A Short Introduction to Health, Illness and Disease in the Context of Ovarian Cancer

What is health? And why is this concept important to define? Throughout history several perceptions and concepts of health have been designed and discussed. With the progression in medicine, there is an urgent need to take into consideration what health is today, how we talk about health, who is declaring a status of ‘good health’, and the limitations of modern medicine in being able to declare ‘good health’.

Health is the harmonious functioning of the organs (Pindar).

Health was first understood as a divine responsibility held by the one who created Man; The Eternal One Himself. In the ancient Greece, the demand of reality being explained through natural causes arose. Dualism: the separation of mind and body, the connection between a person and the environment and the nature of disease, are perspectives brought to life by poets and philosophers like Pindar, Plato, Aristoteles and Hippocrates.

Health is a state of being in complete harmony with the ‘universe’, a universe never affected by old age and disease due to the harmonious synthesis of the four fundamental elements (fire, earth, water and air) providing its sub-stance (Plato).

In the modern world, the perspectives from the ancient Greece are still valid, however new perspectives and concepts of health have emerged. The World Health Organization (WHO) defines health as “A state of complete physical, mental and social well-being and not merely the absence of disease or infirmity” (World Health Organization 1946). The definition has not been amended since it was entered into force in 1948. However, the advances in medicine and science have led us into a new era; the era of precision and personalised medicine, challenging the WHO definition and former philosophical theories of health with new understandings of disease, study of diseases (pathology) and medical phenomena (The Lancet editorial 2009). Other attempts to define health introduce several other elementary ideas, all considered as “paradigm objects of medical concern”: (1) Value; (2) Treatment by physicians; (3) Statistical normality; (4) Pain, suffering and discomfort; (5) Disability; (6) Adaption and (7) Homeostasis (Boorse 1977). All these ideas are part of different conceptual frameworks, or models, of thinking about health, disease and illness. Among these models, we have the biomedical model; the biopsychosocial model; the holistic (religious) model; the ideal model; the humanistic (holistic) model; the psychosomatic model and the existential model (Tamm 1993; Hofmann 2005). All these models present health from different perspectives, both individual and societal.

Perspectives and Concepts of Disease and Illness in Health

Disease is not the opposite of health, however, the understanding of disease and how to define disease is as tricky as defining health. There are several different perspectives and concepts of what disease is, even among health professionals as well as what good health is not, one being disease understood as a generalized phenomenon (the psychological concept) and another one is disease understood as entities (the ontological concept) (Cassell 1991, 4). The medical model provides criteria for something to be a disease, and these criteria are stricter than “just” being un-healthy (Hofmann 2005).

Disease, then, is something an organ has; illness is something a man has (Cassell 1976, 27).

The easy way would be to define disease as a deviation from what is normal, in traditional medicine also called pathophysiology, diagnosed and treated by doctors (Pool and Geissler 2005). However, there are subscales of disease, subscales that have certain normative features reflected in the institutions of medical practice – illness (Boorse 1975). Patricia Benner (1989, 303) once defined illness as “the human experience of dysfunction”. What is important to highlight in that definition is the ‘human experience’. Illness is something that is subjectively experienced by an individual. Let’s look further at the difference between disease and illness.

Health professionals involved in patient treatment relate to concepts, models and perspectives of health, disease and illness. The clinical gaze, the perspective of seeing the patient through a biomedical lens where biology causes disease, was introduced by Michel Foucault in The birth of the clinic in 1963 (Foucault 2003). In the perspective of Hippocrates, the father of medicine, disease was caused by biological factors. He conveyed the dualistic view of mind and body making way for the biomedical model: viewing different aspects of the human body rather than man as a totality – a reductionistic view (Tamm 1993). The biomedical model has made enormous improvements in medical care focusing on physical health, genetic vulnerabilities and drug effects (Tamm 1993), however this model has been criticised for the exclusion of social, psychological and behavioural dimensions of illness introducing the biopsychosocial model (Engel 1977).The biomedical model explain health as defined in the biophysiological world, while the holistic model represents the world of phenomena, promoting the lived experience of health, and dealing with illness and disease (Benner 1985). The holistic model, the expression of wholeness and the care for the whole person; the spiritual, physical, mental and social needs of a person are all related to human good. The criteria of health being the absence of disease is set aside, introducing criteria for health in wellbeing, happiness, human flourishing, ability to realise goals and to promote human functioning as a whole (Hofmann 2005). Compared to the biomedical model, the clinical gaze, focusing on disease, the holistic model gives an important place to illness. As a comparison, in the ideal model of healthdisease is seen as the absence of health and health as the absence of disease.

The different models of health, disease and illness show that there are different framings of these concepts, and different priorities given to a holistic perspective or a more reductionist one. This starts to outline the challenges of communicating the understanding of health, illness and disease between the patients and the clinicians. Arguably, this issue is even more stringent for cancer, as it is an extremely complex disease that evolves over time, and where the patient’s ‘home-world’ is fundamentally changed. Cancer patients live in both the biophysiological world and the phenomena world with their lived experience of health, dealing with illness and disease; two levels of discourse, calling for different explanations (Benner 1985).

How do physicians and patients communicate and understand health, the disease of cancer, the illness caused by cancer and the reality of cancer treatment? In Susan Sontag’s book Illnessas Metaphor and AIDS and Its Metaphores (2005), she writes about metaphors of cancer, especially metaphors regarding cancer and illness. She urges us to take illness literally, it is not a metaphor although it is often treated as one. Illness is a difficult word to understand. At first it sounds negative much due to personal interpretations and misunderstanding of the word, but it can also be healthy and normal when used in its right shape. You may experience illness, but you will return to wellness.

In a context of high biological complexity and uncertainty, where medical decision-making is not guided by clear, full-proof facts, it is easy to be misled by the assumption that the concept of “good health” is not a fixed entity.

In his book Nature of Sufferingand the Goals of Medicine (1991) Eric J. Cassell claims the hallmark of modern medicine to be its dependence on science and technology and the conflict these two creates when dealing with suffering will be a predicament for medicine. The science of modern medicine, in its new meaning, is the science of normal and abnormal biology. Why is the disease the centre of focus in modern medical science instead of the sick patient, what happened?

By defining disease or disability in terms of genetic loci, the relationship to experience is made a step more distant: removed not just from the lived experience of the phenotype, but from the development of the phenotype itself (Scully 2004, 653).

The rapid advances in medicine and the era of precision medicine urge us to provide the ultimate explanation of disease, often to the expense of the more superfluously trapping of “human culture and language” (Benner 1985). In the perfect world of personalised medicine, physicians would help patients adapt to their unique prevailing conditions (The Lancet editorial 2009). But are doctors and patients living in the same world, communicating and understanding by the same language of medicine and health, or are they all lost in translation?

