The deadliest form of cancer

Researchers and funding organisations should identify and evaluate the underlying mechanisms of both new and established risk factors of ovarian cancers
Dr. Mohammed Abul Kalam

World Cancer Day was celebrated earlier this month all over the world to commemorate all the efforts done by the WHO, United Nations, governmental and nongovernmental health organisations towards making the strategy to fight against cancer as well as distributing the real message about this epidemic disease and its treatments including its precautionary measures by uniting all the people a day on global basis. It is celebrated to plan some new strategies as well as implement some new programs which help to make more people aware about this disease. This event is organised on annual basis under the supervision of Union for International Cancer Control (UICC) and other leading health organisations involved for cancer fighting. World Cancer Day 2018 was celebrated all across the world on of February4 including Bangladesh.

There are more than 100 types of cancer. There are top 10 deadliest types of cancers: (1) pancreatic cancer (2) mesothelioma (3) liver (4) bile duct cancers (5) lung cancer (6) gallbladder cancer (7) cancer of the esophagus (8) uterus/ovarian cancer(9) stomach (10) brain as well as some forms of leukemia, round out this grim list.

Although recent years have seen promising advances in cancer research, there remain surprising gaps in the fundamental knowledge about and understanding of ovarian cancer, including basic biology, risk factors, diagnosis, delivery of care, and survivorship. Ovarian cancer is relatively uncommon, yet it is one of the deadliest cancers. Symptoms such as bloating, pelvic or abdominal pain and urinary symptoms can be nonspecific, so they are often not initially seen as indicating a serious illness. Late diagnosis and a high rate of recurrence are major factors contributing to the high mortality rate.

Ovarian cancer is not just one disease; rather, it is a constellation of distinct types of cancer involving the ovary. Epithelial cancers (carcinomas) represent 85 percent of malignant ovarian tumours and are responsible for most ovarian cancer–related deaths. Ovarian carcinomas are further classified into different subtypes, the most common subtype being high-grade serous carcinoma (HGSC).

Recent evidence suggests that many ovarian carcinomas do not arise in the ovary per se.  Instead, they may arise from cells that are not considered intrinsic to the ovary or from other tissues and then metastasise to the ovary.

The biology of ovarian cancer: Ovarian cancer research is complicated by the significant degree of heterogeneity of ovarian carcinomas, both within and between subtypes, yet clinicians and researchers tend to combine them in many types of research. In spite of recent advances, the incomplete understanding of the basic biology of each subtype, including origin and pathogenesis, is an impediment to advances in prevention, screening and early detection, diagnosis, treatment, and supportive care. Gaps in the understanding of ovarian cancer biology have also prevented the emergence of uniform standards for describing the characteristics of the subtypes.

Diagnosis and treatment: Newly diagnosed ovarian cancers are now being more accurately and consistently staged, and a wider variety of treatment options exist. Still, clinicians have few options for drug therapy, and the long-term efficacy of these agents is limited by a high rate of drug resistance. Further, most women will experience a recurrence of the disease, resulting in repeated surgeries and additional rounds of chemotherapy. While women who receive care in accordance with national clinical practice guidelines have considerably better clinical outcomes—including improved survival—less than one-half of women with ovarian cancer receive such care. More research is needed on the barriers to receiving the standard of care and on the use of quality metrics to help drive continuous quality improvement.

Supportive care along the survivorship trajectory: Most ovarian cancer research focuses on disease treatment rather than on how to improve the management of the acute and long-term physical and psychosocial effects of diagnosis and treatment across the trajectory of survivorship. For women with ovarian cancer, shared decision making and the management of the physical and psychosocial effects may be neglected in the effort to urgently address the typically advanced stage of disease at diagnosis. Current research provides little insight as to which women are most likely to suffer physical and psychosocial effects, or the best approaches for managing these effects.

Dissemination and implementation of knowledge: While the knowledge base on ovarian cancers has advanced, not all stakeholder groups are receiving important messages. This may contribute to the variability seen in the delivery of the standard of care which, in turn, affects outcomes. Dissemination of new information among multiple stakeholders—patients, families, health care providers, industry, payers, media, and advocacy groups—is critical.

The following recommendations are intertwined and so need to be considered simultaneously, not sequentially. Their sequence should not be considered as priority of importance or order of implementation.

Recommendation 1: Researchers and funding organisations should design and prioritize preclinical, clinical, and population-based research agendas in the context of the different ovarian cancer subtypes.

