Interfaces, gaps and challenges between bioethics and oncology

Bioethics and oncology are interdisciplinary areas that aim at the integral understanding of the human being. This article made a survey of studies on interface between these areas, identifying possible contributions, gaps and emerging challenges. We carried out an integrative review that sought the descriptors “oncology” or “cancer”; “bioethics” or “ethics”, and found 29 articles. The discussions referred to the knowledge or application of principles of bioethics in oncology; difficulties in the physician-patient communication; and ethical standards in research. Therefore, it is necessary to guarantee the application of bioethics’ principles; to increase investment in the formal teaching of bioethics, to improve interpersonal and physician-patient communication skills; and to disseminate bioethics to the general population. It is hoped that this study will give continuity of those already carried out, and that new interests will arise on the subject.


Interfaces, gaps and challenges between bioethics and oncology
http://dx.doi.org/ 10.1590/1983-80422018263265 Oncology appeared between 1733 and 1788 in France as a specialty of physicians and scientists devoted to systematic studies on cancer 1 . This pathology results from the uncontrollable growth of abnormal cells -triggered by physical, chemical and biological factors -that invade adjacent tissues and, through the bloodstream and lymphatic system, invade other organs, generating metastasis. This disordered and accelerated growth of neoplastic cells results from mitosis cell division, which culminates in the formation of deformed and numerous anaplastic cells. The mass that makes up the cancer is poorly delimited and locally invasive, and may infiltrate adjacent tissues through metastasis 2 .
Formerly restricted to medicine, oncology is today an interdisciplinary area that congregates several branches of knowledge. This science aims to give full attention to the person with cancer and to expand the research in the area from various theoretical-methodological perspectives 2 . It is emphasised that the Ministry of Health's Governmental Order 2,439 of 8th December, 2005 3 stipulates that oncological care should be based on multidisciplinary work, including fields such as clinical psychology, social work, nutrition, physiotherapy, dentistry and psychiatry.
However, although cancer care has been extended beyond the medical and biological aspects of cancer, the amount of research conducted and based on other areas of knowledge is still small. Recent works show that studies on basic biology and the special treatment of cancer, that is, on the production of knowledge about biomarkers and new drugs, are still predominant 1 . Therefore, it is understood that the challenge to cover the different human aspects of cancer remains, being necessary research with other approaches, in order to justify the integrality and interdisciplinarity of oncology.
One field of knowledge that has interacted with other sciences is bioethics. According to the United Nations Educational, Scientific and Cultural Organisation (Unesco), bioethics is a systematic and pluralistic study of ethical, theoretical and practical problems raised by medicine, as well as other life sciences and associated technologies 4 .
A landmark case that prompted the discussion of bioethics occurred in 1962 at the University of Washington when a small group of non-physicians met in Seattle to decide who would receive hemodialysis, a new treatment at the time. The contribution of philosophy, theology and other fields of knowledge in the reflections on the use of the technology, whose choice was so far restricted to the medical class, was remarkable. Since then, bioethics has been characterised by its interdisciplinary character, not limited to only biomedical knowledge 5 .
Although there are records of an earlier use of the term "bioethics" (ethics of life) in history, it is not the purpose of this article to debate who first used the word bioethics. It is recognised, however, that the work published in 1971 by the American oncologist Van Potter, whose title is: Bioethics: Bridge to the future, can be considered the seminal work that launched the modern theoretical bases for the discipline, which has been consolidating as a new science that expresses a systematic-critical reflection, seeking a connection between scientific discoveries and an ethical-humanistic vision for science.
From the theoretical growth of bioethics and its increasing importance in academic and social circles, it has become difficult and problematic to disregard the questions raised by bioethics about the future of humanity when science and technology are developed without an ethical-moral content. Science can not develop at any cost without taking into account the dangers and threats it can pose to the future of humanity and the planet. Bioethics, therefore, believes that scientific-technological knowledge must consider its ethical implications 6 .
