A Systematic Review of the Economic Burden of Prostate Cancer: Direct and Indirect Cost Perspectives.

Key Points for Decision Makers

Introduction
Prostate cancer (PC) is the fourth most common cancer worldwide and the second most common in men, with an estimated 1,467,854 new cases and 397,439 deaths recorded in 2022 [1]. It is projected that approximately one in eight men will be diagnosed with PC during their lifetime [2]. Major risk factors include age, family history, and genetic predisposition, while lifestyle factors such as smoking, diet, lack of physical activity, medication use, and occupational exposures may also contribute to increased incidence [3]. The highest PC incidence rates are reported in North and South America, Europe, Australia, and the Caribbean, with particularly high rates observed among Black and African American populations. In recent years, incidence and mortality rates have either stabilized or declined across most regions [4]. However, trends in incidence remain closely linked to the adoption of prostate-specific antigen (PSA) screening, especially in high-income countries [5, 6].
PC displays highly heterogeneous biological behaviour, ranging from indolent tumours that never metastasize to highly aggressive forms, posing significant challenges for screening, diagnosis, and treatment [7]. To assess how aggressive PC is, several tests and procedures are performed to determine its clinical stage. Stage I indicates that the tumour is small, confined to the prostate, and highly likely to be curable. As the cancer grows, the stage increases. Stage IV indicates that the cancer has metastasized to the lymph nodes or other parts of the body, making it much more difficult to cure [8]. National and international clinical guidelines offer valuable and updated frameworks to guide healthcare providers in delivering standardized, personalized, and multidisciplinary PC care (Supplementary Table 1, see electronic supplementary material [ESM]) [9–20]. These guidelines broadly endorse a risk-adapted approach, although some differences exist in specific recommendations.
In recent years, advances in precision medicine have significantly improved the management of PC. Prostate-specific membrane antigen (PSMA)-targeted approaches have matured, supporting the development of more effective radioligand and immunologic treatments. For castration-resistant prostate cancer (CRPC), next-generation androgen receptor (AR) pathway inhibitors and degraders have expanded therapeutic options. Alongside these innovations, combination therapies are required to optimize PC treatment due to the complexity of tumour heterogeneity [21].
As one of the most common malignancies, PC has been the focus of extensive health economic research. Between 2015 and 2022, numerous publications reviewed various aspects of PC healthcare economics [22–27]. However, none of these reviews fully addressed cost-of-illness data within the context of recent advances in clinical management. A recent systematic review examined PC cost analyses published between 2022 and 2025; however, this limited time frame may have excluded relevant earlier studies and prevented a comprehensive assessment of long-term evidence [28]. Consequently, there is a need for an assessment that incorporates an updated and complete picture of the global economic burden and cost structure of PC care.
The objective of this review is to systematically search, analyse, and summarize recent cost-of-illness (COI) studies evaluating PC direct and indirect costs within the context of the latest clinical guidelines and evolving management strategies. This study provides a comprehensive estimate of the resource demands associated with PC, informing policy decisions, resource allocation, and priority setting within healthcare systems.

Methodology
This systematic literature review was designed and reported following the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to ensure methodological transparency and reproducibility.

Data Sources and Search Strategy
Relevant studies were identified through systematic searches of PubMed, Cochrane Library, and EconLit, chosen for their comprehensive coverage of biomedical and economic journals across all aspects of PC research. The inclusion and exclusion criteria were defined according to the PICOS framework (Population, Intervention, Comparator, Outcomes, Study design), as summarized in Table 1.
Eligible publications were full-length, open-access articles in English, published between January 2015 and October 2025. This timeframe was selected because the 2010 European Association of Urology (EAU) PC guidelines introduced major changes expected to influence diagnostic, treatment, and follow-up resource utilization and related costs. These included the promotion of active surveillance for low-risk patients, the recommendation to repeat PSA testing before biopsy, and the restriction of CT/MRI imaging to intermediate- or high-risk cases [29]. It was anticipated that such clinical practice changes would be reflected in economic evaluations published from 2015 onward, given that cost analyses rely on data collected in the preceding years.
The search strategy applied full-text, and combined controlled vocabulary and free-text terms, designed according to the following inclusion and exclusion criteria:For PubMed and the Cochrane Library: (("prostate cancer" OR "prostatic neoplasm" OR "prostatic neoplasms"[MeSH]) AND (((("cost analysis" OR "health care costs" OR "economic burden" OR "cost of illness"[MeSH]) NOT "cost-benefit analysis"[MeSH]) NOT "cost-effectiveness analysis"[MeSH]) NOT "financial stress"[MeSH])).

