BACKGROUNDTumor response to neoadjuvant chemotherapy using the regimen of cisplatin and 5-fluorouracil could define high-risk patients with locoregionally advanced nasopharyngeal carcinoma (NPC). However, the regimen of docetaxel, cisplatin, and 5-fluorouracil (TPF) appears to be more effective than the regimen of cisplatin and 5-fluorouracil. Therefore, one needs to redefine the high-risk subpopulation of patients receiving neoadjuvant chemotherapy with TPF. METHODSA total of 231 patients from a randomized phase 3 trial with American Joint Committee on Cancer/International Union Against Cancer stage III to stage IVB NPC (except T3-T4N0 disease) who were receiving treatment with the TPF regimen were enrolled. Patient survival rates between different groups were compared. RESULTSOf the 231 patients, the overall response to neoadjuvant chemotherapy was a complete response (CR) for 26 (11.3%), a partial response (PR) for 184 patients (79.6%), and stable disease (SD) for 21 patients (9.1%). Univariate analysis revealed the 3-year failure-free survival (FFS) rates in the CR (88.5% vs 61.9%; P =.017) and PR (81.2% vs 61.9%; P = .01) groups, and the 3-year overall survival rates for the CR (96.2% vs 76.2%; P =.048) and PR (93.4% vs 76.2%; P =.025) groups were obviously higher compared with that of the SD group. In multivariate analysis, CR was established as a favorable prognostic factor for FFS (hazard ratio [HR], 0.210; 95% confidence interval [95% CI], 0.057-0.779 [P =.02]), and PR for FFS (HR, 0.447; 95% CI, 0.213-0.936 [P =.033]) and OS (HR, 0.361; 95% CI, 0.132-0.986 [P =.047]) when compared with SD. No survival difference was observed between the CR and PR groups. CONCLUSIONSTumor response to TPF may be a properly powerful prognosis predictor and help to develop individualized treatment strategies for patients with locoregionally advanced NPC. Cancer 2017;123:1643-1652. (c) 2017 American Cancer Society. Patients with advanced nasopharyngeal carcinoma with stable disease after neoadjuvant chemotherapy appear to have a significantly worse prognosis compared with patients who achieve a partial or complete response. Neoadjuvant chemotherapy could help to identify high-risk patients prior to radiotherapy and help clinicians to develop individualized treatment strategies.