 participants (81%) were stage I according to FIGO, 86 (13%) were stage II and 38 (5.6%) were stage III or IV. FIGO stage was unknown in 6 (0.9%) participants. In the lymphadenectomy group, 532 participants (78%) were stage I according to FIGO, 91 (13%) were stage II and 52 (7.5%) were stage III or IV. FIGO stage was unknown in 11 (1.6%) participants Histological cell types were as follows for standard surgery vs lymphadenectomy: endometrioid 545 (80%) vs 541 (79%); adenocarcinoma NOS 46 (7%) vs 37 (5%); clear cell 10 (1%) vs 17 (2%); serous 21 (3%) vs 32 (5%); squamous 6 (1%) vs 5 (1%); mucinous 1 (< 1%) vs 4 (1%); mixed epithelial stromal 7 (1%) vs 8 (1%); sarcoma 10 (1%) vs 9 (1%); other epithelial 4 (1%) vs 6 (1%); mixed epithelial 31 (5%) vs 25 (4%); unknown 2 (0.5%) in both groups Tumour grade was as follows for standard surgery vs lymphadenectomy: 225 women (33%) vs 213 (31%) had tumour grade 1; 300 (44%) vs 290 (43%) grade 2; 139 (20%) vs 158 (23%) grade 3; and in 19 (3%) vs 25 (4%) women, tumour grade was unknown or was not applicable Of the 1403 women who completed surgery, surgical technique used in the standard surgery group was as follows: laparoscopic 42 (6%); vertical incision 287 (45%); Pfannenstiel incision 311 (49%); other transverse 43 (7%); unknown 6. Surgical technique used in the lymphadenectomy group was as follows: laparoscopic 45 (6%); vertical incision 384 (60%); Pfannenstiel incision 208 (32%); other transverse 49 (8%); unknown 7. Five women (2 standard surgery; 3 lymphadenectomy) did not undergo completed surgery
Interventions	Intervention Lymphadenectomy: Women in the lymphadenectomy group had standard surgery plus a systematic dissection of the iliac and obturator nodes. If the nodes could not be dissected thoroughly because of obesity or anaesthetic concerns, sampling of suspect nodes was recommended and para‐aortic node sampling was done at the discretion of the surgeon Comparison Standard surgery: Women in the standard surgery group had a hysterectomy and BSO, peritoneal washings and palpation of para‐aortic nodes. Nodes that were suspicious could be sampled if the surgeon believed this to be in the woman’s best interest
Outcomes	Overall survival Recurrence‐free survival Surgical complications
Notes	Median duration of follow‐up was 37 months (IQR 24 to 58 months) Specialist gynaecological surgeons who were experienced in pelvic lymphadenectomy undertook all surgical procedures 69 women in the lymphadenectomy group received a different intervention from the intervention to which they were assigned: 3 women had no surgery, 2 had subtotal hysterectomy, 6 women were given unknown intervention and 58 (8%) had no nodes taken In the standard surgery group, 2 had no surgery, 6 had subtotal hysterectomy, 11 were given unknown intervention and 35 (5%) had nodes taken No adjuvant radiotherapy was received by 471 (67%) in the standard surgery group and by 469 (67%) in the lymphadenectomy group
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“We used a method of minimisation. Stratification factors were centre, WHO performance status (0‐1 versus 2 to 4), time since diagnosis (<= 6 weeks versus > 6 weeks), and planned surgical approach (open versus laparoscopic)” Minimisation is a method that attempts to randomly assign while at the same time balancing groups for several prognostic variables, so the method of sequence generation was adequate in this trial
Allocation concealment (selection bias)	Low risk	“Randomisation was done by a telephone call to the Medical Research Council Clinical Trials Unit (MRC CTU)”
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	For multivariate Cox model: % analysed: 1337/1408 (95%)
Selective reporting (reporting bias)	Low risk	All important survival and adverse event outcomes have been reported. Survival outcomes have been analysed using appropriate statistical techniques to account for censoring
Other bias	Unclear risk	Information was insufficient for assessment of whether an important risk of bias existed