Stage-dependent conditional survival and failure hazard of non-metastatic nasopharyngeal carcinoma after intensity-modulated radiation therapy: Clinical implications for treatment strategies and surveillance

Abstract

Purpose: Conditional survival (CS) and failure hazard estimations can provide important dynamic prognostic information for clinical decision-making and surveillance counseling. The current study aimed to investigate the CS and dynamic failure hazard in non-metastatic nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT).

Methods: Conditional overall survival (COS) and progression-free survival (CPFS) estimates adjusted for age and gender against each AJCC 8th stage were calculated. Multivariable Cox regression (MCR) models were fitted in the entire population at baseline and subsequently separate MCR models were fitted in patients who have maintained event-free time of 1 to 10 years to generate respective hazard ratio (HR). Annual hazard rates of death and progression over 10 years for each stage were also estimated.

Results: A total of 1993 patients were eligible for analysis. The estimated 5-year OS and PFS for entire cohort were 79.0% and 70.7% at initial diagnosis. After 5 years of event-free follow-up, additional 5-year COS and CPFS increased to 85.9% and 85.5%, respectively. Stage I/II maintained dramatically favorable CS and low hazard (< 5%) of death and progression over time. Relative to stage I/II, stage III manifested non-significantly higher failure hazard for the first 3 years of survivorship and approached to similar level of stage I/II afterwards. Stage IVA presented most impressive improvement in terms of both COS (∆=9.8%) and CPFS (∆ = 16.8%) whereas still drastically inferior to that of stage I-III across all conditional time points. After 4 years of follow-up, progression hazard of stage IVA became relatively steady of approximate 6%.

Conclusions: Survival prospect of non-metastatic NPC improves over years with distinct dynamic patterns across stages, providing important implications for personalized decision-making in terms of both clinical management and surveillance counseling. Stage-dependent and hazard-adapted clinical management and surveillance are warranted.

Keywords: conditional survival; hazard analysis; intensity-modulated radiotherapy; nasopharyngeal neoplasms; survival analyses.