Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with Mohs micrographic surgery (MMS) offering the highest cure rates among available treatment modalities 1-3. However, treatment can become challenging in select patients with locally advanced tumors, difficult anatomical locations, or psychosocial barriers to care 4, 5. We encountered a 74-year-old female with a large (4 cm), ulcerated BCC on the scalp who initially declined surgery due to social and logistical challenges. Given the tumor's size, ulceration, and location in a high-risk area, we initiated neoadjuvant therapy with vismodegib, a sonic hedgehog pathway inhibitor (SHHI), to control tumor progression and facilitate future surgical management. Following a favorable clinical response, the patient ultimately underwent successful Mohs surgery with clear margins and secondary intention healing. The use of neoadjuvant vismodegib in this case to facilitate Mohs surgery for a large scalp BCC prompted us to explore this strategy; we conducted a systematic review and meta-analysis of studies reporting outcomes of neoadjuvant SHHIs prior to Mohs surgery for locally advanced BCC. Following the PRISMA guidelines, we searched PubMed, Embase, Medline, Web of Science, and Cochrane from inception to February 2025. The study was registered in PROSPERO (CRD420250653798). Two independent reviewers screened, extracted data from eligible articles, and evaluated study quality using the appropriate risk of bias tool. Five studies met our inclusion criteria encompassing 105 patients and 110 tumors (Figure 1). All patients except two were treated with vismodegib 150 mg daily. The other two received sonidegib 200 mg. Treatment durations ranged from 12 to 27 weeks with daily or alternate-day dosing. The primary outcomes included in our study were complete histological clearance following Mohs surgery, defined as successful tumor eradication either at first layer (debulk) or subsequent layers, the number of Mohs stages, and recurrence rates following complete histological clearance (Figure 1). The pooled histological clearance rates following surgery (k = 5; n = 98) was 49% (95% confidence interval CI: 39%–59%, p = 0.43, I2 = 0%) using a random-effects model (Figure 1). Individual study proportions ranged from 46% to 100%. The number of Mohs stages (k = 3; n = 22) ranged from 1 to 6. The pooled recurrence rate (k = 4; n = 24) was 11% (95% CI: 4%–29%, p = 0.98, I2 = 0%) with individual study proportions ranging from 0% to 8% (Figure 1). Our exploratory findings suggest that neoadjuvant SHHI therapy may enhance surgical feasibility in select cases of locally advanced BCC but does not consistently help achieve tumor clearance even after surgery. This relatively low clearance rate following MMS likely reflects multiple factors: the complexity of initially inoperable tumors, which are often extensive and associated with significant morbidity; study and methodological limitation including the small sample size and design of included studies. The wide variability in the number of Mohs stages is likely influenced by factors such as tumor size, location, histologic subtype, and surgical technique. Nonetheless, recurrence rates remained low in successfully treated patients. However, due to the small sample size and variable follow up duration, recurrence may be underestimated. Although adverse events were not systematically analyzed in this review, SHHIs are known to be associated with clinically important side effects, including dysgeusia, muscle cramps, alopecia, fatigue, and weight loss, which may affect adherence and quality of life and should be considered when selecting patients for neoadjuvant therapy. Overall, SHHIs appear to represent a useful adjunct to facilitate MMS management in carefully selected patients with locally advanced BCC. Given the limited number of studies, small sample sizes, and reliance on observational data, the study findings are exploratory and should be interpreted cautiously. Prospective studies with standardized outcome definitions, stratified tumor characteristics, and longer follow-up are needed to better define patient selection and optimize treatment protocols. The authors have nothing to report. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Barnawi et al. (Fri,) studied this question.