Simple Summary Non-melanoma skin cancers (NMSC) represent about one-third of all malignancies. While surgery is the current gold standard treatment, many nonsurgical approaches are available for selected cases. Currently, there are no studies concerning the overall impact of dermoscopy, optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) for NMSC treatment monitoring. Therefore, we aim to review the current literature and provide an updated summary of noninvasive skin imaging in NMSC medical treatment management and the diagnostic accuracy of the most advanced technologies. Background/Objectives: Non-melanoma skin cancer (NMSC) treated with nonsurgical therapies can be monitored with noninvasive skin imaging. The precision of dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in detecting clearance is unclear. We aim to report the proportion of persisting tumors identified with noninvasive technologies available in the literature. Methods: A systematic literature search was conducted on the PubMed and Cochrane Public Library Databases for articles published prior to November 2021. Statistical analyses were conducted with MedCalc 14.8.1 software. Results: A total of eight studies (352 lesions) reporting noninvasive imaging for NMSC clearance following nonsurgical treatment were included. Most (n = 7) reported basal cell carcinoma (BCC), and one study reported squamous cell carcinoma (SCC) clearance. A meta-analysis of the BCC clearance revealed that the summary effect for RCM was higher, as compared to the other techniques. Interestingly, the sensitivity and specificity for OCT were 86.4% (95% CI: 65.1-97.1) and 100% (95% CI: 94.8-100.0), respectively, whilst, for RCM, they reached 100% (95%CI: 86.8-100) and 72.5% (95% CI: 64.4-79.7), respectively. Conclusions: Routine clinical examination and dermoscopy underperform when employed for NMSC clearance monitoring, although they represent the first approach to the patient. OCT and RCM seem to improve the detection of persistent BCC after medical treatment.
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