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Introduction

Psoriasis is a chronic inflammatory disease media­ted by T cells.

Psoriasis affects 3.2% of the adult population in the United States of America⁽¹⁾. Some authors have suggested that patients with psoriasis have an increased risk of cancer. Biological therapies are very effective in psoriasis but have profound effects on the innate and adaptive immune pathways, which can have a negative impact on the mechanisms of cancer immunosurveillance⁽²⁾.

Given the inflammatory nature of psoriasis, of ultraviolet light (UV) therapies and of immunosuppressive therapies, along with the increased prevalence of risk factors for cancer in patients with psoriasis (such as smoking), the risk of malignancy in patients with psoriasis has become a particular concern⁽³⁾.

Studies have shown that patients with more severe psoriasis have an increased risk of cancer-related mortality, and psoriasis has been associated with an increased risk of cancer, including lymphoma^(4-10).

Pouplard et al. performed a meta-analysis in 2013 that showed an association between psoriasis and cancer, but this meta-analysis ruled out cancer with keratinocytes and some cancers, including respiratory and urinary tract cancer, lung cancer and bladder cancer⁽³⁾. This review aims at bringing to the fore the risk of developing cancer in psoriasis patients depending on the therapies used.

Cancer risk of UV therapy

A very high risk of developing especially squamous cell carcinomas has been reported in patients treated with psoralen-UV-A (PUVA)^(11,12). Egeberg et al. showed that the adjusted risk of melanoma and keratinocyte cancer in patients with psoriasis compared to the general population of Denmark was lower but significantly increased for keratinocyte cancer; it is possible that other factors besides PUVA treatment may be involved⁽¹³⁾. It is also essential to keep in mind that patients with psoriasis have frequent visits to dermatologists to facilitate the more frequent detection of keratinocyte cancers than in the general population. Patients with keratinocyte cancer often spend more time in the sun and have been treated with UVB and tar irradiation, which increase the risk of keratinocyte cancer^(14-16). No increase in broadband or narrowband UVB skin cancer was observed, especially at below 100 treatments^(12,17-20).

Cancer risk of non-biological systemic therapy

Methotrexate (MTX) has been associated with an increased risk of malignancies and lymphoproliferative disorders, including rare EBV-positive lymphoma, and has been reported in several cases and small studies^(21-23). An increased risk of lymphoma has been reported in patients treated with MTX for more than three years, who have been followed-up for 30 years⁽²⁴⁾. Low-dose MTX monotherapy (≤30 mg/week orally or 17.5-22.5 mg/week subcutaneously) versus placebo in patients with psoriasis did not show an increased risk of malignancy^(25,26).

Polesie et al. reported a low risk of melanoma in patients treated with MTX in Sweden. This study did not report the diagnosis, the duration of treatment and the dose used⁽²⁷⁾. Also, no increased risk of malignancy was found in patients treated with MTX in a cohort study (PSOLAR registry) that examined the safety of psoriasis treatments⁽²⁸⁾.
 

Cancer risk of biologic therapy

Bongartz et al. revealed in a meta-analysis from 2006 an increased risk of malignancy when using infliximab and adalimumab therapies, these data being subsequently unconfirmed⁽²⁹⁾. Several meta-analyses reporting cases of malignancy after TNF-a inhibitors in patients with rheumatic diseases, inflammatory bowel disease and psoriasis could not highlight an increased risk of cancer. A higher incidence of lymphoma was observed in clinical trials in psoriasis patients treated with anti-TNF-a than in the general population^(30-32).

Following the risk of malignancy in patients with psoriasis treated with etanercept, Pariser et al. performed an integrated analysis of short-term placebo-controlled clinical trials and long-term uncontrolled open-label trials that showed no increase in the incidence of cancer with etanercept compared with the control group and the general population, and the risk did not increase with increasing doses of etanercept⁽³³⁾. Another registry (OBSERVE-5) followed the use of etanercept in psoriasis patients for five years and found cumulative incidences of 3.2% for malignancies and 0.1% for lymphoma; these findings did not meet the expectations⁽³⁴⁾.

Given the current therapies of interest in psoriasis, IL-12, IL-23 and IL-17, and their increasing use, the risks of malignancy have been followed. Trinchieri demonstrated anti-tumor effects of IL-12 in mouse models, improving both innate resistance and adaptive immunity⁽³⁵⁾. Zou and Restifo demonstrated predominantly anti-tumor effects of IL-23 in mouse models by IFN gamma and CD8+ T cell-dependent pathways⁽³⁶⁾. IL-17 is a proinflammatory cytokine that produces anti-tumor effects in immunocompetent mice but pro-tumor effects in mice with immune deficiency⁽³⁶⁾.

Conclusions

We can conclude that some of the treatments used in psoriasis and the disease itself have been associated with an increased risk of malignancy. However, the therapies used in psoriasis seem safe and more studies are needed to determine the exact risk of malignancy.  

Conflict of interests: The authors declare no con­flict of interests.