Perspective

Report outlines research goals, knowledge gaps in ovarian cancer

Ovarian cancer should be considered a group of related gynecologic malignancies rather than a single disease, according to a congressionally mandated report from the National Academies of Sciences, Engineering, and Medicine.

However, knowledge gaps persist in the understanding of the condition, which affect attempts at prevention, early detection, treatment and disease management, according to the report.

“To the best of my knowledge, this is the most comprehensive report in at least a decade to capture the major gaps in ovarian cancer research and understanding why we have not made significant progress in decreasing ovarian cancer mortality,” Kunle Odunsi, MD, PhD, FRCOG, FACOG, professor, deputy director and chair of gynecologic oncology at Roswell Park Cancer Institute, as well as a co-author of the report, told HemOnc Today. “The major aspect here is the understanding that ovarian cancer is not just one disease. There are different subtypes, both at the cellular and molecular level, and this has to be taken into account.”

Kunle Odunsi

Kunle Odunsi, MD, PhD, FRCOG, FACOG

Ovarian cancer is the fifth leading cause of cancer death among U.S. women, with a 5-year survival rate of approximately 46%. More than 21,000 women are diagnosed with the malignancy each year, and approximately 14,000 women die of the disease annually.

Because the condition is often diagnosed at an advanced stage, survival rates over time have been slow to improve, according to a press release issued by the National Academies of Sciences, Engineering, and Medicine. Further, research has shown a decrease in 5-year survival for black women with ovarian cancer, from 42% between 1975 and 1977 to 36% between 2005 and 2007.

“While progress has been made in ovarian cancer research over the past few decades, much remains to be learned,” Jerome F. Strauss III, MD, PhD, dean of Virginia Commonwealth University School of Medicine and chair of the Committee on the State of the Science in Ovarian Cancer Research, said in a press release. “The more that is understood about the basic biology of various types of ovarian cancers, such as where they originate in the body, the more rapidly we can move toward advances in prevention, screening, early detection, diagnosis, treatment and supportive care.”

Not just one disease

The term “ovarian cancer” is a general term used to describe a primary malignancy arising from the ovaries, according to the report. However, the researchers consider the term a misnomer because they view ovarian malignancies as a group of diseases rather than a single cancer.

“Many of the major efforts for the early detection of ovarian cancer have not been successful,” Odunsi said. “In fact, a large study  that was just published in The Lancet — which followed over 200,000 women for more than 14 years — showed essentially no remarkable changes regarding early detection in the general population. Perhaps, we need to identify early detection strategies that might vary from subtype to subtype.”

Ovarian cancers with epithelial differentiation — also called carcinomas — represent the majority of malignant ovarian tumors and lead to the greatest number of disease-related deaths.

However, recent studies suggest many ovarian carcinomas do not originate in the ovary. Rather, they may arise in other areas, such as the fallopian tubes, and then metastasize to the ovaries.

Ovarian carcinomas may also originate in cells not considered intrinsic to the ovary, which is an area that the committee indicated requires more study.

Due to the heterogeneity of ovarian carcinomas, the researchers advocated for increased effort in studying high-grade serous carcinomas, which account for more than 70% of malignant ovarian tumors.

They further highlighted a need for collaboration among researchers in the gynecologic oncology community.

“Given the relative rarity and heterogeneity of ovarian cancers, collaborative research (including the pooling and sharing of data and biospecimen resources, such as through consortia) is essential,” the researchers wrote. “The dissemination of new knowledge and the implementation of evidence-based interventions and practices are the final steps in the knowledge translation process.”

A more precise understanding of ovarian cancer may lead to better treatment options, which is an area of unmet need for these patients, Odunsi said.

“Right now, we essentially treat ovarian cancer uniformly,” he said. “Every woman gets surgery and chemotherapy. But is that the right thing to do for every woman with ovarian cancer? By understanding the molecular subtypes underpinning the immunologic landscape, we can tailor therapies to individual patients.”

Closing the knowledge gap

In addition to the need to understand the subtypes of ovarian cancer, the committee members identified other gaps that likely have prevented research advances and survival improvements. These include an incomplete understanding of genetic and nongenetic risk factors, a lack of effective screening and early detection tools, inconsistency in the delivery of the standard of care and limited attention paid to research on survivorship issues.