A top priority should be elucidating the cellular origins and pathogenesis of each subtype. Particular attention should be paid to: (1) Tumour characteristics such as microenvironment, intratumoral heterogeneity, and progression pathways; (2) Development of experimental model systems that reflect ovarian cancer heterogeneity; and (3) Incorporation of the multi subtype paradigm into prevention, screening, diagnosis, and treatment research.

Recommendation 2: Pathology organisations, 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 cancers and promote the universal adoption of a standardised taxonomy.

Recommendation 3: Researchers, public health practitioners, and clinicians should develop and implement innovative strategies to increase genetic counselling and testing, as well as cascade testing, for known germ line genetic predispositions in appropriate populations (e.g., untested ovarian cancer survivors, relatives of individuals who tested positive). Furthermore, researchers, clinicians, and commercial laboratories should determine the analytic performance and clinical utility of testing for other germ line mutations beyond BRCA1 and BRCA2 and the mismatch repair genes associated with Lynch Syndrome.

Recommendation 4: Researchers and funding organisations should identify and evaluate the underlying mechanisms of both new and established risk factors for ovarian cancers to develop and validate a dynamic risk assessment tool accounting for the various ovarian cancer subtypes. Furthermore, a spectrum of risk factors should be considered, including genetics, hormonal and other biological markers, behavioural and social factors, and environmental exposures.

Recommendation 5: Clinicians, researchers, and funding organisations should focus on quantifying the risk-benefit balance of nonsurgical and surgical prevention strategies for specific subtypes and at-risk populations.

Recommendation 6: Researchers and funding organisations should focus on the development and assessment of early detection strategies that extend beyond current imaging modalities and biomarkers and reflect the pathobiology of each ovarian cancer subtype.

Recommendation 7:To reduce disparities in health care delivery and outcomes, clinicians and researchers should investigate methods to ensure the consistent implementation of current standards of care (e.g., access to specialist care, surgical management, chemotherapy regimen and route of administration, and universal germ line genetic testing for newly-diagnosed women), that are linked to quality outcome metrics.

Recommendation 8:Clinicians and researchers should focus on improvement of current treatment strategies, including: (1)  Development and validation of comprehensive clinical, histopathologic, and molecular characterisations that better inform precision medicine approaches for women with newly diagnosed and recurrent disease (2)  Advancement in the understanding of the mechanisms of recurrent and drug-resistant (e.g., platinum resistant) disease and development of a more informative classification system; (3) Identification of predictors of response to therapy and near-term indicators of efficacy; and  (4) Determination of the optimal type and timing of surgery in women newly diagnosed with ovarian cancer and efficacy of subsequent cytoreduction procedures for women with recurrent disease.

Recommendation 9: Researchers should develop more effective pharmacologic and non-pharmacologic therapies and combinations of therapies that leverage the unique biology and clinical course of ovarian cancer. These approaches should include: (1) Developing immunologic and molecularly driven treatment approaches specific to the different ovarian cancer subtypes, (2) Identifying markers of therapeutic resistance and exceptional response, and (3) Using interdisciplinary teams to design and conduct statistically efficient and information-rich clinical studies.

Recommendation 10: Researchers and funding organisations should study the supportive care needs of patients with ovarian cancer throughout the disease trajectory, including: (1) Identifying the array of factors that put women at high risk for poor physical and psychosocial outcomes, (2) Identifying and overcoming barriers to systematic assessment of physical and psychosocial effects of disease and treatment, (3) Developing and implementing more effective supportive care and self-management interventions, and (4) Defining the parameters that indicate when patients and their families would benefit from transitioning to end-of-life care.

Recommendation 11: Stakeholders in ovarian cancer research, clinical care, and advocacy should coordinate efforts to develop and implement efficient, effective, and reliable methods for rapid dissemination and implementation of evidence-based information and practices to patients, families, health care providers, advocates, and other relevant parties. These efforts should include: (1) Researching impediments to adopting current evidence-based practices; (2) Using multiple existing dissemination modalities (e.g., continuing education, advocacy efforts) to distribute messages strongly supported by the evidence base, and (3) Evaluating newer pathways of dissemination and implementation (e.g., social media, telemedicine with specialists).

Conclusion: While progress has been made in understanding ovarian cancers over the past few decades, much remains to be learned, especially about the origins and mechanisms of development—fundamental knowledge that could change paradigms for prevention, screening and early detection, and treatment. Improved communication is also needed to recognize ovarian cancer as a constellation of many types of cancer involving the

A focus on distinct areas of research within and across the continuum of ovarian cancer care will help improve the lives of all women at risk for or diagnosed with an ovarian cancer.

The writer is former Head, Department of Medical Sociology
Institute of Epidemiology, Disease Control & Research (IEDCR)


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