Beyond the scalpel: Rare and experimental nonsurgical treatments for basal cell carcinoma

Authors

  • Elen Deng Penn State College of Medicine, Hershey, PA, USA Author
  • Amor Khachemoune Premier Dermatology , Department of Dermatology, Istanbul Medipol University, International School of Medicine, Istanbul, Turkey Author

DOI:

https://doi.org/10.25251/z041c253

Keywords:

basal, cancer, nonsurgical, skin, treatment

Abstract

Basal cell carcinoma (BCC) is typically found on sun-exposed skin and is the most common form of skin cancer. Risk factors include male sex, fair skin, increased ultraviolet radiation exposure, prior history of BCC, chronic arsenic exposure, genetic predisposition, and immunosuppression. BCC is a slow-growing tumor that typically presents as a shiny and pink papule or nodule with telangiectasias. However, its presentation varies depending on the histological type, which can be confirmed by biopsy. First-line therapies for low-risk BCC include standard surgical excision and curettage and electrodesiccation, whereas the gold standard for high-risk BCC is Mohs microscopic surgery. This review summarizes the current guidelines for BCC treatment and discusses the mechanism of action and clinical implications of alternative rare, experimental, and anecdotal treatments in the literature.

References

1. Cameron MC, Lee E, Hibler BP, et al. Basal cell carcinoma: Epidemiology; pathophysiology; clinical and histological subtypes; and disease associations. J Am Acad Dermatol. 2019;80:303-317. Erratum in: J Am Acad Dermatol. 2021;85:535. [PMID: 29782900].

2. Wolff K. Johnson RA. & Fitzpatrick TB. In: Fitzpatrick's color atlas and synopsis of clinical dermatology. 6th ed. McGraw-Hill Medical; 2009. p. 287-89.

3. Elder DE, Massi D, Scolyer RA, Willemze R. In: Who Classification of Skin Tumours, 4th ed. Lyon: IARC; 2018. p. 26-34.

4. Schmults, CD, Blitzblau, R, Aasi, SZ, et al. Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network. https://doi.org/10.6004/jnccn.2023.0056 Accessed on Apr 19, 2025.

5. Work Group; Invited Reviewers; Kim JYS, Kozlow JH, Mittal B, et al. Guidelines of care for the management of basal cell carcinoma. J Am Acad Dermatol. 2018;78:540-559. [PMID: 29331385].

6. Dando EE, Abban C, Shehu Wingrove A, et al. Deep Shave Removal of Suspected Basal Cell Carcinoma: A Prospective Study. Dermatol Surg. 2023;49:130-134. [PMID: 36728062].

7. Mazzoni D, Muir J. A guide to curettage and cautery in the management of skin lesions. Aust J Gen Pract. 2021;50:893-897. [PMID: 34845465].

8. Basal cell carcinoma treatment. The Skin Cancer Foundation. 2023. https://www.skincancer.org/skin-cancer-information/basal-cell-carcinoma/bcc-treatment-options/. Accessed on May 8, 2023.

9. Prohaska J, Jan AH. Cryotherapy in Dermatology. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2023. [PMID: 29493944].

10. Paoli J, Gyllencreutz JD, Fougelberg J, et al. Nonsurgical Options for the Treatment of Basal Cell Carcinoma. Dermatol Pract Concept. 2019;9:75-81. [PMID: 31106008].

11. Lewin JM, Carucci JA. Advances in the management of basal cell carcinoma. F1000Prime Rep. 2015;7:53. [PMID: 26097726].

12. U.S. Food and Drug Administration. EFUDEX® (fluorouracil) TOPICAL SOLUTIONS AND CREAM: Valeant Pharmaceuticals. 2005. https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/016831s049lbl.pdf. Accessed on May 8, 2023.

13. U.S. Food and Drug Administration. Aldara® (imiquimod) Cream, 5%, Graceway Pharmaceuticals, LLC. 2010. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020723s022lbl.pdf. Accessed on May 8, 2023.

