Most advanced cancers eventually develop resistance to anticancer therapies, ultimately leading to the progression of the disease, symptom burden, and death [1]. Resistance may occur very early in the course of disease (often called primary resistance) or, in most instances, is acquired under long-term treatment exposure after a favorable initial response (secondary resistance).

Cancer progression, resulting from resistance to therapy, often indicates the onset of an advanced disease that will not be cured, although life expectancy may still be months or years with adequate treatment. This clinical situation represents a critical moment in the course of cancer care. Oncologist-patient communication is then particularly challenging. When resistance occurs, patient information on the severity of the disease, its prognosis, and the therapeutic options must be conducted with utmost subtlety. Patients are informed about alternative cancer treatments, expectations about their effectiveness, and side effects. This information is anxiety provoking, often eliciting the need for emotional support.

Information on prognosis and treatment outcomes is important for achieving a shared perception of the disease status and treatment goals between patients and oncologists [2-4]. A general population survey performed in 7 European countries indicates that 73% of citizens prefer to be informed in case of a poor disease prognosis (≤1 year to live) [5]. In the advanced cancer setting, most patients want a realistic understanding of their current condition and life expectancy; however, not all wish to receive exact or definitive time frames [2,6-9]. Oncologists have difficulty appraising patients’ information preferences [10]. Information on prognosis is often lacking [11], and patients do not understand that the treatment provided is not likely to cure their cancer [12].

In addition, patients with advanced cancer do not participate as much as they wish during consultations [8,13]. Possible explanatory factors include patients forgetting questions, doubting the legitimacy of asking, expressing concerns indirectly, fear of the possible pejorative answer, and a lack of physicians encouraging their questions [14-16]. Patients may also present different needs and expectations, which depend on the time in their disease course [17] or factors such as their attentional coping style or sociodemographic background [10,18,19]. Discordance between the patient’s and oncologist’s perception of treatment aims and the disease timescale may result in medical decisions that do not align with life goals that are important to patients [20,21]. This leads to patients’ greater psychological distress [22].

Patient-centered communication is the cornerstone of high care quality [23]. This allows physicians to better respond to patients’ information and support needs. To this end, guidelines to improve communication skills of health care professionals are available in many countries [24-28]. Effective physician-patient communication may decrease patients’ anxiety, sustain hope [29], and increase satisfaction with care [30-32]. Patient-focused communication aids have also been developed to complement physician communication skills training [18,30-32]. These interventions are designed to enhance patients’ participation in the consultation and thus may increase physicians’ awareness and timely accommodation of their needs and expectations [33-36].

Among patient-focused communication aids, question prompt lists (QPLs) [37-43] may help patients express their information and support needs according to their wishes. A QPL includes a structured list of questions given to the patient before the consultation. This intervention drives patients to more frequently ask questions and express concerns, especially regarding disease prognosis, and may enhance patients’ recall of information and satisfaction with care [38,39,41,42,44-48].

Most QPLs that are already available address early cancers [39,49] or palliative care [41,50-52], specific clinical situations (eg, early breast cancer [53], esophageal cancer [54,55], and myelodysplastic syndrome [56]), care circumstances (eg, clinical trials [57,58]), and populations (eg, older patients with cancer [58] or cultures or ethnicity [53,59])

A QPL for oncology consultations taking place during the first treatment lines after cancer resistance has developed seems to be lacking. Such a QPL is expected to contain questions or concerns related to the following issues: disease severity, extent of spread, future course, medical tests, treatment options, course of symptoms and side effects [60], likelihood of cure, primary goal of cancer care, expected treatment effectiveness and life expectancy [61], psychological needs [62], self-management [63], and cancer care provision and organization [64]. A QPL designed for advanced cancer care in Australia and adapted in the United States [37] and in the Netherlands [18] will serve as a basis.

In Western countries, a shift has been witnessed in models of care from a paternalistic to a patient-centered approach, tailoring information to patient preferences and wishes [65]. However, for example, little information exists on French patients’ wishes to receive information on prognosis [56] and on the concordance between oncologists’ information provision and the expectations of patients with cancer. In a previous study with patients receiving palliative care, we observed that addressing disease prognosis was seen as particularly difficult for clinicians [66]. The cultural adaptation of a QPL may be necessary not only in terms of content but also in terms of implementation modalities. Theoretically, QPLs are simple and cost-effective; however, their acceptability and implementation feasibility should also be verified cross-culturally. Therefore, optimal modalities and procedures of applying this tool in real oncology practice in France will also be explored and delineated. It is possible that a patient coaching or education group intervention may be needed as a complement.

The QPL will be developed in the following two clinical contexts, which are prone to cancer resistance, and contrasted in terms of epidemiology, life expectancy, long-term treatment options, and expected effectiveness: (1) triple-negative and luminal B metastatic breast cancer (MBC) and (2) metastatic uveal melanoma (MUM), both within the first 3 lines of anticancer treatment after treatment resistance has occurred.

