BACKGROUND Patients with advanced ovarian carcinoma of International Federation of Gynecology and Obstetrics (FIGO) Stage IIIC should be treated by radical surgical tumor debulking with the goal of complete tumor resection. Prolonged median survival can be achieved in those patients entirely free of tumor after surgery by the administration of postsurgical platinum/taxane‐based chemotherapy regimens. However, residual tumor is present in the majority of patients, which limits survival prognosis. Different therapy approaches should be utilized to improve prognosis in these patients. Neoadjuvant chemotherapy could induce “downstaging” of the tumor and thus improve operability. Here, evidence of large ascites volume (>500 mL) can be used to identify those patients who could benefit from neoadjuvant chemotherapy. METHODS In a prospective, nonrandomized Phase II study, 31 patients with advanced FIGO Stage IIIC ovarian carcinoma and large ascites volume (>500 mL) received 3 cycles of platinum/taxane‐based combination chemotherapy, followed by tumor debulking surgery and 3 additional cycles of platinum/taxane‐based combination chemotherapy. During the same period, 32 patients with advanced FIGO Stage IIIC ovarian carcinoma and large ascites volume (>500 mL) received conventional therapy (tumor debulking surgery followed by 6 cycles of platinum/taxane‐based combination chemotherapy). The two groups were investigated and compared with respect to tumor resection rates, blood transfusion requirements, morbidity, and mortality during surgery, duration of surgery, and median survival. RESULTS The tumor resection rate in the patient group receiving neoadjuvant chemotherapy was significantly higher (P = 0.04) than that of the conventionally treated group; the median survival time of 42 months versus 23 months also was significantly longer (P = 0.007). Time spent in surgery, blood transfusion requirements, morbidity, and mortality during surgery were not significantly different. CONCLUSIONS Patients with advanced ovarian carcinoma of FIGO Stage IIIC who will benefit only marginally from conventional therapy can be identified by evidence of large ascites volume. Higher tumor resection rates and longer median survival can be achieved in these patients by the use of neoadjuvant chemotherapy. A prospective randomized multicenter study currently is being performed by the Society for Gynecological Oncology in Germany to confirm these findings. Cancer 2001;92:2585–91. © 2001 American Cancer Society.

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Summary Strong evidence has accumulated on the prognostic value of tumour-associated proteolytic factors in patients afflicted with solid malignant tumours, including advanced ovarian cancer. We evaluated the prognostic impact of the protease urokinase plasminogen activator (uPA) and its inhibitor PAI-1 on overall survival in patients with advanced ovarian cancer stage FIGO IIIc in order to select patients at risk. uPA and PAI-1 antigen were determined by ELISA in primary tumour tissue extracts of 86 ovarian cancer patients FIGO stage IIIc enrolled in a prospective study. Univariate and multivariate analyses were performed using the Cox proportional hazard model. The time-varying coefficient model of Gray was used to assess the time-dependent strength of prognostic factors tumour mass, uPA and PAI-1 on overall survival. In all patients, uPA and PAI-1 (optimized cut-offs of 2.0 and 27.5 ng mg -1 protein respectively), in addition to the traditional prognostic parameters of residual tumour mass, nodal status, grading and ascites volume, were of prognostic significance in univariate analysis for overall survival. Even in patients with residual tumour mass (n = 43), the statistically independent prognostic impact of PAI-1 persisted, allowing further discrimination between low-and high-risk patients. In multivariate analysis, residual tumour mass (P < 0.001, relative risk (RR) 4.5), PAI-1 (P < 0.001; RR 3.1) and nodal status (P = 0.022, RR 2.6) turned out to be strong, statistically independent prognostic parameters. Evaluation of the time-dependent prognostic impact of residual tumour mass and PAI-1 on overall survival (n = 86, 50 months) revealed that the prognostic power of these factors increased with time. In patients with advanced ovarian cancer, both residual tumour mass and PAI-1 are statistically independent strong prognostic factors. Even within patient subgroups with or without residual tumour mass, PAI-1 allowed selection of patients at risk who might benefit from individualized therapy protocols.