Present and future perspectives of photodynamic therapy for cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (SCC) is the second most common skin cancer. Surgery remains the main stay of treatment, but some patients are not eligible for surgery and, more importantly, lesions at critical sites need nonsurgical approaches for tissue preservation. In this context, photodynamic therapy (PDT) has been extensively studied as noninvasive or minimally invasive treatment, and studies have shown promising results in terms of safety, efficacy, and cosmetic outcome. Also, studies have proposed different mechanism for its efficacy. However, human studies demonstrating its efficacy are limited in terms of sample size and tumor depth of invasion. Good results are mainly seen in case reports of microinvasive SCC, which is defined as SCC limited to papillary dermis. This inadequacy is due to inadequate penetration of topically applied photosensitizers through keratinized tumor surfaces. To overcome these hurdles, pretreatment with lasers or microneedles and encapsulation of photosensitizers into nanoparticles have been tried. Hence, the present article will discuss studies that have demonstrated the efficacy and safety of PDT for cutaneous SCC, studies that have postulated the mechanism of action of PDT, agents that have been used as PDT enhancers, and finally, the recent use of adjuvant therapy in combination with PDT.