Diagnostic journey and life impact of cholangiocarcinoma: results from surveys of patient and caregiver experiences

Abstract

Aim: To understand cholangiocarcinoma symptoms, diagnosis and treatment experience from the patient and caregiver perspective, including cholangiocarcinoma’s impact on daily life, quality of life (QoL) and mental health. Methods: Patients and caregivers participated in two online surveys (in partnership with the Cholangiocarcinoma Foundation). Results: The patient survey data (n = 707) show a substantial impact of cholangiocarcinoma on QoL and mental health, with 34% of patients reporting symptoms consistent with moderately severe/severe depression. The caregiver survey data (n = 60) show that although caregivers experience satisfaction in their role of caring for a loved one, managing the demands of caregiving exacts a physical, mental and emotional toll. Conclusion: These surveys highlight the need for better palliative and supportive care interventions.

Plain language summary

What is this article about?

It shows results from two surveys, one for people with cholangiocarcinoma (CCA, pronounced kō·lan·jee·ō·car·sin·nō·muh), and one for caregivers (people who take care of family or friends with CCA without payment). CCA is a rare and aggressive cancer. The caregivers we surveyed were not necessarily taking care of the people with CCA who we surveyed. We did the surveys to find out how CCA changed the lives of people in these two groups.

What were the results?

We surveyed 707 people with CCA. Patients reported in the survey that having CCA impacted their daily lives in lots of ways. Most needed help with daily chores like housekeeping and shopping. Both tiredness and anxiety were reported by about two in three people with CCA. More than one in three had said they had symptoms indicating potential depression, which means patients should have their mental health evaluated. CCA also reduced their sexual desire and intimacy with their partner.

We surveyed 60 caregivers who reported both good and bad experiences taking care of a person with CCA. The good experiences included knowing that their loved one was well cared for and learning to deal with difficult situations. Many caregivers also felt closer to their loved one with CCA. The bad experiences included exhaustion and emotional and mental stress. Caregivers felt challenged by trying to understand CCA and the treatment options available.

What do the results of the study mean?

Patients with CCA and their caregivers need more help and support.

Graphical abstract

Keywords: :

• burden
• caregiver
• cholangiocarcinoma
• mental health
• quality of life

Cholangiocarcinoma (CCA) is a rare cancer arising from the biliary tree. Based on the anatomical site of origin, CCA is categorized into intrahepatic CCA and extrahepatic CCA, the latter of which is further classified into perihilar and distal CCA [1]. In the USA, approximately 8000 people are diagnosed with CCA each year [2]. A study of Surveillance Epidemiology and End Results registry data found that between 2001 and 2017, the incidence of CCA increased from 3.08 to 4.43 per 100,000 [3]. The majority of patients (67%) were ≥65 years of age at CCA diagnosis, but the largest percentage increase in the incidence of CCA was reported in younger patients (18–44 years) [3].

Patients with CCA typically present in advanced stages, owing to the aggressive nature of the disease and the fact that the disease can be largely asymptomatic at early stages [4]. Moreover, CCA may be misdiagnosed as another adenocarcinoma, including cancer of unknown primary, owing to a similar histopathology and clinical presentation [5], a paucity of diagnostic markers specific to CCA [6]; thus, CCA is commonly a diagnosis of exclusion [7]. Consequently, CCA is often associated with a poor prognosis [8,9]. In common with other malignancies [10,11], patients with advanced biliary tract cancers including CCA have a decreased quality of life (QoL) with multiple domains of their daily living impacted due to disease-related and treatment-related factors [12–14]. In patients with CCA, commonly reported symptoms that impact their QoL include jaundice, abdominal pain, nausea, fatigue, unintended weight loss and fever [4,15,16]. In a single-center prospective study that assessed QoL in 133 patients with CCA [13], patient-reported QoL showed a general decline with a significant decrease in emotional functioning and financial difficulties after 6 months of treatment.

Caregiving for patients with debilitating diseases, including cancers, can be burdensome [17]. Owing to the disease, treatment side effects and/or other comorbidities, patients with advanced cancers not only need physical support and emotional care, but may also require assistance with basic daily tasks [17,18]. The caregiver role therefore can be demanding and cause substantial burden in various domains of life, including their physical, emotional, and mental health and their overall QoL [19–21]. Ultimately, this can affect the quality of care provided by caregivers.

