The risk of progression of AKs to invasive squamous cell carcinoma (SCC) has been calculated to be between 0.025% and 16% per year.[126]Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet. 1988 Apr 9;1(8589):795-7.
http://www.ncbi.nlm.nih.gov/pubmed/2895318?tool=bestpractice.com
[127]Glogau RG. The risk of progression to invasive disease. J Am Acad Dermatol. 2000 Jan;42(1 Pt 2):23-4.
http://www.ncbi.nlm.nih.gov/pubmed/10607353?tool=bestpractice.com
In older adults with a history of multiple keratinocyte carcinomas, risk of progression is 0.60% at 1 year and 2.57% at 4 years.[128]Criscione VD, Weinstock MA, Naylor MF, et al. Actinic keratoses: natural history and risk of malignant transformation in the veterans affairs topical tretinoin chemoprevention trial. Cancer. 2009 Jun 1;115(11):2523-30.
https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.24284
http://www.ncbi.nlm.nih.gov/pubmed/19382202?tool=bestpractice.com
The calculated lifetime risk of malignant transformation for a patient with AKs followed up for 10 years is between 6.1% and 10.2%.
Although spontaneous regression has been reported to be as high as 25.9% of AKs over a 12-month period, 15% subsequently reappear.[2]Berman B, Bienstock L, Kuritzky L, et al. Primary Care Education Consortium; Texas Academy of Family Physicians. Actinic keratoses: sequelae and treatments. Recommendations from a consensus panel. J Fam Pract. 2006 May;55(5):suppl 1-8.
http://www.ncbi.nlm.nih.gov/pubmed/16672155?tool=bestpractice.com
[53]Quaedvlieg PJ, Tirsi E, Thissen MR, et al. Actinic keratosis: how to differentiate the good from the bad ones? Eur J Dermatol. 2006 Jul-Aug;16(4):335-9.
http://www.ncbi.nlm.nih.gov/pubmed/16935787?tool=bestpractice.com
[129]Marks R, Foley P, Goodman G, et al. Spontaneous remission of solar keratoses: the case for conservative management. Br J Dermatol. 1986 Dec;115(6):649-55.
http://www.ncbi.nlm.nih.gov/pubmed/3801305?tool=bestpractice.com
Misdiagnosis can also affect the outcome. One study showed that 36% of lesions previously diagnosed clinically as AKs were in fact SCC, and 14% of them were SCC in situ.[130]Suchniak JM, Baer S, Goldberg LH. High rate of malignant transformation in hyperkeratotic actinic keratoses. J Am Acad Dermatol. 1997 Sep;37(3 Pt 1):392-4.
http://www.ncbi.nlm.nih.gov/pubmed/9308551?tool=bestpractice.com
In another study, 4% of AKs clinically diagnosed by board-certified dermatologists were in fact SCC, and 5% were considered occult early stage of cutaneous malignancy.[131]Ehrig T, Cockerell C, Piacquadio D, et al. Actinic keratoses and the incidence of occult squamous cell carcinoma: a clinical-histopathologic correlation. Dermatol Surg. 2006 Oct;32(10):1261-5.
http://www.ncbi.nlm.nih.gov/pubmed/17034376?tool=bestpractice.com
In addition, one study showed that 40% of all SCCs developed from clinically normal skin in the prior year, and 60% of SCC arose from previous AKs.[126]Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet. 1988 Apr 9;1(8589):795-7.
http://www.ncbi.nlm.nih.gov/pubmed/2895318?tool=bestpractice.com
It is estimated that 95% of SCCs on the lip develop from a preexisting actinic cheilitis lesion, and metastasis rate for SCCs on the lip are four times higher than cutaneous squamous cell carcinomas (cSCCs).[116]Bakirtzi K, Papadimitriou I, Andreadis D, et al. Treatment options and post-treatment malignant transformation rate of actinic cheilitis: a systematic review. Cancers (Basel). 2021 Jul 4;13(13):3354.
https://www.mdpi.com/2072-6694/13/13/3354
http://www.ncbi.nlm.nih.gov/pubmed/34283099?tool=bestpractice.com
Outcome in high-risk people (e.g., immunocompromised)
The risk of developing new AKs is even higher in immunocompromised people (e.g., transplant patients), in whom AKs have an increased malignant transformation rate.[132]Kinlen LJ, Sheil AG, Peto J, et al. Collaborative United Kingdom-Australasian study of cancer in patients treated with immunosuppressive drugs. Br Med J. 1979 Dec 8;2(6203):1461-6.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1597175/pdf/brmedj00103-0009.pdf
http://www.ncbi.nlm.nih.gov/pubmed/393355?tool=bestpractice.com
[133]Blohme I, Larko O. Skin lesions in renal transplant patients after 10-23 years of immunosuppressive therapy. Acta Derm Venereol. 1990;70(6):491-4.
