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Abstract

Background:

Extremity sarcoma surgery entails significant costs for patients, governments and insurers. Multiple studies have described individual costs, however, the overall impact of cost on the quality of surgical care remains unclear.

Objectives:

A narrative review with a systematic approach was undertaken to compare the impact of cost on the quality of extremity sarcoma care across low-middle-income and high-income countries.

Data Sources:

MEDLINE, EMBASE, Cochrane, PsycInfo, DARE, NHS-EED, HTA.

Methods:

A systematic search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Inclusion criteria were: discussion of costs and the surgical management of primary extremity sarcoma. There were no restrictions on study design, publication type, date, geographic location or publication status. A data extraction table was used to identify study location, type and findings.

Results:

1012 studies were retrieved and 44 met the inclusion criteria. Four additional studies were identified from the reference lists of included articles. 27 studies were published in high-income countries (HIC) including all four full health economic analyses and 20 studies were published in low-middle income countries (LMC). Within LMC, cost impeded access to diagnosis, resection and options for reconstruction. In HIC, cost varied with choice of management, particularly during the long-term postoperative period.

Conclusions:

Within LMC, cost impaired the provision of quality, curative care for patients with extremity sarcoma. Within HIC, while costs varied with chosen management, they were not prohibitive to the provision of quality care. Further research is required, specific to both socioeconomic contexts, to further describe the long-term cost-utility of different methods for the surgical management of extremity sarcoma.

Keywords

Cost health economics sarcoma surgery quality amputation limb sparing surgery

Introduction

The global economic impact of cancer exceeds that of any other disease.¹ Cancer-related disability and premature death cost US$895 billion in 2008.¹ With the development of new treatments, the costs of cancer care are increasing.² As a result, access to cancer care has become increasingly variable, especially for those within low- and middle-income countries (LMCs).² Investment into high-quality cancer treatments and imaging technology could reduce the long-term economic burden of cancer.³ Sarcomas are rare and heterogeneous malignancies originating from mesenchymal tissue that require specialised and expensive care. Sarcomas occur at all ages, however those affecting bone (osteosarcoma, Ewing’s sarcoma) are commonest in children, while soft tissue sarcoma (STS) have higher incidence in those over fifty.⁴

The Australian Optimal Care Pathway for People with Sarcoma has seven steps: (1) Prevention and early detection; (2) Presentation, initial investigations and referral. (3) Diagnosis, assessment and treatment planning; (4) Treatment; (5) Care after initial treatment and recovery; (6) Managing recurrent, residual or metastatic disease; (7) End-of-life care.⁵ These steps can be achieved using various methods of imaging, resection, reconstruction and follow-up. The fundamental elements of sarcoma management are diagnosis and resection with adequate margins, which are critical to life-saving care. Resection may involve limb sparing surgery (LSS) or amputation followed by soft tissue and bone reconstruction, the latter of which may be achieved with an endoprosthesis, allograft, autograft or cement spacer. Cost varies with the method of treatment and may influence what options are feasible.

A number of studies have described and compared individual costs associated with different methods of surgical management. However, no study has compiled these costs across each phase of treatment and analysed the impact of cost on the choice of management and quality of care.

This paper aims to fill this knowledge gap by focussing on steps three to five of the Optimal Care Pathway from diagnosis to postoperative surveillance. It reviews the interplay between surgical management decisions and cost. It assesses the economic considerations within high- and low-middle-income countries and the ways in which cost impacts quality of care.

The primary objective of this narrative review was to analyse the impact of cost on the quality of care in the surgical management of non-metastatic extremity sarcoma. Secondary objectives were to compare the literature published within low-middle-income and high-income countries and to describe the costs incurred at each stage of surgical management.