Real-world studies collect data outside of clinical trials in the context of routine delivery of care. As such, data from these studies may be more representative of real-world patients and outcomes for certain measures, such as QoL, than clinical trials which have strict eligibility criteria [22]. Data from real-world studies can, therefore, complement and increase the generalizability of data from clinical trials. To date, few real-world studies have assessed the QoL of patients with CCA [13,23,24]; except for a study that assessed the QoL of caregivers in Northeastern Thailand [25], the experience of caring for a patient with CCA and the impact on the various domains of a caregiver’s life remain largely unexplored. The lack of knowledge of the impact of CCA on QoL, including physical, mental and emotional aspects, can affect the clinical and palliative management of patients with CCA. Identifying and quantifying both the patient and the caregiver experience of CCA can help to develop more tailored interventions, and provide the support, services and outreach that can help preserve their QoL.

This article reports data from two separate surveys, one focused on the burden that CCA exerts on patients and the other focused on understanding the caregiver’s experience of caring for a patient affected by the disease. The objectives of the patient survey were to understand the diagnosis experience, determine the disease burden and describe the QoL and psychosocial impacts of CCA. The caregiver survey assessed the impact of caregiving on the day-to-day life and QoL of caregivers.

Methods

Study design & QoL assessments

Patients with CCA and caregivers of patients with CCA were recruited in partnership with the Cholangiocarcinoma Foundation (CCF) to participate in two separate online surveys to evaluate the disease burden on both patients and caregivers. The study was advertised on the CCF website and social media, including a link requesting contact information for those interested in participating. Subsequently, an individual single-use link was sent to each interested participant. Each participant completed the survey screen to determine whether they met the eligibility criteria to participate in the survey. Eligibility was determined by responses to screening questions in the surveys. Patients and caregivers were required to be aged ≥18–years and reside in the USA. Patients had to confirm that they had been diagnosed by a medical doctor with one or more of biliary tract cancer, bile duct cancer, or cholangiocarcinoma; patients with ampulla or gallbladder cancer were excluded. Caregivers were required to have currently or previously provided unpaid care to a family member or friend with CCA (biliary tract cancer/bile duct cancer); caregivers were excluded if the person they provided care for also had two or more of the following cancers: gallbladder cancer, liver cancer, ampullary cancer or lung cancer. Participants who met the screening eligibility then were asked to respond to the survey questions. To opt-in to participate and receive the financial incentive for participation (a US$25 gift card), the participants were required to provide their real names and, whenever possible, the CCF patient and caregiver registry was used to verify the identity of patients/caregivers. It should be noted that the caregivers surveyed were not necessarily the caregivers of the patients surveyed. Informed consent was obtained electronically from all patients and caregivers who participated in the study.

The 30 min patient survey was conducted between 23 August 2019 and 20 September 2019. Participating patients were stratified by self-reported stage of CCA into stage 1–2 (early stage), stage 3a (may be able to have surgery), stage 3b (probably cannot have surgery), stage 4 (cancer has spread to another organ), ‘in remission, no evidence of disease’ or ‘don’t know’. The survey assessed demographics, disease staging, symptoms, diagnosis/treatment experience, impact on day-to-day life, QoL and mental health. The survey included the European Organisation for Research and Treatment of Cancer – Quality of Life Questionnaire-BIL21 (EORTC QLQ-BIL21), a validated tool for assessing the QoL of patients with CCA [16]. The EORTC QLQ-BIL21 comprises 21 questions that include several subscales of interest, namely eating, jaundice, tiredness, pain, anxiety, treatment side effects, difficulties with drainage bags/tubes and concerns about weight loss [16]. The EORTC QLQ-BIL21 scoring was calculated on a scale of 0–100 [16]. Screening for depression was conducted using the Patient Health Questionnaire-9 (PHQ-9) [25], which is a nine-item self-reported questionnaire. The PHQ-9 score can range from 0 to 27, with each of the nine symptoms individually scored from 0 (not at all) to 3 (nearly every day). Overall scores of 0–4, 5–9, 10–14 and 15+ indicate no/minimal, mild, moderate and moderately severe or severe depression, respectively. An appended item to the PHQ-9 asks patients “How difficult have these problems made it for you to do your work, take care of things at home, or get along with other people?” [25]. The Work Productivity and Activity Impairment questionnaire [26] was used to assess the impact of general health and disease symptoms on work impairment, absenteeism, presenteeism and daily activity impairment. Data are presented as a percentage from 0% (no impairment/productivity loss) to 100% (maximal impairment/productivity loss). Patients were also requested to indicate their considerations in making treatment decisions as part of the survey. Eleven pre-specified options were presented in a randomized order (see Figure 1C) and patients could also select that they considered ‘other’ considerations and provide details as free text. Patients who selected more than one consideration were then asked to specify the consideration they considered to be of greatest importance from a list of previously selected responses which were presented in the same order as before.

