Cost-Effectiveness of Immediate Lymphatic Reconstruction Versus Structured Surveillance for Preventing Breast Cancer–Related Lymphedema After Axillary Surgery

Cost-Effectiveness of Immediate Lymphatic Reconstruction Versus Structured Surveillance for Preventing Breast Cancer–Related Lymphedema After Axillary Surgery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cost-Effectiveness of Immediate Lymphatic Reconstruction Versus Structured Surveillance for Preventing Breast Cancer–Related Lymphedema After Axillary Surgery Jeremy Mingfa Sun This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8722507/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Breast cancer–related lymphedema (BCRL) is a common and costly complication after axillary lymph-node dissection (ALND). Immediate lymphatic reconstruction (ILR) has been introduced as a preventive surgical strategy, but its economic value relative to structured postoperative surveillance in health systems with established lymphedema services remains uncertain. Methods We conducted a decision-analytic cost-effectiveness analysis comparing three strategies after ALND: opportunistic detection, structured surveillance using bioimpedance spectroscopy and indocyanine green lymphography, and ILR. The model adopted a societal perspective over a 10-year horizon with 3% annual discounting. Clinical probabilities were derived from meta-analyses and local cohort data, while costs were obtained from national tariff benchmarks and institutional billing data. Outcomes were expressed as quality-adjusted life-years (QALYs). Parameter uncertainty was explored using probabilistic and one-way sensitivity analyses, and threshold analyses examined conditions under which ILR might become cost-effective. Results Structured surveillance dominated opportunistic detection, yielding higher QALYs at lower cost. ILR provided a modest additional health benefit but at substantially higher cost, resulting in an incremental cost-effectiveness ratio well above commonly accepted willingness-to-pay thresholds. In probabilistic analyses, structured surveillance was cost-effective in more than 95% of simulations, whereas ILR was not cost-effective in any iteration at conventional thresholds. Threshold analyses indicated that ILR would require substantially lower surgical costs or markedly higher baseline BCRL incidence to become economically viable. Conclusions In a health system with access to structured lymphedema surveillance and early conservative management, routine ILR is unlikely to represent an efficient use of healthcare resources. These findings support prioritising structured surveillance pathways and reserving ILR for selected high-risk or preference-sensitive cases. Cost-effectiveness analysis Breast cancer-related lymphedema immediate lymphatic reconstruction structured surveillance Figures Figure 1 Figure 2 INTRODUCTION Despite advances in systemic therapy and de-escalation of axillary surgery, axillary lymph-node dissection (ALND) continues to be required in selected patients with breast cancer and remains a major source of long-term morbidity. International estimates suggest a 10–33% incidence, varying with surgical technique, nodal burden, radiation exposure, and diagnostic method [ 1 – 3 , 12 , 13 ]. Breast cancer–related lymphedema (BCRL) affects physical function, quality of life, and healthcare utilization, placing a durable burden on patients and surgical systems [ 8 – 11 , 14 – 16 ]. As surgical strategies evolve, attention has increasingly shifted from treatment of established lymphedema toward prevention at the time of cancer surgery or through structured postoperative pathways. Immediate lymphatic reconstruction (ILR), performed at the time of ALND, has gained global attention as a surgical strategy to reduce postoperative BCRL risk. Observational cohorts and recent meta-analyses report relative risk reductions of 50–80% [4–7.17,21–23], and early prospective studies suggest that ILR is feasible and safe. Several US-based economic evaluations have further proposed that ILR may be cost-saving or highly cost-effective [ 4 , 5 , 21 ]. However, these analyses were conducted in healthcare systems characterised by higher costs of chronic BCRL management, extensive reliance on therapist-directed complete decongestive therapy (CDT), and greater long-term expenditure for cellulitis and garment replacement [ 12 , 16 ]. It remains unclear whether ILR confers similar economic value in health systems where early detection and conservative management are accessible and relatively inexpensive. Singapore provides a distinct context in which to evaluate the comparative effectiveness and economic value of BCRL-prevention strategies. The national health system supports early detection through structured surveillance pathways incorporating bioimpedance spectroscopy (BIS) and indocyanine green lymphography (ICG-L), both of which can identify reversible subclinical lymphatic dysfunction [ 18 – 20 , 26 , 29 ]. Prospective surveillance programmes have been shown to substantially reduce progression to chronic BCRL and minimise downstream morbidity [ 18 , 20 , 26 ]. At the same time, Singapore’s publicly funded healthcare environment is marked by comparatively modest long-term BCRL management costs, including lower garment prices, subsidised inpatient care, and limited use of prolonged CDT [ 8 – 11 , 15 ]. These system-level characteristics reduce the potential downstream savings that ILR might provide, thereby altering the balance of benefits and costs seen in US-based models. Beyond clinical outcomes, decisions to adopt preventive surgical strategies for BCRL have important implications for health service organisation and resource allocation. Given these differences, the economic justification for ILR in Singapore remains uncertain, particularly when structured surveillance is available and widely implemented. A direct comparison of opportunistic late detection, structured BIS/ICG-L surveillance, and ILR performed during ALND is needed to inform national policy, guide resource allocation, and clarify the optimal prevention strategy within Singapore’s survivorship care framework. This study therefore developed a decision-analytic model calibrated to Singapore-specific clinical, epidemiological, and cost data to evaluate the long-term cost-effectiveness of ILR relative to structured surveillance and opportunistic detection. By incorporating updated tariffs, contemporary BCRL-management costs, and real-world surveillance patterns, this analysis aims to provide robust evidence to support clinical and policy decision-making in BCRL prevention. METHODS Study Design and Perspective A cost-effectiveness analysis was undertaken to compare three strategies for the prevention of breast cancer–related lymphoedema (BCRL) in women undergoing axillary lymph-node dissection (ALND): Immediate lymphatic reconstruction (ILR) performed during ALND; Structured surveillance using bioimpedance spectroscopy (BIS) and indocyanine green lymphography (ICG-L); Opportunistic detection based on clinical presentation of swelling. The analysis adopted a societal perspective, in accordance with Singapore Ministry of Health pharmacoeconomic guidance. All costs reflected full economic value, excluding transfer payments such as subsidies or copayments. Costs and quality-adjusted life-years (QALYs) were discounted at 3% annually, and results are reported in 2025 Singapore dollars (S$). Model Structure and Time Horizon A deterministic decision-analytic model with a 10-year time horizon was constructed to reflect the period during which most BCRL-related morbidity arises after ALND (Figure 1). A decision-tree structure was selected because BCRL development typically stabilises within the first several postoperative years, and long-term transitions between severity grades contribute minimally to incremental cost-effectiveness. Model validation using an alternative semi-Markov structure yielded <1% differences in total costs and QALYs (Supplementary Table S1), confirming adequacy of the decision-tree approach. Intervention Pathways 1. Opportunistic Detection BCRL was diagnosed only when clinical swelling became apparent. Based on local cohort data, a 10-year probability of BCRL of 0.30 was applied. Patients received: complete decongestive therapy (CDT) compression garments hospital care for cellulitis therapeutic lymphovenous anastomosis (LVA) in 50% of cases due to late-stage presentation 2. Structured Surveillance All ALND ± regional nodal irradiation patients entered a BIS/ICG-L surveillance pathway comprising: BIS every 6 months (20 tests over 10 years; S$120/test) Baseline ICG-L mapping for every patient (S$900) Repeat ICG-L only when BIS thresholds were exceeded (S$900) Early CDT for subclinical BCRL Therapeutic LVA in 25% of cases with persistent or progressive disease despite CDT Based on published diagnostic accuracy and early-intervention trials, the residual 10-year BCRL incidence was set at 0.17. 