Methods

A systematic search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and algorithm. The electronic search was performed using relevant MeSH terms and keywords within MEDLINE, EMBASE, Cochrane, PsycInfo, DARE, NHS-EED and HTA. Publications were retrieved from the start of records until 16 October 2022. One review author conducted the electronic search and analysed results to identify those relevant to the review based on title and abstract. The full text of each article was then screened according to the inclusion and exclusion criteria. Additional records were identified through examination of the reference lists of all included publications. Supplementary Table 1 contains the full search strategy of academic databases. High-income countries were defined according to the World Bank classification using gross national income (GNI) per capita during the year of publication.⁶ The measured outcomes were: study location, type of economic analysis and key findings with relation to cost and stage of management. A data extraction table was designed according to stage of management to identify study demographics and record cost observations. Studies were classified in accordance with the definitions in the Cochrane Handbook for Systematic Reviews of Interventions: Full health economic analyses were those that compared costs and health-related consequences. Partial economic analyses were those that considered only costs or resource use.⁷

The inclusion criteria were: discussion of costs or health economics and surgical management of non-metastatic extremity sarcoma. Results were limited to human studies in English. Metastatic and non-extremity disease were excluded. There were no restrictions on study design, publication type, date, geographic location or publication status. Costs were adjusted to June 2022 Australian Dollars according to Consumer Price Index inflation and exchange rates on 19 October 2022.

Results

The database search yielded 1012 results, 44 of which met the inclusion criteria. Examination of the reference lists of these publications identified four additional articles which were included in the analysis. Supplementary Figure S1 shows the PRISMA flow chart, depicting the number of titles, abstracts and full-text articles screened. Of the 48 included studies, 27 were based within high-income countries (HIC) and 20 within low- and middle-income countries (LMC). Among the studies published within HIC, 16/27 (59%) were health economic evaluations (full or partial). Of those published within LIC, 3/20 (15%) were health economic evaluations. Two studies were based in both HIC and LMC contexts, both partial health economic evaluations. There were four full health economic evaluations, all of these established in HIC. Twelve of the studies published within HIC were partial health economic evaluations and the remaining 11 provided commentary on costs and health economic considerations. Of the 20 studies from LMC, three studies were partial health economic evaluations, the remaining 17 contained commentary. Table 1 compares the key cost impacts observed within LMC and HIC.

Table 1.

Comparison of cost impacts in low- and middle-income countries and high-income countries.

Stage of management		Low- and middle-income countries	High-income countries
Diagnosis, assessment & treatment planning	Diagnosis	Diagnostic scans unavailable or unaffordable.	Advanced imaging technology in development.¹³
	Treatment planning	No data available.	Unplanned excisions associated with greater costs than planned excisions.
	Treatment	Type of resection	Surgical excision often unavailable or unaffordable.¹² Insufficient infrastructure & personnel caused delays and poorer survival.	Limb salvage surgery had greater up-front costs than amputation.^24,25
Type of reconstruction		Endoprosthesis and allograft reconstruction often unaffordable Low-cost reconstruction methods required including rotationplasty, cement spacer with nail, recycling of tumour-bearing bone^19,22,28,29	Endoprosthesis more costly than allograft for reconstruction at knee and humerusFunctional restoration was more costly but had greater cost-utility than soft tissue reconstruction for lower-extremity STS.³³ Staged reconstruction brachytherapy had higher up-front costs than immediate reconstruction brachytherapy.
Choice of endoprosthesis		Imported Western endoprostheses more costly than locally-manufactured devices^{9,19,20,31,36,37} Some low-cost endoprostheses associated with higher frequency of complications.	Most expensive devices were knee endoprostheses capable of nonsurgical lengthening.³⁵
		Adjuvant treatments	Adjuvant chemotherapy and radiotherapy inaccessible.Adjuvant chemotherapy unaffordable without public health insurance.⁴⁰	No data available.
		Patient factors	Paediatric osteosarcoma had higher perceived risk of treatment abandonment.	Lower perceived risk of treatment abandonment.⁸Higher costs with larger, higher grade soft-tissue sarcoma, elevated BMI, diabetes .Unclear impact of tumour site on cost^16,25,33
		Insurance & out-of-pocket costs	Lower overall cost of surgery.Treatment completion, limb salvage and survival were greater with public health insurance.^40,42Greater dependence on out-of-pocket funding for treatment.	Higher overall cost of surgery.⁹Access to health insurance impacted rehabilitation, prostheses and therapy.
Care After Initial Treatment & Recovery	Follow-up	No data available.	Variable methods of follow-up. Limited data comparing cost-utility of these methods.^43–46
	Device maintenance & revision	No data available.	Long-term maintenance following amputation likely more costly than limb-salvage surgery.Staged reconstruction brachytherapy less costly than immediate after 24 months.²⁵Non-invasive expandable endoprostheses less costly in long-term than surgically expandable devices.Comparable long-term costs with knee osteoarticular allograft and knee endoprosthesis.²⁶
		Economic impact on patients	Patients experienced food and employment insecurity.	Paediatric survivors of osteosarcoma had difficulty obtaining health insurance. Those who had amputation less likely to graduate high school or college than those who had limb salvage surgery.⁵³Reduction in employment within one year of STS resection.
Health consequences		Limited available data. Health economic analyses published within high-income countries not applicable to low-middle income countries.²¹	Osteoarticular allograft had better cost utility than endoprosthetic reconstruction at knee.Limb salvage surgery better cost-minimisation than amputation.²⁴Functional reconstruction more cost-effective than soft tissue reconstruction in lower limb STS.Planned excision likely had better cost-effectiveness than unplanned excision.¹⁵

