An evaluation of prognostic factors and tumor staging of resected carcinoma of the esophagus

Abstract

Objective: To evaluate prognostic factors and tumor staging in patients after esophagectomy for cancer.

Summary background data: Several reports have questioned the appropriateness of the sixth edition of the International Union Against Cancer (UICC) TNM guidelines for staging esophageal cancer. Additional pathologic characteristics, besides the 3 basic facets of anatomic spread (tumor, node, metastases), might also have prognostic value.

Methods: All patients who underwent resection of the esophagus for carcinoma between January 1995 and March 2003 were extracted from a prospective database. Univariate and multivariate analysis was performed to identify prognostic factors for survival. The goodness of fit and accuracy of 3 staging models (UICC-TNM, Korst classification, Rice classification) predicting survival were assessed.

Results: A total of 292 patients (mean age, 63 years) underwent esophagectomy. The 5-year overall survival rate was 29% (median, 21 months). pT-, pN-, pm-stage, and radicality of the resection were independent prognostic factors. Subdivision of T1 tumors into mucosal and submucosal showed significant differences in 5-year survival between both groups: 90% versus 47%, respectively (P = 0.01). Subdivision of pN-stage into 3 groups based on the number of positive nodes (0, 1-2, and >3 nodes positive) or the lymph node ratio (0, 0.01-0.2, and >0.2) also refined staging (P = 0.001 and P < 0.001, respectively). The current subclassification of M1 (M1a and M1b) is not warranted (P = 0.41). The staging model of Rice was more accurate than the UICC-TNM classification in predicting survival.

Conclusion: This study supports the view that the current (6th edition) UICC-TNM staging model for esophageal cancer needs to be revised.

FIGURE 1. Patients with esophageal cancer referred to the Erasmus MC for treatment between January 1978 and March 2003. Patients excluded from the present study are shown.

FIGURE 2. Scatter plot of number of positive nodes in the x-axis versus the Martingale residuals, ie, expected risk of death from esophageal cancer in each of 292 patients. Patients above the horizontal line were at increased risk for death compared with expected risk from Cox proportional hazards regression model. Patients below the horizontal line were at decreased risk for death compared with what we would expect. Curved line represents scatterplot smoother. Point at which smoother line crosses horizontal line occurs at 3 positive nodes, indicating that this would be the best cutoff point to predict death from esophageal cancer based on number of positive lymph nodes.

FIGURE 3. Survival according to number of involved lymph nodes for 292 patients with esophageal cancer after resection with curative intent. There was a significant difference in survival between the subgroups (P < 0.0001).

FIGURE 4. Survival according to lymph node ratio (LNR) for 292 patients with esophageal cancer after resection with curative intent. There was a significant difference in survival between the subgroups (P < 0.0001).

FIGURE 5. Survival according to TNM stage grouping (UICC 2002). There is no significant difference in survival between stage III and stage IV (P = 0.15).

FIGURE 6. Survival according to classification of Korst et al. Significant differences in overall survival between all tumor stages (P < 0.0001). Explanation of the N- and M-classifications: N0, no positive nodes; N1, positive locoregional nodes, N2, positive distant nodes; M0, no visceral metastases; M1, visceral metastases. Stage I, T1-2N0M0; stage II, T3N0M0/T1-3N1M0; stage III, T1-3N2M0; stage IV, T4anyNM0/anyTanyNM1.

FIGURE 7. Survival according to classification of Rice et al. No significant difference in survival between stage II and II (P = 0.08). Explanation of the N- and M-classifications: N0, no positive nodes; N1, 1 or 2 nodes positive; N2, 3 or more nodes positive; M0, no distant metastases; M1, distant metastases (nodal and/or organ involvement). Stage I, Tis-1aN0M0; stage II, T1bN0M0/T1aN1M0/T2N0M0; stage III, T3N0M0/T1b-2N1M0/T3N1M0/T4N0M0; stage IV, T4 N1M0/anyTN2M0, anyM1.