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Ultrasound, CT, MRI, or PET-CT for staging and re-staging of adults with cutaneous melanoma

Dinnes, Jacqueline; Ferrante Di Ruffano, Lavinia; Takwoingi, Yemisi; Cheung, Seau Tak; Nathan, Paul; Matin, Rubeta N.; Chuchu, Naomi; Chan, Sue Ann; Durack, Alana; Bayliss, Susan E.; Gulati, Abha; Patel, Lopa; Davenport, Clare; Godfrey, Kathie; Subesinghe, Manil; Traill, Zoe; Deeks, Jonathan J.; Williams, Hywel C.

Ultrasound, CT, MRI, or PET-CT for staging and re-staging of adults with cutaneous melanoma Thumbnail


Authors

Jacqueline Dinnes

Lavinia Ferrante Di Ruffano

Yemisi Takwoingi

Seau Tak Cheung

Paul Nathan

Rubeta N. Matin

Naomi Chuchu

Sue Ann Chan

Alana Durack

Susan E. Bayliss

Abha Gulati

Lopa Patel

Clare Davenport

Kathie Godfrey

Manil Subesinghe

Zoe Traill

Jonathan J. Deeks

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HYWEL WILLIAMS HYWEL.WILLIAMS@NOTTINGHAM.AC.UK
Professor of Dermato-Epidemiology



