Pre-treatment patient-derived esophageal squamous cell carcinoma organoids as a predictive platform for docetaxel, cisplatin and fluorouracil neoadjuvant chemotherapy

Background : Patient-derived organoids (PDOs) are a promising platform for functional precision oncology. In esophageal squamous cell carcinoma (ESCC), docetaxel/cisplatin/fluorouracil (DCF) is a standard neoadjuvant regimen, yet some patients show poor pathological response, underscoring the need for treatment-naïve biopsy-derived PDO models to predict individual benefit. Methods : Treatment-naïve endoscopic biopsies from ESCC patients were used to generate three-dimensional PDOs in Matrigel-based, growth factor-supplemented culture. We analyzed 48 consecutive cases collected after technical standardization. Successful establishment was defined as organoid formation after the first cell seeding, and long-term maintenance as ≥5 passages. Long-term PDOs from patients who received DCF followed by esophagectomy were subjected to 72-hour dose-response assays; IC₅₀ values were compared with pathological response and clinical course. Results : PDOs were successfully established in 45/48 cases, and long-term maintenance was achieved in 10/48. Three long-term PDO cases received preoperative DCF alone and underwent esophagectomy (Cases A-C). Case A (pT2N2M0, Ryan grade 1, Ly0, V0) showed low IC₅₀ values for all three drugs, indicating broad in vitro sensitivity concordant with good pathological response without lymphovascular invasion. Case B (pT3N0M0, Ryan grade 2, Ly0, V0, positive margin) exhibited markedly elevated IC₅₀ values for all drugs, consistent with global drug resistance and suboptimal local control. Case C (pT3N1M0, Ryan grade 2, Ly1b, V1b) showed selective resistance to docetaxel but low IC₅₀ values for cisplatin and 5-fluorouracil, paralleling an intermediate pathological response with persistent lymphovascular invasion. PDO drug sensitivity patterns qualitatively paralleled the degree of pathological response, with triple-sensitive PDOs associated with more favorable regression. Conclusions : Although the current long-term maintenance rate of ESCC PDOs remains modest, PDOs derived from pre-treatment biopsies showed concordance between in vitro DCF sensitivity and clinical response, supporting their potential as a platform to predict neoadjuvant efficacy. Further case accrual and refinement of culture conditions may enable individualized perioperative treatment strategies guided by PDO-derived drug sensitivity.