Figure 1. Patient diagnostic journey.

(A) Initial misdiagnosis is frequent; (B) patient diagnosis journey timeline; (C) key considerations in treatment decisions. In panel B, mean values are reported.

CCA: Cholangiocarcinoma.

The 25 min caregiver survey was conducted between 1 September 2021 to 8 December 2021. Caregivers were stratified by self-reported disease stage of patients into early stage (stages 1, 2, 3a), later stages (stages 3b, 4), ‘CCA patient passed away’, ‘in remission, no evidence of disease’ or ‘don’t know’. The PHQ-9, Caregiver Burden Inventory (CBI) and the Caregiver Burden Scale (CBS) were used to assess the physical, mental and emotional burden of caregiving. The CBI is a diagnostic tool that includes 24 items across five dimensions of caregiver burden, namely physical health, time dependency, social relationships, personal development and emotional health [27]. Each item in each dimension is given a score between 0 (never) and 4 (nearly always), with higher scores indicating greater caregiver burden. Total summary score for the five CBI dimensions can range from 0 to 100 [27].

To assess the perceived burden among caregivers due to patient tasks requiring assistance, the CBS was used [28]. In addition to the original 15 items (housekeeping, shopping, transportation, cooking, decision-making, yard work/farming, making household repairs, administering medication, financial record-keeping, walking, eating, dressing, bathing, leaving patient unattended and toileting) in this scale, ‘childcare (Y/N)?’ and ‘other task (Y/N)?’ items were added.

Caregiver task assistance was determined by the number of tasks for which the patient needed assistance and the caregiver provided assistance. Perceived burden was assessed as the number of tasks for which the patient needed assistance and the caregiver provided assistance and which the caregiver reported as adding to personal stress [28]. For each domain assessed, the possible range was from 0 to 17.

Statistical analyses

All respondents were included in the analyses; data from patients and caregivers were analyzed separately. Data were summarized using descriptive statistics. Two-sided test was used to determine statistical significance; observed p-values were assessed at α = 0.05 level for statistical significance, with no multiplicity adjustment. For all comparisons of means, a pair-wise t-test was performed, and independent z-tests were used for comparisons of percentages. Patient- and caregiver-reported data analysis was performed using SAS^® statistical software, version 9.4 (SAS Institute, Cary, NC, USA). Missing data were not imputed.

Results

Patient survey

Patient demographics & diagnostic journey

Of the 1286 patients invited, 707 (55%) completed the survey, of whom 50% were 45–54 years of age; 77% of patients were male (Table 1). There were 157 patients with stage 1 or 2 CCA, 364 with stage 3a CCA, 140 with stage 3b–4 CCA and 30 in remission; 47% had perihilar CCA, 41% had intrahepatic CCA and 12% had distal CCA.

Table 1. Patient demographics.