For EconLit: (("prostate cancer" OR "prostatic neoplasm") AND ("cost analysis" OR "health care costs" OR "economic burden")).

The searches were conducted in October 2025, and the complete search strings are presented in Supplementary Table 2 (ESM).

Study Selection and Eligibility Criteria
All identified records in both databases were manually screened, with duplicates being removed. Two reviewers (AR and MA) independently screened titles and abstracts for relevance, followed by a full-text review against the predefined inclusion and exclusion criteria (Table 1). Complementary searches were also performed, including citations of specific studies, reference lists of included studies and grey literature reports. Discrepancies were resolved through discussion, with the involvement of a third reviewer (JD) until consensus was reached.

Data Extraction and Quality Appraisal
Data on study setting, population, disease stage, treatment type, and cost outcomes including both direct and indirect costs related to PC were manually extracted into a structured template by AR and MA.
To ensure the reliability of studies, each article was assessed using a simplified version of the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) checklist, adapted for COI studies. Key appraisal domains included clarity of study perspective, description of cost components, data sources, and reporting of assumptions. Studies retrieved were not excluded based on quality, but findings were interpreted in light of their methodological rigor, based on the CHEERS checklist.

Cost Standardization
Cost data was extracted in the original currency and reference year as reported in each study. For consistency across sources, all monetary values were subsequently standardized to 2025 US dollars (USD) following a two-step procedure.
First, values were inflated to 2025 using the country-specific annual inflation rates derived from the International Monetary Fund (IMF) database [30]. Second, for studies reporting costs in currencies other than USD, these were converted using 2025 exchange rates obtained from exchange-rates.org [31]. If the reference year for reported costs was not indicated, the study year was assumed as the base year for cost estimation and adjustment. To enable comparison of time and patient-dependent cost data, expenditures reported over different timeframes (e.g., costs for 6 months per patient or per patient-month) were normalized on a per-patient-year basis, representing the annual cost incurred per individual. When studies presented aggregate or population-level costs (e.g., total national or regional expenditures related to PC), the original reporting format was retained to preserve the contextual interpretation of the results.

Results

Study Selection and Characteristics
A total of 316 records were retrieved and screened. After removing one duplicate, 315 unique records remained for initial evaluation. The review included COI studies that reported all-cause and PC-related costs. During the title and abstract screening, 200 records could not meet the inclusion and exclusion criteria (Table 1) or were behind a paywall and were excluded. Of the remaining publications, two could not be retrieved, leaving 113 full-text articles assessed for eligibility. Following full-text review, 46 studies were excluded because they were not COI analyses, five focused solely on financial toxicity (out-of-pocket costs), four did not provide cost data specific to PC, and three were only abstracts. An additional 48 studies were identified through other sources, including citation searching, reference screening of included articles, and from the UK National Institute for Health and Care Excellence (NICE), in the prostate cancer guidance. After eligibility assessment, four of these were excluded. In total, 95 studies met all inclusion criteria and were included in the final review (Fig. 1).
Publication volume increased over time, peaking in 2022 (n = 14) [47, 49, 50, 59, 63, 67, 79, 103–105, 114, 117, 120, 123], while 2017 had the fewest full-year publications (n = 5) [56, 74, 85–87]. The review included studies from 28 countries, each focusing on a single national context. The United States accounted for the largest share (38 studies, 40%), followed by Canada, Japan, and Iran.