Key study characteristics and findings are summarised in Supplementary Table 2.

Discussion

The literature exploring the cost of extremity sarcoma surgery was heterogeneous, owing to varying methods of management, data collection and cost considerations. Differences were most distinctive when comparing publications from LMC to those from HIC. Publications from HIC were more often partial or full economic evaluations that calculated the costs or cost consequences associated with a particular stage or modality of treatment. Of those published in LMC, only three were partial economic evaluations. The remainder reported individual costs or provided general commentary around economic barriers and needs without formal economic evaluation.

The two studies that compared HIC and LMC observed clear disparities. One study surveyed clinicians from 101 different countries: Clinicians in LMC considered osteosarcoma to have the highest risk of treatment abandonment among all paediatric malignancies. The perceived risk was far lower within HIC.⁸ In another study, the costs of extremity sarcoma surgery in the USA were over 10 times those in Chile.⁹ Even within HIC, the socioeconomic context impacted osteosarcoma survival. In the USA, long-term patient survival was significantly greater within more affluent states compared to less affluent states.¹⁰ One proposed resolution was the development of resource-stratified guidelines that detail management plans according to resource availability. One such guideline described options that ranged from amputation by a general surgeon in basic-resource settings, to LSS with customised expandable endoprostheses by multidisciplinary teams in maximum-resource settings.¹¹

Diagnosis, assessment and treatment planning

Diagnosis

To confirm the diagnosis, MRI, core biopsy and staging CT, PET-CT or bone scan are recommended within a specialist sarcoma unit under the supervision of a multidisciplinary team.⁵ These investigations are essential to determine the nature and extent of disease and to plan treatment. Crucial diagnostic scans were not always available in LMC, such was the case in Nigeria, where many patients could only afford a plain radiograph for staging.¹² In these cases, the cost of accessing expensive investigations generated suboptimal management, whereby disseminated disease may have remained undetected and therefore untreated.

