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Photodynamic Therapy (PDT) for Non-Melanoma Skin Cancer

Authored by

Caroline Mortelliti

Patients frequently ask about the effectiveness of Photodynamic therapy (PDT) as a treatment for non-melanoma skin cancers. But what exactly is PDT, how does it work, when is it appropriate, and how does it compare to other existing topical treatments such as combination Fluorouracil-Calcipotriene cream?


What is it?

Photodynamic therapy (PDT) is a non-surgical treatment option for certain types of non-melanoma skin cancer. It uses a special cream applied to your skin combined with light exposure to destroy cancer cells.(1,2)


How does PDT work?

You will arrive at your dermatologist's office where a photosensitizing cream is applied to the affected areas. This cream is absorbed more readily by abnormal cells than by healthy skin cells. After letting the cream sit for 1-3 hours, the area is then exposed to blue or red light for about 10-20 minutes.(1,3)


When is PDT appropriate?

PDT works best for low-risk, superficial skin cancers, including:

  • Actinic Keratoses (pre-squamous cell skin cancers)

  • Superficial Basal Cell Carcinoma

When is PDT not appropriate?

PDT has important limitations. It should not be used for:

  • Invasive squamous cell carcinoma (4,5)

  • Thick or nodular basal cell carcinomas (6,7)

  • Aggressive basal cell carcinoma subtypes (5,8)

  • High-risk skin cancers on the face (central face, around eyes, nose, and ears)

For these cancers, surgery remains the gold standard with the lowest recurrence rates.(9,10)


When to use PDT:

PDT is an appropriate option if surgery is not feasible due to the location of the cancerous lesion, if you’d like to avoid surgery and cosmetic implications of surgery, or if you have multiple areas/big areas that need treatment.


However, another topical treatment exists which is a preferred alternative to PDT…


PDT vs. Combination Fluorouracil/Calcipotriene Cream (Combination Cream)

What is Combination Cream?

Is a compounded medication you can obtain from your dermatologist. It includes two medications: 5-fluorouracil (a chemotherapy cream) and calcipotriene (a vitamin D derivative). The combination works similarly to PDT by killing abnormal cells, though the mechanisms are not exactly the same.(11,12) The National Comprehensive Cancer Network lists this combination as a "preferred" treatment for widespread affected areas, noting it provides "the longest duration of prophylaxis against squamous cell carcinoma."(13)


How they compare:

Combination cream: Applied twice daily for 4 days to the face and scalp, and 5 days the rest of the body. Importantly, it reduces the risk of developing squamous cell carcinoma on the face and scalp for up to 3 years after treatment.(11,14) Side effects include redness, burning, itching, potentially minor bleeding, with peak reactions occurring around day 10 after treatment.(11,15)


PDT: Usually requires 1-2 treatment sessions at your dermatologists office, each lasting 2-4 hours in total. Side effects of PDT include significant pain during light exposure, redness, swelling, crusting, scabbing.(2,16)


A few things to note

  • A large trial comparing multiple treatments found that 5% fluorouracil alone was more effective than PDT at 12 months (74.7% vs. 37.7% treatment success).(17)

  • In both lines of treatment, your doctor may not examine your skin until after treatment is finished.

Long-Term cancer prevention:

Combination cream has demonstrated a superior long-term protective effect when compared to other treatments and is why guidelines list it as "preferred" for field cancerization.(18,19)


When to choose each treatment:

Combination cream is likely the preferred treatment option per your doctor. However, PDT is still an option if its use meets the criteria stated above, and if you would prefer fewer days of treatment, and a supervised treatment in the office. Some studies suggest that these two treatments can be combined! Pre-treatment with Combination cream 6 days before PDT can improve PDT effectiveness.(20)


In conclusion

PDT is a reasonable option for superficial non-melanoma skin cancers, especially when cosmetic outcomes are a priority or surgery is not ideal. However, for patients with extensive sun damage or multiple precancers, combination 5-FU/calcipotriene cream is often preferred because it not only clears lesions but also provides longer-lasting protection against squamous cell carcinoma.


References

  1. Keratinocyte Carcinoma. Wehner MR. JAMA. 2025;:2840731. doi:10.1001/jama.2025.18749.

  2. European Dermatology Forum Guidelines on Topical Photodynamic Therapy 2019 Part 1: Treatment Delivery and Established Indications - Actinic Keratoses, Bowen's Disease and Basal Cell Carcinomas. Morton CA, Szeimies RM, Basset-Seguin N, et al. Journal of the European Academy of Dermatology and Venereology: JEADV. 2019;33(12):2225-2238. doi:10.1111/jdv.16017.

  3. Ericson MB, Wennberg AM, Larkö O. Review of photodynamic therapy in actinic keratosis and basal cell carcinoma. Ther Clin Risk Manag. 2008;4(1):1-9.