3. Immediate Lymphatic Reconstruction (ILR) ILR was modelled as an intraoperative lymphatic-venous anastomosis performed concurrently with ALND. The cost of ILR used the SE821L tariff lower-bound value of S$24,700. Residual 10-year BCRL risk was calculated by applying a relative risk of 0.28 to baseline incidence (yielding 0.084). Patients who developed BCRL post-ILR received the same downstream management as in the surveillance arm, including therapeutic LVA in 25% of cases. Clinical Parameters Key clinical inputs included: 10-year BCRL incidence: 0.30 (opportunistic), 0.17 (surveillance), 0.084 (ILR) Annual cellulitis hospitalisation: 0.03 episodes per BCRL patient Progression reduction via surveillance: derived from BIS/ICG-L accuracy and early-intervention evidence [18–20,26,29] LVA utilisation: 50% (opportunistic), 25% (surveillance), 25% (ILR) All parameters and distributions used in sensitivity analyses are detailed in Supplementary Table S2. Utility Inputs Chronic BCRL was associated with an annual utility decrement of 0.08, consistent with EQ-5D and SF-6D studies among breast cancer survivors [12,13]. Discounted 10-year utilities matched derived QALY totals: Opportunistic detection: 7.86 Structured surveillance: 7.90 ILR: 8.00 Full derivations are provided in Supplementary Tables S3–S4. Cost Inputs Resource items included procedural fees, diagnostic tests, conservative management, and long-term BCRL costs: ILR and LVA tariff: S$24,700 (SE821L) BIS: S$120/test ICG-L: S$900 (baseline); S$900 (confirmatory) CDT: S$201 × six sessions Compression garments: S$600/year (40% wean after ~2 years; 60% continue for full horizon) Cellulitis admission: S$3,500 per episode Expected 10-year discounted costs were: Opportunistic detection: S$5,150 Structured surveillance: S$5,000 ILR: S$25,650 Base-Case Analysis Incremental cost-effectiveness ratios (ICERs) were computed comparing: Structured surveillance vs opportunistic detection ILR vs structured surveillance Dominance was defined as lower cost with greater effectiveness. Cost-effectiveness was evaluated against Singapore-relevant willingness-to-pay (WTP) thresholds of S$50,000–S$75,000 per QALY. Probabilistic Sensitivity Analysis (PSA) To reflect joint parameter uncertainty, a 10,000-iteration PSA was performed using gamma, beta, log-normal, and fixed distributions derived from Supplementary Table S2. Outputs included: cost-effectiveness planes cost-effectiveness acceptability curves (CEACs) incremental net monetary benefit (INMB) profiles One-Way Sensitivity Analyses Deterministic one-way variation (typically ±20%) evaluated the influence of key epidemiologic, cost, and utility parameters. Policy-relevant parameters—including ILR tariff, baseline BCRL incidence, utility decrement, and LVA utilisation—were prioritised in the tornado analysis (Table 1). Threshold Analyses Break-even ILR tariffs required to achieve cost-effectiveness at WTP values of S$50,000–S$75,000 per QALY were estimated as: S$10,000–S$12,500 given an incremental QALY gain of 0.10 Exploratory analyses also assessed the baseline BCRL incidence required for ILR to become cost-effective. Model Validation Internal validation compared decision-tree results with a simplified semi-Markov model (<1% divergence). External validation confirmed alignment between model-predicted long-term costs and real-world billing data for CDT utilisation, garment replacement, and cellulitis admissions at Changi General Hospital. RESULTS Base-Case Findings Structured surveillance demonstrated the most favourable economic and clinical performance among the three evaluated strategies. It was more effective and less costly than opportunistic detection, thereby dominating it. Over a 10-year discounted horizon: Opportunistic detection: S$5,150; 7.86 QALYs Structured surveillance: S$5,000; 7.90 QALYs The incremental gain of 0.04 QALYs reflected earlier detection of reversible disease and reduced progression to persistent BCRL. Cost savings primarily arose from lower use of CDT, reduced garment replacement, and fewer therapeutic LVA procedures (25% vs 50%). Immediate lymphatic reconstruction (ILR) was substantially more expensive. Its total 10-year discounted cost was S$25,650, with QALYs of 8.00. Compared with structured surveillance, ILR increased costs by S$20,650 and improved effectiveness by 0.10 QALYs, producing an ICER of S$206,500/QALY—far above Singapore’s willingness-to-pay (WTP) thresholds of S$50,000–S$75,000/QALY. These results are summarised in Table 2. Dominance and Incremental Comparison Because opportunistic detection was strictly dominated, only ILR and structured surveillance were included in incremental comparison. Across all base-case and scenario inputs, the ICER for ILR remained above S$200,000/QALY. Variations in assumed BCRL incidence or utility decrement shifted incremental QALYs only marginally, and these changes were insufficient to overcome the cost impact of the S$24,700 ILR tariff, which remained the predominant cost driver. Drivers of Costs and QALYs Cost differences across strategies were driven mainly by variation in long-term BCRL burden: Opportunistic detection incurred higher CDT usage, garment costs, and cellulitis-related care. Because late-stage BCRL was more common, 50% of opportunistic-diagnosed patients required therapeutic LVA. Structured surveillance reduced these downstream costs via earlier detection and lower progression rates, with only 25% of BCRL cases receiving LVA. The QALY differences were modest because surveillance already prevented most progression to irreversible, high-morbidity stages, leaving ILR limited incremental opportunity to improve health outcomes. Threshold Analyses At WTP thresholds of S$50,000 and S$75,000/QALY, ILR would need to limit incremental cost to: ≤ S$5,000 (WTP = S$50,000/QALY) ≤ S$7,500 (WTP = S$75,000/QALY) Given the incremental QALY gain of 0.10, this corresponds to a required ILR tariff of S$10,000–S$12,500—less than half the current S$24,700 benchmark. Exploratory incidence thresholds showed that ILR becomes cost-effective only when the 10-year BCRL incidence exceeds 50–70%, far beyond contemporary clinical rates in Singapore or internationally. One-Way Sensitivity Analyses Deterministic one-way sensitivity analyses showed consistent results: Structured surveillance remained cost-saving compared with opportunistic detection across all parameter ranges. ILR’s ICER was most sensitive to: ILR tariff baseline BCRL incidence utility decrement for chronic BCRL Even under optimistic assumptions, ILR never approached the S$75,000/QALY threshold. Variation in downstream LVA utilisation in the surveillance arm (20–30%) shifted the ILR ICER by <S$10,000/QALY and did not alter conclusions. These trends correspond to the tornado plots (Supplementary Figure S1a–b). Probabilistic Sensitivity Analysis (PSA) Across 10,000 PSA iterations: Structured surveillance was cost-effective in: >95% of simulations at S$50,000/QALY >98% at S$75,000/QALY ILR was not cost-effective in any simulation, consistently occupying the northeast quadrant above both WTP thresholds. The cost-effectiveness acceptability curve (Supplementary Figure S2a) confirmed that ILR never exceeded a 20% probability of being optimal across WTP values up to S$200,000/QALY. Incremental Net Monetary Benefit (INMB) INMB analyses supported the base-case conclusions: Surveillance had positive INMB across all WTP thresholds relative to opportunistic detection. ILR had strongly negative INMB at all WTP values commonly used in Singapore. The ILR vs surveillance INMB curve crossed zero only at S$170,000–S$200,000/QALY, well beyond acceptable ranges. These findings mirror the cost-effectiveness plane (Figure 2) and INMB profiles (Supplementary Figure S3). DISCUSSION In this evaluation of three strategies for preventing breast cancer–related lymphoedema (BCRL) following axillary lymph-node dissection (ALND), structured surveillance using bioimpedance spectroscopy (BIS) and indocyanine green lymphography (ICG-L) emerged as the most favourable approach. Surveillance yielded better health outcomes and lower costs compared with opportunistic detection, reflecting the benefits of identifying subclinical lymphatic dysfunction and initiating early conservative management. In contrast, immediate lymphatic reconstruction (ILR), although clinically promising, offered