Ovarian Cancer Surgery

Surgery is crucial in Ovarian Cancer treatment and should be performed by specialists. Primary treatment of Ovarian Cancer is largely surgery-based, and studies have shown that optimal surgery can significantly increase survival rates (37 vs 17 months) and complete response to chemotherapy (50% vs 20%). It is also reported that survival is dependent on
the expertise and degree of specialization of the surgeon, with a 25% improvement in 3-year survival among patients whose ovarian tumors are removed by a specialized gynecologist. Nevertheless, often times neither surgery nor staging are optimal, rendering the interpretation of some studies difficult. Chemotherapy is currently given after surgical resection of the tumor has been performed, and replacing surgery with chemotherapy is not recommended. However, several clinical trials based around new treatment strategies are currently underway, and these may well offer an alternative approach to therapy in the future.
Designing clinical trials of new drug combinations for OC is complicated by the great heterogeneity of patients with this disease. In 2004, the 3rd International OCCC made a number of recommendations regarding the extent of surgery for patients taking part in first-line chemotherapy trials. Staging should be performed according to FIGO guidelines. For example, this includes at least lymph node sampling and peritoneal staging in early-stage invasive disease (FIGO I–IIA). Up-front maximal surgical effort at cytoreduction with the goal of no residual disease should be undertaken. Conservative surgery should only be considered in
specific cases like well-differentiated (grade 1) stage IA, young patient with low parity, and ability for close follow-up. The role of cytoreductive surgery (CS) in recurrent ovarian cancer (ROC) has not been clearly defined.

Ovarian Cancer IP Chemotherapy

IP chemotherapy has yielded promising results when used in combination with standard IV therapy in the first-line setting for advanced ovarian cancer. Improvement in overall survival has been documented in prospective randomized controlled trials, with attainment of median OS of 66.9 months, the longest ever reported to date in advanced ovarian cancer patients. IP therapy was associated with increased toxicity and difficulty administering all scheduled doses, due to catheter complications and possibly due to the higher doses of cisplatin used IP. Catheter complications may be reduced if port-a-caths are used preferentially over Tenckhoff catheters, and are placed laparoscopically or under radiologic guidance, though prospective data are needed to definitively address these issues. Strategies to decrease chemotherapy related toxicities include the substitution of cisplatin with carboplatin or the use of cytoprotectants like amifostine. In addition, further evaluation for the use of IP carboplatin is necessary. Currently the GOG is conducting studies evaluating the feasibility of administering IP carboplatin with IV
paclitaxel (GOG 9917) and IP carboplatin with paclitaxel (IV and IP) or IP carboplatin, IP paclitaxel and IV docetaxel (GOG 9916). Due to the possible relationship between recent major abdominal surgery and administration of IP chemotherapy, it has been suggested that delaying IP chemotherapy until the second cycle may be better tolerated. Due to the clear advantage in OS, the use of IP chemotherapy needs to be strongly considered for patients with optimally
debulked ovarian cancer, despite the increased toxicity.

Advanced Ovarian Carcinoma

Advanced (FIGO stage III/IV) ovarian carcinoma is only occasionally curable at first presentation and is almost always incurable at relapse. Current standard first-line therapy involves treatment with a platinum agent (cisplatin or carboplatin) in combination with a taxane (paclitaxel or docetaxel) delivered on a 3-weekly cycle for six cycles. Patients optimally cytoreduced can expect a median progression-free survival of 22 months and a median overall survival of 57 months, whereas patients with residual tumor nodules .1 cm in diameter have correspondingly poorer figures for median progression-free survival and median overall survival of 18 and 36 months, respectively. No randomized trials of other intravenous cytotoxic regimens or schedules have demonstrated better survival data in the first-line setting,
although emerging data for intraperitoneal cisplatin–paclitaxel may change that paradigm. Ongoing or planned international randomized trials will integrate novel biologic agents such as inhibitors of angiogenesis (eg, the monoclonal antibody bevacizimab) or epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib) with conventional cytotoxics. The implication is that we may have reached a plateau in outcomes from conventional cytotoxic therapy in this disease.