Cost burden associated with advanced non-small cell lung cancer in Europe and influence of disease stage

Incidence rates of lung cancer in some European countries are among the highest globally [1]. Across Europe, an estimated 400,000 new cases of lung cancer are diagnosed each year [1], and most cases, at least 85%, are non-small cell lung cancer (NSCLC) [2]. With the high mortality burden associated with the disease (an estimated 353,000 deaths each year), lung cancer represents a leading cause of cancer-related death in Europe [1, 3, 4].

The overall economic impact of lung cancer in Europe is substantial, with direct costs of caring for patients with the disease (including primary care, hospital inpatient/outpatient care, and drugs/oxygen) amounting to more than €3 billion per year [5]. When costs related to disability and premature mortality are considered as well, total annual costs amount to more than €100 billion [5]. While highlighting the significant societal cost of lung cancer, these cost estimates tend not to recognize the relatively high financial burden directly experienced by the patients and their caregivers as a result of the symptoms of the disease and associated psychological distress [6‐9], the impact of cancer treatment and related side effects, and the effect of caregiving on the health and psychological wellbeing of the caregiver [10, 11].

There is a relative paucity of data on the cost burden incurred directly by patients with lung cancer and their informal caregivers in Europe. In a study of 128 patients with lung cancer receiving treatment at a University pulmonary department in Greece in 2011, and followed for 32 months, patients lost a total of 27,050 days of productivity and their caregivers lost a total of 1337 days of productivity [12]. Although no monetary value was assigned to this productivity loss, it would undoubtedly impact the earning potential of both patient and caregiver. In another study of 104 patients with NSCLC receiving treatment in 18 Italian oncology departments, costs related to principal (unpaid) caregiver support made up the vast majority (74%) of the overall assistance costs incurred per patient, highlighting the financial burden on informal caregivers [13].

Interestingly, the study by Gridelli et al. also suggested that the financial burden associated with caring for patients with NSCLC increases with the severity of lung cancer symptoms [13]. Furthermore, other studies have indicated that direct medical costs (physician and clinic visits, laboratory tests, medication charges) per patient with NSCLC appear to increase as the disease progresses [14, 15]. This evidence suggests that stage of disease may influence costs incurred by both patients with NSCLC and their caregivers.

Against this backdrop, as part of a large, cross-sectional study of the “real-world” humanistic and financial burden of advanced NSCLC in Europe, an analysis was conducted to quantify the cost of illness from a patient and caregiver perspective, and to evaluate how the stage of disease impacts on wage losses, out-of-pocket expenses, and productivity of patients with advanced NSCLC and their caregivers.

The societal cost burden associated with advanced NSCLC is considerable. In Europe, costs including primary care physician visits, hospital inpatient/outpatient visits, medication, and supportive therapies such as oxygen, amount to more than €3 billion per year [5]. Less well defined are the out-of-pocket expenses accrued directly by the patients themselves and their caregivers. The current analysis was undertaken to better define this cost burden and has revealed mean annual out-of-pocket expenses of €3774 per patient and €1756 per caregiver. These direct out-of-pocket expenses relate to lost wages; costs accrued in relation to physician visits; costs associated with supportive medications for symptom relief or pain management; and other costs related to additional NSCLC-related factors, such as child care, housekeeping/cleaning, and transportation. Moreover, when indirect costs related to productivity losses were included, the combined total direct and indirect out-of-pocket costs exceeded €9000 per patient–caregiver dyad. In calculating the out-of-pocket cost burden of advanced NSCLC among the participating patients and caregivers, financial remuneration received through governmental assistance systems was also considered. Such assistance schemes varied between countries but generally included disability allowance payments, home care benefits, and sick leave remuneration. When combined for patients and caregivers (in a subset of 144 patient–caregiver dyads with full data), the government support amounted to around one-half of the out-of-pocket costs incurred by patients and their caregivers (mean annual support, €4782; mean annual total unadjusted direct and indirect out-of-pocket costs, €9634).

