Adjuvant immunotherapy recommendations for stage III melanoma: physician and nurse interviews

Prior research with patients with resected stage III melanoma and their partners acknowledged the potential for all melanoma clinicians (medical oncologists, surgeons, dermatologists and nurses) to influence their patients’ adjuvant immunotherapy decision-making [10]. As such, purposive sampling [11] enabled the recruitment of melanoma physicians (medical oncologists, surgeons and dermatologists) and nurses with experience treating patients with resected stage III melanoma from three Australian tertiary melanoma centres. Melanoma nurses were clinical nurse consultants providing direct patient care, monitoring treatment toxicities, providing treatment information and psychological support or clinical trials managers coordinating patient recruitment to medical, surgical, and radiation clinical trials. Participants were able to provide informed consent and complete the interview without an interpreter.

The research team included a lead researcher, a health economics PhD candidate (AL), three social scientists (KD, KH and RLM), and four medical oncologists (AMM, GVL, MRS, MSC), three of whom were interviewed. One author (AL) facilitated an individual, face-to-face or telephone interview between July 2019 and March 2020. Interview topic lists were compiled based on a systematic review identifying factors melanoma clinicians considered about immunotherapy; and in-depth discussion with investigators drawing on their clinical knowledge and experience [9]. A semi-structured interview guide facilitated discussion about the factors physicians and nurses considered when recommending adjuvant immunotherapy for resected stage III melanoma (Additional file 1). Most interviews were completed before the recent Australian government reimbursement of adjuvant nivolumab or pembrolizumab for resected stage IIIB-D melanoma. The median interview duration was 42 min (range 22–75), and interviews were audio-recorded and transcribed verbatim by a professional transcribing service. The Sydney Local Health District Human Research Ethics Committee (HREC/18/RPAH/736) granted ethics approval. Participants provided informed written consent, with the Declaration of Helsinki underpinning this study [12].

This qualitative study used an interpretative approach. Consideration of the participants’ beliefs, meanings, perceptions and underlying motivations when recommending adjuvant immunotherapy were explored [13]. Given that physician decision-making was the main focus, expected utility theory was drawn upon, meaning choices are rational and aim to maximise utility for most patients [14]. Data were analysed using thematic analysis, and participants were recruited until data saturation. Saturation was confirmed when no new themes emerged despite continued data collection [15]. HyperResearch software (Researchware, Massachusetts) was used to manage de-identified manuscripts. Transparent reporting was assured using The Standards for Reporting Qualitative Research checklist (Additional file 2) [16]. AL generated the initial codes, using her familiarisation with the data. RLM and AL discussed the codes, and an inductive and iterative data review was undertaken. KD independently reviewed a sample of data and generated a list of codes. All codes were then discussed by AL, RM and KD, refined into main topics and reorganised into sub-themes and themes, resulting in an agreed coding framework. Physician and nurse quotes illustrate sub-themes and themes (Table 2). Peer debriefing and validation by co-authors addressed researcher subjectivity and biases [17].

Factors influencing a patient’s suitability for immunotherapy included: the stage of disease, age, performance status/general health, comorbidities (e.g. autoimmune disease), level of social support, and the patient’s ability to promptly report treatment toxicities.

All participants indicated that the patient’s stage of disease was influential for immunotherapy recommendations. Patients with more extensive disease, stage IIIC/D melanoma, were more strongly encouraged to consider treatment than those with earlier stage melanoma, stage IIIA/B. Most participants agreed that all patients with stage III disease should discuss adjuvant immunotherapy. However, due to the lower risk of recurrence in stage IIIA, many were comfortable when this group decided against treatment.

Patient age and performance status were motivating factors for some physicians’ and nurses’ treatment recommendations. Several were less likely to recommend immunotherapy to those over 80 years with low-performance status, particularly if their melanoma recurrence risk was low or comorbidities limited their life expectancy. Some younger patients felt ‘invincible’ and ‘did not have time for treatment’. However, this often resulted in health care professionals increasing the strength of their immunotherapy recommendation for these individuals. Several medical oncologists raised concerns about recommending immunotherapy for patients they considered less likely to promptly report toxicities, consequently reducing the physicians’ ability to manage treatment safely.

Four sub-themes included the presentation of benefits and harms, evidence-based facts, physician/nurse influence, and the uncertainty about individual treatment efficacy. All participants discussed their role in presenting immunotherapy benefits and harms to patients. All stated their treatment recommendations were linked to their perception of the treatment risk/benefit profile and the absolute immunotherapy benefits and harms for each patient, that is, reducing the risk of melanoma recurrence versus the risk of severe toxicities. Surgeon respondents in our cohort commonly discussed treatment benefits and harms in ‘broad’ terms. All surgeons referred their patients to medical oncologists, enabling adjuvant immunotherapy expertise and discussions regarding individual risk/benefit profiles.

Physicians and nurses felt strongly that their role was to provide evidence-based facts to patients to inform their decision-making. All participants were comfortable discussing adjuvant immunotherapy for stage III melanoma, knowing that most patients could access drugs at ‘no-cost to them’ via compassionate use schemes or clinical trials at the time of interview [5, 6]. Adjuvant immunotherapy for stage II melanoma was viewed as experimental, with many participants discussing access to treatment via clinical trials. Several physicians and nurses discussed modes of information delivery to their patients, including written and verbal, videos and website resources, with many favouring a multimodality approach. Commonly, participants noted that health care professionals repeating information were essential to inform and reconfirm each patients’ level of understanding.

Many participants noted that their opinion was influential during patient immunotherapy decision-making. The dermatologist and surgeons were less likely than other physicians and nurses in our sample to discuss their treatment recommendations with patients. Several participants noted that their emphasis on a particular treatment aspect (for example, survival gains versus harms or toxicities) might impact patient decisions. There was some awareness of positive or negative ‘framing’, mainly by the female participants in our sample.

Physicians and nurses verbalised difficulty determining the efficacy of adjuvant treatment in an individual because there was no visible disease to follow, nor is there a specific biomarker to identify benefits from adjuvant therapy. Many reported uncertainties about disease recurrence and whether adjuvant therapy altered the outcome. For example, if the melanoma did not recur following immunotherapy, it may not have recurred without treatment, and conversely, if recurrence did occur, it could have recurred earlier without therapy. Several medical oncologists and most surgeons discussed the dilemma of treating patients prophylactically after resection versus treating those when the melanoma recurred.

Many participants acknowledged that their personal views and experience might influence patient treatment decisions. Several physicians considered previous patients with poor outcomes, mainly when the circumstances were similar, e.g. the disease stage or the sequence of events. Some considered adjuvant immunotherapy to be less burdensome than adjuvant chemotherapy, with less onerous administration and lower toxicity frequency. Physicians valued the ability to refer patients to competent specialists located in regional centres, reducing rural patients’ need to travel long distances for treatment and follow-up.