Focusing specifically on general medical practice, four principles were outlined by Beuchamp and Childress in 1979 to define bioethics. These terms are currently the most widespread, especially in regard to their application in the relationship between professional and patient or in research: respect for autonomy , that is, the ability of the individual to deliberate on their goals and act from their decisions; beneficence, that is, to act for the benefit of the patient; non-maleficence, which concerns the avoidance of harm; and justice, which means fairness in the distribution of benefits, risks and costs. These principles represent normative ethics to be applied to medical-assistance conflicts. However, their use can not be dogmatic or mechanised, but properly mediated and interpreted, adapting to each case 5 .
Considering bioethics and oncology as interdisciplinary fields, in which it is necessary to fully understand the human being, we question how both have dialogued. In order to better understand this relationship, we conducted a survey research of studies on the two knowledges, identifying possible contributions, gaps and challenges that arise from this interaction. For that, we carried out an integrative review on the theme. It is hoped to encourage reflections on this interdisciplinary Interfaces, gaps and challenges between bioethics and oncology http://dx.doi.org/10.1590/1983-80422018263265 articulation, aiming to improve the contributions to human health, besides problematising it and suggesting future studies.

Method
The integrative literature review synthesised the knowledge produced on the theme, guided by question-focus, critically discussing the theme, considering its applicability and pointing out priorities for future studies 7 . National and international studies published in the last eleven years were searched. The databases accessed were SciELO, PubMed, Lilacs, Web of Science, Scopus and BVS, using the following terms in Portuguese and English, as defined by the Descritores em Ciências da Saúde -DeCS (Health Sciences Descriptors): "oncology" or " cancer " and " bioethics "or" ethics ". The Boolean operator "and" was used in order too combine the search terms.
We included open access articles and theses that analysed human beings and whose main theme were bioethical aspects of interest in the oncology area. We excluded repeated articles, literature reviews, meta-analysis articles, animal research, editorials, declaration/convention articles or validation of instruments not related to bioethics and reports of experiments and texts that referred to ethics only in order to be approved by an ethics committee (without necessarily addressing ethics). Publications with at least two of the terms in the title, in the keywords or in the abstract have been selected for reading in full.
In order to systematize the selected material, the following information from each publication has been prioritized: what is the source of the study (periodic)? Who participated (authoring institution, participants and subject-matter of the research)? What is the possible interface between oncology and bioethics? What are the main gaps and challenges for both areas?
The content was analysed according to the Bardin technique 8 , which seeks to clarify the analysis criteria and the systematicity of the information. Categories to identify those that best expressed the proposals of the text and allowed their division into classes were used 9 . After being characterised, the information was organised, and the data collected were discussed according to the literature, pondering on possible gaps and challenges for future dialogues. 29 surveys were selected after the search and filtering according to the mentioned criteria ( Figure 1).  Characterisation of the studies It can be seen that most publications are in the form of article (26). Only the Revista Bioética (Bioethics Journal), BMC Medical Ethics and the Revista da Associação Médica Brasileira (Journal of the Brazilian Medical Association) published more than one article on the subject. 11 of the institutions searched were Brazilian and 17 were international, which represents, at first glance, the expressive production on the subject in the country. Chart 1. Characterisation of studies on oncology and bioethics -reference, type and source. The researches record different perspectives regarding the interaction between bioethics and oncology. Patients, family members and the general population, representing civil society, have been targeted by more than half of the researches. This may indicate that by giving voice to this public, it is possible to understand personal experiences and important data about those who are directly "affected" by bioethics.

Reference
On the other hand, the number of studies that address the interdisciplinarity of oncology and bioethics is still small when compared to those who address only the aspects related to medical practice. Even smaller is the amount of research on future professionals -there is only one study with nursing students.
The data may indicate a predominance of medical participation in the dialogue between oncology and bioethics, which denotes the incipient discussion of this topic by other professionals who work with cancer patients, as stipulated by the Government Order 2,439/2005 3 . It is questioned whether this data would be related to the gap in knowledge production in the interaction between these areas.

Dialogue between oncology and bioethics
The data collected were analysed in the following categories: 1) level of knowledge or application of bioethics' principles; 2) difficulty in the physician-patient communication; and 3) ethical aspects and standards in research. It is emphasised that in practice the categories are interconnected and were divided only for didactic purposes.
