The persistent risk of genital tumors among men treated with psoralen plus ultraviolet A (PUVA) for psoriasis

doi:10.1067/mjd.2002.124618

Journal of the American Academy of Dermatology

Volume 47, Issue 1, July 2002, Pages 33-39

https://doi.org/10.1067/mjd.2002.124618 Get rights and content

Abstract

Background: In the general population, squamous cell carcinomas (SCCs) of the male genitalia are rare. Ten years ago, we documented a significant dose-dependent increase in the risk of malignant genital neoplasms among men treated with psoralen plus ultraviolet A (PUVA). Since that time, fewer cohort patients have used PUVA, and genital protection among PUVA users is likely to be frequent. Objective: Our aim was to determine the incidence and risk factors for genital neoplasms since 1989 and risk factors for these neoplasms among patients treated with PUVA. Methods: We conducted a prospective cohort study of 892 men first treated with PUVA in 1975-1976. Results: Twenty-four men (2.7%) had 51 genital neoplasms, including 10 patients with a first tumor after May 1, 1989 (the ending date for our 1990 report). Since May 1, 1989, the incidence of invasive penile and scrotal SCCs was elevated 52.6-fold (95% confidence interval, 19.3-114.6) compared with that expected for the general white population. Multivariate models revealed the highest genital tumor risk among men with high-dose exposure to both PUVA and topical tar/ultraviolet B, with an incidence rate ratio of 4.5 (95% confidence interval, 1.3-16.1) compared with the low-dose exposure group. Conclusion: Although use of PUVA has decreased and genital shielding in our cohort has increased, the dose-dependent increase in the risk of genital tumors in men treated with PUVA has persisted. Particularly high risks occur among those with high-dose exposures to both PUVA and topical tar/ultraviolet B. (J Am Acad Dermatol 2002;47:33-9.)

Section snippets

Material and methods

The PUVA Follow-Up Study is a prospective study of a cohort of 1380 patients with psoriasis, including 892 men (97% white), who started treatment with PUVA at 16 university centers between 1975 and 1976. Since then, we have administered 18 follow-up interviews and 10 structured dermatologic examinations to surviving cohort members, irrespective of their continued use of PUVA. In this defined cohort, the study has monitored the development of long-term complications, including skin cancers. All

The PUVA follow-up study cohort

Eight hundred ninety-two men were enrolled in the PUVA Follow-Up Study, with an average age of 46 ± 15 years (mean ± standard deviation) at the time of enrollment. Of these 892 men, 336 (38%) are known to have died. Of the surviving 556 men, 454 (82%) have so far participated in our latest annual follow-up interviews.

The PUVA follow-up study genital tumors

As of November 1, 1998, we have documented 51 genital tumors in 24 men (including one scrotal basal cell carcinoma [BCC] and 2 scrotal tumors diagnosed as keratoacanthomas vs

Discussion

The additional experience of our cohort during a further 10 years of follow-up extends our earlier finding of a substantially increased risk of malignant penile and scrotal tumors among male patients who had started PUVA therapy in 1975-1976, a time when the use of protection was not the standard of care.¹⁵ Even in the decade beginning nearly 15 years after initial exposure to PUVA, new tumors developed in men previously unaffected by such tumors. This risk is dose-dependent, with a 90-fold

Acknowledgements

The following centers and investigators participated in the PUVA Follow-up Study: Stanford University School of Medicine, Stanford, Calif: E. Bauer; University of California Medical School, San Francisco: J. H. Epstein, J. Koo; Baylor College of Medicine, Houston, Texas: J. Wolf; Washington Hospital Center, Washington, DC: T. P. Nigra; University of Michigan Medical School, Ann Arbor: T. F. Anderson; Columbia University College of Physicians and Surgeons, New York: J. Prystowsky; Mayo Graduate

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^☆: ^*A complete list of investigators participating in the PUVA Follow Up Study appears at the end of this article.

^☆☆: Funding sources: National Institute of Arthritis, Musculoskeletal and Skin Disease Contract Number NO 1 AR44214.

^★: Conflict of interest: None.

^★★: Reprint requests: Robert S. Stern, MD, Department of Dermatology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215.

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ReportsThe persistent risk of genital tumors among men treated with psoralen plus ultraviolet A (PUVA) for psoriasis☆,☆☆,★,★★

Abstract

Section snippets

Material and methods

The PUVA follow-up study cohort

The PUVA follow-up study genital tumors

Discussion

Acknowledgements

J Am Acad Dermatol

Fundam Appl Toxicol

Lancet

J Invest Dermatol

Lancet

Chirurgical observations relative to the cataract, the polypus of the nose, the cancer of the scrotum, the different kinds of ruptures, and the mortifications of the toes and feet

‘High single-dose’ European PUVA regimen also causes an excess of non-melanoma skin cancer

Br J Dermatol

Genital squamous-cell carcinoma after PUVA therapy

Dermatology

Skin cancer or premalignant lesions occur in half of high-dose PUVA patients

Br J Dermatol

Skin tumors in photochemotherapy for psoriasis: a single-center follow-up of 496 patients

Dermatology

Psoriasis therapy and the risk of skin cancers

Clin Exp Dermatol

Reports
The persistent risk of genital tumors among men treated with psoralen plus ultraviolet A (PUVA) for psoriasis☆,☆☆,★,★★