Study Perspective
Most studies adopted a healthcare system perspective (n = 46), followed by unspecified payer (n = 17) and societal (n = 16) perspectives. Four analyses were conducted from a United States Medicare perspective [89, 96, 107, 119], three from a patient perspective [55, 103, 105], and seven from other limited viewpoints [41, 48, 87, 91, 99, 110, 115], while eight did not specify the perspective [51, 117, 118, 120–125].
Regarding methodology, 84 studies were retrospective analyses using databases or registries, six were prospective studies, four applied modelling approaches, and one used a mixed method combining expert interviews and modelling. Sample sizes ranged from 90 participants [47] to national-level estimates exceeding 200,000 in Brazil [32] and 590,000 in Egypt [46].

Disease Stage
Patient classification varied widely across studies, including categories by metastatic or hormonal status (e.g., nmCRPC, mCRPC), tumour stage (I–IV), risk stratification, or treatment type (active surveillance, radical prostatectomy or surgery, brachytherapy, external radiotherapy or androgen deprivation therapy). Several prevalence-based studies and cost analyses did not specify disease stage, particularly those estimating national expenditures or focusing on specific cost components (e.g., follow-up, medication, or physician services). This heterogeneity limits comparability across studies; therefore, patient status was harmonized according to categories described in Sect. 3.2.

Direct Costs of Prostate Cancer
A total of 93 articles reporting direct medical costs associated with PC were identified and included in the review (Tables 2, 3, 4). Most studies employed retrospective analyses of patient cohorts using national, institutional, or insurance claims databases. Direct costs were reported across 28 countries, encompassing high-, middle-, and low-income nations. However, significant variation in healthcare systems, cost accounting methods, treatment pathways, and study designs limited direct comparability.
To better reflect differences in economic burden by disease stage, the results are categorized as follows:Studies estimating total direct costs for unspecified or mixed PC subtype cohorts, including national-level COI studies (Table 2).

Studies estimating total direct costs for early stage, localized, or non-metastatic PC (nmPC) (Table 3).

Studies estimating total direct costs for advanced, terminal or metastatic PC (mPC) (Table 4).

Studies were grouped by geographical context (continent and country) and by methodology used to extract and calculate the costs.

Direct Medical Costs in Unspecified Prostate Cancer Phases
Some studies reported direct medical costs for PC without stratifying patients by metastatic status (Table 2). Average total healthcare costs per patient-year ranged from US$2280 in Sweden [70] to US$117,337 in Antigua and Barbuda [112], where treatment accounted for 86% of the total annual expenditure.
Within this overall burden, treatment choice emerged as a major cost driver [69]. Several studies examined costs associated with specific treatment modalities, including medication, surgery, radiotherapy, androgen deprivation therapy (ADT), and active surveillance. Stratification by treatment type revealed substantial cost differences. In the United States, two studies reported total treatment-related costs [92, 96], consistently identifying active surveillance as the least costly approach, followed by ADT. Brachytherapy and radical prostatectomy were associated with comparable costs, while external beam radiotherapy represented the most expensive treatment option [96, 99]. The use of corticosteroids with chemotherapy in patients with CRPC substantially increased costs from US$41,657 per patient-year (no corticosteroids) to US$123,217 per patient-year (high-dose corticosteroids) [92].
Patient characteristics also influenced costs [68]. Age-related differences were observed in both the United Kingdom and the United States, with higher annual costs among patients aged 65 years or older compared with younger patients [78, 80].

