The impacts of neoadjuvant chemotherapy and of debulking surgery on survival from advanced ovarian cancer

Highlights

• Neoadjuvant chemotherapy is associated with an inferior survival compared to primary debulking surgery.

• Optimal debulking is achieved when there is no visible residual disease.

• Aggressive surgical techniques can contribute to the achievement of no residual disease.

Abstract

Objectives

Women with advanced ovarian cancer are treated with chemotherapy either before (neoadjuvant) or after surgery (primary debulking). The goal is to leave no residual disease post-surgery; for women treated with primary debulking surgery this has been associated with an improvement in survival. It has not been shown that the survival advantage conferred by having no residual disease post-surgery is present for women who receive neoadjuvant chemotherapy.

Methods

We reviewed the records of 326 women with stage IIIc or IV serous ovarian cancer. We determined if they received neoadjuvant chemotherapy or primary debulking surgery and we measured the extent of residual disease post-surgery. We estimated seven-year survival rates for women after various treatments.

Results

Women who had neoadjuvant chemotherapy were more likely to have no residual disease than women who had primary debulking surgery (50.1% versus 41.5%; p = 0.03) but they experienced inferior seven-year survival (8.6% versus 41%; p < 0.0001). Among women who had primary debulking surgery, those with no residual disease had much better seven-year survival than women who had any residual disease (73.6% versus 21.0%; p < 0.0001). Women who had no residual disease after debulking surgery and who received intraperitoneal chemotherapy had a seven-year survival of 90%.

Conclusions

Neoadjuvant chemotherapy should be reserved for ovarian cancer patients who are not candidates for primary debulking surgery. Among women with no residual disease after primary debulking surgery, intraperitoneal chemotherapy extends survival.

Introduction

The standard treatment of advanced ovarian cancer is a combination of debulking surgery and chemotherapy. The goal of surgery is to reduce the intra-abdominal tumor burden as much as possible; the survival of patients with no residual disease at the completion of surgery is superior to that of patients with visible residual lesions [1]. To maximize the likelihood that a patient is left with no residual disease, several aggressive surgical techniques have been proposed, including the removal of all visible disease on the diaphragm, the colon, spleen, pelvis and elsewhere in the abdomen [2]. These techniques include diaphragm resection, splenectomy, colon resection and extensive peritoniectomy. Conventional treatment also includes chemotherapy, typically a combination of a platinum-based drug and a taxane [3]. Chemotherapy may be given intravenously or by the intraperitoneal route. In several studies, intraperitoneal chemotherapy has been associated with improved survival [4], [5]. For some patients, chemotherapy is given prior to surgery (neoadjuvant chemotherapy). Neoadjuvant chemotherapy is used to treat patients if it is predicted that adequate debulking surgery is unlikely to be successful or if they are too ill to undergo an extensive and lengthy operation, but in some cases is used to reduce the tumor burden. Patients who are treated with neoadjuvant chemotherapy followed by surgery are more likely to achieve the status of no residual disease than are patients treated with surgery alone [6]. Consequently, it has been proposed that neoadjuvant chemotherapy is justified in order to achieve a status of no residual disease [6], [7]; however, treatment with neoadjuvant chemotherapy has not yet been shown to result in better survival than treatment with primary debulking surgery [6], [8].

The survival of patients with stage III or IV ovarian cancer who have no residual disease after primary debulking surgery is approximately 50% at 10 years [9]. It has not been established if patients who achieve a status of no residual disease through the combination of neoadjuvant chemotherapy and surgery have an equally good prognosis. In one randomized trial, the survival of women who were treated with neoadjuvant chemotherapy was similar to that of women who had primary debulking surgery, but this study is notable for the poor survival rates observed in both groups [6]. We compared seven-year survival rates for women treated for advanced stage serous ovarian cancer (stage IIIc or IV) with and without visible residual disease, who did and who did not receive neoadjuvant chemotherapy. We evaluated the impact of aggressive surgery on survival and we compared survival rates for women who received intraperitoneal chemotherapy or conventional chemotherapy.