14. Velin M, Cardot-Leccia N, Cathelineau AC, et al. Efficacy and safety of 0.05% ingenol mebutate in the treatment of basal cell carcinoma: A prospective study. Skin Health Dis. 2022;10;3:e150. [PMID: 37013127].

15. U.S. Food and Drug Administration. Odomzo (sonidegib) capsules prescribing information, Sun Pharmaceutical Industries Limited. 2015. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205266s004lbl.pdf. Accessed on May 8, 2023.

16. U.S. Food and Drug Administration. Vismodegib (Erivedge), G., Inc. Food and Drug Administration. 2012. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203388lbl.pdf. Accessed on May 8, 2023.

17. U.S. Food and Drug Administration. LIBTAYO® (cemiplimab-rwlc) injection prescribing information: Regeneron Pharmaceuticals, Inc. 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761097s007lbl.pdf. Accessed on May 8, 2023.

18. Sergi MC, Ambrogio F, Della Mura M, Sorino J, Cazzato G. Basal Cell Carcinoma: An Old Friend with Multiple Faces. Cancers (Basel). 2025;17:993. [PMID: 40149326].

19. Puig S, Berrocal A. Management of high-risk and advanced basal cell carcinoma. Clin Transl Oncol. 2015;17:497-503. [PMID: 25643667].

20. Paul S, Knight A. The Importance of Basal Cell Carcinoma Risk Stratification and Potential Future Pathways. JMIR Dermatol. 2023;6:e50309. [PMID: 37902813].

21. Li JY, Kampp JT. Review of Common Alternative Herbal "Remedies" for Skin Cancer. Dermatol Surg. 2019;45:58-67. [PMID: 30096105].

22. Prickett KA, Ramsey ML. Mohs Micrographic Surgery. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2023. [PMID: 28722863].

23. Fravor L, Khachemoune A. Dermatologic uses of bloodroot: a review and reappraisal. Int J Dermatol. 2021;60:1070-1075. [PMID: 33128472].

24. McDaniel S, Goldman GD. Consequences of using escharotic agents as primary treatment for nonmelanoma skin cancer. Arch Dermatol. 2002;138:1593-6. [PMID: 12472348].

25. Punjabi S, Cook LJ, Kersey P, Marks R, Cerio R. Solasodine glycoalkaloids: a novel topical therapy for basal cell carcinoma. A double-blind, randomized, placebo-controlled, parallel group, multicenter study. Int J Dermatol. 2008;47:78-82. [PMID: 18173610].

26. Cham BE, Daunter B, Evans RA. Topical treatment of malignant and premalignant skin lesions by very low concentrations of a standard mixture (BEC) of solasodine glycosides. Cancer Lett. 1991;59:183-92. [PMID: 1913614].

27. Wölfle U, Seelinger G, Schempp CM. Topical application of St. John's wort (Hypericum perforatum). Planta Med. 2014;80:109-20. [PMID: 24214835].

28. Ramsay JR, Suhrbier A, Aylward JH, et al. The sap from Euphorbia peplus is effective against human nonmelanoma skin cancers. Br J Dermatol. 2011;164:633-6. [PMID: 21375515].

29. Kacerovská D, Pizinger K, Majer F, Smíd F. Photodynamic therapy of nonmelanoma skin cancer with topical hypericum perforatum extract--a pilot study. Photochem Photobiol. 2008;84:779-85. [PMID: 18179625].

30. Zhao W, Entschladen F, Liu H, et al. Boswellic acid acetate induces differentiation and apoptosis in highly metastatic melanoma and fibrosarcoma cells. Cancer Detect Prev. 2003;27:67-75. [PMID: 12600419].

31. Fung K, Suhail M, McClendon B, et al. Management of basal cell carcinoma of the skin using frankincense (Boswellia sacra) essential oil: a case report. OA Altern Med. 2013;1:14.

32. Tilli CM, Stavast-Kooy AJ, Vuerstaek JD, et al. The garlic-derived organosulfur component ajoene decreases basal cell carcinoma tumor size by inducing apoptosis. Arch Dermatol Res. 2003;295:117-23. [PMID: 12756587].

