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Secondary surgical cytoreduction (SCR) represents a promising therapeutic strategy for patients affected by ovarian cancer disease recurrence. The aim of this prospective observational trial was to analyze the role of SCR in patients with platinum-sensitive ovarian cancer.Patients with platinum-sensitive ovarian cancer underwent SCR by a single surgical team. Clinical and oncologic data were prospectively recorded. A total of 47 patients underwent SCR from 1999 to 2003.The mean operating time was 210 minutes, and mean blood loss was 500 mL. The most frequent surgical procedures carried out were splenectomy, lymphadenectomy, bowel resection, and extensive peritonectomy. Optimal cytoreduction was achieved in 41 patients. Thirty-seven patients had no visible tumor at the end of SCR. Overall median survival was 49 months. Patients who achieved optimal residual disease had a median survival of 61 months, whereas patients who had residual disease >1 cm had a median survival of 19 months.Positive CA-125 (cancer antigen 125) was identified as a negative prognostic factor at multivariate analysis. After careful selection, optimal cytoreduction can be achieved in most patients who are subjected to SCR with acceptable morbidity. Residual tumor and CA-125 represent the most important prognostic factors.