Outcomes of adjunctive therapies post hedgehog inhibitors in the management of locally advanced basal cell carcinoma: A systematic review and pooled analysis

Management of patients with locally advanced basal cell carcinoma (laBCC) with traditional strategies has yielded suboptimal outcomes. Targeted treatments including hedgehog inhibitor therapy (HHIT) present limitations when utilized as monotherapy. Herein, we report evidence-based outcomes from available literature on multimodality treatments adjuvant to HHIT in laBCC management. Utilizing a systematic search strategy in PubMed, we identified studies published from inception to April 15, 2020, screened for definitive inclusion/exclusion criteria, and performed individual study quality assessment and pooled analysis to assess impact of adjunctive treatment-based responses post-HHIT on clinical response and recurrence outcomes. Twenty-nine studies (n = 103) were included. Primary findings include a complete response (CR) rate of 90.5%, the median follow-up of 12 months post-HHIT completion. The recurrence rate was 10.8% with 12-month median time to recurrence. Mohs micrographic surgery (MMS) had 100% CR post-HHIT, while no difference was observed between surgery and radiation therapy (RT). MMS and surgery had comparable 2-year recurrence free rates (RFR) at 87% and 86% respectively, while RT had the lower 2-year RFR at 67%. Male gender portended a more advanced stage at diagnosis and worse outcomes. In a subset analysis, periorbital laBCCs with orbital involvement had a CR rate of 81.8% versus 100% in those without orbital involvement, with similar rates of recurrence. Limited available quantitative data and possible publication bias were limitations. Pooled analysis of observational data supports use of adjunctive therapies post-HHIT to improve treatment response in patients with laBCC. Longer-term follow-up is needed to study recurrence rates after combination therapy.