In the current study, we retrospectively enrolled 271 lrNPC patients with disease diagnosed from January 2006 to December 2016. Among them, 146 (53.9%) patients received re-RT with or without PCT, while 125 (46.1%) received PCT alone. The median age in the entire cohort was 47 years (range, 22-74 years), and the male:female ratio was 3.7:1. EBV DNA levels could be detected in 154 (56.8%) patients when recurrence occurred. The median follow-up was 20.1 months (interquartile range, 15.3 to 44.6) and a total of 194 of the 271 patients were dead at their last follow-up. The details of patient characteristics are listed in Table 1.
Independent prognosis factors for lrNPC
The results of multivariate analysis are in Table 2. In multivariate analyses, all potential prognostic factors were considered, which included patient age, sex, smoking history, NPC family history, rT stage, rN stage, time intervals (between initial radiation and recurrence) and EBV DNA level. The backward stepwise approach was applied for variables selection. Finally, patient age (>60 vs. ≤60: hazard ratio [HR]: 1.757, 95% confidence interval [CI]: 1.181-2.615, P = 0.005), rT stage (rT2 vs. rT1: HR: 1.725, 95% CI: 0.919-3.241, P = 0.090; rT3 vs. rT1: HR: 2.439, 95% CI: 1.453-4.096, P = 0.001; rT4 vs. rT1: HR: 5.007, 95% CI: 2.989-8.388, P < 0.001) and EBV DNA level (detectable vs. undetectable: HR: 1.825, 95% CI: 1.355-2.459, P < 0.001) remained independent prognosis factors.
RPA-based prognostic model for OS
Based on the independent prognostic factors (age, rT stage and EBV DNA), we developed an integrated prognostic model with the method of RPA. Then, five groups were derived: group A (rT stage 1 + any EBV DNA), group B (rT stage 2-3 + undetectable EBV DNA), group C (rT stage 2-3 + detectable EBV DNA), group D (rT stage 4 + undetectable EBV DNA) and group E (rT stage 4 + detectable EBV DNA) (Figure 1). The Kaplan-Meier curves of each group are shown in Figure 2. Further pair-wise comparisons showed that there was no significant difference in OS between group A and group B, and the same condition was found in group C and group D (Table 3). Therefore, we combined group A and group B as the low-risk group, and combined group C and group D as the intermediate-risk group. In total, 99 (36.5%), 119 (43.9%), and 53 (19.6%) patients were assigned to low, intermediate and high-risk groups, respectively, with corresponding three-year OS rates of 60.9%, 33.3%, and 11.0% (P <0.001 for each of the two groups) (Figure 3).
The role of re-RT in patients according to risk subgroups
We further investigated the treatment value of re-RT in patients with different risk groups. The clinical characteristics in different risk groups were shown in Table 4. Interestingly, the role of re-RT was different in different risk groups. In the low- and intermediate-risk groups, patients treated with re-RT achieved higher three-year OS compared with patients treated with PCT alone (low-risk: 72.8% vs. 42.9%, P = 0.001; intermediate-risk: 37.5% vs. 28.7%, P = 0.017). However, the survival benefit of re-RT for lrNPC was not found in the high-risk group, and the three-year OS rate was similar in these two treatment groups (12.5% vs. 4.8%, P = 0.328) (Figure 4). Then, we conducted three separate multivariate analyses of the low, intermediate and high-risk patients. After adjustment for age, rT stage and EBV DNA level, re-RT was an independent prognostic factor in the low and intermediate-risk groups (low-risk: HR: 0.388; 95% CI: 0.217-0.692; P = 0.001; intermediate-risk: HR: 0.539; 95% CI, 0.357-0.815; P = 0.003). However, re-RT was not associated with better OS in high-risk patients (HR: 0.716; 95% CI: 0.399-1.288; P = 0.265) (Table 5).