To close these gaps, the committee issued 11 overall recommendations that encompass all aspects from prevention to diagnosis to supportive care.

Recommendations included:

  • Researchers and funding organizations should design and prioritize preclinical, clinical and population-based research agendas that recognize different ovarian cancer subtypes, with particular focus given to tumor characteristics, the development of experimental model systems and the incorporation of a multi-subtype paradigm into all aspects of research.
  • Pathology organizations, oncology professional groups and ovarian cancer researchers should reach consensus on diagnostic criteria, nomenclature and classification schemes that reflect the morphological and molecular heterogeneity of ovarian cancer.
  • Genetic counseling should be developed and interpolated into ovarian cancer prevention strategies beyond testing for BRCA mutations and mismatch repair genes associated with Lynch syndrome.
  • Researchers should work to identify underlying mechanisms for new and established ovarian cancer risk factors.
  • Methods should be developed to ensure the consistent implementation of current standards of care that are linked to quality metrics — such as access to specialist care, surgical management, chemotherapy regimen and route of administration, and universal germline genetic testing for newly diagnosed women — to reduce health care disparities.
  • All stakeholders involved in ovarian cancer research should recognize and study the supportive needs of patients with ovarian cancer and their families to provide the best and most effective overall care possible.

The potential advancements associated with these recommendations rest on the facilitation of knowledge sharing in the research community, Odunsi said.

“Ovarian is still a rare cancer at the end of the day,” he said. “The numbers are not as large as breast or lung cancers. So, to accelerate the speed of research, all stakeholders need to come together and work collaboratively. We need to form consortia, share data and make progress.”

Looking forward

Despite the high mortality rates that continue to be associated with ovarian cancer, improved and more precisely focused research has the potential to save lives and lead to a better understanding of the condition.

“The committee felt that there was significant progress made in the understanding of ovarian cancers and that we are at an inflection point,” Strauss said during a public briefing. “This is because of new information and fundamental knowledge that helps us classify the ovarian cancer subtypes, which has a profound impact on our thinking about screening, early detection, prevention and treatment. New knowledge has opened up new pathways across the continuum of care.”

Although it remains a relatively rare condition, ovarian cancer requires focused and continued research, Odunsi said.

“We need to develop more effective screening strategies and gain a better understanding of genetic risk,” he said. “We need to work with immuno-oncology, which will have a role with ovarian cancer. But we need to identify which patients, and which subtypes, will be the most amenable to immunotherapy. The major issue with ovarian cancer treatment has been a ‘one-size-fits-all’ approach. But we know that it is not a one-size-fits-all disease.” – by Cameron Kelsall

References:

Committee on the State of the Science in Ovarian Cancer Research and Board on Health Care Services. Ovarian Cancers: Evolving Paradigms in Research and Care. Washington, D.C.: National Academies Press; 2016.

Jacobs IJ, et al. Lancet. 2015;doi:10.1016/S0140-6736(15)01224-6.

For more information:

Kunle Odunsi, MD, PhD, FRCOG, FACOG, can be reached at kunle.odunsi@roswellpark.org.

Disclosure: Odunsi reports no relevant financial disclosures. HemOnc Today could not confirm the other researchers’ relevant financial disclosures at the time of reporting.

Ovarian cancer should be considered a group of related gynecologic malignancies rather than a single disease, according to a congressionally mandated report from the National Academies of Sciences, Engineering, and Medicine.

However, knowledge gaps persist in the understanding of the condition, which affect attempts at prevention, early detection, treatment and disease management, according to the report.

“To the best of my knowledge, this is the most comprehensive report in at least a decade to capture the major gaps in ovarian cancer research and understanding why we have not made significant progress in decreasing ovarian cancer mortality,” Kunle Odunsi, MD, PhD, FRCOG, FACOG, professor, deputy director and chair of gynecologic oncology at Roswell Park Cancer Institute, as well as a co-author of the report, told HemOnc Today. “The major aspect here is the understanding that ovarian cancer is not just one disease. There are different subtypes, both at the cellular and molecular level, and this has to be taken into account.”

