Biomarker-Driven Initial Systemic Therapy Enabling Curative-Intent Treatment in Non-Metastatic Unresectable Salivary Duct Carcinoma: A Multi-Institutional Retrospective Study

Background: Optimal treatment for non-metastatic unresectable salivary duct carcinoma (SDC) remains unclear. We compared outcomes of upfront biomarker-targeted systemic therapy and radiotherapy. Methods: We retrospectively analyzed the Joint SDC Study Group registry. Thirty-one patients with centrally confirmed non-metastatic unresectable SDC were classified by initial treatment (radiotherapy or systemic therapy). Systemic therapy included trastuzumab plus docetaxel, combined androgen blockade, or chemotherapy. Progression-free survival (PFS) and overall survival (OS) were analyzed. Results: Systemic therapy showed better PFS than radiotherapy (3-year PFS 47.6% vs. 30.0%, p = 0.031) without OS difference. Trastuzumab plus docetaxel showed the highest response rate (75%) and enabled curative-intent treatment in all cases, with the best PFS (3-year 87.5%, p = 0.012). Conclusions: Given the retrospective design and limited sample size, these findings should be regarded as hypothesis-generating. An upfront trastuzumab-based therapy followed by curative-intent treatment may be a promising option for selected patients with HER2-positive unresectable SDC.