The most frequent topic was knowledge about bioethics' principles or, moreover, about their practice in the oncological context. Of all the principles, autonomy was the most discussed, relating to the decision-making power of cancer patients during treatment or their participation in clinical trials.
On this last point, it is important to remember that the termo de consentimento livre e esclarecido -TCLE (informed consent form) is a document in which the patient and/or their person responsible explicitly informs the consent to the performance of a certain procedure. Established by the Resolução do Conselho Nacional de Saúde (National Health Council Resolution) 466 of 12th December, 2012, the term should have clear, objective and easy-to-understand language about the procedure to be applied, the patient's rights as well as risks and benefits involved 39 . The TCLE becomes an instrument to protect the patient's autonomy, assuming that the patient has an interest in making decisions about their treatment 31 and is in good condition to do so 35 .
However, some studies show that the consent term has not always fulfilled its function. Although many patients undergo invasive procedures, they do not have full knowledge of the document to make this decision 10 and this ends up limiting their power of choice in relation to medical treatment 10,27 . Some studies have also shown that many patients have participated in clinical trials to test drugs without knowing possible health damages caused by the drugs 11,36 .
In addition, autonomy was evaluated in people who decided to donate hematopoietic tissue cells to sick relatives. It was found that most donors did not have access to important information about this procedure, and did not even know their rights. The absence of this information and the lack of resulting knowledge, therefore, make an effective decision making unlikely 12 .
Factors relevant to this discussion are the vulnerability in which these patients are and the inadequate communication of information about their condition and therapeutic alternatives, which impairs their autonomy. The fact that the patient is vulnerable by the disease itself can make the patient passive in relation to the alternatives presented, given the small chance of cure 11,27 .
In another study, it was found that most physicians avoid asking the patient to make decisions 28 when the patient is physically and psychologically unable to decide on treatment. According to oncologists in the same study, patients in terminal stage of cancer accept to participate in clinical trials in order to benefit others who are under the same conditions. However, some biologists disagree with this view, believing that these patients are restricted to the circumstances of their terminal condition to make a choice (generally favourable to any treatment, including possible risks) 28 .
In developing countries the autonomy of these patients may be even more compromised because of little or no alternative means of treatment beyond those offered in clinical trials. Half of the participants in a study 18 , who lived in poverty and had low or no schooling , considered the consent forms difficult to understand. In the same study, Interfaces, gaps and challenges between bioethics and oncology http://dx.doi.org/10.1590/1983-80422018263265 most physicians agreed that these forms were not understood by patients.
Class inequality and the patient's dependence on public health also influence the submission to invasive procedures. This raises doubts as to the validity of the consent form in this vulnerable group, since it puts in question the exercise of their autonomy. As the studies analysed in this review demonstrate, a good number of patients do not feel free to make their treatment 13 , which subjects them to unilateral decisions of the physician and reveals a paternalistic attitude towards cancer patients.
Thus, doctors seem to confuse "do good" (protect) to the patient (principle of beneficence) and the right of the patient to make their own decisions (autonomy) in the treatment of cancer 11,[13][14][15][16][17]27 . In this case, extreme paternalism masked by beneficence removes the patient's autonomy and nullifies their right to determine their own destiny.
Some authors have also questioned the dual role of the physician in the relationship with oncology patients because, at the same time that the physician attends the patient, he or she is also a research recruiter. Thus, the inability of the patient to decide, by having their autonomy compromised, can increase trust and dependence on the physician and, because of this, the patient may not have his or her real interests defended 11 .
Many patients do not seem to distinguish participation in clinical research from ordinary treatment and attribute therapeutic intent to research procedures. It is assumed that in this case it is not clear to patients what it means to participate in a clinical trial as, for most of them, research and treatment flow together. This may also be due to the lack of knowledge about consent term and can generate confusion between recruitment for clinical trials and real health needs, as well as concerns about the patient's condition 19 .
Issues of knowledge and application of the principles of beneficence and non-maleficence were also present in the results. Both principles were discussed by comparing the results of seven US clinical trials in which people with cancer received a certain therapeutic procedure for an experiment that tested the effect of a drug. It was observed that the toxic effects (including the number of deaths) of this experiment increased statistically, generating risks and damages to the participants. This treatment, which was said to be innovative, did not even bring benefits 11 .
