Background
Endometrial cancer is the most common gynecologic malignancy in the U.S., with advanced-stage disease accounting for significant morbidity and mortality. Molecular profiling has become pivotal in guiding treatment decisions, particularly for identifying mismatch repair (MMR) deficiencies, TP53 mutations, and POLE mutations. However, the cost and efficiency of universal next-generation sequencing (NGS) versus selective testing strategies remain debated.
Study Design
The study constructed a decision tree model to compare three molecular profiling strategies for newly diagnosed stage III-IVA endometrial cancer patients. The strategies included:
1. MMR/p53 IHC-first
MMR and p53 immunohistochemistry (IHC) at diagnosis, with HER2 IHC if p53 abnormal, and NGS reserved for recurrence.
2. Selective NGS
MMR/p53 IHC at diagnosis, with immediate NGS and HER2 IHC if p53 abnormal, otherwise NGS at recurrence.
3. Universal NGS
NGS and HER2 IHC at diagnosis for all patients. Outcomes measured were costs (2024 US$), timely NGS results, and unnecessary NGS (testing in recurrence-free patients).
Key Findings
The study revealed striking differences in cost and testing efficiency:
Unnecessary NGS
Universal NGS led to unnecessary testing in 57% of patients who remained recurrence-free, compared to 7% with Selective NGS and 0% with MMR/p53 IHC-first.
Cost Analysis
MMR/p53 was the least costly strategy ($3,772 per patient), followed by Selective NGS ($4,186) and Universal NGS ($6,250). The incremental cost-effectiveness ratio (ICER) for Selective NGS versus MMR/p53 was $2,571 per additional timely NGS result, while Universal NGS cost $7,600 more per timely result than Selective NGS.
Clinical Implications
The Selective NGS strategy balanced cost and efficiency, ensuring that high-risk patients (p53-abnormal tumors) received timely NGS while minimizing unnecessary testing in low-risk groups.
Expert Commentary
Dr. Alexandra Bashi, lead author of the study, emphasized, ‘Our findings support a pragmatic approach where selective NGS guided by MMR/p53 IHC optimizes resource use without compromising patient outcomes.’ The study aligns with evolving guidelines favoring biomarker-driven therapy but highlights the need for economic sustainability in precision oncology.
Conclusion
Selective molecular profiling with MMR/p53 IHC and reflex NGS for p53-abnormal tumors offers a cost-effective alternative to universal NGS in advanced endometrial cancer. This approach reduces unnecessary testing by 57%, ensuring timely results for high-risk patients while conserving healthcare resources. Future research should explore real-world implementation and patient outcomes.
Funding and Registration
The study was supported by the National Cancer Institute and conducted using data from the GOG-0258 trial (NCT00942357).