http://www.ncbi.nlm.nih.gov/pubmed/1981421?tool=bestpractice.com
[134]Walder BK, Robertson MR, Jeremy D. Skin cancer and immunosuppression. Lancet. 1971 Dec 11;2(7737):1282-3.
http://www.ncbi.nlm.nih.gov/pubmed/4143536?tool=bestpractice.com
[135]Hardie IR, Strong RW, Hartley LC, et al. Skin cancer in Caucasian renal allograft recipients living in a subtropical climate. Surgery. 1980 Feb;87(2):177-83.
http://www.ncbi.nlm.nih.gov/pubmed/6986671?tool=bestpractice.com
The cumulative incidence of developing skin cancer increases from 7% after 1 year of immunosuppression to 45% after 11 years, and 70% after 20 years.[136]Bouwes Bavinck JN, Hardie DR, et al. The risk of skin cancer in renal transplant recipients in Queensland, Australia. A follow-up study. Transplantation. 1996 Mar 15;61(5):715-21.
http://www.ncbi.nlm.nih.gov/pubmed/8607173?tool=bestpractice.com
Patients with genetic melanin deficiency (e.g., albinism) and DNA instability (e.g., xeroderma pigmentosum) tend to develop AKs early in life, with 91% incidence in people with albinism >20 years old, and 19% in xeroderma pigmentosum patients.
Treatment outcomes
Treatment options often result in undesirable transient adverse effects, but they obtain high efficacy rates.[12]de Berker D, McGregor JM, Mohd Mustapa MF, et al. British Association of Dermatologists' guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol. 2017 Jan;176(1):20-43.
http://www.ncbi.nlm.nih.gov/pubmed/28098380?tool=bestpractice.com
Prevention with adequate broad-spectrum sunscreen has been found to decrease the number of AKs and prevent the development of new lesions.[44]Thompson SC, Jolley D, Marks R. Reduction of solar keratoses by regular sunscreen use. N Engl J Med. 1993 Oct 14;329(16):1147-51.
http://www.ncbi.nlm.nih.gov/pubmed/8377777?tool=bestpractice.com
The usual cure rate of most of the treatments is >90%, with cryotherapy reported to produce 99% clearance.[137]Dinehart SM. The treatment of actinic keratoses. J Am Acad Dermatol. 2000 Jan;42(1 Pt 2):25-8.
http://www.ncbi.nlm.nih.gov/pubmed/10607354?tool=bestpractice.com
[138]Lubritz RR, Smolewski SA. Cryosurgery cure rate of actinic keratoses. J Am Acad Dermatol. 1982 Nov;7(5):631-2.
http://www.ncbi.nlm.nih.gov/pubmed/7142470?tool=bestpractice.com
Cosmetic outcomes have been reported as good to excellent in 94% to 97% of complete response lesions.[139]Thai KE, Fergin P, Freeman M, et al A prospective study of the use of cryosurgery for the treatment of actinic keratoses. Int J Dermatol. 2004 Sep;43(9):687-92.
http://www.ncbi.nlm.nih.gov/pubmed/15357755?tool=bestpractice.com
[140]Zouboulis CC, Rohrs H. Cryosurgical treatment of actinic keratoses and evidence-based review. Hautarzt. 2005 Apr;56(4):353-8.
http://www.ncbi.nlm.nih.gov/pubmed/15580450?tool=bestpractice.com
There is a complete response (or cure) of 83% for freeze times >20 seconds.
Curettage with or without electrodesiccation has been reported to produce high cure rates, and good cosmetic results have been described.[137]Dinehart SM. The treatment of actinic keratoses. J Am Acad Dermatol. 2000 Jan;42(1 Pt 2):25-8.
http://www.ncbi.nlm.nih.gov/pubmed/10607354?tool=bestpractice.com
The overall efficacy for superficial peels has been calculated to be around 75%, with recurrence rates of 25% to 35%.[141]Stockfleth E, Kerl H; Guideline Subcommittee of the European Dermatology Forum. Guidelines for the management of actinic keratoses. Eur J Dermatol. 2006 Nov-Dec;16(6):599-606.
http://www.ncbi.nlm.nih.gov/pubmed/17229598?tool=bestpractice.com
One 2022 study described the 4-year risk of developing cSCC in patients previously treated with 5% fluorouracil, 5% imiquimod, or methyl aminolevulinate photodynamic therapy (PDT).[142]Ahmady S, Jansen MHE, Nelemans PJ, et al. Risk of invasive cutaneous squamous cell carcinoma after different treatments for actinic keratosis: a secondary analysis of a randomized clinical trial. JAMA Dermatol. 2022 Jun 1;158(6):634-40.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9047727
http://www.ncbi.nlm.nih.gov/pubmed/35475852?tool=bestpractice.com
The overall risk was 3.7%, ranging from 2.2% in those treated with fluorouracil to 5.8% in those treated with imiquimod.