COSA‐NZ‐UK 1998.

Methods	Multi‐centre RCT
Participants	1012 women with poorly differentiated endometroid, adenosquamous, clear cell or papillary serous tumours, greater than a third myometrial involvement, involvement into the cervix or spread to the adnexae and surgical complete resection was achieved. Mean age in the trial was 64.5 years (Range: 22 and 60 years). There were 486 women with FIGO Stage Ia, 321 had stage Ib, 148 stage II and 57 had stage III. 215 women had well differentiated tumour grade, 468 had moderate differentiated tumour and 329 had poorly differentiated tumours. Histology was classified as adenocarcinoma in 779 women, adenosquamous in 125, Papillary in 64, Clear cell in 28, Squamous in 2 and histology was unclassified in 6 women and was another form of cancer in a further 8 women. There was no myometrial invasion in 37 women. Myometrial invasion was <33% in 218 women, 33‐66% in 369, 67 to 100% in 350 and Into serosa in 38 women.
Interventions	Intervention: Oral Medroxy progesterone 200 mg twice daily for at least 3 years Control: No active treatment
Outcomes	Overall death rates Endometrial cancer deaths Intercurrent deaths (death from non‐cancer related disease) Relapse from disease MI and CVA related deaths
Notes	Length of follow‐up was between three to 10 years, with a mean of 5.4 years. Performance status: Group 0: 901, Group 1: 81, Group 2: 20, Group 3: 8, Confined to bed: 2 Median time from disease recurrence to death was 7 months. Statistically significant predictors of recurrence were greater myometrial invasion (P < 0.001), later stage (P < 0.001), high grade (P < 0.001), positive pelvic nodes (P < 0.001), increasing age (P < 0.05), and papillary serous or clear cell histology (P < 0.05). By the end of the trial there had been 149/505 deaths in the MPA group and 165/507 in the control group: Endometrial Cancer: 98 deaths in control group, 73 in MPA group. MI: 12 deaths in control, 17 in MPA. CVA: 9 deaths in control, 8 in MPA. Other cancers: 3 deaths in control, 9 in MPA. Other disease: 26 deaths in control 22 in MPA. Unspecified cause: 5 deaths in control, 12 in MPA. The individual causes of death shown in table 3 did not add up to the total number of deaths. The five year disease‐free (recurrence‐free) rates of 83.5% and 78% in the MPA and control groups respectively gave the number of women with disease recurrence as being larger than the reported figures given at the end of the trial. "There were 81 relapses in the MPA group and 107 in the control group (p<0.05)". The number who relapsed using the 5 year percentages were 83 in the MPA group and 112 in the control group and these figures were used in the review.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	Unclear risk	Concealment of allocation is most likely adequate because there was central randomisation, but it is uncertain.
Blinding (performance bias and detection bias) All outcomes	Low risk	"All cases were reviewed by an ‘‘independent’’ committee after randomization and treatment to ensure eligibility and to examine for protocol violation".
Incomplete outcome data (attrition bias) All outcomes	Low risk	% analysed:1012/1012 (100%) and 895/895 in analyses of eligible patients only.
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement
Other bias	Unclear risk	Insufficient information to assess whether an important risk of bias exists