The population participating in this study included patients with locally-advanced (stage IIIB) or metastatic (stage IV) NSCLC. Current data suggest that around 50–60% of patients with NSCLC are diagnosed at these advanced stages, when 5-year survival rates are below 5% [17‐19]. In the analysis of costs by disease stage, patients with stage IV NSCLC incurred significantly greater wage losses (p = 0.0135) and unadjusted direct out-of-pocket expenses (p = 0.0306) than those with stage IIIB disease. The statistical significance between the stages was lost when the direct out-of-pocket expenses were adjusted for governmental financial support received by patients. Indeed, the bulk of the additional out-of-pocket expenses incurred by patients with stage IV disease were offset by additional government financial support, although mean costs remained numerically higher for the patients with stage IV disease.

For caregivers, wage losses and direct out-of-pocket expenses were numerically higher for those caring for patients with stage IV disease than those caring for patients with stage IIIB disease although the differences, with or without adjustment for government financial support, did not reach statistical significance. Of note, the current study was conducted in European countries with established social and financial support systems; in countries with less well-established or comprehensive government financial support systems, such costs would presumably be borne by the patient and/or caregivers.

With regard to productivity losses, a cost borne by employers rather than the individual patient or caregiver, costs per patient did not appear to be majorly influenced by stage of disease. In contrast, the mean cost of productivity losses per caregiver of a patient with stage IV disease was more than double the mean cost per caregiver of a patient with stage IIIB disease, although the difference did not reach statistical significance. This observation may reflect the higher proportion of caregivers of patients with stage IV disease (vs caregivers of patients with stage IIIB disease) who were in full-time employment and the consequent greater scope for caregiving to disrupt their working life.

Previous reports have shown that direct medical costs per patient with NSCLC appear to increase with disease progresses. In 2008, Fox et al. reported the results of a retrospective analysis of cost data for 306 patients with stage IIIB or stage IV NSCLC who were receiving chemotherapy, and compared costs for those with stable disease vs those with progressive disease (defined as a change in chemotherapy regimen and radiologic confirmation of tumour growth) [14]. The total direct cost of care in the 3 months following disease progression increased by approximately one-third compared with the costs of care for patients with stable disease (USD $31,129 vs $18,802, respectively). More recently, Migliorino et al. found that costs including those related to physician visits, hospitalizations, medication, laboratory tests, and palliative care increased as patients experienced disease progression and received sequential lines of therapy [15]. A similar pattern of costs increasing with disease progression was also reported for patients with stage IIIB or stage IV disease receiving treatment with tyrosine kinase inhibitors, with direct medical and associated healthcare costs increasing with disease progression [20]. The current evaluation adds to these observations and has shown that direct out-of-pocket expenses incurred by the patient are influenced by the disease stage.

Prior observational studies have also demonstrated the cost burden of caring for patients with advanced NSCLC. In an analysis of data derived from the 2010/2011 EU National Health and Wellness Survey (covering relatives of patients with lung cancer in France, Germany, Italy, Spain, and the UK) relatives providing care for a patient with lung cancer reported significantly greater work impairments and were associated with higher indirect costs (productivity losses) compared with relatives not providing care [11]. The current analysis takes this further by showing the direct impact of advanced NSCLC on out-of-pocket expenses incurred by the caregiver. Moreover, contrary to the situation observed for the patients, the burden of caregiver expenses and costs was only partly compensated for by government financial support. Indeed, this support was considerably lower for caregivers of patients with advanced NSCLC than for the patients themselves. Consequently, the out-of-pocket expenses directly incurred by caregivers tended to be higher for those caring for patients with a more advanced stage of disease. Costs for caregivers of patients with NSCLC increasing in tandem with symptom severity has been reported previously, and may be regarded as a proxy for advancing disease [13]. Furthermore, Van Houtven et al. have previously shown that caregiver costs increased with increasing stage at diagnosis among carers of patients with lung or colorectal cancer [21]. In this cross-sectional study conducted in the US, caring for a patient diagnosed with lung or colorectal cancer at late stage (stage IV) was associated with a 53.9% higher economic burden than caring for a patient diagnosed at early stage (stage I; p = 0.001).

