Cost of Neoadjuvant Immunotherapy vs Up-Front Surgery in Cutaneous Squamous Cell Carcinoma: A Post Hoc Analysis of a Nonrandomized Clinical Trial.

Importance: There is increasing interest in use of neoadjuvant immunotherapy (NAT) in advanced cutaneous squamous cell carcinoma (cSCC) to reduce surgical morbidity and forego adjuvant therapy, while potentially improving survival outcomes.

Objective: To assess the cost to Medicare of NAT compared with up-front surgery.

Design, setting, and participants: This cohort study was a post hoc analysis of a phase 2 clinical trial evaluating the feasibility of neoadjuvant atezolizumab. The study was conducted from June 2021 to December 2023 at a tertiary-level academic institution among 20 patients with advanced stage II-IV cSCC.

Interventions: Up to 3 doses of neoadjuvant atezolizumab, followed by surgical resection with or without adjuvant radiation therapy.

Main outcomes and measures: Direct medical costs in US dollars of care received on trial were compared with baseline treatment plans of up-front surgery developed a priori from a Medicare payer perspective.

Results: Of 20 patients with advanced cSCC enrolled (median [range] age, 71.5 [53-88] years; 17 male [85.0%]), most individuals had stage III (12 patients [60.0%]) or IV (5 patients [25.0%]) disease. The median (range) follow-up was 14.2 (3.5-28.7) months. Compared with $26 602.67 for up-front surgery, NAT was associated with mean overall costs of $51 561.02, or a 93.8% increase, equivalent to $24 958.36 (95% CI, $22 057.95 to $24 692.43) per patient, which was primarily associated with the drug acquisition costs of atezolizumab ($30 603.96). NAT was associated with mean cost reductions from $12 707.07 to $10 543.71 (17.0%) in surgery and $11 711.97 to $7157.32 (38.9%) in radiation across all patients compared with up-front surgery. Adjuvant radiation therapy was obviated in 5 of 17 patients not previously irradiated (29.4%), reducing costs of radiation. Mean (SD) surgical complexity was reduced from 63.81 (30.55) to 44.71 (32.49) work relative value units (wRVUs; difference, 19.10 wRVU; 95% CI, 5.00 to 33.20 wRVU). NAT was associated with 5 fewer free flaps, 4 fewer neck dissections, 5 more organ-preserving resections, and 3 conversions from inpatient to outpatient surgery.

Conclusions and relevance: This study found that treatment with 3 doses of NAT was associated with an overall cost increase compared with up-front surgery, driven by drug acquisition costs, and cost reductions from less extensive surgical resections and obviated adjuvant radiation. Predictive markers for response to NAT could optimize patient selection and improve cost-effectiveness.

Trial registration: ClinicalTrials.gov Identifier: NCT04710498.