Non-melanoma skin cancer is reduced after switch of immunosuppression to mTOR-inhibitors in organ transplant recipients.

BACKGROUND: Organ transplant recipients are prone to the development of non-melanoma skin cancer. Organ transplant recipients often develop multiple non-melanoma skin cancers and the tumors show an aggressive growth pattern, therefore surgical therapy can be difficult. Switch of the immunosuppressive regimen to mTOR-inhibitors such as everolimus or sirolimus can have an antitumor effect. PATIENTS AND METHODS: In a monocentric retrospective study we evaluated organ transplant recipients who presented with non-melanoma skin cancer in the years 2008-2010. Experience with patients who were switched to an mTOR-inhibitor due to non-melanoma skin cancer are reported in detail, and recent clinical studies are reviewed. RESULTS: 60 organ transplant recipients with non-melanoma skin cancer were evaluated. Due to the development of multiple non-melanoma skin cancer within a few years, the immunosuppressive regimen was switched to everolimus in 7 patients and to sirolimus in 5 patients. Eight patients were evaluable for the effect of mTOR-inhibitors on the development of non-melanoma skin cancer; 4 patients had to discontinue the medication with mTOR-inhibitors early due to various side effects. In the year before the switch to mTOR-inhibitors, 8 patients developed 16 squamous cell carcinomas, 3 Basal cell carcinomas and 22 cases of Bowen's disease. All tumors were histologically confirmed. In the year after switch of immunosuppression, the rate of squamous cell carcinomas (n = 2) and Bowen's disease (n = 3), but not of basal cell carcinomas (n = 2) was significantly reduced. Moreover, 5 prospective randomized trials recently have demonstrated a reduced number of non-melanoma skin cancers in organ transplant recipients after switch of the immunosuppressive regimen to mTOR-inhibitors. CONCLUSION: Switch of the immunosuppressive regimen to mTOR-inhibitors should be considered for organ transplant recipients suffering from multiple non-melanoma skin cancers.

[Therapy of non-melanocytic skin tumors]. / Therapie nicht-melanozytärer Hauttumoren.

Actinic keratosis on sun-damaged skin are very common in individuals with fair complexion. Management encompasses cryosurgery, tretinoin or 5-fluorouracil-cream. Bowen's disease, however, requires surgical excision or radiotherapy. Basal cell carcinoma and squamous cell carcinoma are the two most common malignant skin tumours in Western Europe. Typically these tumours can be managed either by excision and primary wound closure, by cryosurgery or by radiotherapy. The method of choice is determined by the type and location of the tumour and the general condition of the patient. For more difficult-to-treat malignant skin tumours surgical resection with histological margin control is required. Mohs' micrographic surgery is a specialized procedure. This method entails to a full work-up of the excisional margins. The defect is closed only after histological verification of tumour-free surgical margins. Difficult-to-treat tumours are recurrent, sclerodermiform and large (diameter more than 20 mm) basal cell carcinomas. Indications for margin control in squamous cell carcinomas are tumours with more than 20 mm of diameter, with more than 5 mm thickness and with poor histologic differentiation (Broders grade III and IV, desmoplastic squamous cell carcinoma). Therefore, a skin biopsy is often required to plan the optimal treatment of a malignant skin tumour. The collaboration of primary care providers and specialists is beneficial in the management of difficult skin tumours. Renal transplant recipients under immunosuppression are prone to have squamous cell carcinoma of a more aggressive type. Dermatofibrosarcoma protuberans is another good indication for Mohs' micrographic surgery. A regular follow-up for recurrences or secondary tumours, as well as an effective secondary prevention of sun damage are important for skin cancer patients.