Direct Cost in Early, Localized or Regionalized Prostate Cancer
More studies evaluated direct medical costs for patients diagnosed with early stage PC (Table 3), providing insight into the economic burden across disease severity. Mean total costs varied substantially depending on the clinical stage and the type of treatment received. Reported costs ranged widely, from US$1213 per patient-year for low-risk PC in a modelling study in Canada [35], up to US$282,839 per patient-year for patients with central nervous system (CNS)-related adverse events (AEs) in the United States [110].
Disease stage emerged as a key determinant of costs, with more advanced stages generally associated with higher treatment-related expenditures. Patients diagnosed at stage I consistently incurred the lowest costs, reflecting less intensive treatment and more conservative management. Costs increased at stage II due to the use of more aggressive therapeutic approaches, while most studies identified stage III as the costliest disease stage. For example, Reddy et al. reported that stage III patients incurred up to 3-fold higher costs than those diagnosed at stage I [104]. However, absolute cost estimates varied substantially across countries, from US$3380 per patient-year in Iran [54] to US$150,831 per patient-year in Antigua and Barbuda [112], underscoring the influence of healthcare system context.
Beyond disease stage, the choice of treatment significantly affects total direct medical costs. Treatments vary significantly in cost depending on the patient's risk classification, disease progression, and country-specific healthcare costs.Active surveillance emerged as the least costly treatment strategy. Estimated costs ranged from US$1213 per patient-year for low-risk patients in Canada [35] to US$13,021 per patient-year in the United States [87].

Brachytherapy was considered the most affordable radiotherapy option. Low-dose brachytherapy costs US$2494 per patient-year while high-dose brachytherapy costs US$3180 per patient-year in the United States [83]. In Canada, costs were higher, with US$8583 per patient-year for low-risk patients [35].

ADT was considered another affordable option, with costs ranging from US$4822 per patient-year in the United States [99] to US$32,997 per patient-year in Canada [34]. A Swedish study reported that patients receiving ADT who progressed to nmCRPC incurred significantly higher costs—approximately 1.9 times more—than those with non-metastatic hormone-sensitive prostate cancer (nmHSPC), underscoring the critical role of tumour hormone sensitivity in determining the economic burden of PC [71].

Radical prostatectomy showed moderate costs in some settings and relatively high costs in others. In the United States, surgery had costs of US$2719 per patient-year in favourable-risk PC [102]. In other settings, cost increased up to US$35,937 per patient-year in Switzerland for localized PC [126].

External radiotherapy was considered more expensive than brachytherapy. In the United States, stereotactic body radiation therapy amounted to US$3239 per patient-year and intensity-modulated radiotherapy to US$6544 per patient-year [83]. Another study estimated higher costs for radiotherapy: US$54,971 per patient-year [99].

Treatment combination strategies, typically used in aggressive or high-risk diseases, reflect the highest treatment-related expenditure. Costs amounted to US$14,579 per patient-year for radiotherapy + brachytherapy and US$14,468 per patient-year for radiotherapy + ADT per patient-year in intermediate-risk patients [35]. In Switzerland, radical prostatectomy with radiotherapy cost US$56,172 per patient-year [126].

Chemotherapy was considered a cost amplifier, increasing direct costs when added, with cost of care for patients with localized PC increasing from US$21,241 to US$37,666 per patient-year in the United States [81].

Finally, clinical characteristics further shaped the economic burden. Faster PSA doubling time, a marker of aggressive disease, was strongly associated with higher costs, ranging from US$18,751 per patient-year for PSA doubling times > 12 months to US$64,985 per patient-year for doubling times of 2 months or less [41]. Treatment-related AEs, particularly CNS-related complications, also substantially increased costs, raising annual expenditures by > 50% among patients receiving secondary hormonal therapies [97].

