FormalPara Key Summary Points

Why carry out this study?

Throughout the treatment journey, patients and healthcare professionals (HCPs) largely work together to decide on treatment, with patients generally trusting their HCP’s knowledge and expertise

Patients described living longer and maintaining a good quality of life as their most important treatment goals, in addition to avoiding hepatocellular carcinoma (HCC) returning or worsening. Consideration of these factors is important to enhance the patient experience

What was learned from this study?

HCPs identified patients living longer, time without worsening of HCC and managing side effects as important treatment goals

Discussing the benefits and risks of available treatment options with patients is important to ensure they have the opportunity to achieve outcomes aligned to their treatment goals

Introduction

Liver cancer continues to be a serious global health challenge. Incidence rates are increasing, with liver cancer now recognized as the sixth most prevalent cancer diagnosis and the third leading cause of cancer-related mortality. Hepatocellular carcinoma (HCC) is the predominant histological variant of liver cancer and accounts for > 90% of primary liver cancer diagnoses [1]. The global burden of HCC is increasing, although progress in early detection, diagnosis and treatment has broadly improved the overall management of HCC. The etiology of HCC has been studied intensively, with viral factors such as hepatitis B and C identified as major risk factors for the development of HCC in Asian countries [2, 3]. Non-viral factors, such as metabolic dysfunction-associated fatty liver disease (MAFLD), and sustained alcohol use also contribute to the rise in HCC diagnoses in high-income countries [4, 5]. Frequent screening and surveillance of at-risk patients are integral to reducing HCC-related mortality [6].

The Barcelona Clinic Liver Cancer (BCLC), a widely used staging classification, comprises four diagnostic stages (A–D) to facilitate the selection of appropriate treatment(s) for HCC [7]. The size, location and number of tumors are considered when determining a patient’s disease stage. Healthcare professionals (HCPs) subsequently consult international and/or national guidelines, such as the American Association for the Study of Liver Diseases (AALSD), European Association for the Study of the Liver (EASL) or European Society of Medicine (ESMO), to select an appropriate treatment regimen according to the patient’s current disease stage, comorbidities and liver function [8]. Dependent on the patient’s classification, treatment can include surgery/resection, liver transplant, radiofrequency ablation (RFA) and embolization, e.g., transarterial chemoembolization (TACE). Systemic therapy, especially immunotherapy, has become a standard of care in advanced/unresectable liver cancer treatment in recent years and may also aid in the management of intermediate and early stage disease [9]. Prior to the introduction of immunotherapy for uHCC, the 5-year survival rate was estimated at < 10% [10]. An updated exploratory analysis of the HIMALAYA Phase 3 trial showed that at 4-year follow-up, an estimated 25.2% of patients treated with the STRIDE regimen in the US, EU and Japan (Single Tremelimumab Regular Interval Durvalumab) were alive at 4 years versus 15.1% for those treated with sorafenib [11]. The median age of patients in the trial was ~ 65 years with 83% patients being male, and 80% of patients were categorized as BCLC C.

Little qualitative research has been conducted regarding the patient experience of HCC. One qualitative study interviewed patients with HCC to understand disease-related signs, symptoms and impacts [12]. The most prevalent signs/symptoms reported by patients with HCC across disease stages included lack of energy and emotional impacts. The study also identified four sign/symptom categories: eating behavior/weight changes; extremities; fatigue and strength; gastrointestinal pain. A later qualitative literature review illustrated the negative impact of HCC on patient’s quality of life (QoL) related to treatment side effects, psychological impacts and impaired social functioning [13]. Despite advances in overall prognosis of HCC, there is still a significant impact on patient’s QoL [13]. Patients with HCC often feel isolated in their journey [14] and report numerous barriers to their care including poor communication and knowledge from healthcare professionals (HCPs) [15].

The importance of the patient-HCP relationship and shared decision-making throughout the cancer diagnosis and treatment journey have been explored in the literature [16, 17]. However, little is known about the broader HCC journey from both the patient and HCP perspective. Understanding the patient journey of HCC could inform future clinical decision-making and help shape health policies to support these patients. Ultimately, consideration of these factors throughout the cancer diagnosis and treatment journey is important to enhance the patient experience. Therefore, the primary objective of this global, multi-national qualitative interview study was to understand the HCC patient experience from pre-diagnosis to current treatment, including HCC symptoms and impacts, treatment goals and treatment decision-making.