Variable, n (%)	Total patients (N = 707)	Current stage^†
		Stage 1–2 (n = 157)	Stage 3a (n = 364)	Stage 3b–4 (n = 140)	Remission (n = 30)
Age, years
<45	259 (37)	69 (44)	118 (32)	53 (38)	9 (30)
45–54	353 (50)	53 (34)	203 (56)	75 (54)	18 (60)
≥55	95 (13)	35 (22)	43 (12)	12 (9)	3 (10)
Sex
Men	541 (77)	129 (82)	285 (78)	101 (72)	17 (57)
Education
High school or less	196 (28)	28 (18)	118 (32)	43 (31)	6 (20)
Some college	340 (48)	103 (66)	146 (40)	66 (47)	16 (53)
College graduate or higher	170 (24)	26 (17)	100 (27)	31 (22)	7 (23)
Currently employed
Yes	554 (78)	118 (75)	286 (79)	104 (74)	30 (100)
No	153 (22)	39 (25)	78 (21)	36 (26)	0
Marital status
Single	9 (1)	3 (2)	3 (1)	3 (2)	0
Divorced or separated	29 (4)	6 (4)	15 (4)	5 (4)	2 (7)
Widowed	5 (1)	0	5 (1)	0	0
Married/living with partner	661 (93)	148 (94)	340 (93)	132 (94)	27 (90)
Income, $USD
<50,000	58 (8)	12 (8)	26 (7)	14 (10)	6 (20)
50,000–74,999	238 (34)	101 (64)	100 (27)	25 (18)	7 (23)
75,000–99,999	288 (41)	31 (20)	166 (46)	78 (56)	7 (23)
≥100,000	112 (16)	11 (7)	70 (19)	22 (16)	7 (23)
Medical insurance
Private insurance	207 (29)	53 (34)	99 (27)	37 (26)	9 (30)
Medicare	348 (49)	57 (36)	202 (55)	70 (50)	12 (40)
Medicaid	134 (19)	38 (24)	59 (16)	30 (21)	7 (23)
Other medical insurance	17 (2)	9 (6)	4 (1)	3 (2)	1 (3)

† 16 patients reported their disease stage as unknown.

Percentages may not total 100 owing to rounding or incomplete responses.

Initial misdiagnosis was reported by 35% of patients (n = 247); the most common prior diagnosis was gallbladder cancer (52%; Figure 1A). 52% of patients indicated that they had sought multiple opinions from different oncologists after they received a diagnosis of CCA; patients consulted a mean of 2.5 oncologists. The mean age at CCA diagnosis was 44 years; the mean duration from CCA symptom onset to diagnosis was 22 months; and the mean duration from CCA diagnosis to survey completion was 23 months (Figure 1B). Among key considerations for patients in making treatment decisions concerning their primary medical therapy, the most common was physician judgment (61%; primary consideration in 38%), followed by QoL (40%; primary consideration in 16%; Figure 1C). A comparison among patients with different stages of CCA was also performed; significantly more patients with late stage CCA (Stage 3b-4, 17%) were likely to give the highest consideration to time spent in hospitals/treatment facilities compared with those with early stage CCA (stage 1–2, 6%; stage 3a, 10%; p < 0.05). Also, a higher percentage of patients with stage 3b-4 CCA (23%) gave QoL after treatment the greatest importance in treatment decision compared with patients with stage 1–3a CCA (14%; p < 0.05).

Impact on day-to-day life & QoL

All patients reported experiencing at least one symptom potentially associated with CCA. Of 16 symptoms in the survey, patients reported that a mean of 13.8 symptoms had an impact on their daily life. Fatigue was the most commonly reported symptom, with 67% of patients indicating having a “considerable” or “great deal of” impact on daily life (Figure 2A). As assessed using the EORTC QLQ-BIL21, patients overall reported a substantial negative impact of CCA on QoL, with mean scores ranging from 48.9 to 52.9 on all domains. On the same scale, younger patients (18–44–years of age) reported higher mean QoL scores across all domains except weight loss compared with older patients (>45–years; Figure 2B). Overall, 98% of patients reported any impact of CCA on their work status, and 37% reported considerable impact or great deal of impact on work status.

Figure 2. Cholangiocarcinoma impact on quality of life of patients.

(A) Impact of symptoms on day-to-day life; (B) EORTC QLQ-BIL21 scores across different subscales. In A, owing to rounding, some totals may not correspond with the sum of the separate figures. In B, mean values are shown.

CCA: Cholangiocarcinoma; EORTC QLQ-BIL21: European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-BIL21.

Using the Work Productivity and Activity Impairment questionnaire, the 554 patients (78%) who reported that they were currently employed and had worked in the past 7 days, reported a mean of 16.5% of work time lost. Mean reported impairment while working (presenteeism) was 65.3% and mean overall work impairment was 70.4%.

