Rethinking ovarian cancer: recommendations for improving outcomes

Abstract

There have been major advances in our understanding of the cellular and molecular biology of the human malignancies that are collectively referred to as ovarian cancer. At a recent Helene Harris Memorial Trust meeting, an international group of researchers considered actions that should be taken to improve the outcome for women with ovarian cancer. Nine major recommendations are outlined in this Opinion article.

Trial registration: ClinicalTrials.gov NCT00262847 NCT00434642 NCT00483782.

Figure 1. Survival from ovarian cancer

One-, three- and five-year survival post-diagnosis of ovarian cancer patients over the past 20 years. Data from: A) Surveillance, Epidemiology and End Results (SEER, 1980–2004); B) The Cancer Council of Victoria, Victoria, Australia (1990–2004); C) The Cheryl Brown Outcomes Unit, British Columbia, Canada (1980–2004).

Figure 2. The origins of ‘ovarian’ cancer

Ovarian cancer is a collective term for invasive cancers derived from different tissues. A majority of invasive mucinous ovarian cancers are metastases to the ovary, often from the gastrointestinal tract including colon (Co), appendix (Ap) or stomach (St). Endometrioid and clear cell ovarian cancers are derived from endometriosis, which in turn is associated with retrograde menstruation (blue arrow) from the endometrium (En). High grade serous ovarian cancers are derived from the surface of the ovary (Ov) and/or distal fallopian tube (FT) - the relative contribution that the two sites make to these tumours remains unclear. Benign and low malignant potential (borderline) tumours are not included in the diagram. Such tumours are thought to be of ovarian origin, however, the originating cells are not defined and their derivation may be revised in the future. Histological images courtesy of R. Drapkin, Dana-Farber Cancer Institute, USA, and C. Crum, Brigham and Women's Hospital, USA.

Figure 2. The origins of ‘ovarian’ cancer

Ovarian cancer is a collective term for invasive cancers derived from different tissues. A majority of invasive mucinous ovarian cancers are metastases to the ovary, often from the gastrointestinal tract including colon (Co), appendix (Ap) or stomach (St). Endometrioid and clear cell ovarian cancers are derived from endometriosis, which in turn is associated with retrograde menstruation (blue arrow) from the endometrium (En). High grade serous ovarian cancers are derived from the surface of the ovary (Ov) and/or distal fallopian tube (FT) - the relative contribution that the two sites make to these tumours remains unclear. Benign and low malignant potential (borderline) tumours are not included in the diagram. Such tumours are thought to be of ovarian origin, however, the originating cells are not defined and their derivation may be revised in the future. Histological images courtesy of R. Drapkin, Dana-Farber Cancer Institute, USA, and C. Crum, Brigham and Women's Hospital, USA.

Figure 3. Evolution of chemotherapy for ovarian cancer over the last 50 years

It has proved difficult to progress beyond platinum-based therapy, which was introduced in the late 1970s and remains standard of care. Cisplatin and subsequently carboplatin, which has a lower toxicity profile, have been combined with other agents, including taxanes. Most recently, liposomal doxorubicin has become commonly used with carboplatin, especially in a relapse setting. It is notable that the combination of carboplatin and liposomal doxorubicin involve similar drugs to those used in the mid-70s, albeit with reduced side-effects. It is likely that ovarian cancer treatment will evolve significantly in the coming years with the introduction of molecularly targeted agents, such as the poly(ADP-ribose) polymerase PARP inhibitors, histotype-specific treatments, and dose dense regimes, including use of weekly taxane.