The aim of this chapter is to provide an understanding of how the biophysiological, and phenomena worlds interact with each other in the decision-making process and management of ovarian cancer. This chapter discusses changes in health, disease and illness over time, the trajectory, and the discrepancies in knowledge translation, understanding and eventually decision-making in ovarian cancer from a patient perspective and from a doctor’s perspective. In order to explore these questions and concepts, the author will guide you through two fictional journeys, based on literature, focus-group interviews with patients, physicians and the author’s own experience. But first and foremost, there is a need for a short understanding to what ovarian cancer is.

A Brief Introduction to Ovarian Cancer – “The Silent Killer”

In the western world, epithelial ovarian cancer (EOC) is the leading cause of death from gynaecological malignancies (Allemani et al. 2015; Mor and Alvero 2013). EOC is the 8th most common neoplasm with 295,414 new cases in 2018 worldwide, and the 8th leading cause of cancerdeaths in women (Bray et al. 2018). The 5-year survival rates range from 29% to 89%, depending on histological group and advancement of the disease (Timmermans et al. 2018; De Angelis et al. 2014). The cellular origin and pathogenesis of EOC is not well known or understood (Desai et al. 2014; Kurman 2014). EOC can be subdivided into at least five different histological subtypes, each with different aetiologies and genetic, phenotypic, and clinical features (Kurman 2014; Desai and Soon-Shiong 2014).

Symptoms of EOC are non-specific. Women may experience gastrointestinal symptoms like nausea, loss of appetite, early satiety, abdominal distension, bloating, pain, tenesmus and constipation (Goff et al. 2004; Fitch et al. 2002). Others report of symptoms of unusual fatigue, weight loss, urinary symptoms and gynaecological symptoms (Bankhead et al. 2005). All of these symptoms could be related to several other diagnosis, leading to the inevitable result: the majority of women are diagnosed at late and advanced stages with metastases disseminated throughout the peritoneal cavity (Berek et al. 2018a; Kurman 2014). Advanced disease at time of diagnosis is the main reason why the overall survival rate still is <45% (Morgan 2011), giving EOC the reputation of being a “silent killer”.

Staging is the description of the size of the cancer and where it is located. EOC is staged according to the International Federation of Gynaecology and Obstetrics (FIGO) staging system from 2014 (updated in 2018) (Berek et al. 2018b). The stage is set based on perioperative judgements in combination with histopathological evaluation. There are a variety of different EOC subtypes, the high-grade serous ovarian cancer (HGSOC) is the most lethal one of them all as it often presents itself in a high stage (Vang et al. 2009; Lisio et al. 2019). The main treatment of HGSOC, both early and late stages, has been the same for decades; advanced surgery followed by platinum- and taxane-based chemotherapy. Macroscopic visible residual disease has been shown to be the single most important, independent, negative and prognostic factor for survival. At recurrence, which is common, patients still receive multiple therapeutics (primarily chemotherapy and/or targeted drugs), but the attention will change from cure to palliation.

Biomarkers in Epithelial Ovarian Cancer

Cellular biology and cancerbiomarkers are the unique molecular signature of your cells or a protein, like a fingerprint. This is a simple explanation of a research area, that has been unveiled since President Obama announced the research initiative towards a new era of precision medicine in 2015 (Collins and Varmus 2015). Biomarkers are still a young area of research and the era of precision medicine in the landscape of ovarian cancerbiomarkers is yet to come (Ueland 2017).

For many years one believed the origin of the HGSOC to be from the surface epithelium or epithelial inclusions in the ovary, but recent studies indicate its origin to be the fallopian tube (Labidi-Galy et al. 2017; Berek et al. 2018a). The pathogenesis of HGSOC differs from the low-grade serous carcinomas with a high level of chromosomal instability, mutated TP53 and a rapid tempo of tumour development (Vang et al. 2009). This pathogenesis causes diagnosticchallenges in HGSOC, making this histological subtype responsible for 70-80% of all deaths in ovarian cancer (Lisio et al. 2019). Identifying biomarkers that can identify the disease at an early stage is of the outmost importance to reduce deaths in HGSOC. HGSOC, biomarkers that are identified shows to have an impact of diagnostic, predictive and prognostic clinical value as in: symptomatic disease/asymptomatic disease; tumour invasion; ascites; imaging; general health status; carbohydrate antigen (CA125); decrease in CA125; platinum response; BRCA status single molecules versus signatures molecules. As one can see biomarkers have different functions: diagnostic, predictive, prognostic or therapeutic (Hennessy et al. 2008). Diagnosticbiomarkers are used in the determination of whether a patient has HGSOC, indicating the treatment the patient should be offered (FDA-NIH Biomarker Working Group 2016). While predictive biomarkers can predict if the patient will respond to the treatment, prognostic biomarkers will give information of the outcome of the disease (Italiano 2011). Main types of predictive and prognostic biomarkers are clinical markers, histopathologic markers, molecular markers and imaging markers. However, predictive and prognostic biomarkers can be exchanged causing confusion mix-up (Oldenhuis et al. 2008). Therapeutic biomarkers in ovarian cancer can be proteins as target for therapy. Few, or none, are related to early diagnosis and/or patient-centred treatment. Up until recently, ovarian cancerbiomarkers have consisted of single – biomarkers like the CA125, reliable but not very sensitive (Dochez et al. 2019). In the present, biomarkers in ovarian cancer are going towards algorithms consisting of several single – biomarkers like the Multivariate Index Assay, Risk of Malignancy Index (RMI) and the Risk of Ovarian Malignancy Algorithm (ROMA) in order to improve the characteristics of single-biomarkers (Ueland 2017; Dochez et al. 2019).

The Journey and Trajectory of Ovarian Cancer

The word journey is often used as a metaphor by cancer patients when describing their illness experience (Semino et al. 2017) while trajectory is used when describing the course of the disease. You are now to be presented to Anne her journey, her journey of illness: through the curative and the palliative journey of ovarian cancer. Starting with who Anne is then leading to the psychological and cognitive suspicion of something being medically wrong, not knowing what it is or where it will lead her, involving existential and spiritual experiences.

Cancer is a journey, but you walk the road alone. There are many places to stop along the way and get nourishment – you just have to be willing to take it (Emily Hollenberg, cancer survivor, 2020).

Anne – The Suspicion of Something Being Wrong

Anne is living in the twenty-first century, the year is 2020. She was born in 1964, the same year as Martin Luther King Jr. received the Nobel Prize and seven years before President Richard Nixon signed the National Cancer Act later known as his War on Cancer. She spent her childhood and teens in a small industrial community in the western part of Norway, being somewhat happy and fearless, unaware of what the future will bring. Then her mother dies of cancer when Anne is 17 years old, an adolescent now feeling both angry and sad by the loss of her mother, everything she had taken for granted was now thrown into the air. They said the cancer was in her “tummy”, nobody asked for more information and Anne does not want to upset her father by asking. He, her father, is a man of few words. Every day she sees the grief in his face, the same face Anne looks at in the mirror, but without her mother her father becomes the cornerstone in her life, no words are needed.