Methods

Qualitative interviews were conducted with patients diagnosed with HCC and HCPs who treat HCC in the US, France, Germany and Japan. This study was conducted in line with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Western Copernicus Group (WCG) Institutional Review Board (IRB) on 5 February 2022 (IRB study no. 1331769). This study is reported in accordance with the Standards for Reporting Qualitative Research (SRQR). The checklist is available as supplementary information (Supplementary Information 3). Informed consent forms, signed by all participants, stated that data collected for this study would be submitted for publication. Informed consent was obtained from all individual participants included in the study.

Sampling and Recruitment

Patient Interviews

Adults aged > 18 years with a confirmed diagnosis of early (BCLC A defined as one to three cancerous nodules < 3 cm confined to the liver), intermediate (BCLC B defined as three or more tumorous lesions confined to the liver without vascular invasion or one to three tumors where one is > 3 cm) or advanced/unresectable stage (BCLC C defined as involves portal vein invasion, nodal involvement or metastases) HCC located in the US, France, Germany and Japan were eligible to participate in this study. Confirmation of diagnosis was obtained through a clinician-completed case report form or a copy of medical records/treatment history. Purposive sampling, defined as a non-randomized sampling strategy that involves the recruitment of specific individuals in line with the aims and objectives of the study, was adopted to provide a balanced representation of each HCC disease stage across countries. Demographic and clinical information, including age, sex, race, education, source of payment for treatment, diagnosis date, current disease stage, treatment history, smoking status and concurrent conditions, was collected prior to the interview, where available.

HCP Interviews

Oncologists qualified for over 5 years with experience of managing and treating patients with HCC, currently involved in direct patient care at least 50% of the time and based in the US, France, Germany and Japan were eligible to participate. Purposive sampling was applied to ensure representation across countries.

Details of the eligibility criteria for patients and clinicians are available as supplementary information (Supplementary information 1). All participants were recruited through a specialist recruitment agency, Global Perspectives (GP) or US-based patient advocacy group (PAG) who utilized social media, clinician referrals and database searches to identify participants. Written informed consent was obtained from all participants prior to the interview process. All participants received an honorarium aligned with fair market values (FMVs) to compensate them for their time.

Procedures

Patient Interviews

Individual interviews lasting approximately 60 min were conducted remotely using Microsoft Teams between July 2022 and April 2023. Remote interviews enabled the recruitment of a geographically diverse sample. A semi-structured interview guide (Supplementary Information 2) encompassed open-ended concept elicitation questions to understand the patient experience of HCC including the pre-diagnosis and diagnosis experience, treatment decision-making, treatment goals, treatment options and HCC symptom experience. To further explore symptom experience, a saliency task was conducted. This involved asking patients to identify and rank their most bothersome symptoms on a scale of 0 (does not bother) to 10 (extremely bothersome). Rankings were collected regarding how bothersome the symptom was during at the time of interview. Identified concepts were deemed salient if reported by 10% of those patients who completed the saliency task. This equates to concepts reported by 4.3 patients; however, for the purpose of reporting, the decision was made to include concepts if reported by four or more patients. The patient interview guide was reviewed by HCC experts and patient advocates and refined accordingly. Due to the potential emotive nature of discussions, a distress protocol was designed and implemented in instances where participants became upset. All interviews were conducted by trained, experienced interviewers. Interviews conducted with patients in France, Germany and Japan were conducted in the participant’s native language using a formally translated interview guide. Adverse events disclosed during the interviews were reported to each respective country’s drug administration body within 24 h. Nine patients provided feedback on their interview. Overall, patients were positive about their interview experience; most described the interview questions as easy to understand, some appreciated the opportunity to reflect on their overall journey with HCC, while others were pleased to participate in research that may help other patients.

HCP Interviews

Individual interviews were held remotely with HCPs using Microsoft Teams between May and August 2022. A semi-structured interview guide focused on the diagnostic process, treatment goals, treatment pathways and treatment decision-making was utilized.

