Abstract
Background
Approximately 2 million new cases and 1.76 million deaths occur annually due to lung cancer, with the main histological subtype being non-small cell lung cancer (NSCLC). The costs and resource use associated with NSCLC are important considerations to understand the economic impact imposed by the disease on patients, caregivers and healthcare services.
Objective
The objective of this systematic literature review (SLR) is to provide a comprehensive overview of the available direct medical costs, direct non-medical costs, indirect costs, cost drivers and resource use data available for patients with early-stage NSCLC.
Methods
Electronic searches were conducted via the Ovid platform in March 2021 and June 2022 and were supplemented by grey literature searches. Eligible patients had early-stage (stage I–III) resectable NSCLC and received treatment in the neoadjuvant or adjuvant setting. There was no restriction on intervention or comparators. Publication date was restricted to 2011 onwards, and English language publications or non-English language publications with an English abstract were of primary interest. Due to the anticipation of many studies meeting the inclusion criteria, analyses were restricted to full publications from countries of primary interest (Australia, Brazil, Canada, China, France, Germany, Italy, Japan, South Korea, Spain, UK and the US) and those with > 200 patients. The Molinier checklist was applied to conduct quality assessment.
Results
Forty-two full publications met the eligibility criteria and were included in this SLR. Early-stage NSCLC was associated with significant direct medical costs and healthcare utilisation, and the economic burden of the disease increased with its progression. Surgery was the primary cost driver in stage I patients, but as patients progressed to stage II and III, treatments such as chemotherapy and radiotherapy, and inpatient care became the main cost drivers. There was no significant difference in resource use between patients with early-stage disease. However, these data were heavily US-centric and there was a paucity of data relating to direct non-medical and indirect costs associated with early-stage NSCLC.
Conclusions
Preventing disease progression for patients with NSCLC could reduce the economic burden of NSCLC on patients, caregivers and healthcare systems. This review provides a comprehensive overview of the available cost and resource use data in this indication, which is important in guiding the decisions of policy makers regarding the allocation of resources. However, it also indicates a need for more studies comparing the economic impact of NSCLC in markets in addition to the US.
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Avoid common mistakes on your manuscript.
The economic burden of early-stage non-small cell lung cancer (NSCLC) stems from significant healthcare resource utilisation and direct medical costs. |
Direct medical costs increase with stage of disease, primarily driven by the change in treatment administered (surgery [stage I] versus chemotherapy [stage II/III]). |
There is a paucity of published studies reporting direct non-medical and indirect costs; however, the systematic literature review provides a comprehensive overview of the available cost and resource use data associated with early-stage NSCLC. |
1 Introduction
Lung cancer remains one of the most frequently diagnosed cancers worldwide and is the leading cause of cancer-related deaths, with an estimated 2 million new cases and 1.76 million deaths per year [1, 2]. The most common type of lung cancer is non-small cell lung cancer (NSCLC), which represents 80–85% of all lung cancer cases [3]. Complete surgical resection is the recommended treatment for patients presenting with early-stage disease (stage I/II and stage IIIA NSCLC), followed by adjuvant chemotherapy [4,5,6,7]. However, the 5-year survival rate for these patients has been reported to range from 10 to 64%, indicating that many patients relapse and die despite available therapies [8, 9]. In addition, adjuvant chemotherapy is associated with adverse events that negatively impact patients’ quality of life (QoL) [10]. Due to the unmet need for treatments which improve the outcomes of patients with NSCLC, novel targeted therapies and immunotherapies are currently under investigation in clinical trials and have been evaluated by health technology assessment (HTA) agencies [11,12,13].
Despite ongoing advancements in therapeutic approaches, the treatment of NSCLC is associated with high direct and indirect costs for patients, caregivers and healthcare services due to factors that appear to increase them (cost drivers) such as the progressive nature of the disease and associated mortality [14,15,16,17]. Costs are multifactorial but are attributable to components such as hospitalisation, surgery, chemotherapy, radiotherapy, productivity losses and travel for both patients and caregivers (where applicable) [10, 18, 19]. NSCLC therefore places an economic burden on society as a whole[14,15,16,17]. A robust understanding of costs and resource use of NSCLC is therefore a vital component for informing decisions regarding access to new therapies made by HTA agencies and reimbursement authorities.
The objective of this systematic literature review (SLR) was to provide a comprehensive overview of the available direct medical costs, direct non-medical costs, indirect costs, cost drivers and resource use data available for patients with early-stage NSCLC. It uses an exploratory approach; given that issues inherent with the comparison of evidence across studies due to their heterogeneity (which includes methodological variation, differences in sample groups , costing approaches, currency, country, treatments evaluated and follow-up periods) have influenced the estimated costs reported.
2 Methods
2.1 Study Design
An SLR was conducted to identify published cost and resource use data associated with patients with early-stage NSCLC (resectable, stage I–III) receiving treatment in the adjuvant or neoadjuvant setting. The searches were performed in March 2021 and updated in June 2022, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [20].