Impact on patient mental health & sexual function

Based on PHQ-9, 34% of patients (39% with stage 3a CCA) reported symptoms consistent with moderately severe or severe depression (Figure 3A ). Overall, 42 to 51% of patients experienced any given individual symptom of depression nearly every day or more than half of the days (Figure 3B). Furthermore, 72 and 23% of patients said symptoms of depression make their daily lives ‘somewhat’ or ‘very difficult’, respectively.

Figure 3. Cholangiocarcinoma impact on patient mental health and sexual function.

(A) Depression screening based on PHQ-9 scoring; (B) frequency of symptoms of depression and their impact on day-to-day life; (C) impact of CCA and its treatment on sexual function. In A, percentages may not total 100 owing to rounding. In B, owing to rounding, some totals may not correspond with the sum of the separate figures. Significant differences are denoted by a superscript letter to next to the higher percentage: A = early (stage 1–2); B = stage 3a; C = stage 3b–4; D = remission. *Among those bothered by any of these problems (N = 707/100%).

CCA: Cholangiocarcinoma; PHQ-9: Patient Health Questionnaire-9.

Patients were also surveyed regarding impact of CCA on sexual function (Figure 3C). Most patients reported lack of sexual desire (87%) or loss of intimacy (86%); with 51 and 47% reporting a considerable or great deal of impact on sexual desire and loss of intimacy, respectively. Compared with patients with stage 1–2 (48%) and 3a (48%) CCA, a higher percentage of patients in stage 3b–4 CCA (61%) experienced a considerable or great deal of impact on sexual desire. Similarly, a higher percentage of patients with stage 3b–4 CCA (52%) reported a considerable or great deal of impact on loss of intimacy in comparison to patients with stage 1–2 CCA (39%).

Caregiver survey

Caregiver demographics

Of the 109 caregivers invited, 60 (55.0%) completed the survey. Most (85%) were women and 77% were the spouses/partners of their patient with CCA (Table 2). The majority of caregivers were 50–64 years (38%) or ≥65 years of age (38%). At the time of the survey, 73% had been in the caregiving role for less than 2 years and 67% (n = 40) were caregivers for patients with advanced disease (stages 3b and 4). Half of the caregivers reported being employed either full-time or part-time, and 35% reported a household income between US$75,000 and <$150,000.

Table 2. Caregiver demographics.

Variable, n (%)	Total caregivers (N = 60)	Later stages (3b, 4) (n = 40)
Age, years
<45	11 (18)	6 (15)
45–54	9 (15)	4 (10)
≥55	40 (67)	30 (75)
Sex
Women	51 (85)	33 (83)
Patient relation to caregiver
Spouse/partner	46 (77)	33 (83)
Parent	9 (15)	4 (10)
Other family	4 (7)	2 (5)
Education
High school or less	6 (10)	3 (7)
Some college	10 (17)	8 (20)
College graduate or higher	44 (73)	29 (72)
Length of time in caregiver role, years
<2	44 (73)	28 (70)
2–<5	15 (25)	12 (30)
≥5	1 (2)	0
Household income, $USD
<50,000	4 (7)	1 (2)
50,000–74,999	8 (13)	5 (13)
75,000–99,999	11 (18)	8 (20)
≥100,000	24 (40)	17 (43)
Employment status
Full-time/part-time	30 (50)	19 (48)
Retired	22 (37)	17 (43)
Not employed	7 (12)	4 (10)
Student	1 (2)	0

Percentages may not total 100 owing to rounding or incomplete responses.

Impact on emotional & mental health

Most of the caregivers reported several positive aspects to caregiving, citing “satisfaction that loved one is well cared for” (92%), “caregiving has taught me to deal with difficult situations” (88%), “caregiving has brought me closer to my CCA patient” (87%) and “I feel more confident about my abilities” (83%) as personal benefits of caregiving (Figure 4A).

Figure 4. Caregiver burden.

(A) Overall impact of caregiving; (B) uncertainty of CCA; (C) top challenges faced by caregivers; (D) depression screening based on PHQ-9 scoring; (E) impact on day-to-day life. In panel A, owing to rounding, some totals may not correspond with the sum of the separate figures.

