Soft tissue metastasis in p16-positive oropharynx carcinoma: Prevalence and association with distant metastasis

Background: Ungraded extracapsular spread (ECS) has been found non-prognostic in p16-positive, surgically-treated oropharynx squamous cell carcinoma (OPSCC). However, soft tissue metastasis (STM), the highest ECS grade, is reported prognostic. Our study's objective is to explore STM relative to distant metastasis (DM), the most frequent recurrence site in surgically-treated p16-positive OPSCC. Methods: Primary p16-positive OPSCC patients undergoing transoral surgery (TOS) and neck dissections were identified from a prospectively-assembled database. DM and regional recurrence (RR) rates, and DM-free survival (DMFS) were compared in pN+ patients without STM (group I) and with STM (group II). Results: Of 222 patients, 202 had pN+ disease: 147 (73%) in group I and 55 (27%) in group II. The DM rate was 6.7% (n = 15/222) overall. The DM rates were 4% (n = 6/147) vs. 16.4% (n = 9/55), RR rates were 2% (n = 3) vs. 5% (n = 3), and 5-year DMFS rates were 94.8% vs. 82.4%, in groups I and II respectively. STM was significantly associated with poorer DMFS (HR = 4.6, 95% CI: 1.65, 13.03, p = 0.004), an observation driven by its effect in the T3-T4 and not the T1-T2 subset. Amongst patients receiving adjuvant therapy, STM's association with poorer DMFS was lost in multivariable analysis; high T-classification, however, remained significant (HR = 5.16, 95% CI: 1.43, 18.52, p = 0.012). Five-year DMFS for STM patients was 82.2% in chemoradiation (37% T3-T4) vs. 85.6% in radiation (35% T3-T4) group. Conclusions: STM was significantly associated with DM and DMFS, but only in the T3-T4, not T1-T2 subset; no significant association was seen with RR. In patients receiving adjuvant therapy, only high T-classification was associated with DMFS, not STM. Chemoradiation used as adjuvant therapy was not associated with better DMFS in STM patients for any T-classification.