only modest additional health benefit and remained far more expensive than either detection strategy [ 24 ]. The resulting ICER for ILR exceeded S $ 200,000 per QALY, well above Singapore’s commonly applied willingness-to-pay (WTP) thresholds. These findings illustrate the substantial influence of healthcare system context on the economic value of ILR. US-based studies have reported ILR to be cost-saving or cost-effective [ 4 , 5 , 21 ], but these conclusions arise in settings with high downstream costs of chronic BCRL management, including prolonged therapist-directed complete decongestive therapy (CDT), higher garment expenses, and increased long-term utilisation of outpatient and inpatient services [ 12 , 16 ]. In Singapore, long-term BCRL management costs are comparatively modest due to subsidised inpatient care, lower garment prices, and selective use of CDT. Furthermore, structured surveillance substantially reduces progression to irreversible stage II–III disease [ 18 , 20 , 26 ], diminishing the incremental benefit of ILR in averting chronic morbidity. When early detection is routinely available and relatively inexpensive, ILR has fewer cost offsets to leverage, and its surgical tariff becomes the dominant economic determinant [ 27 ]. The threshold analyses reinforce this conclusion. For ILR to meet Singapore’s WTP thresholds, its incremental cost must fall below S $ 5,000–S $ 7,500, corresponding to a surgical tariff of approximately S $ 10,000–S $ 12,500—less than half the current SE821L benchmark. Alternatively, ILR would become cost-effective only if the 10-year BCRL incidence after ALND exceeded 50–70%, far beyond contemporary estimates in Singapore and internationally [ 1 , 2 , 4 , 12 , 13 ]. Such incidence levels would imply an unusually high-risk clinical environment and are not representative of real-world practice, particularly when surveillance programmes are in place. These results do not negate the clinical rationale for ILR but highlight its selective role within Singapore’s care pathways. Randomized evidence suggests that lymphaticovenous anastomosis can improve short-term quality-of-life outcomes in selected patients with established breast cancer–related lymphedema, although long-term durability and economic value remain uncertain [ 25 ]. Because surveillance already prevents most progression to chronic, high-morbidity BCRL, the additional benefit conferred by ILR is inherently limited at the population level. ILR may still be appropriate for carefully selected high-risk patients, such as those undergoing ALND with extensive nodal disease, planned regional nodal irradiation, or multiple risk factors for lymphatic injury. Better stratification tools—potentially incorporating lymphatic imaging, perioperative biomarkers, or machine-learning risk models—may help identify subgroups in whom ILR provides greater clinical and economic value. These findings highlight the importance of evaluating surgical innovation within the context of existing surveillance and conservative management pathways when allocating limited healthcare resources. The broader implications for health policy are clear. Prioritising structured surveillance offers the greatest health gain for the lowest cost and aligns well with survivorship care models emphasising early detection, conservative management, and patient-centred outcomes. Investment in expanding surveillance access, refining BIS/ICG-L workflows, and subsidising compression garments may yield greater population-level benefit than universal adoption of ILR. As more long-term data from prospective ILR cohorts and randomised trials become available [ 28 ], further refinement of clinical pathways will be important. However, under current conditions, ILR does not meet established efficiency thresholds within Singapore’s public healthcare system. From a surgical oncology perspective, the choice between immediate lymphatic reconstruction and structured surveillance reflects a broader tension between operative prevention and postoperative risk mitigation. While ILR represents a technically appealing intraoperative solution, structured surveillance leverages early detection and staged intervention without extending operative complexity at the index cancer procedure. Our findings suggest that, within contemporary breast surgical practice, value-based outcomes may be optimised by reserving immediate operative lymphatic reconstruction for highly selected patients while prioritising standardised postoperative surveillance pathways. LIMITATIONS This analysis has several limitations that should be considered when interpreting the findings. First, although the model incorporated the best available local and international data, several clinical parameters—particularly the long-term durability of immediate lymphatic reconstruction (ILR)—remain incompletely defined. Published ILR outcomes are encouraging but based primarily on observational cohorts with limited long-term follow-up [ 4 – 7 , 21 , 22 ]. The effectiveness of ILR in preventing late-onset or radiation-associated lymphoedema therefore warrants further study. Second, real-world adherence to surveillance protocols, conservative therapy, and compression garments varies across patients and institutions. The model used estimates derived from Singapore practice patterns and prospective surveillance studies [ 1 , 15 , 16 , 18 , 20 , 26 ], but individual deviations may affect disease trajectory and long-term resource use. Third, cost inputs reflect Singapore’s healthcare-financing environment, characterised by subsidised inpatient care, relatively low garment prices, and selective CDT utilisation. These structural features reduce the downstream economic burden of chronic lymphoedema compared with higher-cost health systems and limit the generalisability of the findings to other countries. Fourth, although a 10-year time horizon captures the period during which most BCRL-related morbidity emerges, it does not fully account for lifelong consequences in the minority of patients who develop persistent or progressive disease despite early detection. Finally, several necessary structural simplifications may bias results in conservative ways. In particular: Chronic BCRL costs were applied uniformly across strategies, because stage-specific long-term cost data (including recurrent CDT utilisation and LVA failure rates) are poorly reported. Late-stage BCRL typically incurs higher lifelong costs, which are more common under opportunistic detection. Not modelling these stage-dependent trajectories likely underestimates the true burden of opportunistic detection and therefore understates the economic advantage of structured surveillance. Similarly, although this simplification also applies to ILR, the ILR ICER remained > S $ 200,000/QALY across all sensitivity analyses and was not materially affected by optimistic parameter shifts. Despite these limitations, extensive sensitivity, threshold, and probabilistic analyses demonstrated that the primary conclusions are robust: structured surveillance remains cost-saving and more effective than opportunistic detection, and ILR does not approach accepted willingness-to-pay thresholds under current tariffs and clinical conditions in Singapore. CONCLUSIONS Structured surveillance using bioimpedance spectroscopy and indocyanine green lymphography provides the most clinically effective and economically efficient strategy for preventing breast cancer–related lymphoedema after axillary lymph-node dissection in Singapore. Compared with opportunistic detection, surveillance improves quality-adjusted life-years and reduces downstream BCRL-related costs by enabling earlier identification and intervention. Immediate lymphatic reconstruction, while clinically promising, offers only modest incremental benefit when effective surveillance systems are in place and remains substantially more costly under current surgical tariffs and local disease incidence. These findings support prioritising structured surveillance as the standard of care and reserving ILR for selected high-risk or preference-sensitive cases. As longer-term outcome data and refined risk-stratification tools become available, the role of ILR may be further clarified; however, under present conditions, it does not meet accepted cost-effectiveness thresholds within Singapore’s public healthcare system. Declarations Disclaimers and Disclosure of Conflicts of Interest: None. Prior Presentations: None. Funding: None. Ethics approval and consent to participate: Not applicable. This study was a decision-analytic economic evaluation using secondary data from published sources and publicly available cost information and did not involve human participants. Clinical trial number: Not applicable Author Contribution JM Sun was involved in the data collection, data analysis and manuscript writing. All figures and tables were created by JM Sun Data Availability The data supporting the findings of this study are included in the article and its supplementary materials. 