Aletti 2006a.

Study characteristics
Methods	Retrospective cohort study of consecutive participants identified from surgical records. Surgery carried out at Mayo Clinic, Minnesota (USA)
Participants	Women with FIGO stage IIIC ovarian cancer, where disease status was extracted from surgical exploration notes. Age at study entry: mean 64.4 years; median 64 years; range 24–87 years All women presented with FIGO stage IIIC: 194/194 (100%) Tumour cell type: serous 126 (64.9%), mucinous: 4 (2.1%), endometrioid: 18 (9.3%), clear cell: 7 (3.6%), mixed: 17 (8.8%), seroanaplastic: 17 (8.8%), Müllerian origin: 2 (1%) Tumour grade: 1: 1 (0.5%), 2: 13 (6.7%), 3: 180 (92.8%) ASA score: 1: 7 (3.6%), 2: 87 (44.8%), 3: 88 (45.4%), 4: 7 (3.6%), unknown: 5 (2.6%) Ascites: mean 2076 mL, median 1000 mL, range 0–12,000 mL Extent of disease: carcinomatosis: 144 (74.2%), diaphragm involvement: 137 (70.6%), mesentery: 138 (71.1%), cul‐de‐sac: 163 (84%), omentum: 168 (86.6%), ascites: 160 (82.5%) Residual disease: no gross visible: 46 (23.7%); 0–1 cm: 85 (43.8%); 1–2 cm: 22 (11.3%); > 2 cm: 41 (21.1%) Baseline details for 144 women with carcinomatosis were not reported. However, it is known that 68 (47.2%) women underwent ultra‐radical surgery and 76 (52.8%) underwent standard surgery.
Interventions	Initial surgery performed for diagnosis, staging and surgical cytoreduction. Intervention: ultra‐radical surgery: if any diaphragmatic surgery, bowel resection, splenectomy or extensive abdominal peritoneal stripping or resection. Comparison: standard surgery: hysterectomy, complete omentectomy, stripping of pelvic peritoneum or limited resection of peritoneal‐based nodules.
Outcomes	Disease‐specific overall survival Perioperative mortality Disease‐specific survival: HR for death from advanced epithelial ovarian cancer (adjusted for age, ASA score, carcinomatosis, mesenteric involvement, diaphragmatic involvement, ascites, residual disease and operative time): 0.64 (95% CI 0.40 to 1.04). Provided through personnel communication with the study authors. Median disease‐free survival: 15.9 with ultra‐radical surgery; 19.3 months with standard surgery; significant; not adjusted
Notes	Follow‐up: mean: 3.5 years; median: 2.7 years; range: 0.02–10.5 years Participants were first classified by the extent of peritoneal dissemination. Those with tumour nodules diffusely covering most of the bowel serosa surfaces and the parietal peritoneum of the abdomen and pelvis were classified as having carcinomatosis. In multivariate analysis, only residual disease and radical surgery were independent factors predicting participant survival (Table 4). Quote: "When examining the effect of radical surgery on all patients with carcinomatosis (n = 144), we observed an improved disease‐specific overall survival rate (38% versus 9%; log‐rank test, P=0.001) favouring patients who underwent radical procedures versus non‐radical procedures (Fig. 3)". Quote: "Radical procedures were performed at the same rate regardless of age (49% for age 65 years versus 51% for age 65 years; P = 0.45). Patients with better ASA scores (1 or 2 versus 3 or 4) were more likely to have aggressive procedures performed (59% versus 36%, respectively; P = 0.005), which implies the overall medical condition of the patient at least partially influences the decision to perform aggressive surgery". Quote: "The 5‐year disease‐specific overall survival rate was 46% compared with 13% for patients with radical and non‐radical surgeries, respectively (log‐rank test, P = 0.001; Fig. 4A)". Quote: "The rate of optimal resection (residual disease 1 cm) was 84.5% compared with 51% on the basis of surgeon tendency to use radical procedures". Quote: "Our division of gynaecologic surgery shares a uniform referral base with similar patient demographics, and we practice at a single institution where each surgeon has access to identical services and nursing support".
Risk of bias
Bias	Authors' judgement	Support for judgement
1. Bias due to confounding (a–d)	High risk	Domain had a critical risk of bias: no known prognostic factors that have potential for confounding of the effect on intervention. Information was collected retrospectively.
2. Selection bias (a)	Low risk	Intervention and follow‐up start were simultaneous as a rule for cytoreductive surgery. No evidence of selection into the study due to variables measured after the intervention since participants were included retrospectively.
3. Classification of interventions (a–b)	Low risk	Well‐defined surgical interventions based on aggressive surgery (yes versus no).
4. Deviation from intended interventions (a–c)	Unclear risk	No evidence of any deviations from interventions or usual practice but may be due to omission or that deviations did not happen.
5. Bias due to missing data (a–b)	High risk	Domain had moderate‐to‐high risk of bias: no differential follow‐up or missing data reported; no participant selection due to missing data reported. In some respects, there was no reason to believe there was serious bias due to missing data as the study was sound for a non‐randomised study with regard to this domain but cannot be considered comparable to a well‐performed randomised trial. Therefore, it was sensible to judge the missing data domain at moderate‐to‐high risk of bias.
6. Measurement of outcomes (a–b)	High risk	Domain had a critical risk of bias: disease‐specific survival is not a good outcome measure to use for several reasons, namely the coding of death certificates is notoriously error‐prone. If someone dies because of the treatment they receive, this may not be counted as a death from ovarian cancer. But it is just as important to the patient as a death from ovarian cancer and the evaluation of the relative benefits of the treatments should include these deaths. The study authors would have had access to data for death from all causes.
7. Reporting bias (a–c)	High risk	Domain had a critical risk of bias: there is a serious problem in the multivariate analysis. It adjusted for variables that were measured after the time origin, namely extent of residual disease and operative time (Altman 1995). Also data were reported in a subset of the 144 women with carcinomatosis (more‐extensive disease) only.