Margins in major salivary gland surgery: clinical and pathological criteria for defining margins and their implications on the choice of multimodal therapies. A systematic review

Objective: Major salivary gland malignancies (MSGM) are a rare and heterogeneous group of tumours accounting for 1-5% of all head and neck cancers. When feasible, surgical removal with negative margins is the preferred treatment, reserving adjuvant radiotherapy for adverse clinicopathological features such as high-grade, advanced-stage, extranodal extension, lympho-vascular invasion, perineural invasion, and positive margins. This systematic review aims to evaluate the current literature on the definition of negative and close margins for MSGM, their impact on loco-regional recurrence (LRR), disease-free (DFS), and overall survival (OS), and their implications in the choice of multimodal therapies. Methods: An online search of articles published between 2004 and 2024 was carried out using PubMed via a PICO search strategy for qualitative questions and written following the PRISMA statement guidelines. The following parameters were evaluated: definition of free and close margins, and their impact on local control. Results: The initial search yielded 158 articles. Following the application of inclusion and exclusion criteria, 30 full-text publications were reviewed. All studies were retrospective. A total of 15,985 patients who underwent surgery were considered. Margin involvement ranged widely among the studies from 14.3% to 65.4%. Five out of 30 studies reported no data about association between margins and LRR, DFS, and OS. Twenty of 25 studies reported a significant correlation between positive margins and oncological outcomes regardless of the histological types, while 5 focused on high-stage cancers or more aggressive histotypes and described no association between margin status and oncological outcomes. Nine of 30 studies described close margins in the absence of a univocal definition of threshold for close vs. negative margins. Most studies did not report a significant correlation between close margins and oncological outcomes. Conclusions: Surgical resection achieving negative margins is recommended for MSGM. Positive margin is widely considered an adverse clinicopathological feature and performing adjuvant radiotherapy has documented survival benefits. A consensus involving a definition of close margin is missing, although further treatment is not recommended, preferring a watch-and-wait approach in presence of close margins.