Access to diagnostic investigations was not identified as an issue in HIC such as the UK, where discussions were directed towards the future directions of imaging for sarcoma surgery, such as near-infrared fluorescence imaging, which cost $178,854 per device.¹³

Treatment planning

Treatment planning in extremity sarcoma is complex, requiring a multidisciplinary team to tailor the timing of surgery, type of resection, type of reconstruction and adjuvant therapies. This may involve a period of ‘prehabilitation’ to optimise physical, psychological and social wellbeing prior to planned excision (PE).⁵

Unplanned excisions (UPE) of STS occur without prior treatment planning and are typically resected in error without respecting the specialised tumour guidelines pertinent to sarcoma. Once diagnosed as sarcoma, these tumours often require further re-excision of the previous operative field to remove residual tumour. It is unclear whether the cost of treatment planning impacted the decision to perform UPE rather than PE. One study comparing the costs of PE and UPE in Spain found no difference in diagnostic costs. However, costs were significantly lower when patients were appropriately referred to a specialist sarcoma unit prior to biopsy, rather than when referral was delayed until after biopsy.¹⁴ On average, UPE were associated with greater costs than PE due to the additional requirement of re-excision.^14,15 Due to the technical difficulties associated with re-excision, this procedure alone cost more than PE.¹⁶

In contrast, a study of patients aged over 66 reported significantly greater costs for PE compared to UPE. This was attributed to the clinical setting of excision – UPE was usually performed in lower-cost outpatient centres, PE was performed in inpatient settings. The authors noted that these “provocative findings” may not apply to younger patient.¹⁷ The importance of timely diagnosis and surgical planning was highlighted by a study of sarcoma-related medicolegal cases in the USA. They observed mean indemnity payments of $3.87 million, most pertained to delayed diagnosis, unnecessary amputation and misdiagnosis.¹⁸ No publications detailed the cost considerations for treatment planning specifically within LMC.

Treatment

Type of resection

Resection with adequate oncological margins is the critical step for curative care in extremity sarcoma. Limb sparing surgery (LSS) is the preferred modality of resection. In certain circumstances where LSS is not possible, amputation may be the sole surgical option.⁵ The cost of resection was discussed in both HIC and LMC contexts. In Nigeria, compartmental excision or amputation cost around $1488, which was often inaccessible to patients with financial constraints.¹² This resulted in delayed surgery and poor 5-year survival.¹² LSS required an experienced team of oncologists and surgeons, and expensive infrastructure including transfusion facilities, intensive care unit, and blood bank. Infrastructure constraints led to over-crowding, long waiting lists and delays in treatment.^19–21 There was a shortage of specialist sarcoma surgeons able to perform LSS, with only one orthopaedic oncologist in Nigeria and three in Pakistan.^12,22,23 These institutional and consumer-level cost constraints were major barriers to accessing curative care within LMC.

Within HIC, cost was not reported as a barrier to surgical resection. Instead, the literature focussed on the type of resection, comparing amputation and LSS. One study from 1997 compared the up-front costs of LSS and amputation in the UK. Including the operation, rehabilitation and either endoprosthesis or exoprosthesis, LSS cost $46,440, whereas amputation cost $20,877.²⁴ Another study from 2016 considered recurrent STS in the USA, with more comparable initial treatment costs of $138,393 for amputation and $154,674 for operations other than amputation.²⁵

Type of reconstruction

Following tumour resection, bone can be reconstructed using various types of synthetic or organic grafts. Within HIC, two studies compared the costs of reconstruction with an endoprosthetic implant versus an allograft. The first study was of LSS for knee osteosarcoma in USA.²⁶ Endoprosthetic reconstruction ($82,209) was significantly more expensive than osteoarticular allograft reconstruction ($37,274).²⁶ Similarly, for humeral reconstruction in USA, the costs for a humeral endoprosthesis ($5644–$23,356) were far greater than those for a allograft ($3202).²⁷

Clinicians in LMC often applied innovative techniques to provide financially feasible options for their patients. Endoprostheses were prohibitively expensive, while allografts required a tissue bank which was often unavailable in LMC.^19–21 Rotationplasty was offered in India for $746.¹⁹ This was especially attractive in paediatric osteosarcoma where expandable endoprostheses were unaffordable.²⁸ In cases of proximal humerus osteosarcoma where function could not be preserved, a cement spacer with $16 nail and $99 plate had comparable outcomes to endoprosthesis, with just 10 per-cent of the material costs.^22,28,29 Tumour-bearing bone treated with liquid nitrogen was used as an autograft at various sites including proximal humerus, femur and distal fibula with good functional outcomes.^30,31 At one centre in Egypt, the liquid nitrogen treatment process cost just $80 – far lower in cost than an endoprosthesis.³¹

