Skin Cancer in Organ Transplant Recipients Challenges and Opportunities

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1 Disclosure Skin Cancer in Organ Transplant Recipients Challenges and Opportunities Investigator: DUSA Pharmaceuticals, Inc. Investigator: Genentech Consultant: Gerson Lehrman Group Sarah Tuttleton Arron, MD, PhD High Risk Skin Cancer Program Dermatologic Surgery and Laser Center University of California, San Francisco Skin Cancer Facts: the AT-RISC Fact Sheet Up to 70% of long term transplant recipients will develop skin cancer Skin cancer can significantly decrease transplant recipients quality of life Some patients may develop dozens of cancers per year, and undergo multiple surgical procedures Skin cancer may even cause death After the fourth year post-transplant, 27% of patients in high risk areas die of skin cancer 1

2 Skin Cancer Facts: the AT-RISC Fact Sheet Sun protection is the best strategy to prevent skin cancer Early diagnosis of skin cancer can save lives Sun protection practices are currently inadequate Only 54% of transplant recipients remember receiving skin cancer education Only 40% of transplant recipients regularly use sunscreen Skin Cancer in Transplant Recipients Standard Incidence Ratios Squamous Cell Carcinoma- 65-fold increase SCC of lip- 20 to 38-fold increase Basal Cell Carcinoma- 10-fold increase Melanoma- 1.6 to 3.4-fold increase Kaposi s Sarcoma- 84-fold increase Jensen JAAD 1999;40:17 Hartevelt Transplantation 1990;49:506 Lindelof BJD 2000;143;513 Skin Cancer in Transplant Recipients The Essentials Basal Cell Carcinoma Squamous Cell Carcinoma Melanoma Kaposi s sarcoma Rare cancers Angiosarcoma Merkel cell carcinoma Atypical fibroxanthoma Leiomyosarcoma Cutaneous T-cell lymphoma Cutaneous B-cell lymphoma 2

3 Basal Cell Carcinoma (BCC) Most common cancer in the US Incidence: >1,000,000/yr Location: 85% on head/neck Locally invasive, low risk of metastasis Different types with different appearances Nodular Superficial Morpheaform Features of Nodular (Classic) BCC Features of Superficial BCC Most often on the face, ears and other sunexposed areas Papule with rolled borders Pearly sheen Blood vessels at the edges Central ulceration Non-healing sore Most common on shoulders, chest, back and arms Area of redness, often with scale May have brown color at the border Slow growing Frequently multifocal 3

4 Features of Morpheaform BCC Most often on the face May look like a scar with poorly defined borders and a shiny, taut surface May ulcerate Usually more aggressive Often locally destructive Squamous Cell Carcinoma (SCC) Second most common skin cancer in general population Most frequent cancer in transplant patients 300,000/year in the U.S. Location: 75% on head/neck or hands Risk of metastasis in general population: 0.5-5% Increased for organ transplant patients Actinic Keratosis (First Stage of SCC) Squamous Cell Carcinoma Rough, scaly lesion on a red, irritated base May shed to leave red base--then recur May be more easily felt than seen Individuals often have multiple lesions Lesion progresses from the appearance of an AK Red, scaly patch With or without crusting May develop a nodule or induration 4

5 Recognizing the High-risk SCC Malignant Melanoma Multiple, rapid recurrences High risk locations: ear, lip Large size Aggressive growth Poor differentiation Deep invasion (>4-6 mm), especially fat, muscle, cartilage, bone, nerve Perineural invasion Appx 60,000 cases of invasive melanoma each year in the U.S. Incidence doubles every 15 years Changing or new pigmented lesion Prognosis based on thickness 15% mortality Surgery Wide local excision Sentinel lymph node biopsy Chemotherapy Malignant Melanoma Who is Most at Risk? Assymetry Irregular Border Variations in Color Diameter >6mm Evolving (changing) Some factors are the same for transplant and non transplant patients Age older means higher risk Skin type Fair skin (burns easily), blue, green or hazel eyes, red or blonde hair means higher risk Sun exposure the more sun, the higher the risk History of a previous skin cancer increases the risk for another 5

6 Who is Most at Risk? Basic Principles Some factors are unique to transplant patients Age at transplantation older means higher risk Time since transplantation longer means higher risk Level of immunosuppression higher levels mean higher risk Heart & Lung > Kidney > Liver CsA, Aza > Tacrolimus, MMF > Rapamycin Warts more warts associated with increased risk of skin cancer Prevention Early Detection Aggressive Treatment Prevention Education pre- and post-transplant Sun Avoidance Limit outdoor activities between 10 am - 4 pm Avoid natural tanning, and absolutely NO tanning beds UV Index: Sunscreen Broad spectrum (UVA/UVB) sunscreen SPF >30 Lip balm with SPF Sun protective clothing Long sleeves, long pants UPF fabric, Sunguard rinse ( Broad-brimmed hats Constant reinforcement Sun Exposure and Vitamin D Sunscreen can block up to 95% of Vitamin D production in the skin Pro Vitamin D Inhibits Cancer UV Dietary sources of Vitamin D: Eggs, fatty fish (salmon, tuna, herring) cod liver oil, fortified milk, yogurt, cereal, bread. 400 IU Supplementation Con DNA Mutations Promotes Skin Cancer 6