Years passes, and Anne meets John and becomes pregnant, a boy. She becomes a teacher but studying and caring for her family comes with a cost, Anne and John drifts apart however still connected with a deep desire to keep the family together in marriage. Anne finds comfort in her job, she loves teaching small children, but lately she has been feeling tired and for the first time she is feeling low on energy. She has just turned 57 years old. She can’t remember when the changes started, they probably came gradually. Anne relates it to lack of exercise, she hasn’t found the time or effort to exercising and she is getting older and sensing more stress to most things in life. Her stomach feels “filled up”, her appetite is poor at the same time she struggles with constipation, and she has to admit that her pants are getting too tight. Anne doesn’t like complaining, she thinks the changes in her body are probably normal for her age, her friends are experiencing some of the same changes, however her husband advises her to see her general practitioner (GP), but the GP doesn’t find anything abnormal when examining her, but he wants her to take some blood samples “just to be safe”. Being reassured by her GP, Anne continues her everyday living, accepting that nothing was found but she doesn’t understand why her physical state is not improving, it should improve if nothing is wrong shouldn’t it? Should she return to her GP? Besides, she remembers being to the gynaecologist taking the ultrasound and other tests just six months ago, everything was normal then, things can’t change so fast, or can they?

Now, Anne has been feeling ill for a while, without her GP detecting a disease. She is feeling more tired and is experiencing more undesirable bodily complaints such as weight loss, nausea and shortened of breath. She is however still undermining her symptoms, relating them to bodily changes, maybe more a hope of normality rather than logic normality.

Intermission – Moving from Illness to Disease: Classifying Ovarian Cancer

A survey performed by the World Ovarian Cancer Coalition (World Ovarian Cancer Coalition 2018) found that more than 90% of women diagnosed with ovarian cancer experienced multiple symptoms prior to diagnosis, but even so, almost half of the women waited three to six months before going to the doctor. Increased abdominal size is the most commonly reported symptom in recognising ovarian cancer, but women in general have not heard of ovarian cancer when experiencing the symptom (World Ovarian Cancer Coalition 2018), the women don’t see what’s coming so they don’t react. In Anne’s case, the GP did not find any sufficient physical cause when she consulted him the first time. However, one of the blood samples from Anne’s GP’s appointment turns out to be elevated to 325 kU/L (normal <35 kU/L) – the CA125. This elevation could be caused by several non-malignant processes in her body like endometriosis, infections or heart failure, but Anne doesn’t know that CA125 is very often is increased in patients with EOC and the blood test is used as part of diagnostics for tumour in the abdomen (Rustin et al. 1996; Buamah 2000; Bast et al. 1983). The GP is aware of the uncertainty of the CA125, and doesn’t want to give Anne a preliminary cancerdiagnosis, causing her tremendous agony if not true, but how will he be able to inform Anne of the test result without introducing the word of cancer? Anne will come to trust this indicator, this biomarker, as a cue in which direction her diagnosis is taking, unaware of the knowledge that the CA125 is still considered to be neither a sensitive nor a specific biomarker (Ueland 2017; Moss et al. 2005; Coticchia et al. 2008).

Anne – The Preliminary Diagnosis

The elevated CA125 was not sufficient for a cancerdiagnosis, but in combination with US findings and the fact that Anne is menopausal, all single-biomarkers involved in the RMI algorithm, results in a strong suspicion of ovarian cancer (Javdekar and Maitra 2015). Anne is referred back to her gynaecologist. She dreads it, it’s so intimate being examined in the most private part of her body, but she knows she has to go through with it – there is no other option. New ultrasounds (US) both transvaginal and abdominal are performed by the gynaecologist within two weeks after being to the general practitioner, giving her new unpleasant information: the suspicion of ovarian cancer has been reinforced by the detection of ascites in her abdomen and by abnormal findings on both her ovaries.

Now Anne is scared. She understands the seriousness of the findings, but she doesn’t understand all the words or the meaning of them, they are all representing something new, something frightful. Her assumptions that these changes in her body were normal has been proven wrong, the experience of illness was not her mind playing with her they were all vague symptoms of a malignant disease she had never heard of up until now, now they’re suddenly equal to death. The guilt of not being familiar with her own body hits her like a stone, is she herself to blame for not taking the bodily symptoms for something being wrong? will she get through this? How will she cope? Even though more people survive cancer, more people die of cancer than ever before. How can she tell her family and friends that she has cancer? Her husband, whom is more like a friend than a husband, and her son… Even though he is an adult he is still her boy and she feel close to him. Her father who has experienced the evil of cancer before, how and who will take care of him? She has had the role of being the caretaker for all of the men in her life, now all of a sudden, she feels the need to be taken care of be somebody else. Now, the burden of her own thoughts seems unbearable, but putting them on her husband, son or father seems even more awful. So, she keeps her thoughts and feelings to herself, remaining a wife, mother and daughter as nothing has happened, the roles are maintained although her experience of illness grows. Her home-world as she knows it will forever be changed.

Anne’s gynaecologist sends a referral for a computed tomography (CT) and to the Gynaecologic Oncology unit at the nearest University Hospital. But in spite of the information from her gynaecologist Anne doesn’t understand the seriousness of her disease, not even her gynaecologist understands. None of the examination’s performed, the tests, the biomarkers can predict the stage, prognosis or outcome of her disease – ovarian cancer.

Anne – Her Experienced Symptoms Confirmed into a Diagnosis

Anne receives an appointment for a preoperative computed tomography (CT), a clinically relevant and imaging biomarker for staging and distinguishing between primary cytoreductive surgery and neo-adjuvant chemotherapy in ovarian cancer (Chang et al. 2015; Suidan et al. 2014). She has a friend who has taking an MRI, telling her of the claustrophobic experience of lying inside the machine, not able to move. This is all new to Anne, lying still in an enclosed space with fear of claustrophobia, feeling the contrast fluid moves its way through her veins giving her a sense of flushing in her pelvic. Above all is the fear she is feeling- the fear of the result of the CT scan, to her it’s just another test, an imaging test, and she is not able to differ between the different modalities. She senses something being wrong, it’s almost like she can feel something growing inside of her, and she is afraid. She remembers her mother, dead at the age of 48 from cancer in her tummy. At this time on her journey Jenny, a gynaecological oncologist at the University Hospital, receives the results of Anne’s CT scan, showing a macroscopic peritoneal metastasis beyond the pelvis with metastasis to the retroperitoneal lymph nodes.

Jenny – The Gynaecological Oncologist Meeting Her Patient Anne

Jenny meets Anne at the hospital. She has 30 min to her next appointment. Thirty minutes to read Anne’s history, perform a clinical examination, answer questions from Anne and to establish a physician-patient relationship. By the first glimpse of Anne, Jenny notices the big tummy, the shortened of breath from going from the elevator to the examining room. At first, they talk. Jenny knows the questions to ask, to ask open-ended questions rather than the closed questions, but she also knows open-ended questions takes time and for setting the diagnose she needs also to ask closed questions, questions with answers that may lead to a diagnose when interpreted and translated into the biomedical world. She senses the tension in Anne, her fear. Jenny has to perform a gynaecological examination and palpate Anne’s abdomen. It takes time, she has to do the US and manual examination, translating her understanding of what her eyes can see, and her hands can feel into pathology. She has already seen the CT scan and the CA125 result.

