Chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Who really needs it

The CSCO and ASCO guidelines in 2021 recommend chemotherapy for stage III-IVA (8th edition of AJCC staging) nasopharyngeal carcinoma (NPC). Actually, patients with stage T3-4N0M0 are often excluded from various clinical trials of the locoregionally advanced NPC, and the survival benefit of chemotherapy in such patients has always been controversial. This study aims to explore the benefit of chemotherapy in patients with locoregionally advanced NPC, especially those with negative lymph nodes.

A total of 2741 patients were extracted from the SEER database. After a 1:1 PSM analysis, 272 patients were obtained to further explore whether the addition of chemotherapy would achieve survival benefits.

After PSM, Kaplan-Meier curves showed that the overall survival (OS) of patients receiving chemoradiotherapy (p = 0.031) was higher than those receiving radiotherapy alone. Similar results were observed for cancer-specific survival (CSS). We further stratified the patients according to lymph node status and found that the addition of chemotherapy in patients with positive lymph nodes could significantly improve 5-year OS rates (58.08% vs. 43.95%; p = 0.025) and 5-year CSS rates (67.42% vs. 51.95%; p = 0.015) compared with radiotherapy alone, but there was no additional benefit of chemotherapy in patients with negative lymph nodes. For all 449 cases of T3-4N0M0 NPC, radiotherapy improved the OS rates (HR 0.293, 95% CI 0.203-0.424) and the CSS rates (HR 0.252, 95% CI 0.171-0.371) compared with no radiotherapy, while chemotherapy did not show significant survival benefit compared with no chemotherapy.

Our results reveal that stage T3-4N0M0 NPC may be exempted from chemotherapy, and use radiotherapy alone to reduce toxic and side effects. These results still need to be verified by future prospective trials.