Direct Cost Estimations for Advanced, Metastatic Prostate Cancer Subtype
Direct medical costs associated with mPC increase substantially with disease progression and treatment complexity, reflecting intensified healthcare resource utilization. Evidence across countries consistently shows that the transition from non-metastatic to metastatic disease marks a major escalation in costs, even prior to formal metastatic diagnosis. A large cohort study by Li et al. reported that patients who developed metastases incurred US$44,255 per patient-year preceding diagnosis, rising sharply to US$78,939 per patient-year in the year of metastatic diagnosis [86]. Similar patterns of post-diagnosis cost escalation have been observed in other analyses [107, 111].
Within metastatic disease, tumour hormone sensitivity emerged as a key cost determinant. Two studies highlighted that the economic burden increased substantially, with healthcare costs rising approximately 3-fold for mCRPC compared with mHSPC [71, 109].
Treatment choice was a major driver of the economic burden in mPC. In Italy, systemic therapies accounted for >77% of total costs among patients with mCRPC, with annual expenditures of US$30,400 per patient-year for first-line and US$26,932 per patient-year for second-line treatment [56]. In Greece, first-line therapy similarly accounted for 72% of total costs, while second- and third-line therapies were associated with lower expenditures [116]. Marked cost differences between regimens were also reported in Germany, where costs ranged from US$16,718 per patient-year for best supportive care to US$88,543 per patient-year for docetaxel and US$133,032 per patient-year for cabazitaxel [48]. In the United States, all-cause annual costs for mCRPC exceeded US$230,000 for patients treated with enzalutamide or abiraterone acetate [125].
Finally, complications further amplified costs. Patients experiencing skeletal-related events (SREs) incurred substantially higher expenditures, with costs increasing from US$3622 to US$8383 per patient-year in Canada [37] and from US$44,953 to US$63,536 per patient-year in the United States [82], while another study estimated an additional US$35,000 per patient-year attributable to SREs [90].

Cost Comparisons Between Prostate Cancer Clinical Stages
Studies consistently show that the direct medical costs of PC rise significantly with disease progression. Across international settings, mPC was associated with increases in healthcare costs ranging from 1.1-fold to 35-fold compared with non-metastatic cases [46, 47, 52, 54, 67, 71, 75, 122, 126]. This trend was strongly echoed in the United States, where multiple studies demonstrated substantial cost escalation. Increases ranged from approximately 2-fold to over 5-fold [81, 86, 88, 89, 91, 95, 98, 104, 117]. The most dramatic increases were observed at the point of metastasis and during later-stage therapies.
Though these findings demonstrate that direct medical costs of PC increase consistently with disease progression, some trends and exceptions were observed in other studies. In Antigua and Barbuda, treatment costs for patients diagnosed at stages II and III were found to be higher than those at stage IV, ranging from US$102,748 to US$150,831 per patient-year for non-metastatic stages, compared with US$109,301 per patient-year for metastatic cases, and attributed to the intensive use of surgery and systemic therapies at earlier stages, though the patient population was very small (n = 109) [112].
Additionally, Murtola et al. compared costs for patients before and after metastasis subdivided by treatment followed, obtaining 3.1-fold to 4.1-fold increases for metastatic disease [122].

Indirect Costs of Prostate Cancer
Fifteen studies were identified that evaluated indirect costs related to PC, and 12 have been reported in patient-years [46, 47, 51–54, 59, 70, 72, 76, 80, 118]. Most studies focused on productivity losses, while a smaller number also incorporated informal care (Table 5). Evidence from diverse economic settings indicates that indirect costs constitute a substantial component of the overall economic burden of PC, accounting for approximately 30% of total costs in several analyses [54, 70].
Across countries, annual indirect costs of PC ranged from US$666 per patient-year for non-metastatic patients in Egypt [46] to US$12,895 per patient-year in Iran [53].
Four studies compared morbidity-related and mortality-related productivity losses, consistently demonstrating that the largest share of indirect costs was associated with premature mortality. These mortality-related costs were reported to be 4-fold to 20-fold higher than those morbidity-related losses [47, 58, 59, 72].
Informal care emerged as a significant cost component where assessed, with annual estimates ranging from approximately US$1039 per patient-year in Sweden to nearly US$8866 per patient-year in the United Kingdom [70, 76]. However, the data for the United Kingdom was extracted from patients receiving end-of-life care, likely increasing losses [76].
A study from the United States comparing PC patients with a cancer-free control group estimated that productivity losses ranged from US$4023 per patient-year for individuals aged 18–64 years, to US$7094 per patient-year for those aged 65 years and older [80]. Another study estimated that productivity losses due to absenteeism were US$1753 per patient-year [118].

