P1.145. The pCR Paradox: Unmasking Systemic Failure in Esophageal Cancer Following Neoadjuvant CROSS Therapy

Abstract

Abstract Topic Esophageal Cancer: Surgical Treatment of Esophageal Cancer – long term outcomes Background While neoadjuvant chemoradiotherapy (nCTRT) followed by esophagectomy has established itself as the global standard for locally advanced esophageal cancer - predominant squamous histology, the "Achilles' heel" remains disease recurrence. Although achieving a pathological complete response (pCR) suggests a favourable prognosis, it does not guarantee a cure. We aimed to characterize the specific timing and patterns of failure within this high-risk population. Methods Our single-institution study prospectively tracked 99 patients with resectable esophageal carcinoma who underwent the CROSS regimen (41.4 Gy radiation with concurrent weekly paclitaxel/carboplatin), followed by surgery, between January 2015 and December 2025. The cohort predominantly consisted of Squamous cell carcinoma (85.45%), with Adenocarcinoma (9.09%) and Adeno-squamous carcinoma (5.45%) making up the remainder. Demographics showed a median age range of 55.2 - 60 years and a male-to-female ratio of approximately 1.7:1. We utilized expanded inclusion criteria, encompassing cT4a and N2-3 disease. Following multidisciplinary restaging via PET-CT, radical esophagectomy was performed 6–8 weeks post-nCTRT. Statistical analysis (SPSS 25.0) stratified outcomes between pCR and non-pCR groups to map locoregional versus systemic recurrence pathways (Table 1). Results A pCR was achieved in 56% of the cohort. In the pCR group, failure rates were remarkably low with locoregional failure at 7% and distant metastasis at 4.7%. Conversely, non-pCR patients exhibited significantly higher failures with 15.9% locoregional and 22.9% systemic recurrence. Systemic failures occurred primarily in the lungs, non regional lymph nodes, bone and liver. The median follow-up was 27.8 months. Mean survival for pCR patients was superior at years (95% CI: 6.8 - 8.9) compared to years (95% CI: 3.9 -7.4) for non-pCR patients (p=0.061). Most failures occurred within 30 to 48 months post-surgery. Conclusion Our data confirms that while the CROSS protocol provides excellent locoregional control, systemic escape remains the primary driver of mortality, particularly in non-pCR patients. Even with a "clean" pathology report, a small subset of pCR patients remains at risk for distant failure. These findings underscore the need for more aggressive systemic maintenance or novel adjuvant strategies to bridge the gap between pathological response and long-term cure.