CCA: Cholangiocarcinoma; PHQ-9: Patient Health Questionnaire-9.

Caregivers also reported negative effects, such as being exhausted at bedtime (80%), having too much to do (73%), caregiving creating emotional difficulty (72%) and not having time for themselves (70%; Figure 4A). Additionally, 95% of caregivers agreed that the worst part of caregiving is the uncertainty of the future and 90% agreed that they avoided planning for future events due to uncertainty of patient health (Figure 4B).

Managing the emotional and mental distress of caregiving was reported by 83% of caregivers as a particularly challenging aspect of caring for a patient with CCA (Figure 4C). Notably, based on PHQ-9 scoring, 73% of caregivers reported symptoms consistent with depression, with 38, 25 and 10% reporting symptoms consistent with mild, moderate and moderately severe or severe depression, respectively (Figure 4D). Most caregivers are managing caregiving stress without professional help. Only 32% of caregivers reported being under the care of a therapist, psychologist, psychiatrist, or other counselor.

To further evaluate caregiver burden, the CBI was used to understand the frequency of feelings across several dimensions of life [27]. The mean overall CBI score was 29.62, reflecting the large numbers of caregivers who sometimes, quite frequently or nearly often felt their CCA patient was dependent on them (80%), were physically tired (75%), felt their social life had suffered (75%), were not getting enough sleep (65%) and had expected things would be different at this point in their lives (80%).

Caregiving tasks & impact on daily life

Caregiving responsibilities impact daily life. Among those employed full-time or part-time, nearly half (47%) reported a considerable/great deal of impact on their employment. Caregivers allocated on average 38% of their time assisting with patient-related basic functions (such as bathing or preparing meals) and patient-related tasks (such as taking care of bills or running errands). Some caregivers reported that it was it extremely/very difficult to interact with others (32%), do their own work (23%) and take care of things at home (22%; Figure 4E).

On the CBS, the mean number of tasks the patient needed assistance with, the caregiver provided assistance with, and those that added to the caregiver’s personal stress was 8.2, 7.5 and 3.6, respectively. Tasks that require the most assistance included housekeeping, transportation, household repairs, shopping, cooking and decision-making (Table 3).

Table 3. Tasks requiring caregiver assistance.

	Patient needed assistance (%)	Provided assistance (%)	Task added to personal stress (%)
Housekeeping	82	78	43
Transportation	78	73	22
Shopping	72	72	20
Cooking	68	67	30
Decision-making	65	65	43
Making household repairs	75	60	38
Yardwork or farming	55	48	23
Administering medication	53	53	28
Financial record-keeping	50	50	30
Walking	43	42	8
Eating	30	27	7
Dressing	28	25	7
Bathing	27	22	13
Leaving patient unattended	25	22	20
Toileting	20	15	10
Childcare	5	5	5
Other task	30	23	15

Discussion

CCA is an aggressive cancer associated with substantial morbidity and poor prognosis. Consequently, the burden of the disease is high, especially for patients with advanced-stage CCA and their caregivers. To our knowledge, this is the first report assessing multiple aspects of CCA disease burden on both patients with CCA and caregivers of patients with CCA. Results from the surveys presented here highlight the unmet needs for supportive care for patients with CCA and their caregivers.

The patient survey analysis shows that the diagnosis journey is often long and arduous, with over a third of patients with CCA being initially misdiagnosed despite experiencing disease-related symptoms for nearly 2 years. Indeed, the absence of CCA-specific symptoms in the early stages of the disease makes the diagnosis difficult. Furthermore, patients with CCA develop significant symptoms only at later stages of the disease [29]. Misdiagnosis and/or late diagnosis may be distressing for both patients and their caregivers.

Although most patients noted that their physician’s judgment was the main driver for treatment decisions, the second most frequent response was the impact of treatment choice on QoL. This highlights the fact that QoL remains a key consideration in treatment decisions, despite most patients being diagnosed in later stages of CCA. Several studies assessing patient-reported outcomes have reported psychological distress and physical impairment as common among patients with multiple tumor cancer types [30–32], including those with CCA [13,23,24,33]. In common with these studies, our findings from the patient survey indicated substantial impact of fatigue and anxiety due to CCA and its treatment on daily lives, QoL, work productivity and mental health. Our study therefore bolsters the understanding that physical and mental distress are prevalent symptoms among patients with CCA.