Soft tissue reconstruction may incorporate the replacement of skin and soft tissue, neurovascular structures and muscle.³² In the USA, one study compared the costs of functional restoration using innervated muscle or tendon transfers versus soft tissue reconstruction alone. Functional restoration was significantly more expensive for both upper and lower extremity STS. However, when adjusted for tumour severity, the cost difference was no longer significant within lower extremity cases. Incorporating patient-reported outcomes, they observed greater TESS scores for lower extremity functional restoration, with an ICER of $434 per additional score unit. In the upper extremity, TESS scores were higher for those who received soft tissue reconstruction.³³

The timing of reconstruction alongside adjuvant treatment influenced costs. Among patients with recurrent STS in the USA, staged reconstruction brachytherapy had higher initial costs than immediate reconstruction brachytherapy.²⁵ Additionally, the use of staples rather than sutures following STS excision produced cost savings of up to $85 per patient, with no difference in complication rate.³⁴ No study reported cost considerations specifically for soft tissue reconstruction within LMC.

Choice of endoprosthesis

In both LMC and HIC, the high cost of endoprostheses was discussed. Cost varied with anatomic location, manufacturer and capabilities such as expansion. Within the USA, the most expensive devices were knee endoprostheses capable of nonsurgical lengthening, which cost $58,674. Minimally invasive expanding devices cost $42,893 for the proximal tibia and $34,315 for the proximal or distal femur model.³⁵ For non-expandable endoprostheses, one manufacturer charged $23,356, while another charged $5644 for a proximal humerus device.²⁷ A distal femur or proximal tibia endoprosthesis cost $57,059.²⁶

The cost of imported Western endoprostheses was a shared issue across multiple LMC.^{9,19,20,31,36,37} When using locally made non-expandable endoprostheses rather than imported devices, cost savings were up to $25,110 in China.³⁷ In India, low-cost expandable endoprostheses were available for $9,312, far cheaper than imported devices, available for $37,251.¹⁹ These cost savings were significant in LMC such as Malaysia, where the cost of an endoprosthesis was equivalent to 2 years of patient wages.³⁸ However, the reliability and durability of these low-cost ‘indigenous’ prostheses has been questioned.^28,39 One study reported over 50% infection rates and an inevitability of prosthetic fracture or dislocation with a locally made hinge knee prosthesis.³⁹ Local design and manufacture of tumour endoprostheses offers significant cost savings, but requires rigorous planning, in vitro testing for durability and clinical trials to ensure quality. This was the experience of a research team in India, who over the last 15 years have developed a high-quality, durable tumour knee endoprosthesis.³⁹ Clinical trials are ongoing, however cost savings have already been demonstrated in the durability testing apparatus, which cost just five per-cent of a comparable testing device from overseas.³⁹

Adjuvant treatments

Two studies discussed the costs of adjuvant chemotherapy and radiotherapy during the perioperative period. The up-front cost of radiotherapy ($1397) compounded by expensive device maintenance made it unavailable or inaccessible in most Nigerian centres.¹² Similarly in Taiwan, neoadjuvant chemotherapy cost $17,522, while complete adjuvant chemotherapy cost $41,974. Without the National Health Insurance program, these costs were prohibitive for most patients.⁴⁰

Patient factors

Three studies from the USA considered the impact of patient factors on costs. STS size was associated with an additional $245 per centimetre.¹⁶ Higher grade tumours, elevated patient BMI and diabetes were also associated with greater costs.^16,25 The association between tumour site and cost was unclear. Alamanda and Nelson et al. observed higher costs for lower extremity lesions, however another study by Naghavi et al. found that upper extremity tumours were more costly.^16,25,33 While all three studies were of STS, there were key methodological differences. Naghavi et al. evaluated patients with recurrent STS only. They collected costs over 24 months and included costs of adjuvant therapy. Length of follow-up and inclusion of adjuvant treatment costs was unclear for Alamanda and Nelson’s studies. There were no studies of patient-factors published in LMC.