  4. Methylaminolaevulinate-Based Photodynamic Therapy of Bowen's Disease and Squamous Cell Carcinoma. Calzavara-Pinton PG, Venturini M, Sala R, et al. The British Journal of Dermatology. 2008;159(1):137-44.      doi:10.1111/j.1365-2133.2008.08593.x.

  5. European Guidelines for Topical Photodynamic Therapy Part 1: Treatment Delivery and Current Indications - Actinic Keratoses, Bowen's Disease, Basal Cell Carcinoma. Morton CA, Szeimies RM, Sidoroff A, Braathen LR. Journal of the European Academy of Dermatology and Venereology : JEADV. 2013;27(5):536-44. doi:10.1111/jdv.12031.

  6. Conventional and Combination Topical Photodynamic Therapy for Basal Cell Carcinoma: Systematic Review and Meta-Analysis. Collier NJ, Haylett AK, Wong TH, et al. The British Journal of Dermatology. 2018;179(6):1277-1296. doi:10.1111/bjd.16838.

  7. Non-Melanoma Skin Cancer. Madan V, Lear JT, Szeimies RM. Lancet (London, England).      2010;375(9715):673-85. doi:10.1016/S0140-6736(09)61196-X.

  8. Photodynamic Therapy and Non-Melanoma Skin Cancer. Griffin LL, Lear JT. Cancers. 2016;8(10):E98.      doi:10.3390/cancers8100098.

  9. Guidelines of Care for the Management of Basal Cell Carcinoma. Work Group, Invited Reviewers, Kim JYS, et al. Journal of the American Academy of Dermatology. 2018;78(3):540-559. doi:10.1016/j.jaad.2017.10.006.

  10. Balakirski G, Lehmann P, Szeimies RM, Hofmann SC. Photodynamic therapy in dermatology: established and new indications. J Dtsch Dermatol Ges. 2024;22(12):1651-1662. doi:10.1111/ddg.15464

  11. Randomized Trial of Calcipotriol Combined With 5-Fluorouracil for Skin Cancer Precursor Immunotherapy. Cunningham TJ, Tabacchi M, Eliane JP, et al. The Journal of Clinical Investigation. 2017;127(1):106-116. doi:10.1172/JCI89820.

  12. Calcipotriol and 5-Fluorouracil Combination Therapy for the Treatment of Actinic Keratosis in the Clinic: A Review Article. Dlott AH, Spencer SA, Di Pasqua AJ. Clinical Drug Investigation. 2024;44(10):733-737. doi:10.1007/s40261-024-01392-w.

  13. Squamous Cell Skin Cancer. National Comprehensive Cancer Network. Updated 2025-09-02.

  14. Rosenberg AR, Tabacchi M, Ngo KH, et al. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight. 2019;4(6):e125476. Published 2019 Mar 21. doi:10.1172/jci.insight.125476

  15. Guidelines of Care for the Management of Actinic Keratosis. Eisen DB, Asgari MM, Bennett DD, et al. Journal of the American Academy of Dermatology. 2021;85(4):e209-e233.      doi:10.1016/j.jaad.2021.02.082.

  16. Daylight Photodynamic Therapy With Methyl Aminolevulinate Cream as a Convenient, Similarly Effective, Nearly Painless Alternative to Conventional Photodynamic Therapy in Actinic Keratosis Treatment: A      Randomized Controlled Trial. Rubel DM, Spelman L, Murrell DF, et al. The British Journal of      Dermatology. 2014;171(5):1164-71. doi:10.1111/bjd.13138.

  17. Randomized Trial of Four Treatment Approaches for Actinic Keratosis. Jansen MHE, Kessels JPHM,      Nelemans PJ, et al. The New England Journal of Medicine.2019;380(10):935-946. doi:10.1056/NEJMoa1811850.

  18. Risk of Invasive Cutaneous Squamous Cell Carcinoma After Different Treatments for Actinic Keratosis: A Secondary Analysis of a Randomized Clinical Trial.JAMA Dermatology. 2022. Ahmady S, Jansen MHE, Nelemans PJ, et al.

  19. A Comparison of Invasive Squamous Cell Carcinoma Greater Than 1 year After Treatment With 5-Fluorouracil, Imiquimod, or Photodynamic Therapy With Aminolevulinic Acid.Journal of the American Academy of Dermatology. 2022. Cheng B, Veerabagu S, Miller CJ, et al.

  20. 5-Fluorouracil Enhances Protoporphyrin IX Accumulation and Lesion Clearance During Photodynamic Therapy of Actinic Keratoses: A Mechanism-Based Clinical Trial. Maytin EV, Anand S, Riha M, et al. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research.      2018;24(13):3026-3035. doi:10.1158/1078-0432.CCR-17-2020.

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