The clinical impact of histopathologic response assessment by residual tumor cell quantification in esophageal squamous cell carcinomas

BACKGROUND. The objectives of this study were to investigate histomorphologic features as a response classification after neoadjuvant radiochemotherapy (RTx/CTx) and to correlate the results with clinical outcome parameters (e.g., postoperative morbidity and mortality, recurrence, and survival) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS. Three hundred eleven patients with histologically proven, locally advanced, intrathoracic ESCC (clinical T3 or T4, N0-N+, M0) located at or above the level of the tracheal bifurcation underwent preoperative, combined, simultaneous RTx/CTx followed by esophagectomy. Response to RTx/CTx was classified by the quantification of residual tumor cells. A histopathologic response was defined as < 10% residual tumor cells found within the specimen compared with a histopathologic nonresponse, which was characterized by > 10% residual tumor cells. RESULTS. A histopathologic response was correlated significantly with complete tumor resection status (R0 resection) (P.0001), histopathologic tumor (ypT) category (P < .0001), lymph node involvement (P < .0001), lymphatic vessel invasion (P < .001), and survival (P < .0001). A multivariate Cox regression analysis revealed that histopathologic response classification according to the percentage of residual tumor cells was an independent prognostic factor (P < .0001). Nonresponders had greater postoperative pulmonary morbidity (P = .01), a greater 30-day mortality rate (P = .02), and a dismal Survival rate compared to histopathologic responders (P < .0001). CONCLUSIONS. Histopathologic response evaluation based on the quantification of residual tumor cells provided meaningful information for the assessment of outcomes among patients with ESCC who have underwent neoadjuvant RTx/CTx. The current results indicated that histopathologic responders may represent a subgroup of patients who benefit from neoadjuvant therapy followed by Surgery.