Insurance and out-of-pocket costs

The accessibility of health insurance had significant effects on treatment trajectory, something that was reflected worldwide. Within the USA, varying insurance coverage impeded access to rehabilitation, prostheses and associated therapy.⁴¹ In Taiwan, the implementation of the National Health Insurance program improved nationwide treatment completion and survival for patients with osteosarcoma. Specifically, patients presented earlier, with lower grade tumours, had more limb-sparing procedures and fewer amputations.⁴⁰ In Nigeria, endoprosthetic reconstruction is possible, however out-of-pocket costs hindered access.^23,42 A pilot program that emulated public health insurance in Nigeria created higher treatment completion, improved survival and increased LSS.⁴² The frequency of amputation also increased with the overall rise in treatment completion. Issues arose later in this program when international grants and non-government organisation grants were manipulated and diverted away from sarcoma care.⁴² Dependence on out-of-pocket funding was prevalent within the Asia-Pacific, where 29% of clinicians had patients who depended on personal funds or private insurance for sarcoma care.¹¹

Care after initial treatment and recovery

The most substantial costs along the treatment pathway were incurred during the post-operative period, pertaining to surveillance, device maintenance and revision surgeries. Over time, these costs surpassed those of the initial diagnostic work-up and operation.

Follow-up

Following initial treatment, regular clinical examination is needed to detect local recurrence, while imaging such as CT may be appropriate for complex reconstructions and surveillance of pulmonary metastases.³² In the USA, 54 different STS follow-up strategies were identified, with costs ranging from $1018 to $44,568 over 5 years.⁴³ For an MRI surveillance programme in Scotland, an average of $11,463 was incurred for each detected recurrence. This cost reduced to $7209 per recurrence when the programme was targeted to high-risk individuals.⁴⁴ Ultrasound was also proposed as a cost-effective surveillance strategy following LSS with 95% sensitivity for tumour recurrence; although no cost analysis has been conducted.⁴⁵ In 2019, a multi-centre randomised controlled trial was proposed to compare surveillance strategies, with outcomes including costs, survival and quality of life.⁴⁶ No publication discussed the cost of surveillance within LMC.

Device maintenance and revision surgery

Depending on the modality of resection and reconstruction, individuals require various procedures to maintain their graft or prosthesis. Grimer et al. formulated two equations in 1997 that described the long-term costs of LSS and amputation for lower extremity osteosarcoma.²⁴ These equations included the up-front costs during the perioperative period as well as yearly maintenance costs. They have also formed the basis for more recent cost analyses.^26,35,47 According to Grimer’s estimates, annual maintenance costs would be $17,073–35,475 for the provision and maintenance of a lower limb prosthesis following amputation in the UK.²⁴ Barr et al. questioned whether perpetual maintenance costs were universally applicable, describing them as “an assumption evidently subject to argument”.⁴⁷ Hoffman et al. had lower cost estimates for prosthesis maintenance in USA, ranging from $1476–20,178 (mean $10,010).⁴⁸ Grimer et al. derived their estimate using quotations from service providers, whereas the Hoffman’s study compiled costs recorded by prosthetists over 15.4 years. Hoffman explained that prosthesis costs were variable, as was rate of revision, ranging from 36% to 67% over 10 years. These studies demonstrated the substantial ongoing costs of amputation. However, both reported data from over two decades ago, which may no longer apply given the rapid evolution of prosthetics.⁴⁹