Triple-negative and luminal B MBC represents approximately 15% and 50% of all breast cancer cases, respectively [67], and recurs with distant metastasis in approximately 30% of early-stage patients [68]. MBC is an incurable disease, with a median overall survival of 3 years and a 5-year survival rate of 25% [69]. Patients with MBC are generally followed by their oncologist for years, punctuated by occurrences of treatment resistance for which a new treatment regimen may be offered. This implies successive disclosures of the progressing disease and discussions of alternative treatment regimens [70].

Uveal melanoma is a rare cancer [71]. Up to 50% of patients with uveal melanoma develop metastases, mostly in the liver, within a median time of 2 to 3 years [72]. Once metastasis occurs, the median overall survival ranges from 9 to 12 months because of the lack of effective treatment options [73]. Most patients with MUM are referred to a medical oncologist after a multidisciplinary tumor board meeting. Medical oncologists then inform patients about metastatic progression and possible treatment alternatives. The dismal prognosis and rapid evolution of the disease are challenging aspects in the communication between oncologists and patients. A discrepancy in knowledge appears when the medical oncologist is aware of the patient’s poor prognosis while the patient is still in good shape and does not expect such quick, fatal outcomes.

We propose an original design for the development of a complex intervention based on the Medical Research Council framework [74].

The specific aims are (1) to develop the content of a QPL for adults diagnosed with resistant cancer, who are still eligible for disease-targeted treatment, and (2) to pilot-test the implementation of this intervention in oncology consultations in a French cancer setting. During this process, the implementation will be prepared by investigating potential obstacles and facilitation strategies from the outset.

We expect to obtain a core QPL comprising questions and concerns that patients in the treatment resistance context might generally want to express at the oncology consultation. A common core QPL will be complemented with subsections containing specific issues for either the triple-negative and luminal B MBC or the MUM cancer sites.

This psychosocial study is embedded in an overall medical research program performed within the Institut Curie Integrated Cancer Research Site—Site de Recherche Intégrée sur le Cancer. In France, this framework is equivalent to a comprehensive cancer center and has been labeled by the French National Cancer Institute. This research program deals with treatment resistance in triple-negative and luminal B MBC and MUM. A patient and partner representative committee was created with the objective of fostering public debate and integrating patients’ voices into research development, conduct, and dissemination. This committee was involved in the choice of the psychosocial study research question. Outcome measures were selected according to priorities, experience, and preferences. They found it particularly relevant and timely to address communication difficulties between the oncologist and the patient when treatment resistance occurs. Since 2017, their involvement has taken place at regular steering committees and brainstorming meetings. They provided feedback on this study protocol; the information and consent forms; and the content, format, and burden of the questionnaires.

As shown in Figure 1 and Table 1, we will adopt a sequential design and mixed methods approach [75,76], evolving in successive steps and building on qualitative (individual and focus group interviews) and quantitative (standardized questionnaires, acceptability assessment, and Delphi process) data collection and analysis. It will involve the collaboration of adult patients with MBC or MUM, patients with any type of metastatic cancer (ie, expert patient, defined as “individuals with an experience of cancer diagnosis & treatment and educated knowledge of their disease and treatment trajectory” [77,78]), oncologists, supportive care specialists, cancer care administrators, and laboratory researchers dealing with cancer resistance [79].

The approval for the study was obtained from the French national ethics committee (ID-RCB: 2019-A01713-54). All patients will provide signed informed consent. The study, for which the acronym is HECTOR (Helping Patients Communicate With Oncologists When Cancer Treatment Resistance Occurs), is registered as NCT04118062 in ClinicalTrials.gov.

The second step of the study pilot tests the QPL version 1 for its acceptability, feasibility, potential clinical utility, and sustainability. Consecutive patients (n=80) responding to the same eligibility criteria as in step 1b will be recruited. They will receive the QPL version 1 to prepare their subsequent oncology consultations, either a consultation during which the diagnosis of cancer resistance is communicated or in the course of a new disease-targeted treatment follow-up consultation. They will be invited to complete the same standardized questionnaires as in step 1b.

Additional questions will address the QPL acceptability in terms of uptake (the QPL has been read before the consultation), use (QPL items have been raised during the consultation), and patients’ and clinicians’ perceived helpfulness and satisfaction with this tool and its use in clinical practice.

This protocol describes a study using an innovative, sequential, mixed methods approach and involving patients as well as oncology professionals to collaboratively develop a QPL for cancer resistance in the French cultural context.

This study will be undertaken in 2 clinical settings prone to cancer resistance and contrasted in terms of epidemiology, life expectancy, long-term treatment options, and expected effectiveness. The resulting QPL is expected to comprise core issues related to the cancer resistance context to which specific issues will be added if needed, according to the tumor site. The core QPL is expected to be applicable in other advanced cancer contexts.

