Introduction

Epithelial ovarian cancer (EOC) is a gynecologic malignancy that accounts for approximately 150,000 deaths occurring worldwide annually . Around 70% of EOC cases are diagnosed as an advanced International Federation of Gynecology and Obstetrics (FIGO) stage, resulting in poor 5-year survival rates . Despite the high remission rate reaching 80%, most of the patients develop recurrence . The standard therapy in primary ovarian cancer is surgery followed by systemic chemotherapy with carboplatinum plus paclitaxel. In recurrent situation, an operative approach remains a subject of the international emotional discussion. Several effective chemotherapy regimens dependent on the platinum-free interval are commonly used, despite the fact that most of these regimens have failed to improve the overall survival (OS). In phase III trials with chemotherapies alone or in combination with targeted therapies, only a minority underwent salvage surgery prior to the trials . Therefore, a subgroup analysis of the cohort of patients who were operated before entering these trials was statistically insufficient.

Retrospective studies of multicenter cohorts report a potential survival benefit after complete cytoreduction in patients with platinum-sensitive first relapse patients . However, the selection of patients eligible for the surgery is an essential issue. The palliative/salvage approach versus cytoreduction attempt, direct systemic therapy, or best supportive care should be well considered. Therefore, it is necessary to have clear definitions of different clinical situations as well as types and objectives of surgery in relapsed ovarian cancer. The decision between the surgical approach and/or systemic treatment should be a result of clinical situation, general condition, and patient’s perception and preferences.

The goal of the surgery should be discussed with the patient in detail and should be fully transparent. Patients seem to decide between surgery and chemotherapy, which is not true. In most situations, it is more likely that the decision is made between surgery plus systemic platinum-based chemotherapy and systemic platinum-based chemotherapy alone. In our opinion, no surgery with the goal of influencing the progression-free survival or OS can be indicated without defining the total cancer treatment strategy, including the systemic approach.

This review concentrates on the recent data and highlights the need of further randomized trials to develop and incorporate operative standards in recurrent ovarian cancer.

Surgery and recurrent ovarian cancer

The benefit of surgery on progression-free survival and OS in recurrent ovarian cancer remains debatable. The available data are based on various collectives in different clinical situations. The enrolment of patients with recurrence as well as patients with persistent or progressive disease in trials was not an uncommon proceeding . Consequently, moderate survival rates and relatively high morbidity revealed the surgical approach as controversial . The different patient selection and definition of relapse and surgical outcome limit the interpretation of the available literature significantly (12)

Defined subgroups and nomenclature used with regard to surgical approach remain a subject of discussion. The Gynecologic Cancer InterGroup has introduced the current definition of optimal debulking as a complete resection of all visible tumor manifestations in primary ovarian cancer . This nomenclature is also usually used with regard to secondary cytoreductive surgery; however, published data are lacking.

The pattern of tumor spread in relapse situation shows peritoneal carcinomatosis with the involvement of the upper abdomen in many patients. Our working group presented the differences in tumor spread between primary and recurrent situation in a prospective study. The highest tumor burden in primary ovarian cancer was localized in the lower abdomen in comparison to the recurrent situation in which it was localized in the upper abdomen . Consequently, the higher complexity of surgical approach in these cases requires experienced gynecologist oncologist, developed infrastructure, interdisciplinary cooperation, established logistic processes, and quality management. The typical change in the tumor pattern from the lower into the upper part of the abdomen must be always considered for the planning of any surgery in relapsed ovarian cancer ( Fig. 1–3 ).

En-bloc tumor resection. Multivisceral approach with inv resection of the bowel, peritoneal carcinomatosis, and omental-cake.

En-bloc peritoneum resection.

Resection of liver metastasis.

The indication for surgery in the recurrent disease is salvage operation to remedy the symptoms and (or) cytoreduction with the aim of complete tumor resection. The complete cytoreduction rates range between 9% and 100% in patients with recurrent ovarian cancer . However, surgery was not offered for 7–64% women. Several studies analyzed the association between recurrence-free interval and benefit of secondary surgery with different results . Eisenkop et al. found the recurrence-free interval as the most important prognostic factor in patients with relapse in addition to residual tumor after surgery. Age, CA125 level, symptoms, ascites, and grade were found to be significant factors in this analysis . Complete cytoreduction is associated with significant survival benefits . However, according to other authors, only those patients who underwent surgery with residuals of up to 1 cm benefitted from the surgical approach . Nevertheless, the latter group showed poorer prognosis than completely operated patients. The recent analysis of Feldheiser et al. showed that cytoreductive surgery does not seem to be more challenging in terms of perioperative management compared to that at the primary situation .

The surgery in eligible patients with relapsed ovarian cancer should be complete tumor resection. In the remaining cases, the surgical approach should be as short as possible and limited to the most necessary procedures.

Surgery and recurrent ovarian cancer

The benefit of surgery on progression-free survival and OS in recurrent ovarian cancer remains debatable. The available data are based on various collectives in different clinical situations. The enrolment of patients with recurrence as well as patients with persistent or progressive disease in trials was not an uncommon proceeding . Consequently, moderate survival rates and relatively high morbidity revealed the surgical approach as controversial . The different patient selection and definition of relapse and surgical outcome limit the interpretation of the available literature significantly (12)

Defined subgroups and nomenclature used with regard to surgical approach remain a subject of discussion. The Gynecologic Cancer InterGroup has introduced the current definition of optimal debulking as a complete resection of all visible tumor manifestations in primary ovarian cancer . This nomenclature is also usually used with regard to secondary cytoreductive surgery; however, published data are lacking.

The pattern of tumor spread in relapse situation shows peritoneal carcinomatosis with the involvement of the upper abdomen in many patients. Our working group presented the differences in tumor spread between primary and recurrent situation in a prospective study. The highest tumor burden in primary ovarian cancer was localized in the lower abdomen in comparison to the recurrent situation in which it was localized in the upper abdomen . Consequently, the higher complexity of surgical approach in these cases requires experienced gynecologist oncologist, developed infrastructure, interdisciplinary cooperation, established logistic processes, and quality management. The typical change in the tumor pattern from the lower into the upper part of the abdomen must be always considered for the planning of any surgery in relapsed ovarian cancer ( Fig. 1–3 ).

En-bloc tumor resection. Multivisceral approach with inv resection of the bowel, peritoneal carcinomatosis, and omental-cake.

En-bloc peritoneum resection.

Resection of liver metastasis.

The indication for surgery in the recurrent disease is salvage operation to remedy the symptoms and (or) cytoreduction with the aim of complete tumor resection. The complete cytoreduction rates range between 9% and 100% in patients with recurrent ovarian cancer . However, surgery was not offered for 7–64% women. Several studies analyzed the association between recurrence-free interval and benefit of secondary surgery with different results . Eisenkop et al. found the recurrence-free interval as the most important prognostic factor in patients with relapse in addition to residual tumor after surgery. Age, CA125 level, symptoms, ascites, and grade were found to be significant factors in this analysis . Complete cytoreduction is associated with significant survival benefits . However, according to other authors, only those patients who underwent surgery with residuals of up to 1 cm benefitted from the surgical approach . Nevertheless, the latter group showed poorer prognosis than completely operated patients. The recent analysis of Feldheiser et al. showed that cytoreductive surgery does not seem to be more challenging in terms of perioperative management compared to that at the primary situation .

The surgery in eligible patients with relapsed ovarian cancer should be complete tumor resection. In the remaining cases, the surgical approach should be as short as possible and limited to the most necessary procedures.