2.2 Data Sources and Search Strategy
The following databases were searched on 18 March, 2021 via the Ovid platform: Embase; MEDLINE (including Epub ahead of print, in-process and other non-indexed citations and daily update); Evidence-Based Medicine Reviews (incorporating the Cochrane Database of Systematic Reviews, American College of Physicians [ACP] Journal Club, Database of Abstracts of Reviews of Effects [DARE], Cochrane Clinical Answers, Cochrane Central Register of Controlled Trials [CENTRAL], Cochrane Methodology Register, HTA database and the National Health Service Economic Evaluation Database [NHS EED]); and EconLit. The search was updated on 22 June, 2022. The full search strategy (Online Resource 1 in the electronic supplementary material [ESM]) included free-text words, subject index headings (e.g. medical subject headings [MeSH]) and Boolean terms in order to capture studies which report costs and resource use for early-stage NSCLC. Additional searches of conference proceedings, reference lists of included publications, HTA bodies and additional sources and websites were conducted (Online Resource 2, ESM) using free-text terms.
2.3 Eligibility Criteria
Eligibility criteria for the SLR were defined by the PICO (population, interventions, comparators and outcomes) framework and study design, described in Table 1. There were no restrictions in terms of study country; however, there were some primary territories of interest and restrictions on publication date. These territories of interest and restrictions were relevant to the scope of this review which was conducted as part of a broader body of work. Reference lists of review publications were checked using PICO criteria to ensure any relevant primary studies were considered for inclusion. Full publications reporting cost and resource use were selected for further analysis. Additionally, it was anticipated that a large volume of relevant studies would be identified in the SLR; therefore, the following additional criteria were prioritised for full data extraction and are the focus of this manuscript: full publications; data reported for countries of primary interest; sample size > 200 patients to reduce the potential impact that limitations with small studies can have on the results (e.g. selection bias).
2.4 Study Selection and Data Extraction
Screening was completed by two independent analysts at title/abstract stage (LJ/PH) and at the full publication stage (LJ/PH). Any disputes were referred to a third analyst (SB) and resolved by consensus.
Data extraction was conducted by a single analyst and 100% of data elements were checked by a second analyst. Disputes were referred to a third analyst and resolved by consensus. The extracted parameters included study characteristics (e.g. study design, country, and currency and reference year), sample details (e.g. sample summary, sample size, study period, inclusion and exclusion criteria), cost collection approach and cost valuation method, cost results (direct, indirect, cost drivers and resource use), methods/results of regression analyses and a summary of the study-reported conclusions and limitations.
2.5 Quality and Relevance Assessment
During data extraction, quality assessment of the included cost and resource use studies was undertaken using the checklist adapted to cost of illness by Molinier et al. [21].
3 Results
3.1 Search Yield
The electronic database search conducted in March 2021 identified a total of 3071 citations (Fig. 1). After the removal of duplicates, 2706 titles and abstracts were screened, of which 195 citations were deemed potentially relevant. Following full paper review, a further 96 publications were excluded, and grey literature searches yielded an additional three publications. In total, this search identified 40 full publications in countries of primary interest with a sample size > 200 reporting on cost and resource use for the sample of interest. An additional 29 conference abstracts and 33 publications reporting on countries that were not of primary interest and/or with a sample size of < 200 were also identified. The updated search conducted in June 2022 yielded two additional full publications and one conference abstract reporting on cost and resource use. The 30 conference abstracts and 33 publications from countries that were not of primary interest and/or sample size < 200 (citation details in Online Resource 3 and Online Resource 4, respectively, see ESM) are not considered further in this SLR. The final list of included publications that met the eligibility criteria for inclusion in the SLR and additional criteria for data extraction consisted of 42 full publications.
3.2 Description of Identified Studies
A summary of the characteristics of included studies is provided in Table 2 with full details and extracted results provided in Online Resource 5 (see ESM). The articles were published between 2011 and 2021 and included data from 11 countries (Belgium, Canada, China, France, Germany, Italy, South Korea, Spain, The Netherlands, UK and the US)Footnote 1. Two studies were multi-national; one study considered France, Germany and the UK and one study considered Belgium, the Netherlands and the UK. All other included studies reported cost or resource use in a single country. No data were found specifically for Australia, Brazil, or Japan, which were also countries of primary interest. A total of 28 studies included in the SLR were retrospective analyses [22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49], six were cost analyses (studies which measured cost and/or resource use outcomes only) [14, 15, 50,51,52,53], four were economic evaluations (comparative analyses of the costs and health outcomes of two alternative interventions) [54,55,56,57], three had a prospective cohort design [58,59,60] and one propensity-matched cohort study [61] was also included. Study sample sizes ranged from 232 to 129,893 and studies reported costs or resource use for samples covering multiple or individual stages of NSCLC and different treatment regimens.
