Early imaging in evaluating neoadjuvant chemotherapy response for triple-negative breast cancer: a cost-effectiveness analysis

The KEYNOTE-522 regimen (pembrolizumab plus chemotherapy) is the standard neoadjuvant chemotherapy (NAC) for high-risk, early-stage triple-negative breast cancer (TNBC), achieving pathological complete response (pCR) among 65% of patients. The remaining 35% do not achieve pCR, incurring treatment costs exceeding $100,000 with limited clinical benefit. Early imaging could identify non-responders for timely surgical intervention, but the comparative cost-effectiveness of imaging modalities is unknown, particularly in high-risk, early-stage TNBC patients receiving the KEYNOTE-522 regimen. A decision-analytic model projected lifetime medical costs and quality-adjusted life-years (QALYs) from a U.S. healthcare payer perspective. Standard care was modeled after the KEYNOTE-522 trial protocol without imaging to guide surgery timing. For imaging-based strategies, imaging-classified non-responders proceeded to surgery after an abbreviated NAC course, while responders completed the full KEYNOTE-522 regimen as in standard care. Five imaging strategies—magnetic resonance fingerprinting (MRF), MRI, 18 F-FDG PET/CT, ultrasound, and contrast-enhanced mammography—were compared with standard care. Input parameters were derived from the KEYNOTE-522 trial, literature, and publicly available data. Lifetime medical costs, QALYs, and incremental cost-effectiveness ratios (ICERs) were estimated. A strategy was considered cost-effective if it yielded the highest QALYs with an ICER below a willingness-to-pay threshold, evaluated at $50,000, $100,000, and $150,000/QALY gained. Standard care yielded 14.44 QALYs per patient at a lifetime medical cost of $357,275, while imaging-based strategies provided 13.66–14.15 QALYs per patient at 8%-12% lower costs. MRF was cost-effective (ICER = $11,660/QALY gained) at $50,000 and $100,000/QALY gained, saving $38,342 per patient at a loss of 0.33 QALYs. Standard care was cost-effective at $150,000/QALY gained (ICER = $116,657/QALY gained), and also at $100,000/QALY gained in the scenario where MRF was excluded (ICER = $92,778/QALY gained). In probabilistic sensitivity analysis, MRF had the highest expected net monetary benefit at thresholds up to $120,000/QALY gained and standard care at thresholds above $120,000. In this analysis, an imaging modality like MRF could reduce costs at a small QALY loss relative to standard care, and be cost-effective depending on the threshold considered. These findings warrant future studies to evaluate the benefits and harms of early imaging to guide NAC and surgery timing.