Ovarian cancer is not a single disease, but a heterogeneous constellation of cancers – an emerging idea that should shape the paths of research, prevention, diagnosis, and treatment.
The recent understanding that most ovarian cancers do not arise from ovarian tissue poses a unique set of challenges in all of these areas, according to a new, congressionally mandated report by the National Academies of Sciences. The 400-page report discusses research opportunities that could – if addressed – greatly affect the number of women who are diagnosed with or die from ovarian cancers.
“We are at an inflection point,” in this understanding, and how it will shape ovarian cancer research, Dr. Jerome F. Strauss III, chair of the writing committee, said during a press briefing. “This new knowledge will help us classify subtypes and have a profound impact, and help improve the lives of women who at risk of, or who have been diagnosed, with ovarian cancer.”
The report, “Ovarian Cancers: Evolving Paradigms in Research and Care,” was authored by a panel of 15 experts. It plumbed not only their own expertise, but a wealth of clinical, research, and policy data.
The committee made 11 recommendations in four key areas: preclinical research into ovarian cancer biology; prevention and early detection; diagnosis and treatment; and supportive care during survivorship.
One of the most important points, though, relates not to the acquisition of knowledge, but to its dissemination, said Mary Scroggins, an ovarian cancer survivor, patient advocate, and a member of the writing committee.
“Gathering evidence about risks and treatment and prevention strategies doesn’t ensure that the knowledge will be used,” she said. “We need to act on what we learn. We are calling for coordination among stakeholders to develop and implement rapid dissemination of new findings – and to find out why we are not adopting the current evidence-based practices.”
There is an urgent need to elucidate the biology and pathophysiology of the diverse subtypes of ovarian cancers. As these are more fully understood, appropriate research agendas may be constructed to determine each subtype’s unique biomarkers, which could be used as screening and diagnosis tools, and its unique vulnerabilities, which can be exploited in targeted treatments.
In addition to learning about the tumors themselves, Dr. Strauss said it’s important to understand why the ovary appears to be such a hospitable environment for the proliferation of premalignant and malignant seed cells shed from other reproductive tissues, including the Fallopian tube and endometrium.
As tumor subtypes are identified, they need to be described in a common language. Consensus must be reached on diagnostic criteria, nomenclature, and classification systems.
“This is terribly important,” Dr. Strauss said. “Without it, we cannot build a research agenda and move forward.”
Some tumor subtypes are genetically driven; others are not. Some genetically driven tumors are familial; others arise from spontaneous mutation. Understanding these genetic underpinnings will be crucial to developing targeted therapy. There is a need to increase both genetic testing and counseling, not just for the patient but for her immediate family. This will certainly extend beyond the BRCA 1 and 2 genes as knowledge of tumor subtypes unfolds.
“Our ability to identify women at high risk will have a significant impact on morbidity and mortality,” said committee member Dr. Beth Y. Karlan, a gynecologic oncologist from the University of California, Los Angeles. “We already know that family history and genetic mutations are all strong risk factors that call for genetic counseling, but the referral often doesn’t happen.”
Most of the now-known ovarian cancers are not genetically driven. Research should delve into the underlying mechanisms and risk factors for these tumors as well. Findings here may lead to more effective prevention strategies, as well as risk assessment tools.
Both surgical and nonsurgical treatment approaches should be tailored to individual tumor subtypes. These, as well as preventive measures, should be studied in light of their benefits and potential harms, both for diagnosed patients and those at high risk of developing the disease.
Ovarian cancers are highly lethal, in part, because they are often diagnosed at a late stage. Developing effective early-identification methods will be key to reducing morbidity and improving long-term survival.
“Our efforts at early detection have improved, but have not had a substantial impact on mortality,” Dr. Karlan said. “And, since many tumors don’t arise in the ovary, looking at the ovary may not really be much help in early detection. We need to expand the development of new techniques,” which may differ by tumor subtypes.