Another study investigated the perception of volunteers in a cancer hospital. It was observed that the promotion of well-being generated different perspectives for this group. The first showed that the volunteer was the greatest beneficiary of the work, for reasons of learning, self-improvement, redirection of daily life, and contact with other people. The second perspective, without significant difference in relation to the first one, understood that not only the volunteer benefited, but also the patient, being this perspective more horizontal and empathic in the volunteer-patient relationship.
Lastly, a small number of volunteers attributed the benefits of their participation to the institution and to society. Of particular note is the lack of reflection on the principle of justice in voluntary participation in researches, with a predominance of understanding of beneficence 16 . On the other hand, in research with physicians and biologists, concern for justice predominated, mainly regarding resource allocation, although they did not have knowledge about theories on the subject 28 .
With regard to the knowledge of bioethical principles in general, it should be noted that patients with more schooling were better informed about the matter 21,27 , with the justice principle being the most known principle 21 . Another study which examined second-year nursing students showed that they had no satisfactory knowledge of bioethics in the case of patients with brain death, organ donation, necropsy (know and confirm reason for death), and other principles. On the other hand, the study that evaluated the degree of information of physicians about legal documents that supervise their ethical conduct reveals that those physicians were not up to date with their knowledge on the matter 30 .
Some studies show conflicts among oncology professionals in situations in which bioethical principles are required. One of the studies describes the complex task of palliative sedation in cases of extreme suffering, which results in a shock of values between patient, family and health team 26 . Doctors and nurses are uncertain about the ideal time to discuss the end of life and the clinical balance between the physician's emotional involvement and the patient's wishes 32,37 . Opinions of physicians about requests of patients at the end of life, their willingness to comply with requests such as retention of intubation, application of increasing doses of drugs are related to experience in the area, with substantial change during residency 33 .
Problems of communication between doctors and patients were also frequent in the studies. Research has shown that, generally, the information provided has been very limited, and one hypothesis would be the difficulties and ethical conflicts in the communication between those involved, both in diagnosis and prognosis.
Most oncologists reported the diagnosis at the first visit, although many times the patient was already aware of the disease 14,17,29 . During communication of the diagnosis, most physicians inquired their patients about the desire to know about the disease, waiting for the patient to ask questions about it. When asked, they used medical terms to inform the patient, but they also explained those terms. Oncologists still assessed that the information to the patient was not always complete, demonstrating the frequency of a practice that should be an exception. In fact, properly informing the patient does not cause problems; in most cases the complete diagnosis does not generate conflicts 14 .
To tell the truth in a direct way is considered a difficult task by oncologists and doctors in general 15,16,27 . In the perception of these professionals, this is due to the lack of emphasis on communication during medical graduation, the negative image of cancer, fantastical conceptions related to diagnosis and the difficulties of approaching the the subject of death 15 . The family plays a very important role during the communication of bad news 15,29 , but depending on the family's dynamics (if it is absent or excessively participatory), it can create conflicts that will affect the doctor-patient relationship. For example, when asked by the family, the doctor can omit the diagnosis of the patient, and this will generate ethical conflicts 15 .
As already mentioned, information about diagnostic is usually passed on to patients. However, in researches with these individuals, the correlation is not positive. The result of a research showed that the majority of those affected would like to be informed about the disease, even if it was very serious. When informed about the disease, although most were aware of the therapeutic procedures to which they would be subjected (and their adverse reactions), only 45% knew the true diagnosis 31 .
In another study, this number was less than 10% 21 . When asked about the quality of the information, patients recalled the first diagnosis as a "very bad" experience. Most of them were warned only about the severity of the disease, and just a small part understood everything, even in technical terms 13 . There was also a lack of information about important attitudes to be taken in brain tumor patients, since in this case they are more predisposed to neurocognitive deficits 38 .
There are also ethical difficulties and conflicts in the prognosis. Informing the diagnosis is different from talking about the prognosis, since even the patient interested in all the information about the first one does not necessarily want to be informed about the prognosis 14 . Oncologists tend to rely on the support of the patient's relatives when life expectancy is poor 14,17 . Part of the oncologists communicates patient and family members; another part communicates just the family. There are few who inform only the patient and leave to him or her the decision to tell the relatives or not.