Discussion
This review provides a comprehensive and updated synthesis of the economic burden associated with PC across a broad range of global settings and clinical stages, revealing consistent patterns. PC generates one of the highest total national-level healthcare costs among malignancies, though per-patient cost is relatively moderate compared with cancers that require prolonged systemic therapies. Nonetheless, the economic burden of PC increases substantially with disease progression, emphasizing the value of early detection, timely intervention, integrated care pathways and palliative care planning to optimize resource use during high-cost periods, particularly the initial treatment phase and end-of-life care. Overall, the results described collectively support the design of cost-conscious, patient-centred cancer control policies that balance clinical benefit, equity, and economic sustainability, valuable for health system planners and decision-makers.
PC has been associated with high national healthcare expenditures. Some studies included in the review compared the costs of PC with other cancers. In Australia, one study identified PC as the costliest cancer type, while in the United States, it ranked as the second most expensive cancer [101, 114]. However, on a per-patient basis, PC tends to be less costly than cancers such as breast or colorectal [72, 77]. Mittmann et al. reported that medication costs for PC were relatively low when compared with those for breast, colorectal, and lung cancers, while radiation therapy costs were comparatively higher. This was especially evident at stage I, where only 32% of patients used medication [40]. These findings are consistent with clinical guidelines that favour active surveillance for low-risk patients to avoid overtreatment and associated costs [7, 8, 10, 15, 18–21]. Consequently, the highest treatment-related costs are typically linked to more advanced stages of the disease.
This review examined the cost estimates reported across different clinical stages, confirming a general trend of increasing expenditures as the disease advances. While some exceptions exist, most studies indicate that costs are lowest at early stages and progressively increase through stages II and III. These stages often involve definitive treatments including surgery and radiotherapy—either alone or in combination with ADT and chemotherapy—which significantly elevate overall treatment costs. Freedland et al. further highlighted a relationship between PSA doubling time and treatment costs in patients with nmCRPC, finding that faster PSA doubling time was associated with significantly higher expenditures [41].
The cost implications of various treatment options for nmPC were also analysed. The evidence available identified active surveillance as the least expensive strategy [35, 83, 96, 99, 102]. Among definitive therapies, brachytherapy emerged as the less costly option, followed by radical prostatectomy, while radiotherapy was most expensive [35, 74, 83, 96, 102]. Furthermore, the addition of ADT or chemotherapy substantially increased overall treatment costs, acting as cost amplifiers due to intensified healthcare resource utilization [79, 81].
Costs associated with mPC (stage IV) were found to be considerably higher compared with non-metastatic cases. Multiple factors contribute to the elevated costs observed in mPC. The widespread use of systemic therapies, including hormonal therapies, chemotherapy, and radiopharmaceuticals, introduces a high burden of AEs, which significantly escalate healthcare costs, particularly for SREs and CNS-related AEs [56, 60, 74, 82, 90, 110]. Thus, a substantial proportion of PC treatment costs can be attributed to managing these therapy-associated AEs.
Another important driver of costs is tumour resistance to hormonal therapy. Two studies demonstrated that costs substantially increased when cancer progressed from hormone-sensitive to castration-resistant states [71, 109]. This escalation is likely due to the necessity for more aggressive and systemic treatments, as well as the higher incidence of AEs. Kaye et al., for example, reported notable increases in pharmacy and outpatient service costs for patients with castration-resistant disease [109].
Several studies also quantified the indirect costs associated with PC from a societal perspective. Although PC predominantly affects an older population, the indirect economic burden—particularly in advanced stages—was considered substantial [46, 52, 54].
The types of indirect costs included across studies were highly heterogeneous. Most analyses focused on productivity losses, either related to morbidity (e.g., sick leave or absenteeism) [47, 52–54, 58, 59, 64, 70, 72, 80, 115, 118] and/or premature mortality [47, 52, 53, 58, 59, 70, 72, 123], while several also examined the economic burden of informal caregiving [52, 70, 76]. Among studies comparing productivity losses from morbidity versus mortality, mortality-related losses consistently accounted for the greater share [47, 58, 59]. In Sweden, the costs associated with informal care were estimated to be 2.7 times higher than productivity losses [70], and in the United Kingdom, a considerable portion of the total costs was attributed to informal care needs [76]. These results indicate that indirect costs are often driven more by premature mortality and informal caregiving than by short-term productivity losses from sick leave or absenteeism. Consequently, studies that only consider absenteeism likely underestimate the total indirect burden of PC.
