Optimal surveillance strategies for patients with stage 1 cutaneous melanoma post primary tumour excision: Three systematic reviews and an economic model

Luke Vale, Patience Kunonga, Diarmuid Coughlan, Vasileios Kontogianni, Margaret Astin, Fiona Beyer, Catherine Richmond, Dor Wilson, Dalvir Bajwa, Mehdi Javanbakht, Andrew Bryant, Wanwuri Akor, Dawn Craig, Penny Lovat, Marie Labus, Batoul Nasr, Timothy Cunliffe, Helena Hinde, Mohamed Shawgi, Daniel SalehPam Royle, Paul Steward, Rachel Lucas, Robert Ellis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Malignant melanoma is the fifth most common cancer in the UK, with rates continuing to rise, resulting in considerable burden to patients and the NHS. Objectives: The objectives were to evaluate the effectiveness and cost-effectiveness of current and alternative follow-up strategies for stage IA and IB melanoma. Review methods: Three systematic reviews were conducted. (1) The effectiveness of surveillance strategies. Outcomes were detection of new primaries, recurrences, metastases and survival. Risk of bias was assessed using the Cochrane Collaboration's Risk-of-Bias 2.0 tool. (2) Prediction models to stratify by risk of recurrence, metastases and survival. Model performance was assessed by study-reported measures of discrimination (e.g. D-statistic, Harrel's c-statistic), calibration (e.g. the Hosmer-Lemeshow 'goodness-of-fit' test) or overall performance (e.g. Brier score, R 2). Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). (3) Diagnostic test accuracy of fine-needle biopsy and ultrasonography. Outcomes were detection of new primaries, recurrences, metastases and overall survival. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Review data and data from elsewhere were used to model the cost-effectiveness of alternative surveillance strategies and the value of further research. Results: (1) The surveillance review included one randomised controlled trial. There was no evidence of a difference in new primary or recurrence detected (risk ratio 0.75, 95% confidence interval 0.43 to 1.31). Risk of bias was considered to be of some concern. Certainty of the evidence was low. (2) Eleven risk prediction models were identified. Discrimination measures were reported for six models, with the area under the operating curve ranging from 0.59 to 0.88. Three models reported calibration measures, with coefficients of ≥ 0.88. Overall performance was reported by two models. In one, the Brier score was slightly better than the American Joint Committee on Cancer scheme score. The other reported an R 2 of 0.47 (95% confidence interval 0.45 to 0.49). All studies were judged to have a high risk of bias. (3) The diagnostic test accuracy review identified two studies. One study considered fine-needle biopsy and the other considered ultrasonography. The sensitivity and specificity for fine-needle biopsy were 0.94 (95% confidence interval 0.90 to 0.97) and 0.95 (95% confidence interval 0.90 to 0.97), respectively. For ultrasonography, sensitivity and specificity were 1.00 (95% confidence interval 0.03 to 1.00) and 0.99 (95% confidence interval 0.96 to 0.99), respectively. For the reference standards and flow and timing domains, the risk of bias was rated as being high for both studies. The cost-effectiveness results suggest that, over a lifetime, less intensive surveillance than recommended by the National Institute for Health and Care Excellence might be worthwhile. There was considerable uncertainty. Improving the diagnostic performance of cancer nurse specialists and introducing a risk prediction tool could be promising. Further research on transition probabilities between different stages of melanoma and on improving diagnostic accuracy would be of most value. Limitations: Overall, few data of limited quality were available, and these related to earlier versions of the American Joint Committee on Cancer staging. Consequently, there was considerable uncertainty in the economic evaluation. Conclusions: Despite adoption of rigorous methods, too few data are available to justify changes to the National Institute for Health and Care Excellence recommendations on surveillance. However, alternative strategies warrant further research, specifically on improving estimates of incidence, progression of recurrent disease; diagnostic accuracy and health-related quality of life; developing and evaluating risk stratification tools; and understanding patient preferences. Study registration: This study is registered as PROSPERO CRD42018086784.

Original languageEnglish
Pages (from-to)VII-124
JournalHealth Technology Assessment
Issue number64
Publication statusPublished - 1 Nov 2021

Bibliographical note

Funding Information:
This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health and Social Care.

Funding Information:
The research reported in this issue of the journal was funded by the HTA programme as project number 16/166/05. The contractual start date was in March 2018. The draft report began editorial review in October 2019 and was accepted for publication in July 2020. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Publisher Copyright:
© Queen’s Printer and Controller of HMSO 2021.


  • Cost-Effectiveness Analysis
  • Cutaneous Melanoma
  • Evidence Synthesis
  • Surveillance
  • Systematic Review

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