Abstract
BACKGROUND: The evolution of nasopharyngeal carcinoma (NPC) involves potential transitions among states of recurrence, metastasis, and/or remission. Understanding the dynamics of NPC progression following radical radiotherapy may help optimize surveillance protocols and patient management. OBJECTIVES: To characterize the progression dynamics of NPC following radical radiotherapy. DESIGN: A retrospective study. METHODS: The cohort comprised NPC patients who underwent radical intensity-modulated radiotherapy between 2016 and 2022. A multi-state Markov model was employed to estimate transition intensities and probabilities across various disease states, including failure-free, single failure event (recurrence or metastasis, R/M), multi-event progression (recurrence and metastasis, R&M), and death. A Shiny-based web tool was developed to facilitate the clinical translation of the model. RESULTS: A total of 4800 NPC patients were included, yielding 18,641 disease-state assessments, with a median follow-up of 3.3 years. The transition intensity from metastasis to death (0.025, 95% confidence interval (CI), 0.021-0.029) was 2.3 times greater than that from recurrence to death (0.011, 95% CI, 0.009-0.014). The estimated probabilities of remaining failure-free, experiencing R/M, and deteriorating to death were 89.9%, 7.7%, and 2.1% at 2 years, respectively. Among patients with recurrence, the probabilities of progression to metastasis and death were 3.8% and 24.5%; among those with metastasis, the probabilities of progression to recurrence and death were 2.1% and 45.0%, respectively. Increasing age, male sex, advanced TNM stage, higher pre-treatment Epstein-Barr virus (EBV) DNA, and detectable post-treatment EBV DNA were associated with treatment failure. A web tool was developed to predict NPC disease-state transitions at 2 years. CONCLUSION: These findings provide initial evidence on the dynamic progression of NPC, which may inform clinical management and patient counseling. Risk-stratified screening and targeted interventions could help mitigate disease progression.