Data Analysis

Unique identifiers were allocated to protect participants’ identity using the following formats for patients: [Patient number–Country–Disease stage] and HCPs: [HCP–Country–HCP number–O]. All interviews were audio recorded and transcribed verbatim, with those conducted in France, Germany and Japan directly translated into English. Transcripts were analyzed using directed content analysis techniques [18] facilitated by Atlas.ti v9.1 software.

The analysis adopted an experiential, realist approach, focusing on participants’ individual perspectives and experiences. Following immersion and familiarization with the data, a combined inductive and deductive coding approach was applied to relevant data within the transcripts. The process of inductive coding is a bottom-up data-driven approach, whereby codes are developed from the data itself. The process of deductive coding involves the use of a pre-defined code list developed from existing literature. The initial codes were iteratively reviewed and refined during the coding process. The research team met regularly to discuss their interpretations, reflecting on coding decisions and revising coding where agreed. Codes were then refined further and organized to identify concepts and domains relevant to the study objectives. Demographic and clinical information was descriptively summarized using Microsoft Excel.

A patient journey map (PJM) was developed once coding was finalized using Microsoft PowerPoint to provide a visual representation of the patient experience throughout the HCC journey.

Conceptual Saturation

An assessment of conceptual saturation, defined as the point at which no new concept-relevant information emerges [19], was conducted at the total sample level for patient’s symptom experience. Transcripts were grouped into ten sets in sequential order, and elicited symptom concepts were compared between sets. If no new symptom concepts were identified within the last set, conceptual saturation was considered to be achieved. Exploring saturation determined whether a sufficient sample size had been recruited to achieve study objectives, but multiple topics explored were anticipated to be highly individual and/or impacted by individual experiences to a greater extent than disease factors (e.g., discussions with HCPs, treatment goals). HCC symptoms were expected to be broadly consistent among all patients in all countries and were therefore the focus of saturation analysis.

Results

Conceptual Saturation

Conceptual saturation was achieved for symptom experience reported by patients with HCC. Two concepts, congestion and white stool, were spontaneously elicited in the penultimate set of transcripts by two patients and were not probed within the earlier interviews. No symptoms were spontaneously elicited in the final set of interviews.

Patient Sample Characteristics

A total of 50 patients from the US (n = 15, 30%), France (n = 10, 20%), Germany (n = 15, 30%) and Japan (n = 10, 20%) were interviewed in this study. Most patients were age 55–69 years (60%), with a similar representation of patients diagnosed with BCLC A/early-stage HCC (n = 19, 38%), BCLC B/intermediate-stage HCC (n = 15, 30%) and BCLC C/advanced-stage HCC (n = 16, 32%). Eleven patients (n = 11, 22%) had liver cirrhosis, and 39 patients (n = 39, 78%) did not report liver cirrhosis. Regarding underlying liver disease, patients had metabolicd ysfunction associated fatty liver disease (n = 14, 28%), hepatitis B (n = 11, 22%) and hepatitis C (n = 9, 18%). Demographic and clinical characteristics are presented in Table 1.

Table 1 Patient demographic and clinical characteristics
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HCP Sample Characteristics

In total, n = 12 oncologists treating and managing HCC in the US (n = 3, 25%), France (n = 3, 25%), Germany, (n = 3, 25%) and Japan (n = 3, 25%) participated. Demographic characteristics of HCPs are presented in Table 2.

Table 2 HCP demographic characteristics
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Patient Journey Map

Figure 1 presents a PJM of the patient experience with HCC. The PJM provides a chronological overview of patient’s pre-diagnosis symptoms, factors leading to their initial visit decision and the diagnostic process. The treatment decision-making process and influential factors in treatment decisions are summarized. Patients' prioritization of treatment goals, treatment options, treatment impacts and most bothersome symptoms are presented across early, intermediate and advanced disease stages. The PJM was conceptualized primarily using patient data; however, HCP data were considered to facilitate refinement.

