Assessing Value for Money in Theranostic Nuclear Medicine: A Systematic Review

Radiotheranostic therapy (RTT) is an emerging form of personalized cancer care that combines radiopharmaceutical imaging and radiopharmaceutical therapy (RPT). Although promising clinically, the value for money of RTT remains uncertain. The objective of this study is to review the cost-effectiveness evidence of RTT in cancer and critically appraise the methodologies utilized in conducting the included economic evaluations. <b>Methods:</b> A systematic literature review was conducted in accordance with the PRISMA guidelines. A comprehensive search strategy encompassing key search terms related to economic evaluations of RTT in oncology was performed across 7 electronic databases (CINAHL, Econlit, Embase, PubMed, Scopus, Web of Science, and International HTA database), as well as databases of health technology assessment (HTA) agencies (Canada’s Drug Agency, Medical Services Advisory Committee, and the National Institute for Health and Care Excellence). The final search was conducted in September 2025 and covered published articles, reports, and HTA appraisals from 2015 to 2025. Methodologic quality was assessed using the CHEQUE framework, whereas reporting quality was evaluated using the CHEERS checklist. <b>Results:</b> Sixteen articles or reports and 9 HTA appraisals were included. Among the radiopharmaceutical imaging studies, 80% evaluated ⁶⁸Ga whereas all RPT studies assessed ¹⁷⁷Lu. Half of the model-based economic evaluations focused on prostate cancer and the rest on neuroendocrine tumors. The modeling approach in the evaluations varied, and the reported incremental cost-effectiveness ratio ranged from $21,350 to $146,526/quality-adjusted life-year for radiopharmaceutical imaging and from $66,761 to $397,342/quality-adjusted life-year for RPTs. HTA agencies identified uncertainties in evidence, comparator choice, and model assumptions and highlighted the absence of real-world considerations such as supply, workforce, and infrastructure constraints. <b>Conclusion:</b> This review identifies substantial heterogeneity and methodologic gaps in the economic evaluation of RTTs, contributing to uncertainty around their value for money. These findings underscore the need for fit-for-purpose HTA frameworks that integrate the full theranostic pathway and address system-level constraints and equity considerations.