3.3 Quality Assessment
Quality assessment of the 42 studies revealed that objectives were generally well defined across studies and results were presented consistently with the methodologies adopted (Online Resource 6, see ESM). However, few studies could conduct sensitivity analyses of model input variables (n = 5) [14, 54,55,56,57] and only three of these studies conducted sensitivity analyses to test the robustness of major assumptions [14, 57, 61]. One retrospective study incorporated a sensitivity analysis to determine the impact of varying unit costs on the total costs [38]. Additionally, it was often unclear if costs were appropriately discounted.
Commonly reported limitations acknowledged across the studies included inherent limitations of retrospective study designs (selection bias and unidentifiable confounders) (n = 13) [25, 29, 37, 39, 42, 43, 45, 47, 48, 53, 56, 60, 62]; restricted generalisability of results beyond the study setting to real-world practice (n = 14) [14, 23, 24, 26, 28, 30, 32, 33, 37, 39, 41, 47, 51, 53]; inherent limitations of claims data/databases used in analyses (e.g. missing information, miscoding) (n = 11) [22,23,24,25, 28, 41, 43,44,45, 49, 61]; limited follow-up periods (n = 6) [22, 28, 37, 40, 51, 60]; relatively small sample sizes (n = 5) [15, 45, 55, 56, 62]; and the failure to consider indirect costs (n = 4) [14, 34, 40, 52].
3.4 Direct Medical Costs
A total of 32 studies reported direct medical costs associated with patients with early-stage NSCLC [14, 15, 22, 26,27,28,29, 31, 33,34,35, 37,38,39,40, 45,46,47,48,49,50,51,52,53,54,55,56, 58,59,60,61,62].
3.5 Direct Medical Cost Data by Disease Stage
Eight studies reported direct medical cost data by disease stage (Table 3 and Online Resource 5, see ESM) [14, 22, 28, 40, 49,50,51, 54]. In general, costs were observed to increase with increasing pathological stage of disease, with patients with advanced disease incurring higher costs than those with early-stage disease [14, 28, 40, 49,50,51]. In early-stage disease, surgery was the primary driver of cost, whereas in the more advanced stages, radiotherapy, medical therapy, treatment for progression and supportive care became increasingly important [14, 50]. For example, in one Spanish study, the mean (standard deviation [SD]) cost per patient over the 3 years following diagnosis or until death was €13,321 (€8316) for patients with stage I NSCLC and €15,044 (€14,338) for patients with stage IV NSCLC [50]. Surgery was the primary driver of this cost in stage I patients (58.9%), decreasing to 45.9% and 15.0% in stage II and stage III patients, respectively [50]. In patients with stage III disease, inpatient care (27.1%) and chemotherapy (20.8%) were the primary cost drivers [50]. Similarly, in an Italian study by Buja et al. (2021) [14], the mean (95% confidence interval [CI]) total direct costs per patient during the first year after diagnosis increased from €16,291 (15,284–17,505) in patients with stage I disease to €22,175 (22,127–22,190) in patients with stage IV disease. As the SLR did not include studies that focussed only on patients with advanced NSCLC, the exact conclusion may have differed if they were also included. However, such studies were not included in the review as its main focus is on patients with early-stage NSCLC. Moreover, a comparison of the healthcare resource use and cost of early-stage versus advanced-stage NSCLC patients seems most appropriate when taken from studies that focus on both groups of patients. It is plausible to assume that for studies that only focus on one group of patients, differences in aspects such as data and methodology would limit the possibility of making a comparison.
3.6 Intervention-Specific Direct Medical Cost Data
A total of 14 studies reported costs for different treatment options (surgical approaches and/or radiotherapy) for patients with early-stage NSCLC (Table 4 and Online Resource 5, see ESM) [29, 37,38,39, 46, 50, 52,53,54, 56, 58,59,60,61]. The costs of a range of surgical approaches were reported. In studies reporting costs for surgery, chemotherapy and radiotherapy, surgery was the most expensive treatment in patients with stage I and II NSCLC [38, 50, 54]. Four studies considered the comparison of video-assisted thoracoscopic surgery (VATS) versus open surgery (thoracotomy or sublobar resection) [39, 46, 56, 61]. In general, VATS was associated with lower costs than open thoracotomy [39, 46, 56]. Veluswamy et al. (2020) [46] also compared VATS with robot-assisted surgery (RAS) in patients with stage I–IIIA NSCLC identified from the US-based Surveillance, Epidemiology and End Results (SEER)-Medicare database; RAS-treated patients incurred significantly higher total costs (US$54,702 vs US$48,729; p = 0.02) and pre-operative costs (US$3668 vs US$2803; p < 0.0001) compared with VATS-treated patients. However, costs were similar between the two minimally invasive procedures during the operative (US$28,732 vs US$27,209; p = 0.078) and post-operative (US$22,302 vs US$18,718; p = 0.15) periods [46]. Few studies reported costs associated with adjuvant therapy; however, where reported this was also an important driver of costs across all early stages of disease. One study reported few differences in regimen or healthcare resource use by disease stage associated with adjuvant treatment of patients with stage IB to IIIA NSCLC treated in community oncology practices in the US; the total monthly median cost per patient during adjuvant treatment was US$17,389.75 (interquartile range [IQR]: 8815.61–23,360.85) whereas the monthly cost from diagnosis until the end of the initial systemic therapy regimen after recurrence or the end of medical record was US$1185.08 (IQR: 250.60–2535.99) [22]. In a multi-national study assessing the economic burden of resected stage IB–IIIA NSCLC, the largest monthly direct costs per patient in the UK were for the adjuvant treatment period (€2490, based on 98 patients); whereas in France and Germany, monthly direct costs per patient were highest during the distant metastasis/terminal illness phase followed by the adjuvant phase [15].
