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Prognostic Value of Histological Tumor Regression After Neoadjuvant/Perioperative Treatment of Esophageal Cancer
Frank Makowiec*1, Jens Hoeppner1, Torben Glatz1, Hannes P. Neeff1, Ulrich T. Hopt1, Peter Bronsert2
1Dept. of Surgery, University of Freiburg, Freiburg, Germany; 2Institute of Pathology, University of Freiburg, Freiburg, Germany
Perioperative chemotherapy (periCTx) or neoadjuvant chemoradiation (neoCRT) are increasingly used in patients with adeno- (AC) or squamous cell carcinoma (SCC) of the esophagus. However, no reliable parameters to predict major response have been established so far. As for other GI-cancers recent data suggested a better outcome in patients with total or subtotal histological tumor regression, especially in AC. We therefore investigated tumor regression grade (TRG) and its potential impact on survival in 221 patients after periCTx or neoCRT plus resection for esophageal cancer.
Methods: We analyzed patients who underwent esophageal resection for SCC (n=102) or AC (n=119) after neoCRT or neoCTx since 1995. Patients with 90 day mortality were excluded. Neoadjuvant treatment was performed in patients with (in pretherapeutical staging) at least T3- or node positive tumors. Patients with SCC underwent neoCRT with 36-45 Gy and cisplatin-based CTx. Patients with ACC underwent the same neoCRT (n=69) or neoCTx (ECF- or FLOT protocols; n=50). TRG in the primary tumor was estimated using the MANDARD-classification (TRG 1=total regression, TRG 5=no regression). In a subanalysis patients with total/subtotal TRG but positive nodes were reclassified as poor TRG (corrTRG)
Results: In all 221 patients TRG was 1 (total) in 29%, good to moderate (TRG 2-3) in 41% and poor (TRG 4-5) in 30%. TRG was significantly better after neoCRT than after neoCTx in all patients (p<0.001) and in patients with AC (p<0.02). After correction for positive nodes corrTRG was 1 (22%), 2-3 (33%) or poor (45%).
5 year survival (5ySurv) in all 221 patients was 43%. It was 35% in SCC and 52% in AC (p=0.06). 5ySurv was even 63% in patients with AC and periCTx. Patients with corrTRG 1 had a better survival than patients with corrTRG 2-5 (p<0.03). In multivariate survival analysis however, only lymph node ratio (LNR) < 0.1 (p<0.001), T-stage <3 (p<0.001) and AC (p<0.001) but not TRG or corrTRG were associated with better survival. In the subgroup of patients with SCC corrTRG univariately influenced survival (p<0.03). In multivariate analysis however, LNR was the only independent predictor of survival (in both histological subgroups).
Conclusion: After neoadjuvant therapy of esophageal cancer a relevant proportion showed complete histological tumor regression. However, TRG did not independently predict survival. Best prognosticator (in SCC and AC) was the nodal status (LNR) which may also be influenced by preoperative CRT/CTx. The relative good outcome in patients with AC after CTx may also be due to the postoperative part of CTx whose effects are not detectable in the specimen.
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