33. Kessels J, Voeten L, Nelemans P, et al. Topical Sinecatechins, 10%, Ointment for Superficial Basal Cell Carcinoma: A Randomized Clinical Trial. JAMA Dermatol. 2017;153:1061-1063. [PMID: 28793140].

34. Tjeerdsma F, Jonkman MF, Spoo JR. Temporary arrest of basal cell carcinoma formation in a patient with basal cell naevus syndrome (BCNS) since treatment with a gel containing various plant extracts. J Eur Acad Dermatol Venereol. 2011;25:244-5. [PMID: 20500542].

35. Filippini T, Malavolti M, Borrelli F, et al. Green tea (Camellia sinensis) for the prevention of cancer. Cochrane Database Syst Rev. 2020;3:CD005004. [PMID: 32118296].

36. Greenberg ER, Baron JA, Stukel TA, et al. A clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin. The Skin Cancer Prevention Study Group. N Engl J Med. 1990;323:789-95. Erratum in: N Engl J Med 1991;325:1324. [PMID: 2202901].

37. Jee SH, Shen SC, Tseng CR, Chiu HC, Kuo ML. Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells. J Invest Dermatol. 1998;111:656-61. [PMID: 9764849].

38. Vollono L, Falconi M, Gaziano R, et al. Potential of Curcumin in Skin Disorders. Nutrients. 2019;11:2169. [PMID: 31509968].

39. Kim JK, Kim Y, Na KM, Surh YJ, Kim TY. [6]-Gingerol prevents UVB-induced ROS production and COX-2 expression in vitro and in vivo. Free Radic Res. 2007;41:603-14. [PMID: 17454143].

40. Katiyar SK, Agarwal R, Mukhtar H. Inhibition of tumor promotion in SENCAR mouse skin by ethanol extract of Zingiber officinale rhizome. Cancer Res. 1996;56:1023-30. [PMID: 8640756].

41. Tilley C, Deep G, Agarwal C, et al. Silibinin and its 2,3-dehydro-derivative inhibit basal cell carcinoma growth via suppression of mitogenic signaling and transcription factors activation. Mol Carcinog. 2016;55:3-14. [PMID: 25492239].

42. Prasad RR, Paudel S, Raina K, Agarwal R. Silibinin and non-melanoma skin cancers. J Tradit Complement Med. 2020;10:236-244. [PMID: 32670818].

43. Wei H, Saladi R, Lu Y, et al. Isoflavone genistein: photoprotection and clinical implications in dermatology. J Nutr. 2003;133:3811S-3819S. [PMID: 14608119].

44. Wei H, Bowen R, Zhang X, Lebwohl M. Isoflavone genistein inhibits the initiation and promotion of two-stage skin carcinogenesis in mice. Carcinogenesis. 1998;19:1509-14. [PMID: 9744550].

45. Filip A, Clichici S, Daicoviciu D, et al. Chemopreventive effects of Calluna vulgaris and Vitis vinifera extracts on UVB-induced skin damage in SKH-1 hairless mice. J Physiol Pharmacol. 2011;62:385-92. [PMID: 21893700].

46. Zhao J, Wang J, Chen Y, Agarwal R. Anti-tumor-promoting activity of a polyphenolic fraction isolated from grape seeds in the mouse skin two-stage initiation-promotion protocol and identification of procyanidin B5-3'-gallate as the most effective antioxidant constituent. Carcinogenesis. 1999;20:1737-45. [PMID: 10469619].

47. Rizwan M, Rodriguez-Blanco I, Harbottle A, et al. Tomato paste rich in lycopene protects against cutaneous photodamage in humans in vivo: a randomized controlled trial. Br J Dermatol. 2011;164:154-62. [PMID: 20854436].

48. U.S. Food and Drug Administration. Solaraze‘ (diclofenac sodium) Gel, 3%, PharmaDerm® A division of Fougera Pharmaceuticals Inc. 2011. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021005s013lbl.pdf. Accessed on May 8, 2023.