Most studies included in this review were retrospective analyses, while only six were conducted using a prospective design. In addition, studies were further distinguished according to the source and method of cost data collection, including national administrative databases, hospital-specific electronic health records, patient-level data obtained through personal interviews in selected centres, simulation or modelling approaches, and other mixed methods. Comparing cost estimates between these methodological approaches is challenging, as they differ substantially in scope, population coverage, and types of costs captured. For instance, analyses based on national databases typically reflect broader populations but may lack clinical granularity, whereas hospital- or centre-specific data may provide more detailed cost components at the expense of generalizability. Similarly, prospective studies and interview-based data collection are often limited by smaller sample sizes and narrower care settings, while model-based studies depend heavily on underlying assumptions. The observed variation in cost estimates across studies therefore likely reflects methodological and contextual differences, rather than true differences in resource use. These discrepancies highlight the importance of standardizing costing methodologies and ensuring transparency in study design.
Additionally, it is important to recognize that country-specific healthcare structures significantly influence cost patterns. In the United States, several studies distinguished between patients insured through commercial health plans and those covered by Medicare, consistently finding that Medicare cohorts incurred lower healthcare costs [98, 100, 106, 107]. In smaller countries such as Antigua and Barbuda and Eswatini, cross-border procurement of therapies further exacerbated the economic burden [47, 112]. Additionally, these two studies had a small sample population: 90 for Eswatini and 109 for Antigua and Barbuda. These examples underline the necessity for studies to carefully contextualize cost data within the framework of local healthcare systems, as significant variability in economic burden can arise based on healthcare infrastructure, access, and policy differences.
This review is subject to several limitations. Only free, full-length research articles published in English were included, which may have excluded relevant findings presented in abstracts, non–open-access publications, or studies published in other languages. Additionally, studies focused on cost-effectiveness, cost-utility, or cost-saving analyses were excluded, despite their potential relevance to the economic landscape of PC.
Significant variability was observed across countries and even among studies conducted within the same country. These discrepancies—stemming from differences in methodology, study populations, original currency and healthcare system characteristics—make direct comparisons challenging. Furthermore, there is a marked geographic bias; more than half of the included studies were conducted in North America, with 32 from the United States [80–111] and 10 from Canada [33–42]. Consequently, while the burden of PC is well characterized for these countries, the findings may not fully represent the economic impact in other healthcare settings.

Conclusion
This systematic review provides several policy-relevant insights for health systems and payers. First, prostate cancer imposes a substantial and highly variable economic burden across countries, disease stages, and treatment pathways, reflecting differences in clinical practice, pricing, and health system organization. These variations highlight opportunities for efficiency gains through more consistent adoption of evidence-based care pathways and improved coordination across settings of care. Second, costs increased markedly with disease progression and advanced therapies, underscoring the importance of early detection, timely intervention, and optimized treatment sequencing from a health system perspective. Third, the limited and heterogeneous evidence on indirect costs suggests that the societal burden of prostate cancer remains underestimated in many jurisdictions, potentially biasing resource allocation decisions that rely solely on direct medical costs. Finally, the substantial methodological heterogeneity observed across COI studies limits cross-country comparability and policy transferability. This review emphasizes the need for greater methodological standardization and transparency in cost studies to support robust health technology assessment, budget impact analyses, and value-based pricing decisions in prostate cancer care.

Supplementary Information
Below is the link to the electronic supplementary material.