Even though Jenny and her colleagues are able to set Anne’s diagnosis at an early point of the disease due to diagnosticbiomarkers as CA125 and CT, the outcome of the disease has not improved the last decades (Chandra et al. 2019). Every single test and finding affect what treatment Anne will get and decide her chances for the future, but even so, Jenny knows that according to statistics Anne has a 20% chance of 5 years life expectancy, should she tell her, or not? What will Anne’s reaction be? Jenny and Anne have just met and the power-balance between them are not equal: Jenny has the power in her knowledge, training and experience, Anne is depending on Jenny, literarily laying her life in her hands. The relationship is unbalanced, the doctor-patient relationship is dependent on trust, from both sides. Anne will come to cherish the affective quality of the consultations, both now and in the consultations to come. Jenny seeing Anne as the person she is, not just the disease resulting in a higher quality of life and satisfaction for Anne (Ong et al. 2000).

Anne – Accepting the Decision of Surgery

The positive side of the CT scan is that Anne is eligible for surgery. Jenny informs Anne of the side effects of surgery, bodily changes and potential complications of surgery. In Anne’s mind surgery is the only treatment that can cure her, removing the “disease” leaving her without cancer. The anaesthesiologist examines her and informs her about the anaesthesia while the physiotherapist gives her instructions of how-to breath while protecting her midline incision. The nurse gives her information of everything that will happen before and after surgery while the laboratory technician is taking blood samples from the vein in her arm. This is all too much. Anne’s head is full, she is tired, she is afraid thinking this must be serious. All these people, informing her about everything that might go wrong. Anne is feeling stressed. She finds it hard to cope with her new situation it’s unknown to her, she hovers not knowing where she will land navigating the uncertainty. She cannot control this, or anything, or so it seems. What could be the meaning of this, did she deserve it? Was it something she did or didn’t do? Is this Gods intention? These questions are tearing her apart – WHY HER? Was it not enough that her mother was taken from them at an early age? Time is running fast, too fast. She struggles to look ahead, fearing the future, fearing what the surgeons will find, fearing never to wake up. Not being able to think she goes into surgery three weeks after her appointment with her gynaecologist, four weeks after being to the general practitioner, and approximately five months after sensing the first symptom.

Jenny – Posing a Final Diagnosis

Jenny knows by her training, research and experience that cytoreductive surgery is the most important cornerstone in the treatment of ovarian cancer (Chang and Bristow 2012; Chang et al. 2015) and that going through with the surgery is the best medical advice she can give to Anne. She will perform the surgery herself, being a skilled gynaecologic oncologist at a university hospital, and this will increase Anne’s survival rate (Paulsen et al. 2006). The CT scan has provided Jenny information of what to expect when they “open” Anne, but the complete answer will not be revealed before Anne is lying on the operation table. Jenny was able to give Anne a complete cytoreduction, a major impact on survival along with the chemotherapy that is to come. The final diagnosis, histology, staging and prognosis of ovarian cancer depends on operative findings (Berek et al. 2018a). Jenny receives the histological report from Anne’s surgery showing a high-grade serous ovarian carcinoma and the presence of mutated TP53 strengthen the diagnosis. The germline test for mutations in the BRCA1 and BRCA2 genes were negative, however the pathologist found a somatic BRCA1 mutations when her primary tumour was examined. This finding makes her eligible for Olapraib, approved for this population by The National System for Managed Introduction of New Health Technologies. The findings of somatic mutations in BRCA1/2 predicts she may benefit from PARP inhibitors targeting DNA repair, combined with chemotherapy prolonging her progression-free survival (Ledermann 2016; Moore et al. 2018).

Jenny concludes that Anne has an overall poor prognosis. Findings from the CT scan and surgery indicates that Anne’s disease is at FIGO stage IIIC: Macroscopic peritoneal metastasis beyond the pelvis more than 2 cm in greatest dimension, with or without metastasis to the retroperitoneal lymph nodes (includes extension of tumour to capsule of liver and spleen without parenchymal involvement of either organ) (Berek et al. 2018b). Relapse maybe unavoidable, it will come, but the timing of it is essential for further treatment and prognosis. How will Jenny inform Anne of these devastating findings?

Anne – The Start of Chemotherapy

Anne starts chemotherapy four weeks after her surgery. She has recovered from surgery and her performance status is 0 being fully active and able to carry on all pre-disease performance without restriction (Oken et al. 1982). She will receive six courses of paclitaxel 175 mg/m2 body surface and carboplatin AUC = 5, a platinum-based chemotherapy (6 treatments cycles, 3 weeks interval), followed by olaparib, a PARP inhibitor for 2 years. The chemotherapy is being administered at an oncological day unit. Women bearing ovarian cancer and other gynaecological diseases are sitting next to each other, waiting for their doctor appointment, talking to each other comparing treatment end experiences. Anne starts talking to Linda. Linda has ovarian cancer, apparently the same as Anne, but Linda is receiving bevacizumab and not olaparib. Why so? They have the same disease, should they not receive the same treatment? The differences make they them both stress – Anne can’t help but thinking “I wonder if I am receiving the best treatment for my disease?” Anne is reassured by her doctor’s choice of treatment. During her surgery complete cytoreduction was archived. This means that her risk for recurrence is reduced. In Norway bevacizumab consolidation therapy is only approved for patients with high-risk for recurrence. She read about bevacizumab in the newspapers, but not olaparib.

CA125 dropped to 125 kU/L after the surgery, and it dropped further already after one course of chemotherapy indicating a therapeutically effect and her hope for survival amplifies. She is experiencing some side-effects of the treatment, but they are minor details in her goal of conquering the disease. Her sufferings fell meaningful. When ending her sixth course of chemotherapy Anne continues olaparib maintenance monotherapy hoping for longer overall survival (Ledermann et al. 2016). Anne is not naïve, she knows the relapse probably will come, of course it will, but she doesn’t know when especially since the survival data for use of PARP inhibitors are not yet known. Twenty-seven months after she ended her first line of chemotherapy Anne starts to feel some discomfort, it feels like a fibroid or something similar in her back. She relates it to previous discomfort in her back, not to her cancerdisease, and with no immediate plans to contact her doctor, she not out of control. Instead, she gets an appointment at her physiotherapist, but the discomfort stays and the inevitable occurs – Anne relapses.