Other physicians reported feeling uncomfortable in giving bad news about the prognosis because they believe that they cause more discomfort to the patient, or that the family would become more responsible for the patient than the professional itself 14 . It should be noted that one of the studies pointed to a tendency of religious doctors in dealing better with the communication of bad news 27 .
Ethical protocols were also highlighted in the studies, since problems were observed in compliance with ethical and normative aspects in experimental protocols of oncology research centres. These limitations of some institutions referred to the nonsubmission of the research project to the responsible research ethics committee and the non-assurance of all signatures in the informed consent to indicate consent to participate in the research 23  An ethical procedure investigated was related to obtaining an TCLE by postal system. It is noted that this option may present other risks, such as anxiety (due to receiving a diagnosis at home) and other psychological disorders. Even a simple phone call, telegram, or a hospital call by letter could remit to memories of the disease, bringing emotional maladjustments. Thus, the procedure that would initially be the most relevant and appropriate is not in line with the best practice, challenging the principle of non-maleficence 24 .

Gaps and challenges for future dialogues
As seen, the analysed studies point out some gaps and problems that need attention, suggesting challenges of new dialogues in the interaction of the studied areas. Although bioethical principles are standardised in resolutions, protocols and other documents, there are often failures in Interfaces, gaps and challenges between bioethics and oncology http://dx.doi.org/10.1590/1983-80422018263265 their application, whether in research or medical care. One of the most reported problems was the impairment of patient autonomy. Such a principle can not be limited to the signature of the termo de consentimento livre e esclarecido (informed consent form -TCLE) 14,17,23 , because it is a gradual process based on the physician-patient relationship, in order to provide enough information for the patient's decision-making. The TCLE should not be only a mechanism, but an instrument in favor of autonomy 10 .
In addition, it should be pointed out that this question should not be confused with the respect for the decision of the patient -if the patient is not well informed, he or she will not make well-founded decisions 27 . One must also combat the physician's paternalistic tendency in relation to patients, as well as his or her double role as health care professional and research recruiter. It is suggested, therefore, more effective measures 11,14,15,19,35 , such as availability of recruiters 34 and more spaces, schedules and strategies to clear doubts of the patients 27 .
It is also necessary to improve the quality of information provided to patients and research participants, so that their conditions and real interests are analysed more objectively. To this end, communication between health professionals and the sick is essential in order to provide appropriate treatment to the patient's needs 15 . The doctorpatient communication about diagnosis, prognosis, risks and treatment objectives is made mandatory by the Code of Medical Ethics in force in the country, unless the communication can cause harm. In this case, the professional must communicate with the legal representative of the person affected 40 .
The moment to guarantee autonomy should not be limited to the final phase of the patient, but should also be guaranteed during illness, so that decisions are made consciously in the face of ethical dilemmas that arise. Thus, decisions about more aggressive treatments need not be made only when death is imminent, but throughout the process, while the subject still has autonomy 26,37 . It is recommended to palliative care professionals that they improve their ethical knowledge and axiology 26 .
In the scope of teamwork, consensual, prudent and reasonable decisions are required among all involved 5,19,26 . Conversations, meetings between professionals, family members and the patient are seen as the main instruments to achieve this 26 . Decisions must go beyond universal ontological principles and be sensitive to otherness. In this sense, the ethics of Levina's alterity encompasses the problematic of human dignity and its interpersonal relations, aiming to base criteria in face of bioethical dilemmas to instrumentalise all those involved 41 .
The great amount of studies that claim for the guarantee of knowledge and application of bioethical principles ratifies the medical activity beyond the technique. The profession can not focus on purely technical aspects, since its essence permeates the interrelationship with the other, characterising relationships that refer to moral demands 42,43 .
Some authors of the studies analysed suggest the development of interpersonal skills and communication 29 . It is up to the physician to be prepared to perceive the patient's capacity for understanding and discernment so that the patient can exercise his or her true autonomy 17 . The moment of giving bad news requires preparation and sensitivity 14,15 , and should be thought by the professional from the psychological conditions of the patient, adapting the information in the best possible way 13,14 . It is also necessary to consider gender, schooling, age and socioeconomic conditions for more adequate solutions 14 .
