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Non-Surgical Therapeutic Strategies for Non-Melanoma Skin Cancers

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Opinion statement

Non-melanoma skin cancer (NMSC) is a globally prevalent skin disease, with basal cell carcinoma and squamous cell carcinoma accounting for 99% of NMSC cases. While surgical excision is the most common approach, numerous non-surgical therapies have rapidly advanced in recent years. In cases of low-risk NMSC, alongside surgical excision, priority should be given to physical therapy and photodynamic therapy. Physical therapy modalities, exemplified by electrodessication and curettage, emerge as safe and efficacious alternatives. In juxtaposition, photodynamic therapy, albeit relatively more costly, assumes preference for patients exhibiting heightened cosmetic concerns owing to the scarring risks inherent to physical therapy and surgical excision. Notably, the combination of curettage and photodynamic therapy has exhibited remarkable efficacy in the treatment of nodular basal cell carcinoma. Additionally, for elderly patients who may be intolerant to stimulation, modified photodynamic therapy offers an almost painless option. When surgery is unavoidable, photodynamic therapy can be a valuable adjunct, allowing for a more conservative surgical approach, either before or after the procedure. Radiotherapy holds a prominent role in comprehensive treatment strategies, especially for patients ineligible for surgical intervention or those with lesions precluding further surgical measures. In cases of NMSC exhibiting perineural invasion or lymphovascular involvement, adjunctive radiotherapy is advised; however, potential adverse effects necessitate careful consideration. For advanced NMSC cases where surgery and physical therapy fall short, immunotherapy provide viable solutions. Systemic therapy employing Hedgehog pathway inhibitors can be considered for patients with distant metastatic basal cell carcinoma, despite its low incidence, or individuals with locally advanced lesions who are not surgical candidates, or those encountering recurrences after resection and radiotherapy. However, close monitoring of disease progression and adverse reactions is crucial. In this evolving landscape of NMSC treatment, personalized and multidisciplinary approaches are key, ensuring optimal outcomes while prioritizing patient safety and satisfaction.

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Abbreviations

NMSC:

Non-melanoma skin cancer

BCC:

Basal cell carcinoma

cSCC:

Cutaneous squamous cell carcinoma

MCC:

Merkel cell carcinoma

EMPD:

Extramammary Paget’s disease

UV:

Ultraviolet

AK:

Actinic keratoses

Hh:

Hedgehog

CT:

Computed tomography

PET:

Positron emission tomography

5-FU:

5-Fluorouracil

PD-1:

Programmed cell death-1

FDA:

Food and Drug Administration

EMA:

European Medicines Agency

ORR:

Objective response rates

CR:

Complete responses

PR:

Partial responses

PD-L1:

Programmed cell death-ligand 1

EGFR:

Epidermal growth factor receptor

mTOR:

Mammalian target of rapamycin

PDT:

Photodynamic therapy

MAL:

Methyl aminolevulinate

ALA:

5-Aminolevulinic acid

PpIX:

Protoporphyrin IX

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Funding

This study was supported by the National Key Research and Development Program funding, Grant/Award Numbers: 2022YFC2504700 and 2022YFC2504705 and National Natural Science Foundation of China, Grant/Award Number: 82073013.

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  1. Qingyu Zeng, Chengqian Chen, and Diyan Chen contributed equally to this work and should be considered as co-first authors.

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  1. Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200040, China

    Qingyu Zeng PhD, Chengqian Chen PhD, Student, Diyan Chen PhD, Student, Guolong Zhang PhD & Xiuli Wang PhD

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QZ, CC, and DC contributed equally to the writing of the manuscript and should be considered as co-first authors. XW and GZ provided guidance and support throughout the process. All authors have read and approved the final manuscript.

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Correspondence to Guolong Zhang PhD or Xiuli Wang PhD.

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Zeng, Q., Chen, C., Chen, D. et al. Non-Surgical Therapeutic Strategies for Non-Melanoma Skin Cancers. Curr. Treat. Options in Oncol. 24, 1978–1993 (2023). https://doi.org/10.1007/s11864-023-01154-4

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