Fig. 1
figure 1

Patient journey map. Purple denotes patient factors. Red denotes HCP/clinical factors. Green denotes collaborative elements of journey. *Most commonly reported treatment options per disease stage. †: the most important treatment goals were similar across all disease stages. However, the most frequently reported, most important treatment goal has been included. For some patients, OS and QoL were equally important treatment options per stage. Tx treatment, Dx diagnosis, PAG patient advocacy group, CT computed tomography scan, MRI magnetic resonance imaging, HCC hepatocellular carcinoma, HCPs healthcare professionals

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Diagnosis

Patient quotes relating to pre-diagnosis and diagnosis are shown in Table 3. Most patients across all countries noted that their HCC diagnosis had been an incidental finding of another health-related check (n = 18, 36%), often related to pre-existing risk factors such as chronic hepatitis or liver cirrhosis due to various reasons. HCPs reported similarly, noting that patients may be asymptomatic pre-diagnosis. The number of patients who reported symptoms pre-diagnosis was higher in Germany (n = 12, 80%) and the US (n = 13, 87%) than in patients from France (n = 6, 60%) and Japan (n = 4, 40%).

Table 3 Pre-diagnosis/diagnosis experience—supporting quotes
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Upon receiving their diagnosis, patients reported discussing various topics with their HCP including treatment (options, expectations and goals; n = 45), factors relating to their HCC diagnosis (staging, prognosis and testing; n = 34) and details of onward referrals (n = 26). More patients in Germany reported onward referrals (n = 11, 73%) than in other countries [France: n = 6 (60%); US: n = 5 (33%); Japan: n = 4, (40%)]. Some patients reported that they had not considered or actively engaged with patient support groups to help them cope with their diagnosis. Across all disease stages and countries, patients most frequently reported feeling shocked (n = 32) or worried/concerned/fearful (n = 32) upon receiving a diagnosis of HCC. Patients also reported having thoughts of dying (n = 12) and feeling disbelief (n = 8). Conversely, fewer patients reported positive or neutral emotions at diagnosis such as acceptance (n = 7) and feeling hopeful (n = 7). Patients in the US more frequently reported feeling disbelief (n = 5) rather than acceptance (n = 0).

Treatment Goals

Illustrative quotes detailing patient perspectives on treatment goals are presented in Table 4. QoL (n = 24) and OS (n = 21) were reported as the most important treatment goals by patients across all disease stages. Patients in Japan less frequently reported QoL as their most important treatment goal (n = 2) compared with other countries (France: n = 6; Germany: n = 8; US: n = 8). For some patients, neither OS nor QoL could be prioritized as a single treatment goal, and both were considered equally important. Patients with early stage HCC generally prioritized OS, whereas patients with intermediate or advanced HCC generally prioritized QoL. OS was described as a desire to live as long as possible, extend life and prolong survival. QoL was described as remaining healthy despite HCC and living a normal life without burden and/or bother.

Table 4 Treatment goals—supporting quotes
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Most HCPs in all countries prioritized OS (defined as the length of time that a patient lives from initiation of treatment until death) and progression-free survival (PFS, defined as the length of time that a patient lives during and after treatment without disease progression) across the HCC journey but reported that QoL became more important in BCLC C/advanced stage HCC. Managing treatment safety, especially in advanced stage HCC, took precedence for HCPs. Limiting side effects, preserving sufficient liver function and patient age were all considered important in maintaining QoL in advanced/unresectable HCC.

Most patients reported that their treatment goals had not changed (n = 30). HCPs also acknowledged that treatment goals may change for patients depending on treatment efficacy, progression through lines of treatment and disease progression. A greater proportion of patients in Japan reported that their treatment goals had changed (n = 5, 50%) compared to those who reported that their treatment goals had not changed (n = 5, 50%) than in other countries.

Most patients reported that their treatment goals aligned with their HCP’s treatment goals (n = 32). A smaller proportion of intermediate or patients with advanced HCC reported that their treatment goals did not align with their HCP’s treatment goals (n = 7).

HCPs made efforts to listen to and prioritize patients’ treatment goals. HCPs tried to manage expectations and maintain realistic treatment goals with their patients (n = 6, 50%). Whereas some patients with advanced/unresectable HCC reported targeting cure, some HCPs did not consider this a viable treatment goal at this stage. Both patients and HCPs reported that treatment goals were discussed regularly, beginning before treatment begins and continuing throughout the treatment journey.

