A large number of prospective and retrospective studies have established the value of complete tumor resection with no postoperative residual disease following primary cytoreductive surgery in patients with epithelial ovarian cancer (EOC). Other studies that were primarily retrospective have also shown a benefit of complete tumor resection following secondary or even tertiary cytoreduction. The benefits of complete tumor resection after quaternary cytoreductive surgery are unknown.
The aim of this study was to determine surgical outcome and overall survival (OS) after quaternary cytoreduction (QC) in patients with recurrent EOC. A systematic evaluation was performed of relevant and surgical outcome parameters including the tumor dissemination pattern at surgery, the procedures performed, and operative morbidity and mortality.
The study population was composed of 49 women with EOC undergoing QC over a 12-year period (2000–2012) at an urban hospital in Germany. Participants (mean age, 57 years) had QC with a median of 16 months after previous chemotherapy. The majority of the patients (67.3%) had an initial FIGO stage III tumor; at surgery, 77.6% had peritoneal carcinomatosis, and 67.3% had no ascites. Patients at presentation had tumor involvement of the lower abdomen (85.7%), middle abdomen (79.6%), and upper abdomen (42.9%). Median duration of surgery was 292 minutes. A total macroscopic tumor clearance could be obtained in 32.6% of the patients. Major operative morbidity and 30-day mortality rates were 28.6% and 2%, respectively. Mean follow-up after QC was 18.41 months (95% confidence interval [CI], 12.64–24.18 months), and mean OS was 23.05 months (95% CI, 15.5–30.6 months). Patients who achieved total macroscopic tumor clearance had a mean OS of 43 months (95% CI, 26.4–59.5 months), whereas those with residual disease had mean OS rates of 13.4 months (95% CI, 7.42–19.4 months; P = 0.001). Mean OS was significantly higher among patients who received postoperative chemotherapy compared with patients who received no chemotherapy (40.5 months [95% CI, 27.4–53.6 months] vs 12.03 months [95% CI, 5.9–18.18 months]; P < 0.001). With multivariate analysis, multifocal tumor dissemination was shown to have predictive significance for incomplete tumor resection, higher operative morbidity, and lower OS; systemic chemotherapy subsequent to QC had a significant protective impact on OS. Other factors such as ascites, platinum resistance, high grading, and advanced age had no prognostic significance.
These data indicate that a maximal therapeutic effort combining optimal tumor reduction and chemotherapy even in the setting of the third EOC relapse can significantly prolong survival in a highly selected population of patients.
Department of Gynecology (C.F., P.K., I.E.B., G.P., K.P., J.S.) and Department for General, Visceral and Transplantation Surgery (S.-C.S.), Charité University Medical Center Berlin; Department of Cardiology and Pneumology, Charité (K.S.), Campus Benjamin Franklin, University Hospital, Berlin, Germany