Intermission – The Dichotomy Between Illness and Disease at the Diagnosis Stage

Anne feels unhealthy with a reduced capacity; she is experiencing illness (Niebrój 2006). She is diseased with ovarian cancer and Jenny is the physician who professes to be able to heal her disease. Anne’s feelings of health and illness are a result of her lived experiences; her perceptions, her beliefs, her skills, her practices and her expectations (Benner 1985). The changes in her body, the vague bodily symptoms are often not recognised by health professionals, and women like Anne, may confuse them with normal bodily changes (Fitch et al. 2002). These changes are not detected by the GP or the laboratory, but are all part for Anne’s illness experience, before the diagnose is suspected. There is no connection between the cellular level and her experience of illness, but even so, the experience is real to Anne although no one else can proof them. Should she be angry that her illness experience was not enough, those changes were not seen as alterations in a disease process; they were proof of a disease to her, but not for the biomedical model of disease. The illness Anne is experiencing becomes a disease when “the underlying biological abnormalities that cause the symptoms and signs of the illness are clarified” (Komaroff 2019). The diagnose frees Anne from prejudice, she has a disease not “only” an illness. Her assumptions are no longer signs of something vague, it has left her with an explanation. Although receiving a diagnose rearranges reality to Anne, it also reduces her to a diagnose and not the woman, mother, wife, daughter and friend she is. Being diagnosed with gynaecological cancer may be stigmatizing. Ovarian cancer is a sex- specific disease – only women can have ovarian cancer. The sex-linked factor (the biological differences) like the ovaries and the fallopian tubes, are decisive in ovarian cancer. Is the inevitable status of being a woman itself one of the reasons to why Anne’s disease was diagnosed at a late stage? Do women like Anne have less trust in their own body or a lack of knowledge of how the female body functions? Or is it the intimacy of the disease? It almost seems like the knowledge of anatomy in ones one body is too vague, leading to the inevitable fact: women diagnosed with ovarian cancer have little understanding of what ovarian cancer is or what it will mean to them (Simacek et al. 2017).

Anne’s horizon of her illness meets Jenny’s horizon of disease in the consultation at the hospital, a meeting characterised by misunderstanding, Anne’s understanding of illness and Jenny’s understanding of disease. Their relationship is based on trust; however, their communication of understanding is not straightforward. Together, they are to share and discuss on the basis of the best available evidence, to provide Anne the support she needs to consider her options (Elwyn et al. 2010). But are there really any options? Accept treatment or face death.

Being a physician, Jenny is a natural scientist, trained according to the biomedical model of health and disease, but she is also a mother, a wife, a daughter and friend. Jenny has obtained the knowledge of human organisms in health and disease to cure diseases, diseases as classified by the WHO 11th International Statistical Classification of Diseases and Related Health Problems (ICD-11). Jenny regards Anne both as an object and human, a human organism by which she has the knowledge of. She makes a deduction based on her theoretical knowledge and the object she is seeing in front of her. The decision of which treatment Jenny is to offer Anne is based on several different reasonings, both objective and subjective, reasoning on theoretical knowledge and past experience, but also reasoning by understanding Anne as well as ethical considerations (Wulff 1999). Jenny’s understanding of ovarian cancer is that it has a biological reason, her assignment is to focus on the treatment of the disease rather than a treatment for Anne as a sick person affected by disease (Svenaeus 2005, 97).

Anne – The Meaning of Relapse

Many EOC women will experience relapse of their ovarian cancer, it’s almost inevitable, and it will happen more than once. The fear of recurrence has been lurking in Anne’s thoughts ever since she received the diagnosis. She has found ways of coping with her fear, but now all of a sudden, her fear has become real. When Anne first got the diagnosis and formed an understanding of the diagnosis treatment, she counted the days and weeks till it would be over, it was her way of coping until she would be back to normal, at least her normal. Anne has been tackling cancer as a to-do list, ticking of items and moving on to the next one. During the chemotherapy she developed a new identity of stoic optimistic tenacity, she adjusted her lifestyle making chemotherapy bearable even when she lost her hair, vomited and felt the muscle weakness and the numbness in her feet. Some of them, especially the abnormal heartbeat she fails to tell Jenny, she is afraid she will have a reduced dose of chemotherapy making her odds of cure reduced. What now? Is this it, the point of no return to normal or is this her new normal? Accepting the unacceptable means accepting the unknown, this disease will be the end of her. Living with cancer is her involuntarily new normal, there is no need for holding her breath waiting for cancer to be over, she will not conquer it. Cancer and cancer treatment will be her life. How will she adapt? How will she cope with this? How can she cope with this? She is fighting an internal fight; regard the symptoms hoping them to be normal or facing her fears and contacting Jenny. Contacting Jenny wins, and she is scheduled with an appointment with Jenny after taking a new CT scan.

Jenny – Telling the Truth or Giving False Hope?

CT scan leaves Anne with no hope of the relapse being misinterpreted. Jenny has been anticipating this to happen, although nothing would give her more joy than if Anne would have been one of the few ones, not experiencing a relapse of this ugly disease. This is it. Jenny knows it by her training and by her experience, it is only a matter of time. Anne will never be cured from her ovarian cancer. She wonders if Anne understands the full meaning of the relapse. She has come to know Anne better from the chemotherapy consultations. She thinks of Anne as a woman capable of receiving the truth of her diagnosis and prognosis, although the relapse itself will cause her agony, leaving Anne with no hope. How can Anne find the strength to another round of treatment if there is no hope? Jenny knows that many women experiencing relapse of ovarian cancer have unrealistic expectations of the treatment they are offered, despite the symptom burden, clinging to hope even when reality leaves them with no hope of cure or a long life. Should Jenny be direct informing Anne of her prognosis now or should the reality of her prognosis remain unspoken and rather fight death to the bitter end. In the end there is death, sooner or later, but for Anne it will be sooner rather than later. Postponing death is the new goal, not cure. Jenny advises Anne to have a secondary cytoreduction based on the absence of ascites and her performance status being 1, she has some restrictions in physically strenuous activity, but still, cytoreduction is an opportunity. But does Anne want a new cytoreduction?

Anne – Towards the End of Her Journey

Her husband and son advise Anne to act on what Jenny advises her to, this is her only hope for recovering from this disease. Anne doesn’t want to let them down. If she doesn’t go through with it, what then? Is it a real choice? Choose surgery or choose death, now. Anne is aware of the risk of surgery, she knows it will be tougher this time and that this operation will not cure her, it is just another item to tick off on her cancer journey. But somewhere in her subconscious there is a glimpse of hope that maybe, maybe there will be a cure, a revolutionary new treatment for her so that she will have the opportunity to see her grandchildren grow up and to enjoy the life she had planned for. Now, she is standing at the train station, watching her life passing without knowing if she should jump on.

Once again, Anne has a complete cytoreduction leaving her tumour free although Jenny recommends more chemotherapy, a platinum containing regimen. Will this journey ever end, all this time at the clinic? Her life is being lived at the hospital, being dependent on physicians like Jenny. Coming to the clinic feels like a doubled-edged sword; sometimes it feels like going on a vacation leaving the house, meeting other women undergoing the same treatment as herself, sharing some kind of a bond, then of course it’s the smell of hospital that sometimes makes her stomach twist, the fear of blood, values not being compatible with treatment and last but not the least; Jenny’s veridiction of treatment. Sometimes the women share their experiences of their cancer journey, but more the side-effects than the thoughts. There is a sense of optimism at the clinic, the nurses have the time to talk to them, however the sensitive topics, the thoughts closest to her heart remain inside her. There is never the time nor place to share these thoughts. Sometimes she feels ashamed for not feeling the optimism, but not all days are the same. Is there the slightest amount of hope for her, for her outliving her destiny? Perhaps a clinical trial she can participate in, not with the intention to be cured, but to be given the opportunity of receiving a few more months, maybe then another medicine has been approved and she may gain time postponing the inevitable.

