Objectives To identify patterns of metastasis in patients with recurrent ovarian cancer. The influence of the route of chemotherapy administration and sequence of agents on those patterns is also examined.

Methods A total of 233 women were treated for primary and secondary recurrences after a diagnosis of stage III ovarian cancer. As initial treatment, all underwent optimal debulking surgery followed by combined intraperitoneal/intravenous (IP) chemotherapy with cisplatin/paclitaxel (99 of the 233 women) or intravenous (IV) carboplatin/paclitaxel (134 of the 233 women). Recurrent disease was then treated with either carboplatin with or without liposomal doxorubicin (CLD) or bevacizumab (BEV). The data were reviewed and the types of treatment, sites of metastasis, and timing of recurrence are described.

Results Thirty-five subjects developed extraperitoneal recurrent ovarian cancer, with 26 subjects (74%) after IP treatment, and 9 subjects (26%) after IV treatment. Of these extraperitoneal recurrences, 26 were in the thoracic/pulmonary cavity, 7 were within the central nervous system (CNS), and 2 were in the cutaneous tissues. The CNS and cutaneous lesions were secondary recurrences, and all occurred in subjects who had initially received IP cisplatin/paclitaxel followed by IV BEV for recurrent disease.

Conclusions Extraperitoneal recurrences were more common in women treated with IP chemotherapy for ovarian cancer. Specifically, women treated with IV BEV as secondary therapy after IP were at particularly high risk of extraperitoneal metastases, including in the CNS and cutaneous tissues. Physicians should be aware of the possibility of unusual metastases after the combination of IP chemotherapy and BEV, and future prospective studies of this population should carefully evaluate recurrence site patterns.