The Prognostic Value of Radiological Extranodal Extension in HPV-Positive Oropharyngeal Carcinoma Treated by (Chemo-)Radiation

Purpose/Objective(s)

In HPV-positive (HPV+) oropharyngeal carcinoma (OPC), N-status is defined exclusively by size and laterality of lymph node metastasis. In HPV-unrelated head and neck cancers, extranodal extension has already been included in the clinical N-categories of the TNM-staging system. There is emerging evidence that the presence of radiological extranodal extension (rENE) impacts prognosis and survival for HPV+ OPC. The hypothesis of this study is that the presence of rENE in node positive HPV+ OPC is associated with worse outcome, and rENE may be used to improve prognostication.

Materials/Methods

Consecutive patients treated by definitive radiation or chemoradiation (organ-preservation), using IMRT, for node-positive HPV+ OPC between 2009 and 2018 were retrospectively registered. Baseline diagnostic MRI or CT scans (acquired <60 days of start of treatment) were retrospectively scored for the presence of rENE by two experienced head and neck radiologists, according to previously described methods (Huang et al., JCO 2021) and with scoring for level of certainty for the presence of rENE (Panicek et al., AJR 2016). Outcome measures included Overall Survival (OS), Disease Free Survival (DFS), Locoregional Control (LRC) and Distant Control (DC); each were stratified for rENE status. Multivariate analysis for OS was used to investigate the independent prognostic value of rENE.

Results

This cohort consisted of 111 patients with node-positive HPV+ OPC, treated by organ-preservation. Median age was 62.8 years, gender was male in 78% and female in 22% of cases, median number of pack years of smoking was 15 (range 0-113). T-stage (according to TNM-8) was as follows: T1 in 21, T2 in 34, T3 in 21 and T4 in 35 cases. N-stage consisted of: N1 in 66 cases, N2 in 11 cases and N3 in 1 case. TNM-group staging was stage I in 48, stage II in 27 and stage III in 36 cases. rENE was present (rENE+) in 39 cases (35%) and absent (rENE-) in 72 cases (65%). Median follow-up of all patients was 57 months (range 2-156); median follow-up of patients alive at last follow-up was 63 months (range 31-156). Patients with rENE+ had inferior 5-year OS compared to those with rENE-: 57% vs. 76% (Log-rank p-value = 0.018), inferior 5-year DFS (51% vs. 71%, p-value = 0.016), and inferior 5-year DC (81% vs. 91%, p-value = 0.11) but there was no meaningful difference in 5-year LRC (86% vs. 90%, p-value =0.49). In multivariate analyses, the following factors were independently associated with OS: N-stage (N2 vs. N1, HR 2.66, p-value = 0.01), age (HR 1.05, p-value = 0.005), smoking pack years (HR 1.02, p-value = 0.035) and rENE (HR 2.38, p-value = 0.024).

Conclusion

rENE is indeed an important prognostic factor in a contemporary single-institutional cohort of patients with HPV+ OPC, and is independent of N-stage. rENE may potentially be used to further refine the TNM staging system.