In addition to anxiety, depression appears to be a major psychological challenge for patients with CCA, which impacts on their QoL. In this survey, over a third of patients reported symptoms consistent with moderately severe or severe depression. These findings are similar to another study [23] of 23 patients with early, locally advanced or metastatic biliary tract cancer, 17 of whom reported having an emotional impact (depression), suggesting the need for mental health supportive care for patients with cancer.

Our survey results also show that younger patients reported better QoL scores in most domains measured on the EORTC QLQ-BIL21. As previously observed in patients with other cancers [34–37], this may be because older patients often have several confounding factors that are age-associated, such as comorbidities, changes in daily life activities, circumstances and increased susceptibility to treatment toxicities, all of which have a negative impact on the QoL. Further research and analyses toward understanding this observation in young versus old patients with CCA will help develop suitable supportive therapies.

Another observation that emerged from the patient survey was the large impact that appearance-related symptoms such as loss of hair and unintended weight loss had on the daily lives of patients. To our knowledge, this is the first time these specific aspects affecting the patient’s life have been evaluated. These observations highlight the need for including suitable interventions such as educational sessions to better inform patients with CCA treatment side effects and symptom-management.

Employed patients who had worked in the past week had overall work impairment of 70%. This is consistent with the upper range of overall work impairment values (40–72%) that were reported in a systematic review [38] evaluating the effect of treatment for multiple cancer types on work productivity in patients and their caregivers. A retrospective cohort study using administrative claims data for patients with CCA found substantial productivity loss due to days missed from work [39]. The mean number of days absent for illness per patient per month was 6.0 and 4.3 days for patients with intrahepatic and extrahepatic CCA, respectively. The mean number of days per patient per month on CCA-related short-term disability leave was 6.5 and 4.3 days for patients with intrahepatic and extrahepatic CCA, respectively [39].

We surveyed patients on sexual function and confirmed a considerable or great deal of impact of CCA and its treatment on sexual desire and intimacy. The impact of cancer diagnosis and treatment on sexual function can be substantial and may worsen with time if not addressed [40]. Therefore, healthcare professionals should discuss sexual functioning with their patients to improve QoL. The American Society of Clinical Oncology also provides recommendations and guidelines to help the patient’s healthcare team address sexual problems arising due to cancer and/or treatment [41].

The majority of caregivers of patients with CCA in the present survey were women, consistent with what is seen with other cancer types [19,42]. In this study, most caregivers were a patient’s spouse and many were employed. Caregivers do experience positive aspects throughout the course of caregiving for their loved ones, such as strength to deal with adversity, improved sense of self-worth and increased closeness with the patient [20,43]. In our study, over 80% of caregivers reported that caregiving brought satisfaction that their loved one is well cared for, taught them to deal with adversity and instilled personal confidence. However, caregivers for patients with cancer also experience physical, mental and emotional burdens [19,20,42,44,45]. Likewise, caregivers of patients with CCA reported physical impairment and emotional distress in our survey. The majority of the caregiver respondents reported annual household incomes of US$75,000 or above. Patients with fewer resources may be expected to experience greater burdens.

Work productivity is also affected in caregivers [38]. A systematic review reported overall work productivity loss among caregivers of 21–27% [38]. Because of responsibilities associated with caregiving, caregivers report having to make adjustments at their workplace, such as taking time off, going from full-time to part-time or taking a leave of absence [42]. Caregivers in our survey reported spending over a third of their time on caregiving duties, with nearly a quarter reporting that caregiving made it ‘very’ or ‘extremely difficult’ to work. Those who were employed full-time or part-time reported that their employment status had a great deal or considerable impact.