49. Brinkhuizen T, Frencken KJ, Nelemans PJ, et al. The effect of topical diclofenac 3% and calcitriol 3 μg/g on superficial basal cell carcinoma (sBCC) and nodular basal cell carcinoma (nBCC): A phase II, randomized controlled trial. J Am Acad Dermatol. 2016;75:126-34. [PMID: 27067393].

50. El-Khalawany M, Saudi WM, Ahmed E, et al. The combined effect of CO2 laser, topical diclofenac 3%, and imiquimod 5% in treating high-risk basal cell carcinoma. J Cosmet Dermatol. 2022;21:2049-2055. [PMID: 34333841].

51. U.S. Food and Drug Administration. Itraconazole. A division of Fougera Pharmaceuticals Inc. 2011. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022484s000lbl.pdf. Accessed on May 8, 2023.

52. Yoon J, Apicelli AJ 3rd, Pavlopoulos TV. Intracranial regression of an advanced basal cell carcinoma using sonidegib and itraconazole after failure with vismodegib. JAAD Case Rep. 2017;4:10-12. [PMID: 29387745].

53. Kim DJ, Kim J, Spaunhurst K, et al. Open-label, exploratory phase II trial of oral itraconazole for the treatment of basal cell carcinoma. J Clin Oncol. 2014;32:745-51. [PMID: 24493717].

54. Ally MS, Ransohoff K, Sarin K, et al. Effects of Combined Treatment With Arsenic Trioxide and Itraconazole in Patients With Refractory Metastatic Basal Cell Carcinoma. JAMA Dermatol. 2016;152:452-6. [PMID: 26765315].

55. Kilgour JM, Shah A, Eichstadt S, et al. Treatment of Cutaneous Squamous Cell Carcinoma With the Topical Histone Deacetylase Inhibitor Remetinostat. JAMA Dermatol. 2022;158:105-107. [PMID: 34787644].

56. Kilgour JM, Shah A, Urman NM, et al. Phase II Open-Label, Single-Arm Trial to Investigate the Efficacy and Safety of Topical Remetinostat Gel in Patients with Basal Cell Carcinoma. Clin Cancer Res. 2021;27:4717-4725. [PMID: 34362809].

57. Bailey HH, Kim K, Verma AK, et al. A randomized, double-blind, placebo-controlled phase 3 skin cancer prevention study of {alpha}-difluoromethylornithine in subjects with previous history of skin cancer. Cancer Prev Res (Phila). 2010;3:35-47. [PMID: 20051371].

58. Chen AC, Martin AJ, Choy B, et al. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N Engl J Med. 2015;373:1618-26. [PMID: 26488693].

59. Chen AC, Martin AJ, et al. A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients. Br J Dermatol. 2016;175:1073-1075. [PMID: 27061568].

60. Zhang XB, Zhang SQ, Li CX, Huang ZM, Luo YW. Acitretin systemic and retinoic acid 0.1% cream supression of basal cell carcinoma. Dermatol Reports. 2010;2:e4. [PMID: 25386240].

61. Lippman SM, Lotan R, Schleuniger U. Retinoid-interferon therapy of solid tumors. Int J Cancer. 1997;70:481-3. [PMID: 9033661].

62. Sanmartín V, Aguayo R, Baradad M, Casanova JM. Tratamiento neoadyuvante con acitretino oral e imiquimod tópico en el carcinoma basocelular gigante [Oral acitretin and topical imiquimod as neoadjuvant treatment for giant basal cell carcinoma]. Actas Dermosifiliogr. 2012;103:149-52. [PMID: 21571242].

63. Holló P, Jókai H, Hársing J, et al. Topically applied ascorbic acid solution for the treatment of basal cell carcinoma (BCC). J Am Acad Dermatol. 2016;75:212-3. [PMID: 27317517].

64. Burke B, Bailie JE. Randomized trial of topical ascorbic acid in DMSO versus imiquimod for the treatment of basal cell carcinoma. Biomed Pharmacother. 2022;148:112710. [PMID: 35217280].

