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Alert Number 21

Corticosteroid Therapy and Increased Risk of Skin Cancer

Date: May 12, 2004

In a previous Topics Alert (# 7) we cautioned you regarding the clear and unambiguous correlation between CLL and skin cancer, especially squamous cell carcinoma (SCC). When SCC occurs in CLL patients, it is likely to be much more aggressive and dangerous.

Cancer survivors are living longer these days, thanks to improved therapies. But the other side of the coin is that longer survival after cancer therapy is highlighting the risk of developing secondary cancers. Besides DNA damaging and therefore potentially carcinogenic chemotherapy drugs, we are also seeing increasing use of steroidal drugs such as prednisone, dexamethasone, etc., at varying dose levels and in different therapy regimes. Steroidal drugs such as prednisone work by means of potent immune suppression. It is generally accepted that secondary cancers get a toe-hold and flourish in CLL patients because they have poorly functioning immune systems. Less than effective immune surveillance means your body is unable to detect and kill the secondary cancer cells before they have a chance to establish themselves. Another scenario where immunosuppressive drugs are used a great deal is in solid organ transplants and bone marrow transplants.

The valid question to consider is whether steroid therapy-induced suppression of the immune function may further increase your risk of a second malignancy. It would be a shame to be "cured" of CLL, only to discover a secondary cancer of aggressive squamous cell carcinoma! One of the problems I have with clinical trial designs is that they do not follow the patients who participate in them long enough to get a good handle on secondary cancers that might result a few years down the road as a consequence of the original therapy, especially if they used high doses of immunosuppressive steroidal drugs.

Below is a Reuters Health report, which directly links increased risk of skin cancer to use of steroidal drugs such as prednisolone / prednisone. The same message is re-iterated in the 2001 report from Dartmouth Medical School. This is an important risk factor that you should be aware of, part of the risk versus benefit analysis that must be done prior to making pragmatic therapy decisions. A risk profile that might be acceptable in a "salvage" situation may be not such a good deal as a frontline therapy, especially if you have other less risky options open to you.

If you wish to learn more about the greatly increased risk of skin cancers in CLL patients read a recent article Dying to Get a Tan?

Be well,

Chaya
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Steroid Use Linked to Increased Risk of Skin Cancer, Lymphoma

NEW YORK (Reuters Health) May 05 - The risk of squamous cell carcinomas, basal cell carcinomas and non-Hodgkin lymphoma is increased in patients treated with glucocorticoids, according to a brief communication in the Journal of the National Cancer Institute for May 5th.

Immunosuppressive therapy is associated with increased cancer risk in patients with renal transplantation, Dr. Henrik Toft Sorensen and associates in Denmark note. But the immunosuppressive effects of glucocorticoid treatment in other diseases are less clear.

Dr. Sorensen, at Aarhus University Hospital, and his team extracted data from the population-based North Jutland Prescription Database for individuals prescribed glucocorticoids between 1989 and 1996. There were approximately 59,000 patients who received at least one prescription for a glucocorticoid, but no other cytostatic or immunosuppressive drugs, before the end of follow-up in 1998. Cancer incidence rates obtained from the Danish Cancer Registry were used to estimate standardized incidence ratios (SIR).

For patients prescribed a glucocorticoid at least 15 times, the SIR for basal cell carcinoma was 1.52; for squamous cell carcinoma it was 2.45, and for non-Hodgkin lymphoma it was 2.68. There was also a trend toward increased risk of melanoma (SIR = 1.59). The authors note, however, that their findings do not exclude the possibility that that the diseases treated with glucocorticoids, rather than the drugs themselves, may have been associated with the elevated risk.

"Results of our cohort study indicate that immunosuppression by glucocorticoids may be a shared risk factor for these malignancies," they conclude.

J Natl Cancer Inst 2004;96:709-711.
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Br J Cancer. 2001 Sep 1;85(5):683-6. Br J Cancer. 2003 Sep 1;89(5):951-2;

Non-melanoma skin cancers and glucocorticoid therapy

Karagas MR, Cushing GL Jr, Greenberg ER, Mott LA, Spencer SK, Nierenberg DW.

Departments of Community and Family Medicine, Medicine, Pharmacology and Toxicology, and the Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire.

Non-melanoma skin cancer (NMSC) is an important cause of morbidity and long-term mortality in organ transplant recipients receiving immunosuppressive drugs such as azathioprine and cyclosporin, often combined with adrenocortical steroids (glucocorticoids). At lower doses, glucocorticoids alone are prescribed for other conditions including musculoskeletal, connective tissue and respiratory disorders. Presently, it is unknown whether patients taking glucocorticoids are at an increased risk of skin malignancies. In a population-based case-control study in New Hampshire, USA, we compared use of glucocorticoids in 592 basal cell carcinoma (BCC) and 281 squamous cell carcinoma (SCC) cases and in 532 age and gender matched controls; neither cases nor controls had a history of organ transplantation. Participants underwent a structured personal interview regarding history of medication use and skin cancer risk factors. We used unconditional logistic regression analysis to compute odds ratios associated with glucocorticoid use for 1 month or longer while controlling for potential confounding factors. Risk of SCC was increased among users of oral glucocorticoids (adjusted odds ratio = 2.31; 95% CI = 1.27, 4.18), and risk of BCC was elevated modestly (adjusted odds ratio = 1.49; 95% CI = 0.90, 2.47). In contrast, risk of both SCC and BCC were unrelated to use of inhaled steroids. Our data suggest that use of oral glucocorticoids may increase risk of NMSC, and SCC in particular, among patients other than organ transplant recipients. We hypothesize that immunosuppression induced by oral glucocorticoids may allow these cancers to emerge from immunosurveillance. Copyright 2001 Cancer Research Campaign.

PMID: 11531252
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