Neoadjuvant chemoradiation changes the relationship between pT and pN status, and their prognostic significance in esophageal cancer

Abstract

BACKGROUND: Chemoradiation therapy is widely used in the treatment of esophageal cancer. After chemoradiation, it is not clear if pathologic TNM stage after resection will have the same prognostic significance compared to patients without neoadjuvant treatment. Two hypotheses were tested: (1) pT stage has different relationship to pN stage compared to patients without prior treatment, (2) pT and pN stage has different prognostic significance compared to patients without chemoradiation therapy. METHOD: From 1995 to 2004, 279 patients were selected from a prospectively collected database for analysis. All patients had squamous cell cancers of the thoracic esophagus. Neoadjuvant chemoradiation comprised of 2 courses of Cisplatin and 5-FU concurrent with 40Gy of external beam irradiation. Patients were given chemoradiation either as part of a randomized controlled trial comparing neoadjuvant chemoradiation with surgical resection alone, or because of advanced disease at presentation. Pathologic staging data were analyzed in relation to long-term survival. RESULTS: 170 patients had surgical resection only without prior treatment, while 109 had neoadjuvant therapy. Transthoracic resection with two-field lymphadenectomy was the preferred approach, which was carried out in 93% of patients. In the surgery alone group, pT1, 2, 3, 4 disease were found in 15, 17, 104, and 34 patients, their respective N1 rates were 13.3%, 29.4%, 57.7% and 64.7%, p = 0.001. In the chemoradiation group, pT0, T1, 2, 3, 4 were found in 48, 12, 23, 21, and 5 patients, their respective N1 rates were 31.3%, 16.7%, 21.7%, 52.4% and 20%, p = 0.15. Logistic regression analysis of factors predictive of N1 status showed that for the surgery alone group, pT stage correlated with N1 status: OR 5.230 (95% CI = 2.12–12.9), while for the chemoradiation group, pT status lost its predictive value. Cox regression analysis of factors predictive of survival showed that in the surgery alone group, pT and pN status were independent prognostic factors. HR for pT = 1.901 (95% CI = 1.42–2.55), and HR for pN = 1.758 (95% CI = 1.17-2.64). In contrast, for the chemoradiation group, while pN status remains prognostic: HR = 2.257 (95% CI = 1.34–3.8), pT status has lost its significance. Instead, female gender (HR = 0.252 (95% CI = 0.08–0.81), and R-category (HR = 8.984 (95% CI = 3.78–21.4) became important. CONCLUSIONS: After chemoradiation, the clear relationship between advancing pT stage and more frequent N1 status was diminished. While nodal status remains of prognostic significance for survival, pT status lost its independent prognostic value.