3.7 Direct Non-medical Costs
Only two studies were identified that reported direct non-medical costs, one of which was in patients with early-stage NSCLC [15] and the other was in patients with newly diagnosed lung cancer, the majority of whom were patients with early-stage NSCLC [57].
Andreas et al. [15] estimated the burden and cost of illness associated with completely resected stage IB–IIIA NSCLC in France, Germany and the UK. Out-of-pocket (OOP) expenses were estimated based on the patient survey 3-month recall period and included childcare costs and transportation costs. The mean (95% CI) total OOP expenses per patient were €0 in France, €126 (100–158) in Germany and €132 (120–145) in the UK. The lack of OOP expenses in France was due to the high coverage of these costs by the national health insurance. These OOP costs may represent the total direct non-medical costs.
Stone et al. [57] reported that implementation of a multidisciplinary cancer clinic (MDC) model led to a reduction in patient visits and direct patient and caregiver costs compared with a traditional model of care for patients with lung cancer in Canada. Data were extracted for 78 patients with lung cancer (69 had NSCLC) from the traditional model and 350 patients (260 had NSCLC) from the MDC model. Total OOP savings for all patients studied in the MDC model compared with the traditional model was Can$24,167, or Can$69 per patient. This was attributed to Can$2226 in parking costs and Can$21,941 in return travel costs.
3.8 Indirect Costs
Two studies were identified that reported indirect cost data associated with patients with early-stage NSCLC [15, 60] and one study was identified that reported indirect cost data associated with patients newly diagnosed with lung cancer (the majority of which had NSCLC) [57].
Andreas et al. [15] estimated the costs associated with loss of productive time (changes in job status and lost workdays) and OOP expenses for patients with completely resected stage IB–IIIA NSCLC in France, Germany and the UK. Mean total indirect costs (95% CI) per patient were estimated to be €696 (292–1172) for France, €2476 (1716–3289) for Germany and €1414 (620–2336) for the UK. In the study by Zhang et al. [60], the mean indirect costs associated with robotic thoracic surgery and VATS in patients with early-stage NSCLC were compared. Indirect costs included hospital overhead cost and amortisation of capital equipment, including of the purchase and maintenance of minimally invasive platforms. The results revealed a higher mean indirect cost in the robotic group (n = 298) compared with the VATS group (n = 476; US$4300.20 [SD US$23.00] vs US$338.30 [SD US$19.80]; p < 0.01).
Stone et al. [57] calculated the change in patient and caregiver productivity to derive the total productivity gains of an MDC treatment model for patients with lung cancer in Canada compared with a traditional model. The study also calculated the time forgone for return travel, parking and finding the clinic, as well as clinic visit costs, calculated from administrative personnel hourly wages. Due to 371 fewer visits to MDC than the traditional model clinic, total productivity gains of Can$23,714 (Can$6379 for patients and Can$17,335 for caregivers) were reported. In addition, due to the reduction in visits associated with the MDC model, net administrative savings for the time spent booking clinic visit appointments of Can$508 (Can$1.37 per visit) were estimated.
3.9 Resource Use
A total of 16 studies reported resource use data associated with patients with early-stage NSCLC (Online Resource 5, see ESM) [15, 22,23,24, 26, 28, 35, 38, 41, 46,47,48,49, 51, 55, 57]. Five studies reported resource utilisation by patients with different stages of disease [22, 28, 35, 49, 51]. Resource use was not found to differ significantly by stage in studies that considered only patients with early-stage disease [22]; however, there were differences in resource use between patients with early and advanced (stage IV) disease stages (28, 49, 51]. For instance, Cowper et al. [51] found that brain imaging was used more often to stage patients with advanced disease (46% for stages II–IV vs 30% for stage I) and invasive mediastinal staging was less common in pathological stage I patients than in those with more advanced disease (28.9% vs 41–50%). Similarly, Gildea et al. [28] reported that per patient per month healthcare utilisation after lung cancer diagnosis was significantly higher among patients diagnosed at stage IV disease and lowest among patients diagnosed at stage I disease. Both studies were US-based [28, 51].
The choice of treatment approach also had an impact on healthcare resource utilisation rates [27, 29, 37,38,39, 41, 46, 59, 60]. For instance, Veluswamy et al. [46] reported lower rates of positron emission tomography scans, chest computed tomography scans and mediastinoscopy in patients undergoing RAS compared with both VATS and open thoracotomy. In addition, geographical region was demonstrated to influence resource utilisation regardless of treatment approach. For example, Mahar et al. [38] conducted a population-based retrospective cohort study of patients with resected NSCLC in Canada and reported that rates of chemotherapy usage, the proportion of patients who received any imaging scans, hospitalisations, specialist visits, emergency room visits, mean number of imaging scans, General Practitioner visits and blood transfusions all varied significantly among Canadian geographic regions over a 4-year follow up period.