Intermission – The Dichotomy Between Illness and Disease at the Stage of Relapse

What is the dichotomy between illness and disease at the stage of relapse? Are EOC women aware the differences between the experience of illness and the symptoms of disease indicating relapse, what to look for? Are the women fully aware of their diagnosis, even after relapse? The answer is not unanimous, there is not a yes or no answer to it. Some women will say they are not fully aware of which symptoms to look for, their disease, nor the treatment options, but some women would say yes, however, within the yes lies death as imminent despite incurability (Finlayson 2017).

Anne has been experiencing illness for a very long time, long before the disease was a fact. The disease could come back any place in her body, causing her vague symptoms and/or problems of pain, bloating, nausea or constipation. Anne has been through two major surgeries in her abdomen, and she had twelve courses of chemotherapy. These symptoms could be just a result of her previous cancer treatment, not necessarily the symptoms of relapse. How can she be sure whether the illness she is experiencing is part of the disease or as a result of cancer treatment, not just something she is sensing or is normal? In the physician-patient communication there is a risk of talking past each other’s purposes, talking but not reaching the other, not as a result of bad practice from the physician, but rather different realities and relations to illness (Toombs 1987). Again, their horizons are not the same, they are not living in the same world.

Anne is in a vulnerable situation expecting alleviation and the best possible service from Jenny. Jenny professes her willingness to help and heal Anne, by doing so she promises to act to benefit Anne rather than harming her; to do good. However, for Jenny doing ‘good’ is not necessarily the same as doing biomedical good when considering Anne’s values and her experience of illness. Jenny’s actions of medicine should lead to a ‘correct healing decision’. As a result of the advances in modern medicine as well as in medical research, and the consequences of these advances, Jenny is not in a position of control to always act in Anne’s interest, to protect her ‘good life’ and facilitate for her to make value choices in decision-making (Pellegrino 1981). Jenny is controlled by the administrative burden placed upon her, legal restraints, industrial seduction and implicit rationing making her unable to act in the best interest of Anne (Bircher 2005). Jenny considers herself being a realist not bound by theorists or philosophers, believing in what works in clinical practice rather than theories of clinical practice leading to unhappy results, removing the why and potentially causing discomfort for the patient (Cassell 1991).

When suffering from a life-threatening illness the timeframe, needs and interactions with health-services become important, even more and yet unspoken when “how long have I got” hides the “what will happen” for both patients and carers (Murray et al. 2005). Physicians, like Jenny, may be reluctant in speaking of the prognosis of a disease even though this unspeaking of prognosis may leave to patients and relatives with hope and a drive to fight death with palliative treatment that are unlikely to benefit them (Murray et al. 2005).

Anne – Accepting the Inevitable

In the depth of her mind, Anne knows this disease will be the end of her. The surgery, the chemotherapy, another surgery and another chemotherapy, they were all part of a hope, a hope for cure. She raises the question of how long time she has left, but the unspoken question was: what will happen to me? Anne doesn’t feardeath, she is more afraid of not being able to breathe because her lungs are filled up with fluids, or her stomach being large and hard also making it hard to breath. Will this happen to her? Her legs so filled with water making the skin feel like it should blast? Anne knows it’s an ugly death dying of ovarian cancer and it takes time, but when death comes, she will be free of her sufferings.

As time has gone by, the acceptance of this outcome as become clearer to her. She keeps these thoughts inside, not sharing them with her husband, her son or father, she doesn’t want to cause them more pain and misery. She is alone. She wonders if her mother felt the same way at the end of her journey. When looking into the mirror she sees a different person, her face is swollen by the medications, her skin is grey, making her look older than she is, her shoulders are thin, her abdomen is tense, and her legs are swollen. The resemblance with a pear comes to her resulting in a smile on her face. Her eyes are clear, in them she is still 24, what happened to the rest of her? It’s been three years and seven months and it seems like a lifetime. She senses a void inside, causing feelings of loss and alienation living in this unpredictable body (Sekse et al. 2013). This alienation of her body and the taken-for-granted world she has been living in, has come to her in a way she could never imagine.

Courage is knowing what not to fear (Plato).

Her life has a new perspective, a new horizon, while her surroundings remain as they were. She is ever so alone. Has her journey through the landscape of cancer treatment been worth all of her suffering? The answer remains unanswered to Anne, it’s too difficult to answer. The choice of treatment was not a real choice to her at the time, however there are so many things she would like to have known before it all started: the real consequences of treatment, the change of family roles, the social distances, friendships that fade away, the feeling of been inadequate, the loss of home-world, being a burden to both her family, friends and society, being alone. It has been a journey, a single journey, with days, people, feelings and experiences she would never have had if it was not for the cancer, experiences that have made her life richer in many ways. In a sense she has adapted to her environment, “the horizon of our total attitude” (Ludwig 1940), she is in a state of balance; not healthy and not free of disease or disability, feeling illness not being well, not wanting to die, but tired of disease and longing for relief. She is not at ease within, and she is alone.

If, the woman thinks, she were an airplane that crashed and someone located the little black box, that would be the sentence they found, to hear water, but not to see it … (Øyehaug 2016, 53).Footnote 1

The Future of Ovarian Cancer: Anne’s Story in 2040

The history just presented took place in 2020. Today, there are biomarkers of clinical value exist for patients with ovarian cancer, but some promising biomarkers are emerging that hopefully can improve both time of diagnosis and prognosis. Science is moving rapidly but the process of translating scientific findings into clinical practice takes time.

Imagine now that Anne’s story is taking place in 2040, would there be any differences? The following projection is based on knowledge that is yet to be implemented in clinical practice.

Jenny performs a gynaecological examination without US but by performing the PapSEEK test. The PapSEEK test may detect both endometroid and ovarian cancer at an early stage, with a specificity of up to 45% in ovarian cancer (Wang et al. 2018). In addition, the test is minimally invasively and can be performed at a routine office visit, as in Anne’s case, at her general practitioner. The test comes out positive for ovarian cancer but instead of being referred to the gynaecologist and to a CT scan, Anne is referred to a new form of PET-CT where an ovarian cancer specific tracer is used (Hernot et al. 2019). This examination combined with a new AI algorithm predict the biological signature and disease distribution (see also later). In addition, Anne has a laparoscopy performed with a fluorescence camera, and a biopsy resulting in a histological diagnosis: ovarian cancer: FIGO stage IIIC. It’s the same diagnosis as in 2020 with a somatic mutation in BRCA1, but instead of waiting four weeks for her diagnosis she’s now receives the results in 5 days. They also identify an inherited mutation for hereditary nonpolyposis colorectal cancer (HPNCC). Now all of a sudden this could be her legacy, first perhaps from her mother to her, and now this is something her son will inherit. She will have to inform him, and he has to make the choice of whether or not to have a genetic test. But perhaps even more difficult; he will have to decide whether or not he wants this knowledge of his own genes and the knowledge of the impact it may have on his life.