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Use of a prospective surveillance model to prevent breast cancer treatment-related lymphedema: a randomized controlled trial. Breast Cancer Res Treat. 2016;160(2):279-286. Rochlin DH, Coriddi MR, Nelson JA, Dayan JH, Mehrara BJ. Immediate Lymphatic Reconstruction and the Current Value Problem. Ann Surg. 2023 Jun 1;277(6):e1197-e1199 Coriddi M, Dayan J, Bloomfield E, McGrath L, Diwan R, Monge J, Gutierrez J, Brown S, Boe L, Mehrara B. Efficacy of Immediate Lymphatic Reconstruction to Decrease Incidence of Breast Cancer-related Lymphedema: Preliminary Results of Randomized Controlled Trial. Ann Surg. 2023 Oct 1;278(4):630-637. Ridner SH, Dietrich MS, Cowher MS, et al. A randomized trial evaluating bioimpedance spectroscopy versus tape measurement for the prevention of lymphedema following treatment for breast cancer: interim analysis. Ann Surg Oncol. 2019;26(10):3250-3259. Tables Tables 1 and 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.docx table2.docx supplementarymaterialfigures1.3.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 04 Mar, 2026 Reviewers agreed at journal 24 Feb, 2026 Reviewers invited by journal 24 Feb, 2026 Editor invited by journal 04 Feb, 2026 Editor assigned by journal 02 Feb, 2026 Submission checks completed at journal 02 Feb, 2026 First submitted to journal 28 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8722507","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":596332527,"identity":"c2074da8-682a-4000-b93f-31636b000abb","order_by":0,"name":"Jeremy Mingfa Sun","email":"data:image/png;base64,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","orcid":"","institution":"Changi General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Jeremy","middleName":"Mingfa","lastName":"Sun","suffix":""}],"badges":[],"createdAt":"2026-01-28 15:09:54","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8722507/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8722507/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103724363,"identity":"9e4811f9-f331-49c7-a753-19241f06b9ad","added_by":"auto","created_at":"2026-03-02 07:57:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":51517,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDecision-analytic model comparing prevention strategies for breast cancer–related lymphoedema (BCRL) after axillary lymph-node dissection (ALND). \u003c/strong\u003eThis model evaluates three pathways following ALND: \u003cstrong\u003e(i)\u003c/strong\u003e immediate lymphatic reconstruction (ILR), performed intraoperatively; \u003cstrong\u003e(ii)\u003c/strong\u003e structured surveillance incorporating 6-monthly bioimpedance spectroscopy (BIS), baseline indocyanine green lymphography (ICG-L), BIS-triggered repeat ICG-L, early complete decongestive therapy (CDT), and delayed lymphovenous anastomosis (LVA) for refractory cases; and \u003cstrong\u003e(iii)\u003c/strong\u003e opportunistic detection based on clinical swelling. Probabilities, utilities, and costs were applied to downstream branches (not shown). Abbreviations: ALND, axillary lymph-node dissection; BCRL, breast cancer–related lymphoedema\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8722507/v1/19ed0b0c3a342bd4ae132fd3.png"},{"id":103724397,"identity":"612cc18b-0d76-437b-9cb7-dbc3c4fd2bef","added_by":"auto","created_at":"2026-03-02 07:57:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":49436,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCost-effectiveness plane from probabilistic sensitivity analysis (10,000 iterations). \u003c/strong\u003eEach point represents a representative sample from a 1,000-iteration PSA, drawn from an underlying 10,000-iteration simulation. Green points: structured surveillance vs opportunistic detection. Red points: ILR vs structured surveillance. Structured surveillance lies predominantly in the southeast quadrant, indicating it is less costly and more effective than opportunistic detection.\u003cbr\u003e\nILR occupies the northeast quadrant, reflecting higher cost (10-year cost S$25,650) and modest incremental effectiveness (+0.10 QALYs) relative to surveillance. Diagonal lines denote Singapore willingness-to-pay (WTP) thresholds of S$50,000 and S$75,000 per QALY. ILR lies above both in all simulations, indicating a near-zero probability of cost-effectiveness. Abbreviations: ILR, immediate lymphatic reconstruction; QALY, quality-adjusted life-year; PSA, probabilistic sensitivity analysis; WTP, willingness to pay.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8722507/v1/dcc13360a0530148756e2d2c.png"},{"id":104399914,"identity":"c4a26247-e9d2-425d-b060-d70338cc5d6f","added_by":"auto","created_at":"2026-03-11 12:08:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":862551,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8722507/v1/8962232b-1197-4ec7-8f58-a3af534ad0b8.pdf"},{"id":103724392,"identity":"f1f07654-ec56-4c42-aab7-520ed53339b8","added_by":"auto","created_at":"2026-03-02 07:57:08","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":17842,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8722507/v1/8199293e70e0e7ace163b56f.docx"},{"id":103724389,"identity":"12fb54d7-4ede-4b09-bb73-69c1c32fd077","added_by":"auto","created_at":"2026-03-02 07:57:07","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":17222,"visible":true,"origin":"","legend":"","description":"","filename":"table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-8722507/v1/aa3fdabcf78bad449e14f9c2.docx"},{"id":103724387,"identity":"59488727-bf76-47fc-be60-807f1211b82c","added_by":"auto","created_at":"2026-03-02 07:57:06","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":156820,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarymaterialfigures1.3.docx","url":"https://assets-eu.researchsquare.com/files/rs-8722507/v1/b6c39c8f8429db4329fd7665.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cost-Effectiveness of Immediate Lymphatic Reconstruction Versus Structured Surveillance for Preventing Breast Cancer–Related Lymphedema After Axillary Surgery","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eDespite advances in systemic therapy and de-escalation of axillary surgery, axillary lymph-node dissection (ALND) continues to be required in selected patients with breast cancer and remains a major source of long-term morbidity. International estimates suggest a 10\u0026ndash;33% incidence, varying with surgical technique, nodal burden, radiation exposure, and diagnostic method [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Breast cancer\u0026ndash;related lymphedema (BCRL) affects physical function, quality of life, and healthcare utilization, placing a durable burden on patients and surgical systems [\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. As surgical strategies evolve, attention has increasingly shifted from treatment of established lymphedema toward prevention at the time of cancer surgery or through structured postoperative pathways.\u003c/p\u003e \u003cp\u003eImmediate lymphatic reconstruction (ILR), performed at the time of ALND, has gained global attention as a surgical strategy to reduce postoperative BCRL risk. Observational cohorts and recent meta-analyses report relative risk reductions of 50\u0026ndash;80% [4\u0026ndash;7.17,21\u0026ndash;23], and early prospective studies suggest that ILR is feasible and safe. Several US-based economic evaluations have further proposed that ILR may be cost-saving or highly cost-effective [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, these analyses were conducted in healthcare systems characterised by higher costs of chronic BCRL management, extensive reliance on therapist-directed complete decongestive therapy (CDT), and greater long-term expenditure for cellulitis and garment replacement [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. It remains unclear whether ILR confers similar economic value in health systems where early detection and conservative management are accessible and relatively inexpensive.