4 Discussion
The objective of this SLR was to provide a comprehensive overview of the available direct medical costs, direct non-medical costs, indirect costs, cost drivers and resource use data available for patients with early-stage NSCLC.
The majority of studies reported direct medical cost data. In general, direct medical costs were observed to increase with increasing pathological stage of disease [14, 15, 22, 26,27,28,29, 31, 33,34,35, 37,38,39,40, 45,46,47,48,49,50,51,52,53,54,55,56, 58,59,60,61,62]. Cost drivers varied according to disease stage, with surgery being the predominant contributor to costs in the early stages of disease, and radiotherapy, medical therapy, treatment for progression and supportive care becoming increasingly important with more advanced disease [14, 50]. Treatment approach was also found to influence direct medical costs, with minimally invasive surgery options generally incurring less costs than more traditional open surgical approaches [39, 46, 56]. Robotic surgical systems have also been shown to be safe and effective in resectable NSCLC and could make up for the deficiencies of traditional thoracoscopic surgery; however, the relatively expensive cost has become a major factor in limiting their widespread use [31]. Overall, the evidence collated highlights the costs and healthcare requirements associated with early-stage NSCLC and is in line with a recent review of the economic burden of lung cancer (all histological subtypes), which also demonstrated the considerable economic burden that lung cancer imposes on patients and healthcare systems [17].
The strengths of this SLR include the design of the search strategy and the wide range of data sources searched. Only full publications were analysed as the limited reporting in conference abstracts implies a lack of robustness as a data source in comparison with full publications. Despite the identification of a reasonable number of studies (n = 42), the ability to compare results was limited due to study heterogeneity. Methodological variations between the included studies as well as differences in sample groups (cancer types and stages), costing approaches, currency, country, treatments evaluated and follow-up periods influenced the estimated costs reported. Findings from this review must also be interpreted with consideration of the individual study caveats and limitations of the overarching evidence base. Prospective studies with extended follow-up periods would help to reduce bias (e.g. due to sample selection, missing information) and ensure that long-term information relating to costs and resource utilisation are appropriately captured in this sample.
The current review has highlighted a number of data gaps in the published literature. Firstly, there is a paucity of robust evidence relating to the indirect costs and direct non-medical costs associated with patients with early-stage NSCLC in the primary countries of interest. This limits the ability to make comparisons of the economic impact of different treatments. Future studies should seek to build on the current evidence base by calculating a comprehensive cost of illness of early-stage NSCLC, including both direct and indirect costs, to fully elucidate the burden of this disease. There is also a clear need for more studies comparing the apparent advantages of RAS with the increased cost of technology [42, 46]. The current evidence base is heavily US-centric (20/42 studies) and patients from other markets will need to be included in future studies to address international and regional variations in costs and resource utilisation. This will assist with wider generalisability, ensuring that analyses that may rely on this data (e.g. economic evaluations) are appropriate to the territory of interest given differences in healthcare resource use and the cost of healthcare resources across markets. As treatment burden was found to vary markedly across patients and treatment types, future work should identify opportunities to further understand and ameliorate this burden [41], such as studies evaluating the value of MDC models outside of Canada.
5 Conclusion
This study summarises the costs and healthcare resource use associated with early-stage NSCLC. Moreover, certain studies that were identified demonstrate that the economic burden of NSCLC may increase with disease progression [14, 28, 40, 49,50,51]. Preventing disease progression for patients with early-stage NSCLC therefore has the potential to reduce the economic burden of NSCLC on patients, caregivers and healthcare systems. Despite the data gaps identified, this review provides a comprehensive overview of the available cost and resource use data in this indication, which is fundamental for helping to understand the economic impact of NSCLC [14, 50].
Notes
Note that multi-national studies which included countries of primary interest also included additional countries.
References
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. 2021;71(3):209–49.
Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS. Lung cancer. Lancet (London, England). 2021;398(10299):535–54.
American Cancer Society. What is lung cancer? 2019. https://www.cancer.org/cancer/lung-cancer/about/what-is.html#:~:text=About%2080%25%20to%2085%25%20of,carcinoma%2C%20and%20large%20cell%20carcinoma. Accessed 31 Aug 2022.
Remon J, Soria JC, Peters S. Early and locally advanced non-small-cell lung cancer: an update of the ESMO clinical practice guidelines focusing on diagnosis, staging, systemic and local therapy. Ann Oncol. 2021;32(12):1637–42.
Howington JA, Blum MG, Chang AC, Balekian AA, Murthy SC. Treatment of stage I and II non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5):e278S-e313S.
