Winter 2008.

Study characteristics
Methods	Retrospective review of 4 RCTs. The current study was a retrospective review of data from women with stage IV EOC treated with platinum and paclitaxel combination chemotherapy on one of four prospective randomised clinical trials conducted by the GOG: protocols 111, 132, 152 and 162
Participants	360 women with stage IV invasive EOC who underwent primary surgical cytoreduction followed by paclitaxel/platinum chemotherapy while participating in one of four GOG clinical trials. The median age of women was 59 years (range: 24 to 86 years) 317 (88%) women were white, 28 (8%) were black and 15 (4%) were of other ethnic origin 97 (27%) had GOG performance status 0, 203 (56%) had status 1 and 60 (17%) had status 2 24 (7%) women had tumour grade 1, 112 (31%) grade 2 and 224 (62%) had grade 3 disease Histology was as follows: serous 268 (74.5%), endometrioid 28 (8%), mucinous 7 (2%), clear cell 12 (3%), adenocarcinoma unspecified 9 (2.5%), mixed epithelial 22 (6%), undifferentiated 9 (2.5%), other 5 (1.5%). The median residual tumour size was 3 cm (range 0.0 to 40.0) Stage IV disease site was as follows: distant: 45 (12.5%), parenchymal liver: 64 (17.75%), pleural effusion: 172 (47.75%), subcutaneous: 32 (9%), others: 3 (1%), multiple sites: 44 (12%)
Residual disease details	The maximum diameter of residual tumour that was used to define optimal cytoreduction: 1 cm (in original RCTs). All 4 RCTs included suboptimal disease (> 1 cm). Residual disease was noted as follows: NMRD: 29 (8%) SVRD of 0.1 cm to 1 cm: 78 women (22%) LVRD of 1.1 cm to 2 cm: 50 women (14%) LVRD of 2.1 cm to 3 cm: 40 women (11%) LVRD of 3.1 cm to 4 cm: 30 women (8.25%) LVRD of 4.1 cm to 5 cm: 44 women (12%) LVRD of 5.1 cm to 6 cm: 30 women (8.25%) LVRD larger than 6 cm: 59 women (16.5%) 'Optimal' cytoreduction was defined as RD < 1 cm and a sensitivity analysis was performed defining RD as < 2 cm All women were treated with primary surgical cytoreduction and 6 cycles of a 24‐hour infusion of intravenous paclitaxel 135 mg/m2, followed by intravenous cisplatin 75 mg/m2
Outcomes	Overall survival: HR adjusted for several prognostic categories Optimal: NMRD: SVRD (< 1 cm) vs NMRD: HR 1.93 (95% CI 1.17 to 3.20) 1 cm to 5cm vs NMRD: HR 1.83 (95% CI 1.14 to 2.94) > 5 cm vs NMRD: HR 2.72 (95% CI 1.65 to 4.47) Optimal: SVRD (≤ 1.0 cm): LVRD (> 1 cm) HR 1.30 (95% CI 1.00 to 1.59) Optimal: ≤ 2 cm RD: LVRD (> 2 cm) HR 1.17 (95% CI 0.92 to 1.49) Progression‐free survival: HR adjusted for several prognostic categories Optimal: NMRD: SVRD (< 1 cm) vs NMRD: HR 1.99 (95% CI 1.24 to 3.18) 1 cm to 5cm vs NMRD: HR 2.15 (95% CI 1.38 to 3.34) > 5 cm vs NMRD: HR 2.96 (95% CI 1.86 to 4.71) Optimal: SVRD (≤ 1 cm) RD: LVRD (> 1 cm) HR: 1.49 (95% CI 1.16 to 1.92) Optimal: ≤ 2.0 cm RD: LVRD (> 2 cm) HR: 1.27 (95% CI 1.01 to 1.61)
Risk of bias (QUIPS)	1. Study participation (a‐f): low risk Adequate number of participants and description of target population. Baseline characteristics, eligibility criteria, sampling frame and period/place study took place presented clearly. 2. Study attrition (a‐e): unclear risk Unclear if patients with incomplete follow‐up were excluded before arriving at the stated sample size. Insufficient information to permit judgement. 3. Prognostic factor measurement (a‐f): low risk Valid and reliable measurement of RD Outcome level assessment: Outcome: overall survival 4. Outcome measurement (a‐c): low risk Valid and reliable measurement of outcome 5. Adjustment for other prognostic factors (a‐g): unclear risk Multivariate model for OS adjusted for histology and stage IV disease site 6. Statistical analysis and reporting (a‐d): unclear risk In methods, authors reported that all variables considered as potential prognostic factors were included in multivariate analyses, suggesting some conceptual framework. However, age, race, GOG PS and tumour grade were excluded secondary at univariate analysis due to their P values falling above significance threshold Outcome: progression‐free survival 4. Outcome measurement (a‐c): low risk Valid and reliable measurement of outcome 5. Adjustment for other prognostic factors (a‐g): unclear risk Multivariate model for PFS adjusted for histology and stage IV disease site 6. Statistical analysis and reporting (a‐d): unclear risk In methods, authors reported that all variables considered as potential prognostic factors were included in multivariate analyses, suggesting some conceptual framework. However, age, race, GOG PS and tumour grade were excluded secondary at univariate analysis due to their P values falling above significance threshold
Notes	The median length of follow‐up was 28 months When evaluating the association of clinicopathologic factors with residual disease status, there was no difference between the RD groups and demographic, clinical and pathologic factors Stage IV site did not seem to have significant association with RD group distributions