Anne feels everything is going so fast with tests and examinations, her body senses stress, stress that doesn’t go away. The changes in her body have been causing her stress for a long time and she has not yet found her way of coping, unaware of the significant impact on biological stress response (Antoni and Dhabhar 2019). Another test is performed: the two cytokines IL-6 and IL-1β. Overexpressed IL-6 and IL-1β makes her eligible for a clinical trial testing the effect of a psychosocial intervention with cognitive training to reduce stress by coping mechanisms with the aim of reducing biological stress response.

The RMI algorithm and other algorithms used in 2020 have been found to be too complex for clinical practice and not capable of handling the increasingly number of biomarkers, leading the way for artificial intelligence (AI) (Enshaei et al. 2015). Now, the decision of Anne’s surgical resection will be based on AI. The AI predicts Anne is likely to end up with suboptimal cytoreduction and rather benefit of neo-adjuvant chemotherapy. So instead of primary cytoreduction she starts her treatment with chemotherapy: paclitaxel 175 mg/m2 body surface and carboplatin AUC=5-6, a platinum-based chemotherapy along with a humanized monoclonal antibody directed against transforming growth factor beta (TGF-b) as the overexpression revealed may lead to chemotherapy resistance and stimulation of tumor blood vessel growth (Arend et al. 2019). The CA125 decreases during chemotherapy, Anne is responding to the treatment with minor side-effects. After her third course of chemotherapy, she is finally eligible for and to have benefit of cytoreduction. Anne has been taking a lot of tests and imaging, most of them she doesn’t understand the full meaning of. One of the imaging came positive for a biomarker to improve surgical outcome: the CD24, a potential biomarker for image-guided surgery (Kleinmanns et al. 2020; Wang, Fan, et al. 2018). In 2040, Jenny has a real-time intraoperative guidance increasing Anne’s chances for a complete and safe tumor reduction (Hernot et al. 2019). The surgery is followed by maintenance therapy of olaparib and anti-WEE1.

First after 5 years she recurs, the recurrence is identified with the use of liquid biopsies in the for of circulating tumor cells. The mass cytometry profiling shows a profiling that advocates anti-CD73 and anti-PD-L1 treatment. A test for intracellular signaling performed already hours into the 1st treatment cycle indicates that Anne will respond. After being assigned to the treatment for 2 years, she has still relapsed. So still a live, with a disease that might recur again and with her illness. Tired, alone and not at all healthy.

Intermission – The Dichotomy Between Illness and Disease in an Era of Precision Medicine

Personalised medicine, as a result of translating new findings of biomarkers into clinical practice by AI, may improve the prognosis of ovarian cancer, or it may not. It may improve her time of progression-free survival and reduce the agony and violence of cancer treatment, or it may not However, Anne will have a more personalised treatment, giving her less side-effects due to be given treatment specified for her.

As mentioned earlier in this chapter, advanced disease at time of diagnosis is the most important reason to why ovarian cancer is called “the silent killer”. Early diagnosis of ovarian cancer is not a quick-fix research area. The journey along the ovarian cancer pathway will be more direct and mobilized with resources needed to conquer the disease, but will the use of more sophisticated biomarkers and the ideal of precision medicine reinforce the dichotomy between illness and disease and improve Anne’s journey? Their horizons will still be different, the bridge between them perhaps even further away by their inability to communicate their understanding of illness and disease. The gap between the biophysiological world and the phenomena world will increase. Unless, of course, by 2040 the translation between these two worlds is improving resulting in a new more humanistic meaning of personalised medicine. However, it is likely that the more precise the development in medicine, the greater the distance between illness and disease. Anne’s perspective is still the experience of her illness, and perhaps the feeling and experience of her illness will be even more remote from and mismatched with the biological conception of her disease when medical advances increase in sophistication and precision.

The Challenges of Communicating Illness, Disease and Health Between Patients and Clinicians

Ever since Hippocrates in the ancient Greece, physicians have been communicating with patients for reasons of biological, psychosocial and social art. Since the birth of modern medicine, communication with the intent to building a therapeutic relationship have been and still is the heart and art of medicine (Ha and Longnecker 2010). However, communicating the understanding of health, illness and disease, transforming the perspectives and experiences from one person to another in order to share the same understanding and the same horizon, still leaves patients and physicians lost in translation. It seems like as though physicians are having difficulties with building a bridge of understanding towards patients, making it impossible for physicians and patients to see the same horizon leaving a gap between them.

Biomarkers are the future of cancer, at least in the biophysiological world, but also in the phenomena world. The need for science, the need for progress and the desire for a cure is the aim and hope for cancer patients as well as physicians. The glory lies the potential future cure for the disease, because there is no glory in illness, there is no meaning to it and there is no honour in dying of [it]” (Green 2012).

Making Sense of and Finding Meaning Around Health, Illness and Disease

Being diagnosed with ovarian cancer is a traumatic life event. The loss of home-world, the loss of life as Anne knew it before the diagnosis and treatment, demands a new understanding of life, resolving loss and finding a new meaning of life. How Anne meets these demands are crucial for whether or not she will experience good health. The inability to cope may be seen as a sign of disease, with regard to Anne’s symptoms that needs intervention like drug treatment or surgery (Bircher 2005).

Anne’smeaning of life is fundamentally reshuffled. Beyond the extreme complexity to think about life’s meaning in general, how can Anne think about her own new meaning in life with her disease, and communicate that to the physicians? Has it even crossed her mind that this should be worth sharing and discussing? Are physicians equipped to help patients find a new meaning in life with their disease? Moreover, finding meaning in a life with cancer can also trigger guilt: “Nothing is more punitive than to give disease a meaning” and “the more mysterious the disease is made to seem, the more likely we are to supply it with meaning and the greater of moral – if not literal – contagion” (Sontag 1978). How can one give meaning into a disease like cancer? For many people cancer is a disease that equals death; so, what could the meaning be, of having cancer? What must one have done to deserve such a fate? As Sontag argues, it is easier on the patient if he/she manages to not read any guilt-triggering meaning into such diagnosis. Rather, we are born and then we die, and that’s it. But beyond those considerations around guilt, some women will find meaning and significance in receiving a cancer diagnose (Davis et al. 1998). They will find meaning in the positive implications of the disease itself, and the experience of loss of home-world. For instance, the small things in life that would have gone unnoticed before, are now perceived as important sources of happiness: the smell of flowers in the spring, the pleasure of experiencing yet another day, to be able to live in the present and not worrying about tomorrow (meaning as significance). Other women will try to find an explanation to why they got cancer. It could be genetic as in BRCA – then it’s not your fault, a kind of sense making (meaning as comprehensibility) (Davis et al. 1998). So in many ways, being diagnosed with a disease changes your home-world, and that can constitute a push to find meaning in this new situation. By investigating people’s experiences of illness, meaning around illness, and how these experiences of and meaning around illness lead to a disease, it is participating to valuing illness. Looking at meaning also arguably helps bridge illness and disease in more profound and meaningful ways.