\u003c/p\u003e \u003cp\u003eSingapore provides a distinct context in which to evaluate the comparative effectiveness and economic value of BCRL-prevention strategies. The national health system supports early detection through structured surveillance pathways incorporating bioimpedance spectroscopy (BIS) and indocyanine green lymphography (ICG-L), both of which can identify reversible subclinical lymphatic dysfunction [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Prospective surveillance programmes have been shown to substantially reduce progression to chronic BCRL and minimise downstream morbidity [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. At the same time, Singapore\u0026rsquo;s publicly funded healthcare environment is marked by comparatively modest long-term BCRL management costs, including lower garment prices, subsidised inpatient care, and limited use of prolonged CDT [\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. These system-level characteristics reduce the potential downstream savings that ILR might provide, thereby altering the balance of benefits and costs seen in US-based models. Beyond clinical outcomes, decisions to adopt preventive surgical strategies for BCRL have important implications for health service organisation and resource allocation.\u003c/p\u003e \u003cp\u003eGiven these differences, the economic justification for ILR in Singapore remains uncertain, particularly when structured surveillance is available and widely implemented. A direct comparison of opportunistic late detection, structured BIS/ICG-L surveillance, and ILR performed during ALND is needed to inform national policy, guide resource allocation, and clarify the optimal prevention strategy within Singapore\u0026rsquo;s survivorship care framework.\u003c/p\u003e \u003cp\u003eThis study therefore developed a decision-analytic model calibrated to Singapore-specific clinical, epidemiological, and cost data to evaluate the long-term cost-effectiveness of ILR relative to structured surveillance and opportunistic detection. By incorporating updated tariffs, contemporary BCRL-management costs, and real-world surveillance patterns, this analysis aims to provide robust evidence to support clinical and policy decision-making in BCRL prevention.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cstrong\u003eStudy Design and Perspective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA cost-effectiveness analysis was undertaken to compare three strategies for the prevention of breast cancer\u0026ndash;related lymphoedema (BCRL) in women undergoing axillary lymph-node dissection (ALND):\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eImmediate lymphatic reconstruction (ILR) performed during ALND;\u003c/li\u003e\n \u003cli\u003eStructured surveillance using bioimpedance spectroscopy (BIS) and indocyanine green lymphography (ICG-L);\u003c/li\u003e\n \u003cli\u003eOpportunistic detection based on clinical presentation of swelling.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThe analysis adopted a societal perspective, in accordance with Singapore Ministry of Health pharmacoeconomic guidance. All costs reflected full economic value, excluding transfer payments such as subsidies or copayments. Costs and quality-adjusted life-years (QALYs) were discounted at 3% annually, and results are reported in 2025 Singapore dollars (S$).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eModel Structure and Time Horizon\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA deterministic decision-analytic model with a 10-year time horizon was constructed to reflect the period during which most BCRL-related morbidity arises after ALND (Figure 1). A decision-tree structure was selected because BCRL development typically stabilises within the first several postoperative years, and long-term transitions between severity grades contribute minimally to incremental cost-effectiveness.\u003c/p\u003e\n\u003cp\u003eModel validation using an alternative semi-Markov structure yielded \u0026lt;1% differences in total costs and QALYs (Supplementary Table S1), confirming adequacy of the decision-tree approach.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention Pathways\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1. Opportunistic Detection\u003c/p\u003e\n\u003cp\u003eBCRL was diagnosed only when clinical swelling became apparent. Based on local cohort data, a 10-year probability of BCRL of 0.30 was applied. Patients received:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003ecomplete decongestive therapy (CDT)\u003c/li\u003e\n \u003cli\u003ecompression garments\u003c/li\u003e\n \u003cli\u003ehospital care for cellulitis\u003c/li\u003e\n \u003cli\u003etherapeutic lymphovenous anastomosis (LVA) in 50% of cases due to late-stage presentation\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e2. Structured Surveillance\u003c/p\u003e\n\u003cp\u003eAll ALND \u0026plusmn; regional nodal irradiation patients entered a BIS/ICG-L surveillance pathway comprising:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eBIS every 6 months (20 tests over 10 years; S$120/test)\u003c/li\u003e\n \u003cli\u003eBaseline ICG-L mapping for every patient (S$900)\u003c/li\u003e\n \u003cli\u003eRepeat ICG-L only when BIS thresholds were exceeded (S$900)\u003c/li\u003e\n \u003cli\u003eEarly CDT for subclinical BCRL\u003c/li\u003e\n \u003cli\u003eTherapeutic LVA in 25% of cases with persistent or progressive disease despite CDT\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eBased on published diagnostic accuracy and early-intervention trials, the residual 10-year BCRL incidence was set at 0.17.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.\u0026nbsp;\u003c/strong\u003eImmediate Lymphatic Reconstruction (ILR)\u003c/p\u003e\n\u003cp\u003eILR was modelled as an intraoperative lymphatic-venous anastomosis performed concurrently with ALND. The cost of ILR used the SE821L tariff lower-bound value of S$24,700. Residual 10-year BCRL risk was calculated by applying a relative risk of 0.28 to baseline incidence (yielding 0.084).\u003cbr\u003e\u0026nbsp;Patients who developed BCRL post-ILR received the same downstream management as in the surveillance arm, including therapeutic LVA in 25% of cases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Parameters\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKey clinical inputs included:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e10-year BCRL incidence: 0.30 (opportunistic), 0.17 (surveillance), 0.084 (ILR)\u003c/li\u003e\n \u003cli\u003eAnnual cellulitis hospitalisation: 0.03 episodes per BCRL patient\u003c/li\u003e\n \u003cli\u003eProgression reduction via surveillance: derived from BIS/ICG-L accuracy and early-intervention evidence [18\u0026ndash;20,26,29]\u003c/li\u003e\n \u003cli\u003eLVA utilisation: 50% (opportunistic), 25% (surveillance), 25% (ILR)\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eAll parameters and distributions used in sensitivity analyses are detailed in Supplementary Table S2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUtility Inputs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChronic BCRL was associated with an annual utility decrement of 0.08, consistent with EQ-5D and SF-6D studies among breast cancer survivors [12,13]. Discounted 10-year utilities matched derived QALY totals:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eOpportunistic detection: 7.86\u003c/li\u003e\n \u003cli\u003eStructured surveillance: 7.90\u003c/li\u003e\n \u003cli\u003eILR: 8.00\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eFull derivations are provided in Supplementary Tables S3\u0026ndash;S4.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCost Inputs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResource items included procedural fees, diagnostic tests, conservative management, and long-term BCRL costs:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eILR and LVA tariff: S$24,700 (SE821L)\u003c/li\u003e\n \u003cli\u003eBIS: S$120/test\u003c/li\u003e\n \u003cli\u003eICG-L: S$900 (baseline); S$900 (confirmatory)\u003c/li\u003e\n \u003cli\u003eCDT: S$201 \u0026times; six sessions\u003c/li\u003e\n \u003cli\u003eCompression garments: S$600/year (40% wean after ~2 years; 60% continue for full horizon)\u003c/li\u003e\n \u003cli\u003eCellulitis admission: S$3,500 per episode\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eExpected 10-year discounted costs were:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eOpportunistic detection: S$5,150\u003c/li\u003e\n \u003cli\u003eStructured surveillance: S$5,000\u003c/li\u003e\n \u003cli\u003eILR: S$25,650\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eBase-Case Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIncremental cost-effectiveness ratios (ICERs) were computed comparing:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eStructured surveillance vs opportunistic detection\u003c/li\u003e\n \u003cli\u003eILR vs structured surveillance\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eDominance was defined as lower cost with greater effectiveness.