Recurrence risk stratification based on a competing-risks nomogram to identify patients with esophageal cancer who may benefit from postoperative radiotherapy

Abstract

Background: A reliable model is needed to estimate the risk of postoperative recurrence and the benefits of postoperative radiotherapy (PORT) in patients with thoracic esophageal squamous cell cancer (TESCC).

Methods: The study retrospectively reviewed 3652 TESCC patients in stage IB-IVA after radical esophagectomy, with or without PORT. In one institution as the training cohort (n = 1620), independent risk factors associated with locoregional recurrence (LRR), identified by the competing-risks regression, were used to establish a predicting nomogram, which was validated in an external cohort (n = 1048). Area under curve (AUC) values of receiver operating characteristic curves were calculated to evaluate discrimination. Risk stratification was conducted using a decision tree analysis based on the cumulative point score of the LRR nomogram. After balancing the baseline of characteristics between treatment groups by inverse probability of treatment weighting, the effect of PORT was evaluated in each risk group.

Results: Sex, age, tumor location, tumor grade, and N category were identified as independent risk factors for LRR and added into the nomogram. The AUC values were 0.638 and 0.706 in the training and validation cohorts, respectively. Three risk groups were established. For patients in the intermediate- and high-risk groups, PORT significantly improved the 5-year overall survival by 10.2% and 9.4%, respectively (p < 0.05). Although PORT was significantly associated with reduced LRR in the low-risk group, overall survival was not improved.

Conclusion: The nomogram can effectively estimate the individual risk of LRR, and patients in the intermediate- and high-risk groups are highly recommended to undergo PORT.

Keywords: esophageal cancer; nomogram; radiotherapy; recurrence; risk classification.

Figure 1.

Nomogram for locoregional recurrence developed from the training cohort.

Figure 2.

(a) Receiver operating characteristic (ROC) curves for 1-, 2-, and 3-year locoregional recurrence (LRR) according to the nomogram in the training cohort. The area under the curve (AUC): blue line (1-year), yellow line (2-year), gray line (3-year). (b) ROC curves for 1-, 2-, and 3-year LRR rates according to the nomogram in the validation cohort. AUC: blue line (1-year), yellow line (2-year), gray line (3-year). (c) Calibration plot for 3-year LRR prediction according to the nomogram in the training cohort. (d) Calibration plot for 3-year LRR prediction according to the nomogram in the validation cohort.

Figure 3.

(a) Decision tree analysis according to the effect of nomogram score on locoregional recurrence (LRR) in unirradiated patients. (b) Cumulative incidence of LRR rate and distant metastasis (DM) rate. (c) Cumulative incidence of DM. (d) Cumulative incidence of mortality.

Figure 4.

Cumulative incidence of locoregional recurrence (LRR) rate, distant metastasis (DM) rate, and overall survival (OS) in the low-risk group (a–c), intermediate-risk group (d–f), and high-risk group (g–i), respectively. S: surgery; PORT: postoperative radiation therapy.