Who are the long-term survivors of high grade serous ovarian cancer?

Although the median survival for epithelial ovarian cancer (EOC) is <5years, approximately 15% of patients will survive for >10years. A better understanding of these exceptional responders could reveal opportunities to improve the dismal prognosis of most EOC patients. In this review, we examine the clinical and genomic features that have been associated with long-term survival, which is generally defined as survival of >7-10years after initial diagnosis. Clinical features influencing long-term survival have been best reported in large retrospective population-based studies. These studies find that long-term survival is associated with previously validated prognostic factors, including younger age at diagnosis, earlier clinicopathologic stage, lower grade, non-serous histology, absence of ascites, primary debulking surgery, and optimal cytoreduction at primary surgery. Duration of survival after a recurrence also contributes to long-term survival and depends both on recurrence location and response to subsequent chemotherapy or surgery. Germline BRCA mutations, although associated with short-term chemosensitivity, do not appear to improve long-term survival. Unfortunately, the relative lack of recurrent somatic mutations in EOC has made the identification of genomic signatures associated with long-term survival difficult. Although six independent gene expression analyses of long-term survivors (LTS) have identified signatures associated with prolonged survival, different gene sets are identified in each study. Genes differentially expressed in tumors of LTS are broadly involved in cell proliferation, tumor-stromal interactions, the cytoskeleton, metabolism of nutrients, and immune/stress response. We anticipate that consistent selection of control and LTS groups, combined with the use of emerging transcriptomic, epigenomic, and proteomic platforms, is likely to identify conserved features associated with long-term survival. Further elucidating the factors contributing to long-term survival has the potential to contribute to our understanding of the biology of ovarian cancer, with the goal of improving the survival of all EOC patients.