QPLs seem effective in raising patients’ asking questions [38,42,94]; however, a complementary coaching intervention may be needed to further patients’ support [95,96,97]. Coaching is the provision of nondirective support by an individual (either in-person or remotely eg, by telephone or the internet) [98]. It is expected to help patients assess their information needs (ie, about treatment options such as disease-targeted treatment [standard or experimental], best supportive care, watchful waiting, and their benefits and harms) [18], prepare and rehearse questions [33], express their concerns or emotions [99], and prioritize issues to discuss during the consultation.

This study’s sequential collaborative mixed methods approach is innovative; the following methodological aspects are expected to be fruitful. First, a triangulation of perspectives is foreseen as it involves patients, clinicians, and researchers, and thus a better grasp of the specific realities of oncology consultation communication in resistant cancer care.

Second, the quantitative and qualitative data collection approaches are complementary, and the results will be sequentially and iteratively integrated. In-depth interviews with different protagonists who are experts in cancer resistance at their own level are expected to increase the appropriateness and acceptability of the tool. Considering the modalities and procedures of tool implementation from the outset is also meant to promote its adoption in routine practice. Focus group discussions and exploratory quantitative analyses will help decide for whom, when, and how the QPL will be implemented in clinical routine.

Third, the quantitative assessment allows the assessment of the specific information and support needs that are experienced when faced with cancer resistance. These data may be compared between 2 groups: before (step 1b) versus after (step 2) the availability of the QPL. This will offer initial information on the clinical utility of the tool tailored to cancer resistance in the French cultural context.

Owing to consecutive sampling, information will be available about the number of patients willing to use the QPL and the number of oncologists who will engage in its use during consultations [92]. Furthermore, the resulting QPL will be pilot-tested on outcomes such as patients’ beliefs about primary cancer treatment goals or satisfaction with the information provided about prognosis and treatment, which are important [93] and previously lacking effect measurement of QPL use [2].

Finally, focus group discussions will specifically elicit collaborative work. The reactions and proposals of various appropriate persons [100] will help prepare the modalities of QPL use in routine practice and promote its long-term adoption [101], that is, the tool use in real-world clinical practice [102]. Moreover, the Delphi process aims to reach consensus among patients and oncology professionals on a QPL version 1 and explicit guidance for clinical implementation [103,104]. We anticipate that these persons will have diverging views and opinions about the tool [91]; thus, a consensus will have to be developed.

This protocol has several limitations. The methodology described herein is an innovative but long process. It may not be systematically applied as a new clinical context in need of a QPL. However, this study offers the opportunity to reveal unnecessary steps and thus indicate an optimized process for future research.

We focus on the communication between oncologists and patients; however, other oncology professionals such as nurses or psychologists may also play an important role in responding to patients’ information and support needs; therefore, further research is needed to address their specific role in addressing these needs. In addition, patients’ relatives may also present their specific information and support needs and may interact with the patient when facing this information. The QPL may also be useful to them, as such or adapted, and this must be evaluated.

The assessment of patients at step 1b and step 2 of this study is cross-sectional; therefore, we also need to consider that information is not collected on the same individual patients over their evolving needs and information processing.

A clinically and culturally specific QPL complemented, if necessary, by a coaching intervention is expected to facilitate patients’ participation in oncology consultations to improve oncologists’ responses to their information and support needs. This tool allows patients to control the provided information according to their wishes and thus respects their potential ambivalence and need for hope. Digital health interventions provide patients with evidence-based interventions through software apps. The availability of QPLs through these technologies is increasing [55,105,106]. Digital health interventions are easily accessible to patients from their homes through mobile devices or websites. Studies suggest that they are cost-effective, increase uptake by patients and clinicians, and provide clinical benefits [107]. Therefore, this French-adapted QPL will be available not only in paper form (brochure) but also as an app (MyCurie app) and on the institutional website. It will contain information about the purpose, interests, and modalities of use of the brochure or web document. Moreover, studies have shown the importance of clinicians’ endorsement of the tool, encouraging its use by patients; therefore, particular attention will be given to an implementation guide that recommends communication about this tool during the consultation. Patient and partner representatives of the Institut Curie will be invited to attend the local public and scientific conferences planned to communicate about this study. They will be solicited for their feedback on articles to disseminate results nationally and internationally through popular or scientific journals.

This research proposes an original methodology to adapt and further develop a QPL for patients with resistant cancer and enable its implementation in the French cultural context. It is expected to facilitate patients’ expression of questions, concerns, and emotions and, in that way, improve oncologists’ responses to their information and support needs. Clinically, this study will also improve the understanding of patients’ and clinicians’ experiences, difficulties, obstacles, and strategies in discussing prognosis and treatment options in the first anticancer treatment lines after cancer resistance has developed. Methodologically, it will be possible to infer an efficient method for designing and guiding the implementation of communication aids for patients with advanced cancer.