Surgery plays a crucial role in all phases of the management of ovarian cancer and, when applied as part of a multidisciplinary approach, affords patients the highest likelihood of a favorable outcome. For most patients with ovarian carcinoma, surgery is not curative because of dissemination of tumor cells throughout the abdominal cavity. Therefore, successful management generally requires additional treatment.
The use of postoperative chemotherapy is standard for all patients with advanced-stage disease and for many patients with early-stage disease. Adjunctive chemotherapy significantly prolongs survival, with most current data supporting the use of platinum- and taxane-based regimens.
Despite a long history of the use of radiation therapy in ovarian carcinoma, because of the low sensitivity of ovarian cancer to radiation in general, opinions on indications for its use differ widely. Presumably, this controversy is due to the limited amount and adequacy of data comparing radiotherapy with modern chemotherapy regimens, as well as concerns regarding potential toxicities. Studies using radiation in both radical and palliative settings have been published, but standardization of the use of radiation varies significantly worldwide.
Clearly, comprehensive surgical staging is necessary to properly identify patients with stages I and II ovarian carcinoma. Beyond surgery, the need for adjuvant treatment with chemotherapy has been recently supported, with the exception of patients with stage I disease and well-differentiated histology.
Suspicious adnexal masses should be excised intact and submitted for frozen section. If a malignancy is confirmed and there is no obvious metastatic spread, complete surgical staging should be undertaken. As discussed previously (see section on "Staging and Prognosis"), it is of critical importance that surgical staging be performed systematically and completely. Inadequate staging may result in inappropriate postoperative treatment, which can severely compromise the chances for cure.
Data from the American College of Surgeons community hospital–based tumor registry show that almost 75% of the primary surgeries for ovarian cancer performed in this country are done so without the involvement of a gynecologic oncologist. This finding is unfortunate given the fact that with physical examination, measurement of CA-125 levels, and appropriate imaging tests, the majority of cases of ovarian cancer can be identified preoperatively. Results from other studies suggest that when a gynecologic oncologist is not present at the initial operation, staging is more often inadequate, cytoreduction is more often suboptimal, and long-term survival is poorer.
Conservation of reproductive organs. In a woman of reproductive age with cancer limited to one ovary, it may be possible to conserve the uterus and opposite fallopian tube and ovary if she wishes to maintain the option of future fertility. To facilitate such intraoperative decision making, it is essential that the surgeon's preoperative discussion with the patient and her family address the possibility of malignancy and review the surgical options for both benign and malignant diseases.
Operative laparoscopy. Recent advances in the instrumentation for operative laparoscopy have led to an increase in the proportion of adnexal masses being managed with this technique. Physicians should exercise caution in selecting patients with adnexal masses for operative laparoscopic approaches. Unless the surgeon's laparoscopic skills are extraordinary, suspicious masses are best managed by laparotomy. For masses that are approached laparoscopically, the same surgical principles of removal without spill and complete surgical staging apply.
Systemic chemotherapy for early-stage disease
The current management of patients with early-stage disease focuses on comprehensive surgical staging and the identification of high-risk features. Patients with stage IA or IB tumors with well-differentiated histology have excellent 5-year survival rates, and adjuvant chemotherapy is generally not used in such patients. High-risk features include moderately to poorly differentiated tumors, stage IC or II disease, and clear-cell histology.
The reported survival rates of 60% to 80% in patients who have early-stage tumors with high-risk features suggested a potential role for adjuvant therapy. The Italian Interregional Cooperative Group (IICG) conducted two randomized trials to evaluate the role of adjuvant therapy in patients with stage I disease. The first trial compared cisplatin(Drug information on cisplatin), 50 mg/ m2 q28d × 6, with observation in 85 patients with stage IA or IB, grade 2–3 disease. The 5-year disease-free survival rate was higher in patients treated with cisplatin than in those who were observed (83% vs 63%), but the 5-year overall survival rate was similar in the two groups (88% vs 82%).
The second trial compared cisplatin (same dose) with phosphorus-32 (P-32) administration in 161 patients with stages IA–IB, grade 2, or stage IC disease. The 5-year disease-free survival rate again favored the platinum arm (85% vs 65%), but the 5-year overall survival rate was unchanged and similar to that reported in the previous trial. P-32 administration was associated with more long-term toxicity.
More recent data have provided support for a survival benefit to the immediate use of adjuvant chemotherapy in patients with early-stage disease. The results of the European Organisation for Research and Treatment of Cancer (EORTC)–Adjuvant Treatment in Ovarian Neoplasms (ACTION) trial and the International Collaborative on Ovarian Neoplasms (ICON) 1 trial were combined and reported. An absolute 5-year survival rate improvement of 8% was reported for those who received immediate chemotherapy compared with reserving chemotherapy for those who relapsed (74% vs 82%; 95% CI, 2%–12%).
Improvements in systemic chemotherapy for advanced ovarian cancer with associated improvements in survival are relevant to the design of regimens for early-stage disease. The Gynecologic Oncology Group (GOG) 157 evaluated three vs six cycles of paclitaxel(Drug information on paclitaxel) and carboplatin(Drug information on carboplatin) in patients with stage IA or IB, grade 2–3; stage IC; or stage II disease. The trial completed accrual in 1995, and final results showed no significant benefit to the longer regimen. The GOG replacement trial evaluated three cycles of paclitaxel plus carboplatin with or without additional weekly paclitaxel (40 mg/ m2) in patients with early-stage disease. These data are reported in abstract form, but no benefit to extended-schedule paclitaxel was seen.
In the absence of additional data, taxane- and platinum-based systemic chemotherapy should be considered the standard approach for patients who have early-stage disease with the exception of well-staged IA or IB, grade 1 disease. The optimal number of cycles is currently unclear, but three cycles were considered the standard arm in the GOG 157 trial, although many clinicians offer six cycles of therapy in the absence of prohibitive toxicity.
Past GOG trials have established that patients with stages IA–IB, well-differentiated or moderately differentiated tumors have a 5-year survival rate of 90% to 98%, which does not seem to improve with adjuvant chemotherapy. However, patients with less favorable neoplasms by virtue of higher grade or stage have poorer outcomes (80% 5-year survival rate among treated patients).
Whole-abdominal irradiation. The techniques used for whole abdominal irradiation (WAI) have changed dramatically over the past 40 years. Initially, treatments with a moving field of radiation caused an unacceptably high risk of bowel complications. Subsequent evolution to an AP-PA approach also produced potential liver, bowel, kidney and bone marrow toxicity. In the modern era, the use of intensity-modulated radiation therapy (IMRT) may be considered. IMRT reduces the bone marrow dose and liver dose, and tailors treatment in a more conformal manner. This technique is currently being tested in many institutions. The efficacy of WAI in ovarian cancer has been widely reported over many years but has always been hampered by the toxicities incurred. One study (Hepp et al: Int J Radiat Oncol Biol Phys 2002) found WAI to be an effective adjuvant therapy in patients with optimally debulked tumors. In a series of 60 patients, the 5-year survival rate was 55%, with a median follow-up of 96.5 months. Patients who received chemotherapy (n = 41) fared slightly worse than those who received radiation therapy only. The abdominal control rate was 83%, and the grade 3 and 4 late toxicity rates were 7% and 3%, respectively.
The findings indicate that 5- and 10-year survival rates obtained with WAI are at least equivalent to results obtained using modern systemic agents. However, in view of the recognized limitations of these trials, more rigorously gathered data will be required to establish the role of WAI with modern techniques such as IMRT in these patients.