Abstract

© 2019 The Cochrane Collaboration. Background Melanoma is one of the most aggressive forms of skin cancer, with the potential to metastasise to other parts of the body via the lymphatic system and the bloodstream. Melanoma accounts for a small percentage of skin cancer cases but is responsible for the majority of skin cancer deaths. Various imaging tests can be used with the aim of detecting metastatic spread of disease following a primary diagnosis of melanoma (primary staging) or on clinical suspicion of disease recurrence (re-staging). Accurate staging is crucial to ensuring that patients are directed to the most appropriate and effective treatment at different points on the clinical pathway. Establishing the comparative accuracy of ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)-CT imaging for detection of nodal or distant metastases, or both, is critical to understanding if, how, and where on the pathway these tests might be used. Objectives Primary objectives We estimated accuracy separately according to the point in the clinical pathway at which imaging tests were used. Our objectives were: • to determine the diagnostic accuracy of ultrasound or PET-CT for detection of nodal metastases before sentinel lymph node biopsy in adults with confirmed cutaneous invasive melanoma; and • to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for whole body imaging in adults with cutaneous invasive melanoma: ○ for detection of any metastasis in adults with a primary diagnosis of melanoma (i.e. primary staging at presentation); and ○ for detection of any metastasis in adults undergoing staging of recurrence of melanoma (i.e. re-staging prompted by findings on routine follow-up). We undertook separate analyses according to whether accuracy data were reported per patient or per lesion. Secondary objectives We sought to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for whole body imaging (detection of any metastasis) in mixed or not clearly described populations of adults with cutaneous invasive melanoma. For study participants undergoing primary staging or re-staging (for possible recurrence), and for mixed or unclear populations, our objectives were: • to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for detection of nodal metastases; • to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for detection of distant metastases; and • to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for detection of distant metastases according to metastatic site. Search methods We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists as well as published systematic review articles. Selection criteria We included studies of any design that evaluated ultrasound (with or without the use of fine needle aspiration cytology (FNAC)), CT, MRI, or PET-CT for staging of cutaneous melanoma in adults, compared with a reference standard of histological confirmation or imaging with clinical follow-up of at least three months’ duration. We excluded studies reporting multiple applications of the same test in more than 10% of study participants. Data collection and analysis Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2)). We estimated accuracy using the bivariate hierarchical method to produce summary sensitivities and specificities with 95% confidence and prediction regions. We undertook analysis of studies allowing direct and indirect comparison between tests. We examined heterogeneity between studies by visually inspecting the forest plots of sensitivity and specificity and summary receiver operating characteristic (ROC) plots. Numbers of identified studies were insufficient to allow formal investigation of potential sources of heterogeneity. Main results We included a total of 39 publications reporting on 5204 study participants; 34 studies reporting data per patient included 4980 study participants with 1265 cases of metastatic disease, and seven studies reporting data per lesion included 417 study participants with 1846 potentially metastatic lesions, 1061 of which were confirmed metastases. The risk of bias was low or unclear for all domains apart from participant flow. Concerns regarding applicability of the evidence were high or unclear for almost all domains. Participant selection from mixed or not clearly defined populations and poorly described application and interpretation of index tests were particularly problematic. The accuracy of imaging for detection of regional nodal metastases before sentinel lymph node biopsy (SLNB) was evaluated in 18 studies. In 11 studies (2614 participants; 542 cases), the summary sensitivity of ultrasound alone was 35.4% (95% confidence interval (CI) 17.0% to 59.4%) and specificity was 93.9% (95% CI 86.1% to 97.5%). Combining pre-SLNB ultrasound with FNAC revealed summary sensitivity of 18.0% (95% CI 3.58% to 56.5%) and specificity of 99.8% (95% CI 99.1% to 99.9%) (1164 participants; 259 cases). Four studies demonstrated lower sensitivity (10.2%, 95% CI 4.31% to 22.3%) and specificity (96.5%,95% CI 87.1% to 99.1%) for PET-CT before SLNB (170 participants, 49 cases). When these data are translated to a hypothetical cohort of 1000 people eligible for SLNB, 237 of whom have nodal metastases (median prevalence), the combination of ultrasound with FNAC potentially allows 43 people with nodal metastases to be triaged directly to adjuvant therapy rather than having SLNB first, at a cost of two people with false positive results (who are incorrectly managed). Those with a false negative ultrasound will be identified on subsequent SLNB. Limited test accuracy data were available for whole body imaging via PET-CT for primary staging or re-staging for disease recurrence, and none evaluated MRI. Twenty-four studies evaluated whole body imaging. Six of these studies explored primary staging following a confirmed diagnosis of melanoma (492 participants), three evaluated re-staging of disease following some clinical indication of recurrence (589 participants), and 15 included mixed or not clearly described population groups comprising participants at a number of different points on the clinical pathway and at varying stages of disease (1265 participants). Results for whole body imaging could not be translated to a hypothetical cohort of people due to paucity of data. Most of the studies (6/9) of primary disease or re-staging of disease considered PET-CT, two in comparison to CT alone, and three studies examined the use of ultrasound. No eligible evaluations of MRI in these groups were identified. All studies used histological reference standards combined with follow-up, and two included FNAC for some participants. Observed accuracy for detection of any metastases for PET-CT was higher for re-staging of disease (summary sensitivity from two studies: 92.6%, 95% CI 85.3% to 96.4%; specificity: 89.7%, 95% CI 78.8% to 95.3%; 153 participants; 95 cases) compared to primary staging (sensitivities from individual studies ranged from 30% to 47% and specificities from 73% to 88%), and was more sensitive than CT alone in both population groups, but participant numbers were very small. No conclusions can be drawn regarding routine imaging of the brain via MRI or CT.

Citation

Dinnes, J., Ferrante Di Ruffano, L., Takwoingi, Y., Cheung, S. T., Nathan, P., Matin, R. N., …Williams, H. C. (2019). Ultrasound, CT, MRI, or PET-CT for staging and re-staging of adults with cutaneous melanoma. Cochrane Database of Systematic Reviews, 2019(7), Article CD012806. https://doi.org/10.1002/14651858.CD012806.pub2

Journal Article Type Article
Acceptance Date May 28, 2019
Online Publication Date Jul 1, 2019
Publication Date Jul 1, 2019
Deposit Date Jun 6, 2019
Publicly Available Date Mar 28, 2024
Journal Cochrane Database of Systematic Reviews
Electronic ISSN 1469-493X
Publisher Cochrane Collaboration
Peer Reviewed Peer Reviewed
Volume 2019
Issue 7
Article Number CD012806
DOI https://doi.org/10.1002/14651858.CD012806.pub2
Public URL https://nottingham-repository.worktribe.com/output/2152623
Publisher URL https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012806.pub2/full