The current analysis differs from conventional “cost of illness” studies in that it did not consider the costs of primary treatments for NSCLC (i.e., costs of chemotherapy, etc.) and therefore allowed a more focused assessment of the financial burden on patients and their caregivers, as well as costs to the government and employers in relation to the patients and their caregivers. Although such analyses have previously been conducted for caregivers, there is limited literature on the influence of disease stage on direct out-of-pocket costs to patients, and this analysis has confirmed such costs to be substantial.

The strengths of the current analysis included the cross-sectional, multinational design and the multidimensional approach including wage losses, out-of-pocket expenses, and productivity losses. In addition, by recruiting consecutive patients attending for physician consultation, the potential for selection bias was limited. Moreover, by excluding patients actively involved in clinical trials at the time of data collection, the opportunity to capture “real-world” cost data was increased.

The reliance on participant self-reporting and, because the analysis was based on cross-sectional data rather than longitudinal data, the associated reliance on the recall of the participant, means that the cost data should be considered an over or underestimation of true costs. A further potential limitation was that, as participants could omit responses, cost data were missing for a proportion of patients and caregivers – the resultant relatively small sample size for some subgroups is likely the reason that statistical significance was rarely seen. Furthermore, although the questionnaires contained explicit instructions aimed at focusing the cost impact on the patient and caregiver separately, the possibility of some double costing cannot be discounted. Another potential limitation is the use of average country-specific earnings in the calculation of wage losses, which may not be optimal for this older population whose income may reflect a higher-earning, more experienced workforce. In addition, the study did not capture information on all factors that could influence cost burden on patients and caregivers. It must be acknowledged that a wide variety of factors could potentially influence the economic burden, particularly for caregivers (e.g., age of caregiver, presence of children at home, etc.) [22]. It is also important to recognize that, because this study almost exclusively included patients receiving systemic therapy (primarily chemotherapy), the absolute costs reported may be somewhat conservative. Based on recent large-scale real-world research, between one- and two-thirds of patients with advanced NSCLC do not receive systemic therapy [17, 19]. Since it would be fair to assume that the patients contraindicated for chemotherapy would be the sickest, it is possible that costs related to their care would surpass those for the patients evaluated in this study. Finally, it must be noted that the costs reported herein were captured based on relatively short time horizons (a week up to 3 months) and then annualized, but only a minority of patients with stage IIIB–IV disease survive for a year after diagnosis [17], further emphasizing that the cost data is likely an over-estimate of true costs.

The current analysis supports others that suggest the financial burden of advanced NSCLC is considerable to society, patients, and their caregivers, and appears to be influenced by stage of disease, with direct and indirect costs increasing as the disease progresses. To our knowledge, this study is the first to demonstrate the influence of stage of disease on direct patient wage-related and out-of-pocket costs including the cost of secondary NSCLC–related treatments, non-medical costs related to primary care and hospital visits, and other non-medical monetary burden costs. Beyond this, the findings of these analyses also suggest that, while government financial support programmes may be somewhat successful in taking much of the increased cost burden away from patients as the disease advances to the metastatic stage, the same cannot be said for caregivers. The implications of the observations reported here are that there is a need for newer, more effective, and safer treatments for NSCLC that slow or even prevent disease progression. In addition, the results might have more wide-ranging implications such as (i) highlighting a need for improved financial support programmes aimed at easing the economic burden of caring for patients with advanced NSCLC, particularly in relation to non-spousal caregivers who may not benefit from patient-focused financial support; and (ii) suggesting that financial counselling/advice needs to be tailored for NSCLC patient–caregiver dyads as the disease advances to the metastatic stage.