Kunle Odunsi

Kunle Odunsi, MD, PhD, FRCOG, FACOG

Ovarian cancer is the fifth leading cause of cancer death among U.S. women, with a 5-year survival rate of approximately 46%. More than 21,000 women are diagnosed with the malignancy each year, and approximately 14,000 women die of the disease annually.

Because the condition is often diagnosed at an advanced stage, survival rates over time have been slow to improve, according to a press release issued by the National Academies of Sciences, Engineering, and Medicine. Further, research has shown a decrease in 5-year survival for black women with ovarian cancer, from 42% between 1975 and 1977 to 36% between 2005 and 2007.

“While progress has been made in ovarian cancer research over the past few decades, much remains to be learned,” Jerome F. Strauss III, MD, PhD, dean of Virginia Commonwealth University School of Medicine and chair of the Committee on the State of the Science in Ovarian Cancer Research, said in a press release. “The more that is understood about the basic biology of various types of ovarian cancers, such as where they originate in the body, the more rapidly we can move toward advances in prevention, screening, early detection, diagnosis, treatment and supportive care.”

Not just one disease

The term “ovarian cancer” is a general term used to describe a primary malignancy arising from the ovaries, according to the report. However, the researchers consider the term a misnomer because they view ovarian malignancies as a group of diseases rather than a single cancer.

“Many of the major efforts for the early detection of ovarian cancer have not been successful,” Odunsi said. “In fact, a large study  that was just published in The Lancet — which followed over 200,000 women for more than 14 years — showed essentially no remarkable changes regarding early detection in the general population. Perhaps, we need to identify early detection strategies that might vary from subtype to subtype.”

Ovarian cancers with epithelial differentiation — also called carcinomas — represent the majority of malignant ovarian tumors and lead to the greatest number of disease-related deaths.

However, recent studies suggest many ovarian carcinomas do not originate in the ovary. Rather, they may arise in other areas, such as the fallopian tubes, and then metastasize to the ovaries.

Ovarian carcinomas may also originate in cells not considered intrinsic to the ovary, which is an area that the committee indicated requires more study.

Due to the heterogeneity of ovarian carcinomas, the researchers advocated for increased effort in studying high-grade serous carcinomas, which account for more than 70% of malignant ovarian tumors.

They further highlighted a need for collaboration among researchers in the gynecologic oncology community.

“Given the relative rarity and heterogeneity of ovarian cancers, collaborative research (including the pooling and sharing of data and biospecimen resources, such as through consortia) is essential,” the researchers wrote. “The dissemination of new knowledge and the implementation of evidence-based interventions and practices are the final steps in the knowledge translation process.”

A more precise understanding of ovarian cancer may lead to better treatment options, which is an area of unmet need for these patients, Odunsi said.

“Right now, we essentially treat ovarian cancer uniformly,” he said. “Every woman gets surgery and chemotherapy. But is that the right thing to do for every woman with ovarian cancer? By understanding the molecular subtypes underpinning the immunologic landscape, we can tailor therapies to individual patients.”

Closing the knowledge gap

In addition to the need to understand the subtypes of ovarian cancer, the committee members identified other gaps that likely have prevented research advances and survival improvements. These include an incomplete understanding of genetic and nongenetic risk factors, a lack of effective screening and early detection tools, inconsistency in the delivery of the standard of care and limited attention paid to research on survivorship issues.

To close these gaps, the committee issued 11 overall recommendations that encompass all aspects from prevention to diagnosis to supportive care.

Recommendations included:

  • Researchers and funding organizations should design and prioritize preclinical, clinical and population-based research agendas that recognize different ovarian cancer subtypes, with particular focus given to tumor characteristics, the development of experimental model systems and the incorporation of a multi-subtype paradigm into all aspects of research.
  • Pathology organizations, oncology professional groups and ovarian cancer researchers should reach consensus on diagnostic criteria, nomenclature and classification schemes that reflect the morphological and molecular heterogeneity of ovarian cancer.
  • Genetic counseling should be developed and interpolated into ovarian cancer prevention strategies beyond testing for BRCA mutations and mismatch repair genes associated with Lynch syndrome.
  • Researchers should work to identify underlying mechanisms for new and established ovarian cancer risk factors.
  • Methods should be developed to ensure the consistent implementation of current standards of care that are linked to quality metrics — such as access to specialist care, surgical management, chemotherapy regimen and route of administration, and universal germline genetic testing for newly diagnosed women — to reduce health care disparities.
  • All stakeholders involved in ovarian cancer research should recognize and study the supportive needs of patients with ovarian cancer and their families to provide the best and most effective overall care possible.