\u003cbr\u003e\u0026nbsp;Cost-effectiveness was evaluated against Singapore-relevant willingness-to-pay (WTP) thresholds of S$50,000\u0026ndash;S$75,000 per QALY.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProbabilistic Sensitivity Analysis (PSA)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo reflect joint parameter uncertainty, a 10,000-iteration PSA was performed using gamma, beta, log-normal, and fixed distributions derived from Supplementary Table S2. Outputs included:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003ecost-effectiveness planes\u003c/li\u003e\n \u003cli\u003ecost-effectiveness acceptability curves (CEACs)\u003c/li\u003e\n \u003cli\u003eincremental net monetary benefit (INMB) profiles\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eOne-Way Sensitivity Analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDeterministic one-way variation (typically \u0026plusmn;20%) evaluated the influence of key epidemiologic, cost, and utility parameters.\u003cbr\u003e\u0026nbsp;Policy-relevant parameters\u0026mdash;including ILR tariff, baseline BCRL incidence, utility decrement, and LVA utilisation\u0026mdash;were prioritised in the tornado analysis (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThreshold Analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBreak-even ILR tariffs required to achieve cost-effectiveness at WTP values of S$50,000\u0026ndash;S$75,000 per QALY were estimated as:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eS$10,000\u0026ndash;S$12,500 given an incremental QALY gain of 0.10\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eExploratory analyses also assessed the baseline BCRL incidence required for ILR to become cost-effective.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eModel Validation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInternal validation compared decision-tree results with a simplified semi-Markov model (\u0026lt;1% divergence).\u003cbr\u003e\u0026nbsp;External validation confirmed alignment between model-predicted long-term costs and real-world billing data for CDT utilisation, garment replacement, and cellulitis admissions at Changi General Hospital.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003eBase-Case Findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStructured surveillance demonstrated the most favourable economic and clinical performance among the three evaluated strategies. It was more effective and less costly than opportunistic detection, thereby dominating it. Over a 10-year discounted horizon:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eOpportunistic detection: S$5,150; 7.86 QALYs\u003c/li\u003e\n \u003cli\u003eStructured surveillance: S$5,000; 7.90 QALYs\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe incremental gain of 0.04 QALYs reflected earlier detection of reversible disease and reduced progression to persistent BCRL. Cost savings primarily arose from lower use of CDT, reduced garment replacement, and fewer therapeutic LVA procedures (25% vs 50%).\u003c/p\u003e\n\u003cp\u003eImmediate lymphatic reconstruction (ILR) was substantially more expensive. Its total 10-year discounted cost was S$25,650, with QALYs of 8.00. Compared with structured surveillance, ILR increased costs by S$20,650 and improved effectiveness by 0.10 QALYs, producing an ICER of S$206,500/QALY—far above Singapore’s willingness-to-pay (WTP) thresholds of S$50,000–S$75,000/QALY. These results are summarised in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDominance and Incremental Comparison\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBecause opportunistic detection was strictly dominated, only ILR and structured surveillance were included in incremental comparison.\u003cbr\u003e\u0026nbsp;Across all base-case and scenario inputs, the ICER for ILR remained above S$200,000/QALY.\u003cbr\u003e\u0026nbsp;Variations in assumed BCRL incidence or utility decrement shifted incremental QALYs only marginally, and these changes were insufficient to overcome the cost impact of the S$24,700 ILR tariff, which remained the predominant cost driver.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDrivers of Costs and QALYs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCost differences across strategies were driven mainly by variation in long-term BCRL burden:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eOpportunistic detection incurred higher CDT usage, garment costs, and cellulitis-related care.\u003c/li\u003e\n \u003cli\u003eBecause late-stage BCRL was more common, \u003cstrong\u003e50%\u003c/strong\u003e of opportunistic-diagnosed patients required therapeutic LVA.\u003c/li\u003e\n \u003cli\u003eStructured surveillance reduced these downstream costs via earlier detection and lower progression rates, with only \u003cstrong\u003e25%\u003c/strong\u003e of BCRL cases receiving LVA.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe QALY differences were modest because surveillance already prevented most progression to irreversible, high-morbidity stages, leaving ILR limited incremental opportunity to improve health outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThreshold Analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt WTP thresholds of S$50,000 and S$75,000/QALY, ILR would need to limit incremental cost to:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e≤ S$5,000 (WTP = S$50,000/QALY)\u003c/li\u003e\n \u003cli\u003e≤ S$7,500 (WTP = S$75,000/QALY)\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eGiven the incremental QALY gain of 0.10, this corresponds to a required ILR tariff of S$10,000–S$12,500—less than half the current S$24,700 benchmark.\u003c/p\u003e\n\u003cp\u003eExploratory incidence thresholds showed that ILR becomes cost-effective only when the 10-year BCRL incidence exceeds 50–70%, far beyond contemporary clinical rates in Singapore or internationally.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOne-Way Sensitivity Analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDeterministic one-way sensitivity analyses showed consistent results:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eStructured surveillance remained cost-saving compared with opportunistic detection across all parameter ranges.\u003c/li\u003e\n \u003cli\u003eILR’s ICER was most sensitive to:\u003cul type=\"circle\"\u003e\n \u003cli\u003eILR tariff\u003c/li\u003e\n \u003cli\u003ebaseline BCRL incidence\u003c/li\u003e\n \u003cli\u003eutility decrement for chronic BCRL\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eEven under optimistic assumptions, ILR never approached the S$75,000/QALY threshold.\u003c/li\u003e\n \u003cli\u003eVariation in downstream LVA utilisation in the surveillance arm (20–30%) shifted the ILR ICER by \u0026lt;S$10,000/QALY and did not alter conclusions.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThese trends correspond to the tornado plots (Supplementary Figure S1a–b).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProbabilistic Sensitivity Analysis (PSA)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAcross 10,000 PSA iterations:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eStructured surveillance was cost-effective in:\u003cul type=\"circle\"\u003e\n \u003cli\u003e\u0026gt;95% of simulations at S$50,000/QALY\u003c/li\u003e\n \u003cli\u003e\u0026gt;98% at S$75,000/QALY\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eILR was not cost-effective in any simulation, consistently occupying the northeast quadrant above both WTP thresholds.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe cost-effectiveness acceptability curve (Supplementary Figure S2a) confirmed that ILR never exceeded a 20% probability of being optimal across WTP values up to S$200,000/QALY.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIncremental Net Monetary Benefit (INMB)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eINMB analyses supported the base-case conclusions:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eSurveillance had positive INMB across all WTP thresholds relative to opportunistic detection.\u003c/li\u003e\n \u003cli\u003eILR had strongly negative INMB at all WTP values commonly used in Singapore.\u003c/li\u003e\n \u003cli\u003eThe ILR vs surveillance INMB curve crossed zero only at S$170,000–S$200,000/QALY, well beyond acceptable ranges.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThese findings mirror the cost-effectiveness plane (Figure 2) and INMB profiles (Supplementary Figure S3).