This interpersonal handling in the doctorpatient relationship can improve the disclosure of diagnosis and therapeutic agreements, improving the autonomy of cancer patients. The professional should not only provide information about the patient's clinical condition (physical or neurocognitive aspects) 38 , but also prepare the patient for the last phase of their life. However, more objective guidance would be needed on when to start this communication, so that patients with advanced cancer can make the most conscious choices 37 .
In the paediatric context, it is recommended that health professionals consider the participation of children, providing quality care and explaining procedures and behaviours to which they will be submitted. Improving the quality of communication and interaction between medical staff and children may favor their autonomy, in addition to improving their capacity for questioning, self-esteem and self-care 25 .
The formal medical school curriculum or continuing medical education can be a way of learning to improve the communication between doctor and patient, and to increase the bioethical knowledge of the health professional. However, this education can not be restricted to theoretical content, but also to practice and Interfaces, gaps and challenges between bioethics and oncology http://dx.doi.org/10.1590/1983-80422018263265 experience [14][15][16]25,27,30,32,34 . It is also worth mentioning the need for studies on training strategies, their influence on medical performance and the impact on the quality of ethical decisions 33 .
The teaching of medical ethics has been encouraged by the Resolution of the Câmara de Educação Superior do Conselho Nacional de Educação (National Board of Higher Education of the National Council of Education) -Resolution CNE / CES 3/2014 44 -which establishes the Diretrizes Curriculares Nacionais do Curso de Graduação de Medicina (National Curricular Guidelines of the Medicine Course) and proposes a general, humanistic, critical, reflective and ethical medical education. The importance of the teaching at all academic levels 45 is stressed, as well as the need to reconcile the critique between medical precepts and dispositions of the ethical-political context, which makes teaching a political and ethical activity. The humanist formation, which allows the student to establish values referring to the idea of humanity from their personal experiences, will be the differential of the doctor and will even allow the transmitting of confidence to people who are ill. For this purpose, methodologies that discuss experiences about situations that have caused conflicts and ethical dilemmas are suggested 47 . It is also recommended the update of bioethical knowledge and the improvement of technicalscientific collaboration and ethical basis, in order to favour future generations and the well-being of the population 45 .
Given the lack of knowledge of patients, family members and society in general, there is a need for further studies to verify the understanding of bioethics and its impact on cancer diagnosis and therapy 21 . In this context, the main themes of bioethics should be disseminated throughout the society 12,22,31 . There are gaps especially in the fulfilment of justice when it comes to vulnerable and marginalised people, whether due to cancer or other diseases. In this case, bioethics must strengthen its links with social movements in defense of these groups 20 . The fulfilment of beneficence and non-maleficence also presented flaws in the research. Therefore, it is always necessary to assure participants of all possible benefits and minimize harm by providing clear information about the risks to which the patients will be submitted and approach therapeutic misconceptions in cancer research 36 .
It is also important to emphasise the care that medical researchers must have in order not to cause harm that would further damage the time of life of the cancer patients 11 . It is necessary to guarantee beneficence in relation to the care provided, aiming the well-being of the patients and, for those who are in the terminal phase, a dignified death 25 .

Final considerations
This review work has raised 29 studies that deal with topics about oncology and bioethics. Proportionally, Brazil was the locus of most of the researches found, and cancer patients corresponded to the public most approached in the surveys. The discussion about the interconnection between oncology and bioethics focused mainly on the knowledge and application of bioethics' principles, difficulties in the physician-patient communication, as well as ethical aspects and norms in research.
There are still many challenges to improve the relationship between these areas, as well as to ensure the application and dissemination of bioethical principles, to increase investment in formal education in bioethics and in interpersonal and physician-patient communication skills.
It is expected that dialogues between the topics on focus will encourage more discussion and help improve the assistance and development of research with oncology patients and others involved. In addition, it is expected that more studies will emerge, giving continuity to those already carried out, and that will spark new interests from then on.