The Meaning and Sense of Biomarkers – From a Patient Perspective

Biomedicine is portrayed through its metaphors as a warlike force that seeks to defeat the enemy, the use of military metaphors like cancer being the war to be defeated.

What is the meaning of biomakers? The meaning of biomarkers as they appear in humans: a bloodsample, tissuesample or acites. Howevere they all have a side one can not see at the first glimpse. Even from different persepctives they may still appear the same, but based on experience different functions of biomarkers appears. They are extremely complex and the link between the presence (or absence) of biomarker and type of treatment is far from being straightforward.

No one can claim to have a perfect understanding of what a biomarker is and how exactly it will guide clinical decision-making. So, what is the general understanding among cancer patients of what a biomarker is? Even at Anne’s first visit at the hospital, before the diagnosis was established, different tests had been performed and biomarkers had been measured. Are the patients informed about the fingerprints they have left behind in these different tests, and more importantly: are they aware of what it will mean to them?

For many EOC women, receiving the malignant diagnosis is equal to receiving a death sentence: the last stop on their journey. At the beginning of the disease, it is rare that patients are able to fully understand what the use of a biomarker implies for their course of treatment, and their lives in general. This is not facilitated by the fact that the media often portray biomarkers and precision oncology in a very positive and hopeful light, inducing the public to think that cancer cures are just about to be realised (in this book, see the chapter from Stenmark and Nilsen). New cancerdrugs are “great hopes” and “revolutionary treatments” – who would not want to have that treatment? To complete this ‘ideal’ picture of biomarker research and precision oncology, new biomarkers are often depicted as an opportunity for drug development and market growth. When diagnosed with cancer, and having been introduced to biomarkers as hopes and revolutions in the media, patients will claim their right to receive the best, newest treatment and nothing less, regardless of what it might induce in terms of loss for them. Indeed, this treatment might possibly prolong their life, but by how long, and at what cost in terms of quality of life? There is also rarely the explicit consideration that the treatment might not prolong their life at all, or even shorten it.

The question of “what is a good (enough) biomarker” was raised in the book CancerBiomarkers:Ethics, Economics and Society book in a chapter by Blanchard and Wik (2017). What is a good biomarker for HGSC women? Would a diagnosticbiomarker in HGSC able to detect 100% sensitivity and specificity, be a perfect biomarker? The uncertainty of biomarkers, like the CA-125, are causing anxiety to EOC patients (Moss et al. 2005). All women of ovarian cancer are familiar with CA-125, it’s almost like the CA-125 is the one dependent factor that decides the effect of their treatment, their hope of being cured from cancer relies on a blood sample, on something they can’t control or even trust. This biomarker, and others, does not necessarily correlate to the women’s health; their experience of wellbeing, or correspond to their clinical state (Strimbu and Tavel 2010).

We performed a focus group interview with women diagnosed and treated for ovarian cancer, asking for their perception on what a good biomarker would be and their perceptions of the concept of biomarkers. The women we interviewed were diagnosed before 2015, and were diagnosed at a late stage of cancer. They had undergone first line therapy with both surgery and chemotherapy. Most of them had received several lines of therapy due to relapse. The overall conception was the lack of information from health professionals of what a biomarker is. None of the participants could remember being introduced to the word biomarker during diagnosis or treatment.

In addition to the difficulty to grasp the complex notion of cancerbiomarker, the high hopes and expectations of cancer patients (fuelled by optimistic media discourses like seen above) make it difficult to accept that a biomarker is something complex and imperfect, that is not likely to bring a cure. In the beginning, patients expect to be cured of their cancerdiagnosis. They expect to be treated in a unique manner that perfectly matches their diagnostics. They expect to be given the best, newest treatment available and at any cost. If living is the outcome, even for just a few more months, this should be worth it. In addition, patients often expect biomarkers to be safe, as they are described everywhere as the fingerprints of your cancer – there should therefore not be room for error or misinterpretation. They will be disappointed. As said above, there are rarely thorough discussions about the fact that even if you are in a terminal phase of cancer, you have things to lose. Trying any treatment at any cost can actually leave you worse off.

In addition, how should one accept that the same biomarker might grant access to some patients to a treatment, while denying it to others? How can patients accept that they are unique, but in the sense that they are denied the right to try a treatment that they would not benefit from? From a patient’s perspective, it may seem unfair, especially in the context of numerous, vocal campaigns claiming the right to try experimental drugs for instance. But if something is to be considered unfair, it would mean that they would have been subjected to injustice, partiality or deception. Patients may have the feeling of being treated unfairly, and this is to be expected when knowing that they are regularly confronted with media discourses about new cancerdrugs and new revolutionarycancer treatments. It is perceived as unfair and inexplicable that patients with the same diagnosis and condition are not receiving the same cutting-edge medicine. So, I am unique, but not in a good way, and I am being treated unfairly. We have to bear in mind that many cancer patients, still receiving cancer treatment, were diagnosed before 2015, before President Obama announced the research initiative towards a new era of precision medicine (Collins and Varmus 2015). Many of them have not been informed about biomarkers and how the use of biomarkers is affecting what treatment they are offered.

Biomarkers are measured and identified ‘objectively’ (at least according to their definition), and they have a key bearing on how we think about our health. How can patients understand and make decisions about their lives when their disease is objectively measured and a biomarker ‘decides’ the treatment, not considering how patients experience symptoms and the way they are dealing with illness and sickness? Disease seems very far from the lived experiences of illness and sickness in the patient, especially in this context of precision medicine.

Conclusion

The aim of this chapter was to give a glimpse of the challenges in communicating the understanding of health, illness and disease, and eventually decision-making in ovarian cancer from a patient’s perspective and a physician’s perspective. The two fictional narratives of Anne the patient, and Jenny the gynaecologist was based on literature, focus-group interviews, physician’s and the author’s own experiences. There is a fine distinction between health, disease, disability, wellbeing and illness, but at the same time it seems difficult to separate them. They belong together as a part of the whole human; alone they would only be fragments of something greater, more complex and multifaceted. In addition, the increasingly precise and targeted advanced in medical research and practice lead to a reframing of these concepts. There is therefore an urgent need for refining the definitions of health and disease to fit with present and future medical culture. The different models of health and disease are still valid, but perhaps it would be useful to consider them side by side, with more holistic perspectives meet more precise and personalised ones. Arguably, the more complex the scientific advances, the more space should be given to patients to voice what health is and what disease is, according to their own experience. What patients want for their life, how they want to manage their disease, and where they find meaning, are crucial aspects in an era of precision oncology.