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this evaluation of three strategies for preventing breast cancer\u0026ndash;related lymphoedema (BCRL) following axillary lymph-node dissection (ALND), structured surveillance using bioimpedance spectroscopy (BIS) and indocyanine green lymphography (ICG-L) emerged as the most favourable approach. Surveillance yielded better health outcomes and lower costs compared with opportunistic detection, reflecting the benefits of identifying subclinical lymphatic dysfunction and initiating early conservative management. In contrast, immediate lymphatic reconstruction (ILR), although clinically promising, offered only modest additional health benefit and remained far more expensive than either detection strategy [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The resulting ICER for ILR exceeded S\u003cspan\u003e$\u003c/span\u003e200,000 per QALY, well above Singapore\u0026rsquo;s commonly applied willingness-to-pay (WTP) thresholds.\u003c/p\u003e \u003cp\u003eThese findings illustrate the substantial influence of healthcare system context on the economic value of ILR. US-based studies have reported ILR to be cost-saving or cost-effective [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], but these conclusions arise in settings with high downstream costs of chronic BCRL management, including prolonged therapist-directed complete decongestive therapy (CDT), higher garment expenses, and increased long-term utilisation of outpatient and inpatient services [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In Singapore, long-term BCRL management costs are comparatively modest due to subsidised inpatient care, lower garment prices, and selective use of CDT. Furthermore, structured surveillance substantially reduces progression to irreversible stage II\u0026ndash;III disease [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], diminishing the incremental benefit of ILR in averting chronic morbidity. When early detection is routinely available and relatively inexpensive, ILR has fewer cost offsets to leverage, and its surgical tariff becomes the dominant economic determinant [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe threshold analyses reinforce this conclusion. For ILR to meet Singapore\u0026rsquo;s WTP thresholds, its incremental cost must fall below S\u003cspan\u003e$\u003c/span\u003e5,000\u0026ndash;S\u003cspan\u003e$\u003c/span\u003e7,500, corresponding to a surgical tariff of approximately S\u003cspan\u003e$\u003c/span\u003e10,000\u0026ndash;S\u003cspan\u003e$\u003c/span\u003e12,500\u0026mdash;less than half the current SE821L benchmark. Alternatively, ILR would become cost-effective only if the 10-year BCRL incidence after ALND exceeded 50\u0026ndash;70%, far beyond contemporary estimates in Singapore and internationally [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Such incidence levels would imply an unusually high-risk clinical environment and are not representative of real-world practice, particularly when surveillance programmes are in place.\u003c/p\u003e \u003cp\u003eThese results do not negate the clinical rationale for ILR but highlight its selective role within Singapore\u0026rsquo;s care pathways. Randomized evidence suggests that lymphaticovenous anastomosis can improve short-term quality-of-life outcomes in selected patients with established breast cancer\u0026ndash;related lymphedema, although long-term durability and economic value remain uncertain [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Because surveillance already prevents most progression to chronic, high-morbidity BCRL, the additional benefit conferred by ILR is inherently limited at the population level. ILR may still be appropriate for carefully selected high-risk patients, such as those undergoing ALND with extensive nodal disease, planned regional nodal irradiation, or multiple risk factors for lymphatic injury. Better stratification tools\u0026mdash;potentially incorporating lymphatic imaging, perioperative biomarkers, or machine-learning risk models\u0026mdash;may help identify subgroups in whom ILR provides greater clinical and economic value.\u003c/p\u003e \u003cp\u003eThese findings highlight the importance of evaluating surgical innovation within the context of existing surveillance and conservative management pathways when allocating limited healthcare resources. The broader implications for health policy are clear. Prioritising structured surveillance offers the greatest health gain for the lowest cost and aligns well with survivorship care models emphasising early detection, conservative management, and patient-centred outcomes. Investment in expanding surveillance access, refining BIS/ICG-L workflows, and subsidising compression garments may yield greater population-level benefit than universal adoption of ILR. As more long-term data from prospective ILR cohorts and randomised trials become available [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], further refinement of clinical pathways will be important. However, under current conditions, ILR does not meet established efficiency thresholds within Singapore\u0026rsquo;s public healthcare system.\u003c/p\u003e \u003cp\u003eFrom a surgical oncology perspective, the choice between immediate lymphatic reconstruction and structured surveillance reflects a broader tension between operative prevention and postoperative risk mitigation. While ILR represents a technically appealing intraoperative solution, structured surveillance leverages early detection and staged intervention without extending operative complexity at the index cancer procedure. Our findings suggest that, within contemporary breast surgical practice, value-based outcomes may be optimised by reserving immediate operative lymphatic reconstruction for highly selected patients while prioritising standardised postoperative surveillance pathways.\u003c/p\u003e \u003cdiv id=\"Sec26\" class=\"Section2\"\u003e \u003ch2\u003eLIMITATIONS\u003c/h2\u003e \u003cp\u003eThis analysis has several limitations that should be considered when interpreting the findings. First, although the model incorporated the best available local and international data, several clinical parameters\u0026mdash;particularly the long-term durability of immediate lymphatic reconstruction (ILR)\u0026mdash;remain incompletely defined. Published ILR outcomes are encouraging but based primarily on observational cohorts with limited long-term follow-up [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The effectiveness of ILR in preventing late-onset or radiation-associated lymphoedema therefore warrants further study.\u003c/p\u003e \u003cp\u003eSecond, real-world adherence to surveillance protocols, conservative therapy, and compression garments varies across patients and institutions. The model used estimates derived from Singapore practice patterns and prospective surveillance studies [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], but individual deviations may affect disease trajectory and long-term resource use.\u003c/p\u003e \u003cp\u003eThird, cost inputs reflect Singapore\u0026rsquo;s healthcare-financing environment, characterised by subsidised inpatient care, relatively low garment prices, and selective CDT utilisation. These structural features reduce the downstream economic burden of chronic lymphoedema compared with higher-cost health systems and limit the generalisability of the findings to other countries.\u003c/p\u003e \u003cp\u003eFourth, although a 10-year time horizon captures the period during which most BCRL-related morbidity emerges, it does not fully account for lifelong consequences in the minority of patients who develop persistent or progressive disease despite early detection.\u003c/p\u003e \u003cp\u003eFinally, several necessary structural simplifications may bias results in conservative ways. In particular:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eChronic BCRL costs were applied uniformly across strategies, because stage-specific long-term cost data (including recurrent CDT utilisation and LVA failure rates) are poorly reported.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eLate-stage BCRL typically incurs higher lifelong costs, which are more common under opportunistic detection.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eNot modelling these stage-dependent trajectories likely underestimates the true burden of opportunistic detection and therefore understates the economic advantage of structured surveillance.