Highlights
- •Long-term survivors of advanced-stage EOC are a heterogeneous group.
- •Clinical and pathologic factors are not sufficient to predict long-term survival.
- •Germline genetic mutations are not associated with long-term survival.
- •Models based on differential gene expression can classify long-term survivors.
- •More research on genomics, transcriptomics, and epigenomics of LTS is needed.
Abstract
Although the median survival for epithelial ovarian cancer (EOC) is <5 years, approximately 15% of patients will survive for >10 years. 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 >7–10 years 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.
Abbreviations:
EOC (epithelial ovarian cancer), HGSOC (high-grade serous ovarian cancer), LTS (long-term survivor), OCPP (Ovarian Cancer Prognostic Profile), OS (overall survival), SEER (Surveillance, Epidemiology and End Results), STS (short-term survivors)Keywords
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Article info
Publication history
Published online: November 08, 2017
Accepted:
October 26,
2017
Received in revised form:
October 25,
2017
Received:
August 22,
2017
Identification
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© 2017 Elsevier Inc. All rights reserved.
