The role of perineural invasion in parotid malignancy outcomes: A systematic review and meta-analysis

Abstract

Purpose: At present, perineural invasion is used as a histologic indicator of aggressive salivary gland disease. In other head and neck malignancies, perineural invasion impacts staging of cancer lesions and therefore affects treatment options.

Objective: To compare survival outcomes in primary parotid malignancies with and without perineural invasion.A systematic review pooled data from the scientific literature in patients with any primary parotid malignancy to investigate the prognosis of those with perineural invasion.

Data sources: PubMed (Medline), Scopus and Cochrane databases were queried from inception to July 2020 without any initial search constraints. Additional publications were included from review of pertinent articles.

Study selection: Our inclusion criteria included primary parotid cancers with reported perineural invasion on survival outcomes. Exclusion criteria were non-English language text, non-human studies, reviews, textbooks, abstracts, case reports and case series. Two authors independently reviewed articles for inclusion. Of the initial 465 records, 83 articles were reviewed in full to yield a final collection of 14 studies.

Data extraction and synthesis: PRISMA-p guidelines were used in the reporting of our studies. A MOOSE Checklist was also used. MINORS criteria were applied to assess risk of bias. Random-effects models were used to estimate pooled effect sizes. No institutional review board review was needed for our study.

Main outcomes and measures: Primary study outcomes were set prior to data collection and included overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS) and distant-metastasis-free survival (DMFS) in patients with and without perineural invasion.

Results: Fourteen studies contributed to this meta-analysis. Compared to patients without perineural invasion, the pooled rate of mortality (HR = 3.64), time to recurrence (HR = 3.56), disease-specific mortality (HR = 2.77) and distant metastasis (HR = 3.84) was significantly higher for patients with PNI (all p <.001). Controlling for perineural invasion status, no moderator was associated with these survival outcomes (all p >.05). Given the clinical severity of perineural invasion, few studies were null as shown in a panel of publication bias plots.

Conclusion: Perineural invasion portends a poor survival outcome in patients with parotid malignancies.

Keywords: Mortality; Outcomes; Parotid tumor; Salivary neoplasms; Survival.