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSimilarly, although this simplification also applies to ILR, the ILR ICER remained\u0026thinsp;\u0026gt;\u0026thinsp;S\u003cspan\u003e$\u003c/span\u003e200,000/QALY across all sensitivity analyses and was not materially affected by optimistic parameter shifts.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eDespite these limitations, extensive sensitivity, threshold, and probabilistic analyses demonstrated that the primary conclusions are robust: structured surveillance remains cost-saving and more effective than opportunistic detection, and ILR does not approach accepted willingness-to-pay thresholds under current tariffs and clinical conditions in Singapore.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eStructured surveillance using bioimpedance spectroscopy and indocyanine green lymphography provides the most clinically effective and economically efficient strategy for preventing breast cancer\u0026ndash;related lymphoedema after axillary lymph-node dissection in Singapore. Compared with opportunistic detection, surveillance improves quality-adjusted life-years and reduces downstream BCRL-related costs by enabling earlier identification and intervention. Immediate lymphatic reconstruction, while clinically promising, offers only modest incremental benefit when effective surveillance systems are in place and remains substantially more costly under current surgical tariffs and local disease incidence.\u003c/p\u003e \u003cp\u003eThese findings support prioritising structured surveillance as the standard of care and reserving ILR for selected high-risk or preference-sensitive cases. As longer-term outcome data and refined risk-stratification tools become available, the role of ILR may be further clarified; however, under present conditions, it does not meet accepted cost-effectiveness thresholds within Singapore\u0026rsquo;s public healthcare system.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDisclaimers and Disclosure of Conflicts of Interest:\u003c/strong\u003e None.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrior Presentations:\u003c/strong\u003e None.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eNot applicable. This study was a decision-analytic economic evaluation using secondary data from published sources and publicly available cost information and did not involve human participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number:\u003c/strong\u003e Not applicable\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJM Sun was involved in the data collection, data analysis and manuscript writing. All figures and tables were created by JM Sun\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data supporting the findings of this study are included in the article and its supplementary materials. Model inputs were derived from published sources and publicly available cost data, as described in the Methods.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHing JX, Chung WKF, Lim SY, et al. 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Cost-effectiveness analysis of lymphaticovenous anastomosis in reducing cellulitis recurrence in 150 lymphoedema cases followed-up over 24 months. J Plast Reconstr Aesthet Surg. 2025 Jul;106:42-49. \u003c/li\u003e\n\u003cli\u003eBaid D, Lakdawalla DN, Finkelstein EA. Societal Preferences for Subsidizing Treatments Targeting Patients With Advanced Illness: A Discrete Choice Experiment. Value Health Reg Issues. 2024 Sep;43:101003.\u003c/li\u003e\n\u003cli\u003eJonis YMJ, Wolfs JAGN, Hummelink S, Tielemans HJP, Keuter XHA, van Kuijk S, Ulrich DJO, van der Hulst RRWJ, Qiu SS. The 6 month interim analysis of a randomized controlled trial assessing the quality of life in patients with breast cancer related lymphedema undergoing lymphaticovenous anastomosis vs. conservative therapy. Sci Rep. 2024 Jan 26;14(1):2238.\u003c/li\u003e\n\u003cli\u003eYang EJ, Kim SI, Lee WH, Lim JY. Use of a prospective surveillance model to prevent breast cancer treatment-related lymphedema: a randomized controlled trial. Breast Cancer Res Treat. 2016;160(2):279-286.\u003c/li\u003e\n\u003cli\u003eRochlin DH, Coriddi MR, Nelson JA, Dayan JH, Mehrara BJ. Immediate Lymphatic Reconstruction and the Current Value Problem. Ann Surg. 2023 Jun 1;277(6):e1197-e1199\u003c/li\u003e\n\u003cli\u003eCoriddi M, Dayan J, Bloomfield E, McGrath L, Diwan R, Monge J, Gutierrez J, Brown S, Boe L, Mehrara B. Efficacy of Immediate Lymphatic Reconstruction to Decrease Incidence of Breast Cancer-related Lymphedema: Preliminary Results of Randomized Controlled Trial. Ann Surg. 2023 Oct 1;278(4):630-637.\u003c/li\u003e\n\u003cli\u003eRidner SH, Dietrich MS, Cowher MS, et al. A randomized trial evaluating bioimpedance spectroscopy versus tape measurement for the prevention of lymphedema following treatment for breast cancer: interim analysis. Ann Surg Oncol. 2019;26(10):3250-3259.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cost-effectiveness analysis, Breast cancer-related lymphedema, immediate lymphatic reconstruction, structured surveillance","lastPublishedDoi":"10.21203/rs.3.rs-8722507/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8722507/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eBreast cancer\u0026ndash;related lymphedema (BCRL) is a common and costly complication after axillary lymph-node dissection (ALND). Immediate lymphatic reconstruction (ILR) has been introduced as a preventive surgical strategy, but its economic value relative to structured postoperative surveillance in health systems with established lymphedema services remains uncertain.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a decision-analytic cost-effectiveness analysis comparing three strategies after ALND: opportunistic detection, structured surveillance using bioimpedance spectroscopy and indocyanine green lymphography, and ILR. The model adopted a societal perspective over a 10-year horizon with 3% annual discounting. Clinical probabilities were derived from meta-analyses and local cohort data, while costs were obtained from national tariff benchmarks and institutional billing data. Outcomes were expressed as quality-adjusted life-years (QALYs). Parameter uncertainty was explored using probabilistic and one-way sensitivity analyses, and threshold analyses examined conditions under which ILR might become cost-effective.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eStructured surveillance dominated opportunistic detection, yielding higher QALYs at lower cost. ILR provided a modest additional health benefit but at substantially higher cost, resulting in an incremental cost-effectiveness ratio well above commonly accepted willingness-to-pay thresholds. In probabilistic analyses, structured surveillance was cost-effective in more than 95% of simulations, whereas ILR was not cost-effective in any iteration at conventional thresholds. Threshold analyses indicated that ILR would require substantially lower surgical costs or markedly higher baseline BCRL incidence to become economically viable.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn a health system with access to structured lymphedema surveillance and early conservative management, routine ILR is unlikely to represent an efficient use of healthcare resources. These findings support prioritising structured surveillance pathways and reserving ILR for selected high-risk or preference-sensitive cases.\u003c/p\u003e","manuscriptTitle":"Cost-Effectiveness of Immediate Lymphatic Reconstruction Versus Structured Surveillance for Preventing Breast Cancer–Related Lymphedema After Axillary Surgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-02 07:55:57","doi":"10.21203/rs.3.rs-8722507/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"170450177316192141303885635860996430173","date":"2026-03-04T18:18:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"211327599448728520743720212850751615624","date":"2026-02-24T13:19:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-24T12:19:51+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-04T19:57:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-02T10:54:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-02T10:53:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Health Services Research","date":"2026-01-28T13:57:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d5848ee8-eaa7-4a09-8f58-bb94a93c9665","owner":[],"postedDate":"March 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-02T07:56:02+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-02 07:55:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8722507","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8722507","identity":"rs-8722507","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}