7 Safe Sun Can Still Be Fun! Early Detection Regular surveillance by dermatologist Transplant dermatology clinic recommended Monthly self skin exam Monthly self nodal exam for patients with a history of SCC or MM Recommended Interval For Complete Skin And Nodal Exams Treatment No history of skin cancer h/o AKs h/o NMSC h/o multiple NMSC h/o high risk SCC h/o metastatic SCC Yearly Every 6 months Every 6 months Every 4 months Every 3 months Every 2 months Individual tumors managed according to traditional principles, with increased diligence Electrodesiccation and Curettage Excision Mohs Micrographic Surgery Sentinel Lymph Node Biopsy Lymph Node Dissection Radiation Chemotherapy Consider reduction or revision of immunosuppression 7

8 Skin Cancer Scenarios Transplant MD Consensus Opinion Level of Reduction/Revision of Immunosuppression to Consider CARDIAC RENAL LIVER 1. No history of actinic keratoses or skin cancer None None None 2. History of actinic keratosis None None None 3. History of < 1 NMSC per year None Mild Mild 4. History of 2-5 NMSC per year Mild Mild Mild 5. History of 6-10 NMSC per year Mild Mild Mild 6. History of NMSC per year Mild Mild Mild 7. History of > 25 NMSC per year Mild Moderate Moderate 8. Individual high risk skin cancer (average risk SCC; cutaneous and oral KS; stage IA melanoma) 9. Individual high risk skin cancer (moderate risk SCC; stage IB melanoma) 10. Individual high risk skin cancer ( high risk SCC; early Merkel cell carcinoma; stage IIA melanoma) 11. Individual high risk skin cancer (very high risk SCC; stage IIB melanoma) Otley et al., Br J Dermatol Mar;154(3): Individual high risk skin cancer (metastatic SCC; stage IIC/III melanoma; aggressive Merkel cell carcinoma; visceral KS) 13. Individual high risk skin cancer (untreatable metastatic SCC; stage IV melanoma; metastatic Merkel cell carcinoma) None Mild Mild Mild Mild Mild Mild Moderate Moderate Mild Moderate Moderate Moderate Severe Moderate Severe Severe Severe Field Treatment of Actinic Keratoses Topical 5-Fluorouracil cream Efudex, Carac Topical retinoids Tretinoin, Retin-A, Renova Topical NSAIDs Diclofenac, Solaraze Topical immune response modifiers Imiquimod, Aldara, Zyclara Photodynamic therapy Levulan, Metvixia, ALA, Blu-U Photodynamic Therapy Photosensitizers Topical 5-aminolevulinic acid HCl stick (ALA) Methyl-esterified ALA (mala) cream Photoactivating light 417nm (ALA-PDT) 630nm (MAL-PDT) Others inflammation 8

9 inflammation inflammation desquamation resolution Chemoprophylaxis- Systemic Retinoids Oral retinoids can reduce the number of new SCCs Reduce actinic keratoses and warts Side effects generally well tolerated Mucocutaneous effects (dryness, alopecia) Elevation of blood lipid levels, particularly triglycerides Increase in liver function tests Mood alterations Severe birth defects- caution use in childbearing women Rare SE: pseudotumor cerebri Rebound effect off therapy Chemoprophylaxis is not an FDA approved indication When I Consider Oral Retinoids Need for repeated field treatments Numerous skin cancers per year (5-10/year) One high risk skin cancer Large size, location on ear or lip, perineural invasion, desmoplasia, poor differentiation Any metastatic skin cancer In conjunction with revision of immunosuppression 9

10 Combination Field Therapy ALA-BluU, Efudex and Acitretin Multidisciplinary Approach is Key Dermatology/ Dermatologic surgery Transplant medicine Pathology/ Dermatopathology Radiology Otorhinolaryngology Plastic surgery Ophthalmology/ Oculoplastic Surgery Radiation Oncology Medical Oncology UCSF High Risk Skin Cancer Program Combined medical and surgical dermatology clinic for patients at high risk for skin cancer Solid organ transplant recipients Bone marrow transplant recipients HIV-positive patients Leukemia/lymphoma Genetic predisposition to skin cancer Pretransplant skin evaluation Ongoing research studies on skin cancer Patient Guide to Skin Cancer for OTRs: Take Home Message: Prevention must come early Skin cancer can ruin or even take a life Dermatologic surgeons and dermatologists want to work with you Resources are available AT-RISC ( ITSCC ( SCOPE ( UCSF HRSCC ( 10