Risk-Adapted Postmastectomy Radiotherapy Decision Based on Prognostic Nomogram for pT1-2N1M0 Breast Cancer: A Multicenter Study

Abstract

Purpose: The aim of this study was to develop a widely accepted prognostic nomogram and establish a risk-adapted PMRT strategy based on locoregional recurrence for pT1-2N1M0 breast cancer.

Methods and materials: A total of 3,033 patients with pT1-2N1M0 breast cancer treated at 6 participating institutions between 2000 and 2016 were retrospectively reviewed. A nomogram was developed to predicted locoregional recurrence-free survival (LRFS). A propensity score-matched (PSM) analyses was performed in risk-adapted model.

Results: With the median follow-up of 65.0 months, the 5-year overall survival (OS), disease free survival (DFS) and LRFS were 93.0, 84.8, and 93.6%, respectively. There was no significant difference between patients who received PMRT or not for the entire group. A nomogram was developed and validated to estimate the probability of 5-year LRFS based on five independent factors including age, primary tumor site, positive lymph nodes number, pathological T stage, and molecular subtype that were selected by a multivariate analysis of patients who did not receive PMRT in the primary cohort. According to the total nomogram risk scores, the entire patients were classified into low- (40.0%), moderate- (42.4%), and high-risk group (17.6%). The 5-year outcomes were significantly different among these three groups (P<0.001). In low-risk group, patients who received PMRT or not both achieved a favorable OS, DFS, and LRFS. In moderate-risk group, no differences in OS, DFS, and LRFS were observed between PMRT and no PMRT patients. In high-risk group, compared with no PMRT, PMRT resulted in significantly different OS (86.8 vs 83.9%, P = 0.050), DFS (77.2 vs 70.9%, P = 0.049), and LRFS (90.8 vs. 81.6%, P = 0.003). After PSM adjustment, there were no significant differences in OS, DFS, and LRFS in low-risk and moderate-risk groups. However, in the high-risk group, PMRT still resulted in significantly better OS, DFS and improved LRFS.

Conclusions: The proposed nomogram provides an individualized risk estimate of LRFS in patients with pT1-2N1M0 breast cancer. Risk-adapted PMRT for high-risk patients is a viable effective strategy.

Keywords: breast neoplasms; mastectomy; molecular subtype; nomogram; prognosis; radiation therapy; recurrence; risk-adapted therapy.

Figure 1

Nomogram predicting 5-year locoregional recurrence-free survival (LRFS) for patients with pT1-2N1M0 breast cancer. The nomogram assigns a point to each variable value according to its contributions. The sum of these numbers is located on the total points axis and can be translated to predicted probability of LRFS for a patient.

Figure 2

Internal validation of the nomogram to predict LRFS likelihoods in the primary cohort patients. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.735 (A). The calibration curve for the prediction of 5-year LRFS (B). External validation of the nomogram to predict LRFS likelihoods in the validation cohort patients. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.703 (C). The calibration curve for the prediction of 5-year LRFS (D).

Figure 3

OS and DFS and LRFS for all patients. (A) pT1-2N1M0 breast cancer, (B) OS, and (C) DFS, and (D) LRFS for patients with pT1-2N1M0 breast cancer stratified into the low- and moderate- and high-risk groups.

Figure 4

Comparison of OS and DFS and LRFS between with PMRT and without PMRT for low-risk pT1-2N1M0 patients. For patients with PMRT or without PMRT, OS before (A) and after (B) match stratification; DFS before (C) and after (D) match stratification; LRFS before (E) and after (F) match stratification.

Figure 5

Comparison of OS and DFS and LRFS between with PMRT and without PMRT for moderate-risk pT1-2N1M0 patients. For patients with PMRT or without PMRT, OS before (A) and after (B) match stratification; DFS before (C) and after (D) match stratification; LRFS before (E) and after (F) match stratification.

Figure 6

Comparison of OS and DFS and LRFS between with PMRT and without PMRT for high-risk pT1-2N1M0 patients. For patients with PMRT or without PMRT, OS before (A) and after (B) match stratification; DFS before (C) and after (D) match stratification; LRFS before (E) and after (F) match stratification.