Treatment Decision-Making

Across all countries and disease stages, patients described both active and passive/collaborative roles with their HCP regarding treatment decisions (Table 5). Where treatment decisions were mostly led by a HCP, patients were comfortable with this approach and preferred that their HCP controlled their treatment decisions. Patients were keen to rely on their HCP’s expertise to make decisions in their best interests. Some patients in Japan described a more active role in treatment decision-making, describing challenging their HCP’s decisions where they felt necessary based on either independent research or previous treatment experiences.

Table 5 Treatment decision-making—supporting quotes
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HCPs reported that efforts were made to involve patients in their own care with one HCP acknowledging that active patient collaboration was indicative of modern medicine. In instances where a patient’s desired treatment goal did not align with their own, HCPs made efforts to involve patients in the decision-making process to arrive at a shared, realistic goal.

HCPs from different specialties were reported by patients as involved in their treatment decisions, including oncologists (n = 17), surgeons (n = 13), gastroenterologists (n = 12) and hepatologists (n = 7). Patients acknowledged the role of multidisciplinary teams (MDTs) in their treatment decision-making (n = 10). Country level differences were noted; US patients primarily noted oncologists to be involved in treatment decision-making, while surgeons were primarily involved in Germany. Gastroenterologists were primarily involved in decision-making in both France and Japan. HCP reports corroborated patient findings, detailing the role of MDTs in convening and evaluating optimal treatment pathways based on each patient’s unique clinical and demographic characteristics.

Clinical factors (n = 15), treatment burden (n = 13), disease progression (n = 10) and treatment efficacy (n = 8) were considered by either patients or their HCPs, or discussed collaboratively during the treatment decision-making process. Access to treatment was not considered a major barrier to treatment by most patients, a finding echoed by HCP data. However, approximately 25% of patients in the US received Medicaid, and some patients reported that their preferred treatment had previously been declined. Broadly, access to treatment was a factor in the US but seemed less influential for patients in Germany, France and Japan. Notably, some patients in Japan identified high treatment costs as a burden, which negatively affected their emotional wellbeing.

Patients noted areas of their care that they felt could have been improved. Most patients reported that they would have liked more information throughout their treatment journey, relating to available treatment options, treatment outcomes and guidance regarding their treatment (n = 8). Some of these patients expressed a desire for information to be in a format that was easy to understand. Other areas for improvement identified by patients included more time from their care team (n = 4), improved treatment options (n = 4), pain relief (n = 3) and faster diagnosis/treatment (n = 3).

Treatment Options

Across all disease stages and countries, most patients reported, at the time of their respective interviews, having either previously undergone or been offered surgery at some point in their HCC journey (n = 43). Systemic therapy was also commonly reported (n = 33; BCLC A, n = 9, BCLC B, n = 8, BCLC C, n = 16). More patients in Japan (n = 10) and France (n = 7) reported that they were offered embolization throughout their journey than in Germany (n = 3) and the US (n = 3). Patients mostly reported that they felt satisfied (n = 35) with their treatment options, even if only one treatment option had been presented to them.

The most common treatment option for patients with early stage HCC was surgery/resection (n = 19). For patients with intermediate HCC, the most common treatment options across all countries were surgery (n = 11) and systemic therapy (n = 8, 53%). HCPs in Japan (n = 3) and France (n = 2) reported offering/using chemotherapy (e.g., TACE) in some instances for patients with intermediate stage HCC. Across all countries, systemic therapy was the most commonly reported treatment option for patients with advanced/unresectable HCC (n = 16); sorafenib, lenvatinib, atezolizumab and bevacizumab were frequently reported systemic therapies by HCPs.

Patients also described emotional and physical impacts of their treatment. Surgery caused emotional impacts such as fear (n = 7), anxiety/worry (n = 7) and relief (n = 4). HCPs also noted that patients often felt fearful of surgery. Patients reported physical impacts such as unspecified pain (n = 9), needing a period of recovery (n = 6) and hospitalization post-surgery (n = 5). Systemic therapy was most commonly associated with fatigue (n = 16), diarrhea (n = 9), hair loss (n = 6) and weakness (n = 5).

