Post-neoadjuvant Metabolic Response Assessed by ¹⁸F-FDG PET/CT Predicts Pathologic Complete Response and Survival in Esophageal Squamous Cell Carcinoma Treated with the CROSS Regimen.

BACKGROUND: Metabolic response on ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) after neoadjuvant chemoradiotherapy may predict pathologic complete response (pCR) in esophageal squamous cell carcinoma (ESCC). However, optimal imaging timing and thresholds for percentage change in standardized uptake value (SUVmax) remain undefined in homogeneous cohorts.

METHODS: This retrospective study included 110 consecutive patients with mid- or lower-third ESCC treated with the CROSS regimen (41.4 Gy radiotherapy plus weekly paclitaxel/carboplatin) between 2017 and 2024. All underwent baseline (PET0) and post-treatment (PET1; 6-10 weeks) FDG PET/CT. Percentage reduction in maximum SUVmax was calculated for the primary tumor and involved lymph nodes. Primary endpoint was pCR (ypT0N0); secondary endpoint was overall survival (OS).

RESULTS: pCR was achieved in 62 patients (56.3%). Mean percentage reduction in tumor SUVmax was 83.3% in pCR patients versus 70.5% in non-pCR patients (P < 0.001); nodal reduction was 60.4% versus 40.2% (P < 0.001). Receiver operating characteristic analysis identified ≥ 67% reduction in tumor SUVmax as optimal (AUC 0.634, 95% CI 0.530-0.739; sensitivity 80%, specificity 56%). Multivariate logistic regression confirmed tumor SUVmax reduction (OR 1.025 per 1% increase; P = 0.011) and nodal SUVmax reduction (OR 1.009; P = 0.034) as independent pCR predictors. Median OS was 38 months with pCR versus 33 months without (log-rank P = 0.023). Cox regression showed HR 0.51 for pCR (95% CI 0.28-0.94; P = 0.030) and 0.58 for ≥ 67% tumor SUVmax reduction (P = 0.086).

CONCLUSION: In patients with esophageal squamous cell carcinoma treated with the CROSS regimen, a ≥ 67% reduction in primary tumor SUVmax on FDG PET/CT at 6-10 weeks after neoadjuvant chemoradiotherapy is an independent predictor of pathologic complete response with high sensitivity. However, the moderate specificity and area under the curve suggest that this metabolic parameter should be interpreted cautiously and integrated with multimodal assessment rather than used in isolation.