McGuire 1995.

Study characteristics
Methods	Retrospective analysis of a prospective randomised controlled trial comparing different chemotherapy dosing schedules. It aimed to determine the importance of chemotherapy dose intensity on survival, progression‐free survival (PFS) and response. This was not a trial of surgery but the report allows a comparison of survival outcomes for subgroups women with stage III ovarian cancer who have had < 2 cm or ≥ 2 cm of residual disease following surgery and therefore is relevant to this review.
Participants	458 women with FIGO stage III and IV epithelial ovarian cancer were recruited. These were women who had more than 1 cm residual disease following initial surgery. 27 women were ineligible: incorrect stage (n = 5), incorrect primary tumour (n = 9), incorrect cell type (n = 7), history of prior malignancy (n = 3), prior chemotherapy (n = 1) and other (n = 2) Women with borderline ovarian tumours (low malignant potential) were excluded Recruitment was from December 1986 to April 1990 and all women had undergone a surgical procedure The median age at study entry was 60 years (range: 20 to 83) 305 (67%) and 153 (33%) women had FIGO stage III and IV disease, respectively Tumour cell type: serous 312 (68.1%), endometrioid: 64 (14%), mucinous; 12 (2.6%), clear cell: 12 (2.6%), other: 58 (12.7%) Tumour grade: 1: 26 (9%), 2: 114 (39%), 3: 152 (52%), not specified 2 (1%) GOG score: 0: 150 (32.8), 2: 213 (46.5%), 3: 95 (20.7%)
Residual disease details	Residual disease was noted as follows: LVRD between 1 cm and 2 cm for women with stage III disease: 31 (6.8%) LVRD greater than 2 cm for women with stage III disease: 274 (58.9%) LVRD between 1 cm and 2 cm for women with stage IV disease: 54 (11.8%) LVRD greater than 2 cm for women with stage IV disease: 99 (21.6%) Definition of optimal surgery: All women were 'suboptimally' cytoreduced with > 1 cm of residual disease Chemotherapy: 2 trial arms with women receiving either standard chemotherapy: cyclophosphamide 500 mg/m2 and cisplatin 50 mg/m2 intravenously every 3 weeks for 8 courses OR intense chemotherapy: cyclophosphamide 1000 mg/m2 and cisplatin 100 mg/m2 intravenously every 3 weeks for 4 courses. Dose modification was rigidly controlled to maintain intensity.
Outcomes	Overall survival and progression‐free survival: HR adjusted for age, GOG performance status, histological sub‐type, stage/residual disease and measurable disease using Cox model: III, ≥ 2 cm vs III, 1 to 2 cm: HR 1.91 IV, 1 cm to 2 cm vs III, 1 to 2 cm: HR 1.89 IV, ≥ 2 cm vs III, 1 to 2 cm: HR 2.29 Overall and progression‐free survival (PFS) were measured from the date of randomisation. All eligible women were included in the analysis of outcomes. All causes of death were used to calculate survival, and the estimates were based on Kaplan‐Meier procedures.
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. OS was measured from the date of randomisation. 5. Adjustment for other prognostic factors (a‐g): unclear risk Multivariate model for OS adjusted for age, GOG performance status, histological subtype and measurable disease 6. Statistical analysis and reporting (a‐d): high risk No conceptual framework; unclear of variable selection criteria in multivariate model. Magnitude of effect not reported with confidence interval and only P value was available. Outcome: progression‐free survival 4. Outcome measurement (a‐c): low risk Valid and reliable measurement of outcome. PFS was measured from the date of randomisation. 5. Adjustment for other prognostic factors (a‐g): unclear risk Multivariate model for PFS adjusted for age, GOG performance status, histological subtype and measurable disease 6. Statistical analysis and reporting (a‐d): high risk No conceptual framework; unclear of variable selection criteria in multivariate model. Magnitude of effect not reported with confidence interval and only P value was available.
Notes	Mean and median length of follow‐up were not reported. Since this trial was a trial of chemotherapeutic regimens, the randomisation did not aim to compare the effect of different degrees of surgical debulking. The findings borne out on multivariate analysis are similar to those in retrospective and cohort studies. The prospective nature of this study has, however, facilitated the collection of a fairly complete data set and gives this work some authority. Other variables in Cox model: Age (years): reference group: women aged less than 55 years (P = 0.47): 55 to 65: HR 1.08; > 65: HR 1.38 GOG performance status: reference group: GOG 0 (P = 0.009) 1: HR 1.26, 2: HR 1.56 Histological subtype: reference group: serous adenocarcinoma (P < 0.001): Endometrioid: HR 0.951, mucinous: HR 8.31, clear cell: HR 1.79, other: HR 0.84 Measurable disease: reference group: No: (P = 0.01) Yes: HR 1.43 From the study both advancing age and worsening performance status were associated with poorer survival. In addition, mucinous histology is associated with an 8.3 times greater death rate than serous histology (P < 0.001). The study shows residual disease after surgery impacts on survival. Even in 'suboptimal' cytoreduction (residual disease greater than 1 cm), women with stage III disease and residual disease diameter less than 2 cm exhibited lower death rates than either those with stage III diease and residual disease diameter of ≥ 2 cm, or those with stage IV disease.