Clinical outcomes in perineural spread of cutaneous squamous cell carcinoma via the ophthalmic nerve
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Updated: Aug 4, 2026

A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Published on: January 5, 2017
Lachlan Crawford1, James Bowman1,2, Mitesh Gandhi2
1Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Background:
There are no large studies reporting oncological or survival outcomes for patients diagnosed with perineural spread (PNS) of cutaneous squamous cell carcinoma (cSCC) via the ophthalmic nerve (V1). Where orbital exenteration may be necessary for curative treatment, it is critical to have survival data with which the morbidity associated with surgical treatment can be justified. Furthermore, with the emerging treatment option of immunotherapy, current standard of care outcomes are needed to help guide future trial design and eventually changed management guidelines.
Objective:
To determine the oncological and survival outcomes observed in patients with PNS of cSCC via V1.
Materials And Methods:
Retrospective analysis of prospectively maintained cohort of patients with PNS of cSCC via V1 treated in a tertiary Australian head and neck oncology/skull base referral center. Consecutive sample of 53 patients managed between March 1, 1999 and April 30, 2020. Follow-up closure date was September 1, 2021. Curative-intent surgery, curative-intent radiotherapy, or palliative care was undertaken. Endpoints included five-year overall, disease-specific, and disease-free survival from the date of treatment.
Results:
Five-year Kaplan-Meier overall survival was 61.9% (95% CI 46.2%-74.3%), with disease-specific survival of 74.6% (95% CI 58.8%-85.3%), and disease-free survival 62.1% (95% CI 46.5%-74.3%). Survival was superior in patients treated via surgery and adjuvant radiotherapy than in those receiving surgery alone or definitive radiotherapy. Survival was superior among patients with less advanced disease as assessed by the Williams zonal staging system; patients with Zone 1 disease had disease-specific survival of 94.1% at 5 years with 82.5% disease-free survival.
Discussion:
Five-year oncological and survival outcomes in this cohort were favorable. Superior survival was observed in patients treated with curative-intent surgery and adjuvant radiotherapy. Less extensive disease as delineated by the Williams zonal staging system was associated with improved survival.
Conclusion:
Surgical resection with adjuvant radiotherapy confers favourable oncological and survival outcome in patients with V1 PNS, particularly with early disease limited to Zone 1.
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