Vansteenkiste J, Crinò L, Dooms C, Douillard JY, Faivre-Finn C, Lim E, et al. 2nd ESMO consensus conference on lung cancer: early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up. Ann Oncol. 2014;25(8):1462–74.
Pisters K, Kris MG, Gaspar LE, Ismaila N. Adjuvant systemic therapy and adjuvant radiation therapy for stage I–IIIA completely resected non–small-cell lung cancer: ASCO guideline rapid recommendation update. J Clin Oncol. 2022;40(10):1127–9.
American Cancer Society. Lung cancer survival rates. 2022. https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html. Accessed 31 Aug 2022.
Bilfinger T, Keresztes R, Albano D, Nemesure B. Five-year survival among stage IIIA lung cancer patients receiving two different treatment modalities. Med Sci Monit. 2016;22:2589–94.
Bezjak A, Lee CW, Ding K, Brundage M, Winton T, Graham B, et al. Quality-of-life outcomes for adjuvant chemotherapy in early-stage non-small-cell lung cancer: results from a randomized trial, JBR.10. J Clin Oncol. 2008;26(31):5052–9.
Yuan M, Huang L-L, Chen J-H, Wu J, Xu Q. The emerging treatment landscape of targeted therapy in non-small-cell lung cancer. Signal Transduct Target Ther. 2019;4(1):61.
National Institute for Health and Care Excellence. Atezolizumab for adjuvant treatment of resected non-small-cell lung cancer Technology appraisal guidance [TA823]. 2022. https://www.nice.org.uk/guidance/ta823. Accessed Nov 2022.
National Institute for Health and Care Excellence. Osimertinib for adjuvant treatment of EGFR mutation-positive non-small-cell lung cancer after complete tumour resection Technology appraisal guidance [TA761]. 2022. https://www.nice.org.uk/guidance/ta761/chapter/2-Information-about-osimertinib. Accessed Nov 2022.
Buja A, Rivera M, De Polo A, Brino ED, Marchetti M, Scioni M, et al. Estimated direct costs of non-small cell lung cancer by stage at diagnosis and disease management phase: a whole-disease model. Thorac Cancer. 2021;12(1):13–20.
Andreas S, Chouaid C, Danson S, Siakpere O, Benjamin L, Ehness R, et al. Economic burden of resected (stage IB-IIIA) non-small cell lung cancer in France, Germany and the United Kingdom: a retrospective observational study (LuCaBIS). Lung Cancer. 2018;124:298–309.
Cherny N, Sullivan R, Torode J, Saar M, Eniu A. ESMO European Consortium Study on the availability, out-of-pocket costs and accessibility of antineoplastic medicines in Europe. Ann Oncol. 2016;27(8):1423–43.
Yousefi M, Jalilian H, Heydari S, Seyednejad F, Mir N. Cost of lung cancer: a systematic review. Value Health Reg Issues. 2022;33:17–26.
Friedlaender A, Addeo A, Russo A, Gregorc V, Cortinovis D, Rolfo CD. Targeted therapies in early stage NSCLC: hype or hope? Int J Mol Sci. 2020;21(17).
Sangha R, Price J, Butts CA. Adjuvant therapy in non-small cell lung cancer: current and future directions. Oncologist. 2010;15(8):862–72.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9.
Molinier L, Bauvin E, Combescure C, Castelli C, Rebillard X, Soulié M. Methodological considerations in cost of prostate cancer studies: a systematic review. Value Health. 2008;11(5):878–85.
Buck PO, Saverno KR, Miller PJE, Arondekar B, Walker MS. Treatment patterns and health resource utilization among patients diagnosed with early stage resected non-small cell lung cancer at US community oncology practices. Clin Lung Cancer. 2015;16(6):486–95.
Cai B, Fulcher N, Boyd M, Spira A. Clinical outcomes and resource utilization after surgical resection with curative intent among patients with non-small cell lung cancer treated with adjuvant therapies in a community oncology setting: a real-world retrospective observational study. Thoracic Cancer. 2021;12(14):2055–64.
Erb CT, Su KW, Soulos PR, Tanoue LT, Gross CP. Surveillance practice patterns after curative intent therapy for stage I non-small-cell lung cancer in the medicare population. Lung Cancer. 2016;99:200–7.
Farrow NE, An SJ, Speicher PJ, Harpole DH, D’Amico TA, Klapper JA, et al. Disparities in guideline-concordant treatment for node-positive, non-small cell lung cancer following surgery. J Thorac Cardiovasc Surg. 2020;160(1):261.
Flanagan MR, Varghese TK, Backhus LM, Wood DE, Mulligan MS, Cheng AM, et al. Gaps in guideline-concordant use of diagnostic tests among lung cancer patients. Ann Thorac Surg. 2015;100(6):2006–12.
Geller AD, Zheng H, Mathisen DJ, Wright CD, Lanuti M. Relative incremental costs of complications of lobectomy for stage I non-small cell lung cancer. J Thorac Cardiovasc Surg. 2018;155(4):1804–11.