For LSS with endoprosthetic reconstruction, Grimer’s equation combined perioperative costs with outpatient visits, servicing and revision procedures. Considering the likelihood of such procedures, the overall maintenance cost was $3138 annually. Comparing lower extremity LSS and amputation, Grimer’s model indicated that the high perioperative costs of LSS were eventually outweighed by the substantial maintenance costs of amputation. Over 20 years, their model predicted $253,852 cost savings with LSS over amputation.²⁴ Two additional papers agreed with this summation, stating that even for the most costly, expandable endoprostheses, the maintenance costs associated with amputation would prove more expensive within a decade.^35,47 Conversely, Craft et al. contended that hospitalisations, complications and revisions associated with endoprosthetic surgery would likely cost more than amputation in the long-term.⁵⁰ One study of recurrent STS found no difference in costs for amputees compared with non-amputees after 24 months. However, their study excluded prosthesis-related costs.²⁵

A publication in the USA compared long-term costs for patients with recurrent STS who received either immediate reconstruction (IR) or staged reconstruction (SR) brachytherapy. After 24 months, IR had significantly greater costs than SR. The most significant change in costs occurred at 12–18 months, coinciding with the highest rates of local failure among IR patients.²⁵

Skeletally immature children need expandable endoprostheses and regular lengthening procedures.^35,50 Expandable endoprostheses may require lengthening procedures (minimally invasive) or may be capable of non-operative expansion (non-invasive). In the USA, one study compared the costs of expandable implants.³⁵ Considering lengthening procedures, surgical complications and anticipated bone growth, non-invasive expandable endoprostheses were less costly in the long-term. For a four-year-old boy undergoing 1-cm surgical lengthening procedures at the distal femur, the total cost to skeletal maturity was $671,667.³⁵

Another study in USA compared knee osteoarticular allograft to endoprosthesis using a predictive model that incorporated various patient pathways and their likelihoods based on existing sarcoma and total knee arthroplasty literature. This included costs of surgery, complications and revisions. At 12 months, the model predicted comparable totals of $106,350 for allograft and $106,697 for endoprosthesis. The authors acknowledged that costs varied with different complication and revision rates, and that data from the total knee arthroplasty literature may not apply to osteosarcoma.²⁶

All studies that described long-term costs were published in the USA and UK, with none in LMC.

Economic impact on patients

Within both HIC and LMC, the financial impact of sarcoma extended beyond treatment costs alone. The costs of accessing treatment included transport, accommodation and absenteeism from work.^24,50,51 Some patients in Kenya experienced food and employment insecurity as a result of treatment commitments.⁵¹ Those who had LSS for STS in USA experienced reductions in employment status in the first year following their operation.⁵² Comparing paediatric survivors of osteosarcoma who received amputation or LSS, there was no difference in overall employment after 16 years of follow-up, with 97% achieving employment.⁵³ However, 30% reported difficulty obtaining health insurance, with amputees less likely to be insured than non-amputees. Amputees diagnosed under 12 years old were less likely to graduate high school, while amputees of all ages were less likely to graduate from college than non-amputees.⁵³ Following STS resection, there was no observed difference in employment, earning potential nor out-of-pocket costs comparing amputees and non-amputees in the USA.⁵⁴ In Iran, there was no difference in perceived financial impact between amputees and non-amputees following osteosarcoma resection.⁵⁵

Health consequences

An essential component of health economic evaluation is the identification and measurement of consequences.⁵⁶ Only four publications were full health economic evaluations considering both costs and consequences, all of these published in HIC. Grimer et al. conducted a cost-minimisation analysis, assuming equal outcomes for LSS and amputation.²⁴ Morattel and Nelson et al. conducted cost-effectiveness analyses, analysing costs and MSTS and/or TESS scores. Morattel et al.¹⁵ found no difference in MSTS or TESS scores after 5 and 10 years for PE and UPE, with preference for PE given its lower costs . Nelson et al.³³ observed trending improvements in TESS scores with functional reconstruction over soft tissue reconstruction for lower extremity STS. Functional reconstruction had an incremental cost-effectiveness ratio (ICER) of $434 per additional TESS unit.