Limitations of this study included the single time point data collection, which prevents assessing the change in burden over time. There are disadvantages common to survey research, such as subject recall bias and that certain response options (e.g., “some impact” vs “considerable impact”) may be open to interpretation by the respondents. In addition, respondents who are less comfortable using a computer may be hesitant to participate in an online survey. Another limitation is the small sample size of caregivers participating in this study; particularly the sample size of those caring for patients in stages of CCA other than advanced-stage CCA. Surveying a larger caregiver population, perhaps with more diverse demographics and caring for patients across different stages of CCA, could provide a better understanding of the caregiver burden. However, as the majority of patients with CCA are diagnosed at advanced stages, this may be difficult. Moreover, patients and caregivers experiencing higher burdens may have been more likely to decline participation, so our results may underestimate the burden on both these groups.

A strength of this study was the comprehensive descriptive analysis of the burden of CCA on patients’ and caregivers’ lives, with respect to living with a CCA diagnosis, treatment and the impact on QoL including sexual function. Moreover, given the evolving treatment landscape of CCA, it is important to have a detailed understanding of the patient and caregiver experience in order to assess and benchmark how their contribution influences clinical care. The voices of patients and caregivers are vitally important when imparting clinical care decisions, as well as in clinical trial design.

Conclusion

In summary, findings from the patient survey emphasize the need for tailored palliative and supportive care interventions for patients with CCA, especially those with advanced disease. The unequivocal positive benefits of early palliative care on QoL for patients with advanced cancer are well-known [46–48]. For example, a randomized control trial [48] evaluating the impact of a palliative care intervention – involving regular educational sessions to encourage patient activation, self-management, and empowerment – showed better QoL scores and improved mean mood score among patients in the intervention group, compared with a ‘care-as-usual’ control group. The results from the present study support the recommendations of the American Society of Clinical Oncology and World Health Organization that interdisciplinary palliative and supportive care services be made available for patients with cancer and their caregivers [49,50]. Patients need to be made aware of cancer support programs and services. Useful resources include support groups, discussion boards, and educational videos that can be accessed on the American Cancer Society and Cholangiocarcinoma Foundation websites [2,51]. This study also highlights the high caregiver burden and the need for developing resources to better support, educate and connect caregivers. Identification, intervention, education and coordination of services may help to alleviate caregiver burden and improve QoL for both patients and caregivers.

Summary points

• Cholangiocarcinoma (CCA) is a rare and aggressive cancer that typically presents in advanced stages and has a poor prognosis.

• Patients with CCA often have a decreased quality of life (QoL) and require a caregiver due to negatively impacted daily living caused by disease and treatment-related factors.

• This study is the first report to assess the multiple aspects of CCA disease including the impact on daily life, QoL, and mental health in both patients with CCA and caregivers of patients with CCA.

• Results showed fatigue and anxiety were the most common symptoms reported to have a ‘considerable’ or ‘great deal of’ impact on the daily life of patients with CCA and patients reported a negative impact of CCA on QoL.

• This study identifies depression as a major psychological challenge for patients with CCA and over one third of patients experienced symptoms consistent with moderately severe or severe depression.

• Over 80% of caregivers reported positive aspects to caregiving including satisfaction that their loved one is well cared for, and that caregiving has taught them to deal with difficult situations.

• The majority of caregivers spent over one third of their time on caregiving duties and reported negative effects including physical impairment and emotional distress.

• This study demonstrates there is a need for tailored palliative and supportive care to be made available for patients with CCA and caregivers of patients with CCA.

Author contributions

All authors contributed to the acquisition, analysis and interpretation of data, as well as to the drafting and critical review of the manuscript, and approved the final version for publication.

Financial disclosure

This study was funded by Incyte Corporation (Wilmington, DE, USA). TD Jackson and H Ren are employees and receive stock options from Incyte Corporation. K Bibeau, A Lindley and F Blanco are former employees of Incyte Corporation. M Bachini and S Lindsey are the Director of Patient Services and Founder & CEO of Cholangiocarcinoma Foundation, respectively. C LaFiura is the co-founder of Envision Health Partners. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

Medical writing assistance was provided by Upasna Thapar (Envision Pharma Group, PA, USA), and funded by Incyte Corporation.

Ethical conduct of research

The authors state that Western Institutional Review Board reviewed and provided exemption status to this study under 45 CFR §46.104(d)(2). In addition, survey respondents provided permission for their data to be analyzed and published.

Data sharing statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author (email: [email protected]).

Open access

This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

Acknowledgments

The authors wish to thank the patients and caregivers who completed the survey.