The potential advancements associated with these recommendations rest on the facilitation of knowledge sharing in the research community, Odunsi said.

“Ovarian is still a rare cancer at the end of the day,” he said. “The numbers are not as large as breast or lung cancers. So, to accelerate the speed of research, all stakeholders need to come together and work collaboratively. We need to form consortia, share data and make progress.”

Looking forward

Despite the high mortality rates that continue to be associated with ovarian cancer, improved and more precisely focused research has the potential to save lives and lead to a better understanding of the condition.

“The committee felt that there was significant progress made in the understanding of ovarian cancers and that we are at an inflection point,” Strauss said during a public briefing. “This is because of new information and fundamental knowledge that helps us classify the ovarian cancer subtypes, which has a profound impact on our thinking about screening, early detection, prevention and treatment. New knowledge has opened up new pathways across the continuum of care.”

Although it remains a relatively rare condition, ovarian cancer requires focused and continued research, Odunsi said.

“We need to develop more effective screening strategies and gain a better understanding of genetic risk,” he said. “We need to work with immuno-oncology, which will have a role with ovarian cancer. But we need to identify which patients, and which subtypes, will be the most amenable to immunotherapy. The major issue with ovarian cancer treatment has been a ‘one-size-fits-all’ approach. But we know that it is not a one-size-fits-all disease.” – by Cameron Kelsall

References:

Committee on the State of the Science in Ovarian Cancer Research and Board on Health Care Services. Ovarian Cancers: Evolving Paradigms in Research and Care. Washington, D.C.: National Academies Press; 2016.

Jacobs IJ, et al. Lancet. 2015;doi:10.1016/S0140-6736(15)01224-6.

For more information:

Kunle Odunsi, MD, PhD, FRCOG, FACOG, can be reached at kunle.odunsi@roswellpark.org.

Disclosure: Odunsi reports no relevant financial disclosures. HemOnc Today could not confirm the other researchers’ relevant financial disclosures at the time of reporting.

    Perspective
    Joshua P. Kesterson, MD

    Joshua P. Kesterson, MD

    The so-called “war on cancer” started more than 40 years ago when President Nixon signed into law the National Cancer Act of 1971 to “more effectively carry out the national effort against cancer.” That war is still being fought; however, its spoils are dubious depending on the particular cancer. 

    Ovarian cancer affects more than 20,000 women each year in the United States, a majority of whom will ultimately succumb to the disease. Although incremental strides have been made regarding the types of chemotherapy used — as well as the combinations of, sequencing of and route of administration — the cumulative pace has been somewhat pedestrian compared with progress made in other disease sites. In certain populations, it has even been notably regressive.

    In “Ovarian Cancers: Evolving Paradigms in Research and Care,” the Committee on the State of the Science in Ovarian Cancer Research have comprehensively, yet eloquently, generated a detailed typography of the current landscape of ovarian cancer, with a particular appreciation for the heterogeneity of the various entities incorporated under the rather broad taxonomic category of ovarian cancer. The committee makes multiple specific recommendations aimed at reducing ovarian cancer morbidity and mortality. These include: increasing penetrance of genetic counseling and screening, developing screening strategies, improving current treatment approaches and reducing disparities in health care delivery and outcomes.

    This report highlighting the current state of ovarian cancer research and the opportunities for future research will hopefully serve as a blueprint for a unified approach to improving current and future outcomes for women with ovarian cancer. For, as noted by the ancient military strategist Sun Tzu, “If you know the enemy and know yourself, your victory will not stand in doubt.”

    • Joshua P. Kesterson, MD
    • Penn State Hershey Medical Center

    Disclosures: Kesterson reports no relevant financial disclosures.