Cost-utility analyses (CUA) evaluate costs against health state preference values such as quality-adjusted life-years (QALYs). However, two papers that endorsed the value of CUA noted that experiences following LSS and amputation are heterogeneous. The overall health-related quality of life (HRQoL) score may not represent the diversity of individual circumstances.^21,47 This exemplifies the importance of qualitative studies that detail patient experiences. Additionally, the current literature was limited to the HRQoL of Western patients and may not apply in LMC due to socioeconomic and philosophical differences.²¹ Wilson et al. conducted a CUA comparing osteoarticular allograft to endoprosthetic reconstruction. The allograft had a 2.29 QALY benefit over endoprosthesis. As allograft costs were lower than endoprosthesis costs, the latter procedure was dominated, with $151 saved per QALY.²⁶

No study in the review conducted a cost-benefit analysis.

Future directions

Formal health economic evaluation is essential to guide future investments and determine which interventions are most cost-effective within the LMC context. There were no full health economic evaluations within this context and there remains limited data describing the long-term costs of follow-up, device maintenance and revision surgeries. These areas should be the target for future studies. Combined with patient-reported outcome measures specific to the LMC population, such a study would guide clinicians towards achieving more accessible and effective sarcoma interventions.

Within HIC, there remains a need for formal, full health economic evaluations that consider both costs and consequences. Future studies should aim to discern the specific treatment pathway with the greatest long-term cost utility, considering the methods of investigation, resection, reconstruction and follow-up. This would involve collecting cost data and patient-reported outcome measures at each stage of the treatment pathway, with stratification of patients according to age, tumour site, grade and stage.

There are potential limitations to this study. The literature search was limited to studies in the English language. A narrative format was chosen due to the heterogeneity of publications and to obtain a broad perspective of costs and economic impact. A systematic search was utilised to reduce the risk of selection bias. A future systematic review with meta-analysis could further reduce the risk of bias and provide additional information regarding the quality of the published literature.

Conclusion

Within LMC, cost was an enduring barrier to the provision of quality, curative care for patients with extremity sarcoma. The fundamental steps of curative treatment – diagnosis and resection – were obstructed by the out-of-pocket costs of investigations and surgery. Compounding barriers were the costs of overheads including infrastructure, staff and machinery. The prospect of a cure can only be realised by eliminating these economic barriers. As such, any future funding projects should focus on these costs. The expenses associated with endoprosthetic reconstruction often required clinicians to opt for cheaper materials, low-cost reconstructive methods or ablative surgery.

Cost was a consideration within multiple HIC but was not prohibitive to the provision of curative care in diagnosis and resection. Instead, discussions compared management methods at each step of the treatment pathway, analysing their costs and functional outcomes. Planned excisions of STS were generally associated with lower costs when compared with unplanned excisions and their subsequent re-excision. Considering resection, the initial cost of amputation was lower than that for LSS. However, the greatest cost differences were seen in the long-term post-operative period. Most costing models predicted vast cost savings with LSS, owing to the high costs of prosthesis maintenance following amputation. Among reconstructive methods for LSS, the most expensive procedures involved non-invasive, expanding endoprostheses, while allograft reconstructions proved less expensive than endoprosthetic reconstructions in the long-term.

Supplemental Material

Supplemental Material - The impact of cost on quality of surgical management in non-metastatic extremity sarcoma: A cross-country narrative literature review with a systematic approach

Supplemental Material for The impact of cost on quality of surgical management in non-metastatic extremity sarcoma: A cross-country narrative literature review with a systematic approach by Timothy Kuek, Chris G Schilling, and Peter F Choong in Journal of Orthopaedic Surgery.

Footnotes

Acknowledgements

The authors wish to acknowledge Anna Lovang from the Carl de Gruchy Library for her advice and guidance with the systematic literature search in this review.

Author contributions

TK performed the literature search, as well as writing this article. PC reviewed and edited the manuscript as the senior supervisor of the project. CS provided guidance and expertise in the health economics aspects of the project. All authors have read and approved the final submitted manuscript.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Timothy Kuek

Supplemental material

Supplemental material for this article is available online.

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