Gildea TR, Byfield SD, Kyle Hogarth D, Wilson DS, Quinn CC. A retrospective analysis of delays in the diagnosis of lung cancer and associated costs. ClinicoEconomics Outcomes Res. 2017;9:261–9.
He J, Shao W, Cao C, Yan T, Wang D, Xiong XG, et al. Long-term outcome and cost-effectiveness of complete versus assisted video-assisted thoracic surgery for non-small cell lung cancer. J Surg Oncol. 2011;104(2):162–8.
Hu Y, McMurry TL, Isbell JM, Stukenborg GJ, Kozower BD. Readmission after lung cancer resection is associated with a 6-fold increase in 90-day postoperative mortality. J Thorac Cardiovasc Surg. 2014;148(5):2261-7.e1.
Huang J, Li J, Li H, Lin H, Lu P, Luo Q. Continuous 389 cases of Da Vinci robot-assisted thoracoscopic lobectomy in treatment of non-small cell lung cancer: experience in Shanghai Chest Hospital. J Thorac Dis. 2018;10(6):3776–82.
Hubert J, Bourdages-Pageau E, Garneau CAP, Labbe C, Ugalde PA. Enhanced recovery pathways in thoracic surgery: the Quebec experience. J Thorac Dis. 2018;10(Supplement4):S583–90.
Jean RA, Bongiovanni T, Soulos PR, Chiu AS, Herrin J, Kim N, et al. Hospital variation in spending for lung cancer resection in medicare beneficiaries. Ann Thorac Surg. 2019;108(6):1710–6.
Kennedy MPT, Hall PS, Callister MEJ. Factors affecting hospital costs in lung cancer patients in the United Kingdom. Lung Cancer. 2016;97:8–14.
Lanuti M, Hong H, Ali S, Stock C, Temel J, Mathisen D, et al. Observations in lung cancer over multiple decades: an analysis of outcomes and cost at a single high-volume institution. Eur J Cardiothorac Surg. 2014;46(2):254–61.
Lee SE, Cho WH, Lee SK, Byun KS, Son BS, Jeon D, et al. Routine intensive monitoring but not routine intensive care unit-based management is necessary in video-assisted thoracoscopic surgery lobectomy for lung cancer. Ann Transl Med. 2019;7(7):129.
Li JT, Liu PY, Huang J, Lu PJ, Lin H, Zhou QJ, et al. Perioperative outcomes of radical lobectomies using robotic-assisted thoracoscopic technique vs. video-assisted thoracoscopic technique: retrospective study of 1,075 consecutive p-stage I non-small cell lung cancer cases. J Thorac Dis. 2019;11(3):882–91.
Mahar AL, Coburn NG, Johnson AP. A population-based study of the resource utilization and costs of managing resectable non-small cell lung cancer. Lung Cancer. 2014;86(2):281–7.
Mei J, Guo C, Xia L, Liao H, Pu Q, Ma L, et al. Long-term survival outcomes of video-assisted thoracic surgery lobectomy for stage I-II non-small cell lung cancer are more favorable than thoracotomy: a propensity score-matched analysis from a high-volume center in China. Transl Lung Cancer Res. 2019;8(2):155–66.
Mittmann N, Liu N, Cheng SY, Seung SJ, Saxena FE, Look Hong NJ, et al. Health system costs for cancer medications and radiation treatment in Ontario for the 4 most common cancers: a retrospective cohort study. CMAJ Open. 2020;8(1):E191–8.
Presley CJ, Soulos PR, Tinetti M, Montori VM, Yu JB, Gross CP. Treatment burden of medicare beneficiaries with stage I non-small-cell lung cancer. J Oncol Pract. 2017;13(2):e98–107.
Radkani P, Joshi D, Barot T, Williams RF. Robotic video-assisted thoracoscopic lung resection for lung tumors: a community tertiary care center experience over four years. Surg Endosc. 2016;30(2):619–24.
Rosen JE, Salazar MC, Dharmarajan K, Kim AW, Detterbeck FC, Boffa DJ. Length of stay from the hospital perspective: practice of early discharge is not associated with increased readmission risk after lung cancer surgery. Ann Surg. 2017;266(2):383–8.
Puri V, Patel AP, Crabtree TD, Bell JM, Broderick SR, Kreisel D, et al. Unexpected readmission after lung cancer surgery: a benign event? J Thorac Cardiovasc Surg. 2015;150(6):1496–505.
Singnurkar A, Swaminath A, Metser U, Langer DL, Darling GE, Pond GR. The impact of synchronous malignancies on survival in patients with early stage curable non-small-cell lung cancer. Cancer Treat Res Commun. 2020;25: 100246.
Veluswamy RR, Whittaker Brown SA, Mhango G, Sigel K, Nicastri DG, Smith CB, et al. Comparative effectiveness of robotic-assisted surgery for resectable lung cancer in older patients. Chest. 2020;157(5):1313–21.
Vernon J, Andruszkiewicz N, Schneider L, Schieman C, Finley CJ, Shargall Y, et al. Comprehensive clinical staging for resectable lung cancer: clinicopathological correlations and the role of brain MRI. J Thorac Oncol. 2016;11(11):1970–5.
