Histologic Origin as a Prognostic Factor in Salivary Duct Carcinoma

Introduction: Prognostic factors are essential for guiding treatment in salivary duct carcinoma (SDC) due to the absence of standardized treatment protocols. It remains controversial whether SDC arising de novo versus SDC ex pleomorphic adenoma (PA) have different prognoses. This study evaluated the association between histologic origin and survival in SDC.

Methods: This single-institution retrospective cohort study included treatment naïve patients from 2000-2024 with a pathologic diagnosis of SDC. Histologic origin was determined by pathology or clinical presentation. Kaplan-Meier analysis and log-rank tests were used to estimate the effect of histologic origin on overall survival (OS) and disease-free survival (DFS). Cox regression calculated hazard ratios (HR) and 95% confidence intervals (CI) for 13 covariates.

Results: This study included 68 patients with a median follow-up of 19.8 months (range: 3–60). Of the n=25 SDC ex PA cases, there were 3 deaths and 6 recurrences (5 distant and 1 regional). Median time to recurrence was 20 months (range: 1.3-45). Of the n=43 SDC de novo cases, there were 10 deaths and 19 recurrences (16 distant, 2 regional, and 1 local). Median time to recurrence was 12 months (range: 1.4-120).

Log-rank tests showed no statistically significant difference in OS (p = 0.28) or DFS (p = 0.19) between SDC ex PA and SDC de novo, though there was a trend towards improved survival in the SDC ex PA cohort. Histologic origin was not associated with OS (univariate p = 0.29) or DFS (univariate p = 0.19; multivariable p = 0.23). Covariates associated with worse DFS in multivariable analysis included pathologic nodal metastasis (HR = 4.0 (95% CI: 1.8-9.0), p< 0.001) and non-parotid tumor location (HR = 2.3 (1.0-5.4), p=0.045).

Conclusions: SDC arising de novo versus SDC ex PA may be distinct clinical entities that will require further investigation in larger cohort studies. Distant metastasis is the primary mechanism of failure for both SDC ex PA and de novo. Future clinical trials should focus on novel treatment paradigms, such as neoadjuvant therapies, in an effort to reduce the rate of distant failure in SDC patients.