Symptom/Treatment Experience

Of the total sample, (n = 43) patients completed the saliency task exploring their symptom/treatment experience. Patients identified 41 distinct symptoms and/or side effects related to their experience with HCC. The most frequently reported symptoms included fatigue (n = 24, 56%), nausea (n = 12, 28%), abdominal pain (n = 10, 23%), and diarrhea (n = 9, 21%). Of these symptoms/sides effects, as illustrated in Fig. 2, fatigue was identified as the most prevalent bothersome symptom/side effect across all disease stages and countries to patients based upon frequency of reports and mean bothersome ratings (Fig. 2).

Fig. 2
figure 2

Saliency Graph1. 1To explore symptom/treatment experience, patients were asked to report which symptoms or side effects of their treatment were most bothersome to them currently (at the time of interview) on a scale of 0 (does not bother) to 10 (extremely bothersome at the time. The mean of participant bothersome scores was calculated to denote average current disturbance ratings

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Discussion

This multi-national qualitative interview study explored the patient and HCP experience of the treatment journey across HCC. Interviews with both patients and HCPs facilitated a unique comparison of perspectives of the HCC journey, including treatment goals and treatment decision-making.

Patients in all countries reported similar signs/symptoms before diagnosis, including fatigue, general malaise, jaundice, lack of appetite, stomach pain and weight loss, corroborating previous findings regarding patient symptom experience [12]. A substantial proportion of patients were asymptomatic and reported good health before receiving their diagnosis, especially patients living with early stage HCC. Consequently, the presence of HCC was often an incidental finding after patients had completed routine monitoring/testing due to lifestyle-related risk factors (e.g., alcoholism) or clinical risk factors (e.g., hepatitis B or C). Active surveillance can lead to earlier HCC diagnosis and an increased likelihood of curative treatment especially among patients with a risk factors for HCC [6, 20]. The findings of this study support the utility of regular surveillance activities, especially in patients who present with one or more risk factors for HCC such as those living with liver cirrhosis [21]. Existing evidence supports the efficacy of surveillance and early detection of HCC as an important factor in patients prognoses [22].

Diagnosis of HCC had a notable emotional/psychological impact on patients in all countries. Previous research has elucidated the important role of social support throughout the cancer journey [23, 24]. Ensuring that patients are encouraged to involve friends/family throughout the HCC journey should remain of critical importance to care teams. In instances where patients are unable to rely on a social support network, care teams should strive to provide alternative resources to patients with HCC, such as PAGs, to facilitate adaptive coping. PAGs provide emotional support to patients living with HCC and offer an opportunity for peer support and advocacy. Additionally, they can help patients access up to date and reliable information about HCC and its treatment, to help them manage their condition and improve outcomes. Therefore, it is important that PAGs are appropriately highlighted to patients throughout their journey.

Patients reported that their most important treatment goals were OS and/or QoL, and some patients prioritized both equally. Some patients prioritized cure. However, there were differences by disease stage; patients with BCLC A/early-stage HCC prioritized OS, which was described as a desire to live as long as possible, whereas patients with BCLC B/intermediate or BCLC C/advanced stage HCC prioritized QoL. Patient treatment goals generally aligned with HCP treatment goals; most HCPs prioritized OS and PFS at all disease stages but reported that QoL became more important in BCLC C/advanced stage HCC. Patients and HCPs in all countries frequently discussed treatment goals together throughout the course of the treatment journey. Key to ensuring that treatment goals are truly collaborative is understanding how both patients and HCPs conceptualize key clinical terms during interactions. Previous research has highlighted how oncologist’s use of clinical terms and contradictory language can leave patients feeling confused by what is obtainable with their treatment [25]. Adequate communication training programs for HCPs should be prioritized to maximize effectiveness of these interactions, thus promoting patient confidence.