Voong KR, Liang OS, Dugan P, Torto D, Padula WV, Senter JP, et al. Thoracic oncology multidisciplinary clinic reduces unnecessary health care expenditure used in the workup of patients with non-small-cell lung cancer. Clin Lung Cancer. 2019;20(4):e430–41.
Shah S, Blanchette CM, Coyle JC, Kowalkowski M, Arthur ST, Howden R. Healthcare utilization and costs associated with COPD among SEER-Medicare beneficiaries with NSCLC. J Med Econ. 2018;21(9):861–8.
Corral J, Espinas JA, Cots F, Pareja L, Sola J, Font R, et al. Estimation of lung cancer diagnosis and treatment costs based on a patient-level analysis in Catalonia (Spain). BMC Health Serv Res. 2015;15:70.
Cowper PA, Feng L, Kosinski AS, Tong BC, Habib RH, Putnam JB, et al. Initial and longitudinal cost of surgical resection for lung cancer. Ann Thorac Surg. 2020.
Ramos R, Masuet C, Gossot D. Lobectomy for early-stage lung carcinoma: a cost analysis of full thoracoscopy versus posterolateral thoracotomy. Surg Endosc. 2012;26(2):431–7.
Sancheti MS, Chihara RK, Perez SD, Khullar OV, Fernandez FG, Pickens A, et al. Hospitalization costs after surgery in high-risk patients with early stage lung cancer. Ann Thorac Surg. 2018;105(1):263–70.
Louie AV, Rodrigues GB, Palma DA, Senan S. Measuring the population impact of introducing stereotactic ablative radiotherapy for stage I non-small cell lung cancer in Canada. Oncologist. 2014;19(8):880–5.
Rintoul RC, Glover MJ, Jackson C, Hughes V, Tournoy KG, Dooms C, et al. Cost effectiveness of endosonography versus surgical staging in potentially resectable lung cancer: a health economics analysis of the ASTER trial from a European perspective. Thorax. 2014;69(7):679–81.
Smith BD, Jiang J, Chang JY, Welsh J, Likhacheva A, Buchholz TA, et al. Cost-effectiveness of stereotactic radiation, sublobar resection, and lobectomy for early non-small cell lung cancers in older adults. J Geriatr Oncol. 2015;6(4):324–31.
Stone CJL, Johnson AP, Robinson D, Katyukha A, Egan R, Linton S, et al. Health resource and cost savings achieved in a multidisciplinary lung cancer clinic. Curr Oncol. 2021;28(3):1681–95.
Abdellateef A, Ma X, Chen Z, Wu L, Cai J, Jiang L. Subxiphoid uniportal thoracoscopic pulmonary segmentectomy for stage I non-small cell lung cancer: feasibility, quality of life and financial worthiness. Thoracic Cancer. 2020;11(6):1414–22.
Yang C, Mo L, Ma Y, Peng G, Ren Y, Wang W, et al. A comparative analysis of lung cancer patients treated with lobectomy via three-dimensional video-assisted thoracoscopic surgery versus two-dimensional resection. J Thorac Dis. 2015;7(10):1798–805.
Zhang Y, Chen C, Hu J, Han Y, Huang M, Xiang J, et al. Early outcomes of robotic versus thoracoscopic segmentectomy for early-stage lung cancer: a multi-institutional propensity score-matched analysis. J Thorac Cardiovasc Surg. 2020;160(5):1363–72.
Bouabdallah I, Pauly V, Viprey M, Orleans V, Fond G, Auquier P, et al. Unplanned readmission and survival after video-assisted thoracic surgery and open thoracotomy in patients with non-small-cell lung cancer: a 12-month nationwide cohort study. Eur J Cardio-thorac Surg. 2020.
Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366: l4898.
Acknowledgements
The authors would like to acknowledge Rebecca Sullivan of Mtech Access for medical writing assistance in the preparation of this manuscript, funded by F. Hoffmann-La Roche Ltd.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
The research was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Conflict of interest
NJ, SA, DDM and RB are employees of F. Hoffmann-La Roche Ltd, Basel, Switzerland. PF, SB and LGJ were paid consultants to F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Availability of data and material
Not applicable.
Ethics approval
Not applicable.
Consent to participate
Not applicable.
Consent for publication
Not applicable.
Code availability
Not applicable.
Author contributions
NJ, SB, DDM and RB assisted with the SLR design, data analysis and manuscript preparation. PH designed the SLR and collected and analysed the data. SB collected and analysed the data. LGJ collected and analysed the data and assisted with manuscript preparation. All authors read and approved the final version of the manuscript.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
About this article
Cite this article
Jovanoski, N., Abogunrin, S., Di Maio, D. et al. Systematic Literature Review to Identify Cost and Resource Use Data in Patients with Early-Stage Non-small Cell Lung Cancer (NSCLC). PharmacoEconomics 41, 1437–1452 (2023). https://doi.org/10.1007/s40273-023-01295-2
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40273-023-01295-2