Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study

Background Intralesional methotrexate (MTX–il) has been used as neoadjuvant therapy for keratoacanthoma but has only been utilized in a few isolated cases of cutaneous squamous cell carcinoma as neoadjuvant therapy (cSCC). Objectives The objective of this study was to evaluate the effectiveness in clinical practice of presurgical MTX–il infiltration to reduce the size of the cSCC. Safety and the impact on subsequent reconstructive surgical techniques was also assessment. Methods Single, retrospective, observational study of two historical cohorts differentiated in time. Subjects included were diagnosed with infiltrating cSCC. Patients included in group-A received neoadjuvant MTX–il and patients included in group-B underwent scheduled surgery without prior infiltration. Univariate and multivariate analyses were performed. Results Group-A patients (n = 43) showed an average reduction in the tumour area of 0.52 cm2, while in group-B (n = 43), the area increased by 0.49 cm2. A multivariate linear regression analysis demonstrated that MTX–il was the only independent variable that significantly reduced the tumour size [mean 42.6% (95% CI: 31.17–54.03)]. Tumours ≥2 cm in size required significantly a lower percentage of complex reconstructions (P = 0.026). Lower lip tumours showed a higher reduction in group treated with MTX–il (P = 0.045). The only complication observed was discomfort during methotrexate infiltration (60.47%). Conclusions Neoadjuvant MTX–il reduced the presurgical size of cSCC lesions and could simplify their subsequent surgery.