HCPs in all countries described attempting to involve the patient in their own treatment decision-making where possible. Some differences were noted—at early stage, surgery/resection was prioritized where possible, whereas at advanced-stage HCC there were different options of systemic therapy. While HCPs reported that patients were active collaborators in treatment decision-making, the patients' findings did not entirely concur. Patients typically reported that their HCP had proposed treatment options to them and that the patient had given final approval. Although patients indicated a preference for HCP-led decisions, shared decision-making can be beneficial for patients [17]. Providing patients with appropriate resources throughout their disease journey could improve patient confidence and support them in engaging in informed choices regarding their care.

The results of this study highlight the overall importance of survival and QoL in treatment decision-making; patients and HCPs agree that extending survival as long as possible is critical, and doing so while maintaining a good QoL is ideal. In a study published by Zhang et al., the authors have identified that curative intent treatment was the strongest predictor for survival > 5 years among patients with HCC [26]. With the recent approval of the STRIDE regimen, which has shown long-term OS benefit, future research is warranted to understand the impact of newer systemic therapies not only on patient prognoses but also in relation to quality of life in long-term survivors. To realize the ambition of extended survival, treatment should focus on preventing relapse, particularly in patients living with early stage HCC.

Study Strengths and Limitations

This study had several strengths. The perspectives of participants from four countries across three different continents were obtained during the interviews. This multi-national approach provides unique insights into the patient experience of HCC across different cultural contexts. The sample also included approximately equal numbers of patients with early, intermediate and advanced stage HCC. This allowed for comparisons across disease stages, particularly in relation to prioritized treatment goals. The inclusion of HCP interviews provides important context regarding patient findings such as understanding perspectives on treatment goals, availability of treatment options in each country and treatment guidelines. Patient centricity was also prioritized throughout the study. The implementation of a distress protocol to actively manage patient’s distress and the involvement of patient advocates during interview guide development ensured that patient perspective was considered throughout study activities.

There are limitations to this study that should be acknowledged. All HCPs interviewed were oncologists who primarily treated patients with intermediate or advanced stage HCC. Therefore, data collected from HCPs relating to early stage HCC may be limited. Despite this, patient and HCP reports of treatment options, goals and experiences at early stage HCC are aligned. In addition, patients were interviewed regarding their entire journey with HCC. Therefore, some patients diagnosed with advanced/unresectable HCC had experienced and reported more variation in treatment options offered, treatment goals targeted and HCP interactions. While the patient perceptions provided valuable insights, due to the qualitative nature of the study, the symptoms caused by the disease vs the treatment-related side effects could not be distinguished. Additional quantitative research is needed to understand the burden associated with the disease as well as the treatment side effects. A small number of patients with early stage HCC had yet to receive planned treatment and subsequently had a reduced range of experiences to report. Also, the sample size for each stage of HCC was limited; hence, no meaningful difference across the stages was observed in the study. Finally, conceptual saturation was performed on symptom concepts only, despite broader study objectives exploring the patient experience of HCC.

Conclusion

OS is of critical importance to both HCPs and patients, but treatment goals can change across the disease/treatment journey. Goals were frequently discussed between patients and HCPs at diagnosis and before, during and after treatment. Across all countries, QoL is important to patients at all disease stages whereas HCPs prioritized QoL at advanced disease stages. Generally, patients prioritized living as long as possible (extending OS) as well as preserving optimal quality of life while dealing with debilitating side effects. Patients in Japan less frequently reported QoL as their most important treatment goal compared to other countries. Patients' treatment goals mostly align with their HCP. HCPs and patients described treatment experiences similarly, noting the range of side effects, physical impacts and emotional impacts of treatment. Patients in Germany and the US reported experiencing symptoms pre-diagnosis more frequently than patients in France and Japan.

Overall, HCPs and patients collaborate to decide upon treatment and achieve shared treatment goals. HCPs generally involve patients in decision-making, and patients typically trust their HCP’s recommendations before giving their final approval. Patients in Japan described a more active role in treatment decision-making. Patients were mostly satisfied with the treatment options presented to them. Discussing the benefits and risks of available treatment options with patients is important to ensure they have the opportunity to achieve outcomes aligned with their treatment goals. Consideration of these factors is important in order to enhance the patient experience where possible. This will become increasingly important as new treatment options emerge/become available.