65. Bánvölgyi A, Lőrincz K, Kiss N, et al. Efficiency of long-term high-dose intravenous ascorbic acid therapy in locally advanced basal cell carcinoma - a pilot study. Postepy Dermatol Alergol. 2020;37:548-558. [PMID: 32994778].

66. Sertznig P, Seifert M, Tilgen W, Reichrath J. Activation of vitamin D receptor (VDR)- and peroxisome proliferator-activated receptor (PPAR)-signaling pathways through 1,25(OH)(2)D(3) in melanoma cell lines and other skin-derived cell lines. Dermatoendocrinol. 2009;1:232-8. [PMID: 20592797].

67. Martin-Gorgojo A, Gilaberte Y, Nagore E. Vitamin D and Skin Cancer: An Epidemiological, Patient-Centered Update and Review. Nutrients. 2021;13:4292. [PMID: 34959844].

68. Ince B, Yildirim MEC, Dadaci M. Assessing the Effect of Vitamin D Replacement on Basal Cell Carcinoma Occurrence and Recurrence Rates in Patients with Vitamin D Deficiency. Horm Cancer. 2019;10:145-149. [PMID: 31254251].

69. Gade A, Hwang JR, Hoegler K, Khan S, Khachemoune A. Therapeutic Use of Trace Elements in Dermatology. Altern Ther Health Med. 2023;29:246-252. [PMID: 34264859].

70. Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA. 1996;276:1957-63. Erratum in: JAMA 1997;277:1520. [PMID: 8971064].

71. Reid ME, Duffield-Lillico AJ, Slate E, et al. The nutritional prevention of cancer: 400 mcg per day selenium treatment. Nutr Cancer. 2008;60:155-63. [PMID: 18444146].

72. Kamal S. Non-surgical Removal of Basal Cell Carcinoma by Apis Mellifera L Venom. Clinical Medical Reviews and Reports. 2020;2:01-06. 10.31579/2690-8794/056.

73. Lazo-Dizon, Johanna & Salud, Charissa & Jr, Manuel & Cubillan, Eileen & Datuin, Maria Suzanne. Topical Cashew Nut Extract (DeBCC) for the Treatment of Basal Cell Carcinoma: A Randomized Double-blind, Vehicle-Controlled Trial. Acta Medica Philippina. 2013;47:45-51. 10.47895/amp.v47i4.1264.

74. M Ashraf S, Rathinasamy K. Antibacterial and anticancer activity of the purified cashew nut shell liquid: implications in cancer chemotherapy and wound healing. Nat Prod Res. 2018;32:2856-2860. [PMID: 28934859].

75. Mahen KK, Markley L, Bogart J, et al. Topical N-phosphonacetyl-l-aspartate is a dual action candidate for treating non-melanoma skin cancer. Exp Dermatol. 2023. [PMID: 37309615].

76. Zhang X, Kundoor V, Khalifa S, et al. Chemopreventive effects of sarcophine-diol on skin tumor development in CD-1 mice. Cancer Lett. 2007;253:53-9. [PMID: 17321042].

77. Zhang X, Bommareddy A, Chen W, et al. Chemopreventive effects of sarcophine-diol on ultraviolet B-induced skin tumor development in SKH-1 hairless mice. Mar Drugs. 2009;7:153-65. [PMID: 19597578].

78. Caini S, Cattaruzza MS, Bendinelli B, et al. Coffee, tea and caffeine intake and the risk of non-melanoma skin cancer: a review of the literature and meta-analysis. Eur J Nutr. 2017;56:1-12. [PMID: 27388462].

79. Conney AH, Lu YP, Lou YR, Kawasumi M, Nghiem P. Mechanisms of Caffeine-Induced Inhibition of UVB Carcinogenesis. Front Oncol. 2013;3:144. [PMID: 23785666].

80. Frandsen SK, Gehl J. A Review on Differences in Effects on Normal and Malignant Cells and Tissues to Electroporation-Based Therapies: A Focus on Calcium Electroporation. Technol Cancer Res Treat. 2018;17:1533033818788077. [PMID: 30012047].

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Published

01/05/2026