Title: Optimal surveillance strategies for AJCC stage I cutaneous melanoma post primary tumour excision: an evidence synthesis and economic evaluation
Funder: Department of Health and Social Care

Abstract: Aim: The aim is to evaluate effectiveness and cost-effectiveness of different surveillance strategies for patients with American Joint Committee on Cancer (AJCC) stage I melanoma after surgical excision of the primary cutaneous tumour. Background: Cutaneous melanoma is the 5th most common cancer in the UK; with 17,000 patients diagnosed annually. It remains the leading cause of cancer related death in 20-35 year olds. After removal of the primary tumour the majority of melanomas are cured, however, up to 30% of all primary melanomas progress to metastatic disease, with extremely poor 5-year survival rates of only 5–15%. Consequently, there are 2500 melanoma associated deaths in the UK annually. The total annual cost due to skin cancer to the NHS was £106–£112 million in 2008. This cost is expected to rise to over £180 million by 2020. Although surgical treatment of primary melanoma is effective, there has been a rapid pace of change recently with additional early investigatory techniques such as sentinel lymph node biopsy, various radiological modalities, as well as a raft of advances with the treatment of metastatic disease. However, a structured, uniformly adopted, evidence based model of patient follow-up after initial diagnosis is lacking. Current national guidelines vary across the world, with most based upon anecdotal evidence and expert opinion. In this application, we will use existing data to determine the relative clinical effectiveness and cost-effectiveness of alternative surveillance strategies for patients who have undergone primary tumour excision of AJCC stage I cutaneous melanoma. Methods: In this application, we will systematically review existing literature to identify different surveillance strategies and follow-up regimens of patients with AJCC stage I melanoma, as well as their clinical effectiveness in terms of detecting cancer recurrences, metastases and overall survival. We will describe surveillance strategies in terms of follow up duration, frequency, tests and prognostic biomarkers and risk models used within each surveillance strategy. We will then develop and compare alternative surveillance strategies. As these strategies may risk stratify patients after initial surgery we will systematically review and meta-analyse data of novel and existing biochemical and biophysical markers and existing risk models to stratify patients based on their risk of recurrence and metastasis. A further systematic review will determine the diagnostic accuracy of tests that are recommended within different surveillance strategies. Finally we will develop a decision analytic model which will incorporate the findings from these reviews to model the effectiveness and cost-effectiveness of alternative surveillance regimens. Other parameter estimates for the model will be obtained from additional focused searches for clinical effectiveness of different treatment options, costs and utilities. We will conduct value of information (VOI) analysis to demonstrate whether more research is worthwhile. Outcome: The results obtained will inform the design of care for AJCC stage I melanoma care to maximise the health of patients within available NHS resources. Timeframe/team: The project will be undertaken over a 15 months period by an experienced multidisciplinary team including PPI representatives. The team will be supported by an advisory group comprising relevant leading clinical and methodological experts.

Lay abstract: Malignant melanoma is the deadliest of skin cancers. The number of melanomas is increasing worldwide, and it is now the fifth most common cancer in the UK with 17,000 people developing a melanoma each year. This number is expected to continue to increase by over 900 people each year. Although surgical removal of the melanoma will be a cure for the majority of people; over 1/3 (around 5700) of people who are diagnosed with melanoma will go on to develop metastasis of the melanoma to other sites in the body. If this happens then the likelihood of surviving 5 years is low with a chance of surviving 5 years of between 1 in 7 to 1 in 20. As a consequence, 2500 die from melanoma in the UK every year. At present, melanoma is treated by surgical removal. After a melanoma is removed, patients have regular check-ups to look for signs of the melanoma reoccurring in their scar, in lymph nodes or other places within the body. Patients are also checked for new melanomas. It is felt that the earlier that melanoma spread is detected, the better the chance of future treatment working. A key question is, how best to follow-up patients after initial melanoma surgery? There is published evidence around how this might be done, but these have never been analysed together, and standard practice for follow-up around the world is very different. We plan to look at the available evidence from published data and current guidelines from around the world. Initially, we will look at the different ways that patients are followed up after surgery. We will concentrate on the earliest stage of melanoma (AJCC stage I) as this affects the majority of patients diagnosed with melanoma (>60%) and it is likely how people are followed up will vary. For the different ways to follow-up patients we will then look at how good they are at detecting metastatic disease in the skin or elsewhere in the body. We will then look at how good the different tests (e.g. different tests on the skin removed during surgery, or follow-up blood-tests, ultrasounds etc) and physical examinations are that can be used by clinicians to identify which people with melanoma are at the highest risk of it spreading or reoccurring following surgery. Finally, by working with our patient and clinical advisors, and drawing upon the information we have gathered we will design a number of different possible melanoma follow-up strategies. Each strategy will then be assessed on its ability to detect the early spread of the melanoma, whether it improves on patients’ well-being and survival, and how well it uses the limited NHS resources that we have. The results obtained from this study will enable health policy-makers to identify which surveillance strategy is optimal for AJCC stage I melanoma patients and best value to the NHS. The study will be carried out by clinical experts in this area, patients with experience of melanoma and researchers with all the skills necessary to identify and combine the existing data. Funds have been requested to cover the cost of the researchers and to bring together the patients and clinical experts so that they can direct this research.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: CANCER AND NEOPLASMS