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American Journal of Clinical Dermatology

18-04-2024 | Melanoma | Systematic Review

Ultrasound Surveillance in Melanoma Management: Bridging Diagnostic Promise with Real-World Adherence: A Systematic Review and Meta-Analysis

Authors: Zhao Feng Liu, Amy Sylivris, Johnny Wu, Darren Tan, Samuel Hong, Lawrence Lin, Michael Wang, Christopher Chew

Published in: American Journal of Clinical Dermatology

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Abstract

Background

Ultrasound surveillance has become the new standard of care in stage III melanoma after the 2017 Multicenter Selective Lymphadenectomy Trial II (MSLT-II) demonstrated non-inferior 3-year survival compared with complete lymph node dissection.

Objective

We aimed to quantify diagnostic performance and adherence rates of ultrasound surveillance for melanoma locoregional metastasis, offering insights into real-world applicability.

Methods

Conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we systematically searched the Medline, Embase, Cochrane Library, CINAHL, Scopus, and Web of Science databases from inception until 11 October 2023. All primary studies that reported data on the diagnostic performance or adherence rates to ultrasound surveillance in melanoma were included. R statistical software was used for data synthesis and analysis. Sensitivity and specificity were aggregated across studies using the meta-analytic method for diagnostic tests outlined by Rutter and Gatsonis. Adherence rates were calculated as the ratio of patients fully compliant to planned follow-up to those who were not.

Results

A total of 36 studies including 18,273 patients were analysed, with a mean age of 56.6 years and a male-to-female ratio of 1:1.11. The median follow-up duration and frequency was 36 and 4 months, respectively. The pooled sensitivity of ultrasound examination was 0.879 (95% confidence interval [CI] 0.878–0.879) and specificity was 0.969 (95% CI 0.968–0.970), representing a diagnostic odds ratio of 224.5 (95% CI 223.1–225.9). Ultrasound examination demonstrated a substantial improvement in absolute sensitivity over clinical examination alone, with a number needed to screen (NNS) of 2.95. The overall adherence rate was 77.0% (95% CI 76.0–78.1%), with significantly lower rates in the United States [US] (p <  0.001) and retrospective studies (p <  0.001).

Conclusion

Ultrasound is a powerful diagnostic tool for locoregional melanoma metastasis. However, the real applicability to surveillance programmes is limited by low adherence rates, especially in the US. Further studies should seek to address this adherence gap.
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Literature
1.
Arnold M, Singh D, Laversanne M, Vignat J, Vaccarella S, Meheus F, et al. Global burden of cutaneous melanoma in 2020 and projections to 2040. JAMA Dermatol. 2022;158(5):495–503.PubMedPubMedCentralCrossRef
2.
Karimkhani C, Green AC, Nijsten T, Weinstock MA, Dellavalle RP, Naghavi M, et al. The global burden of melanoma: results from the Global Burden of Disease Study 2015. Br J Dermatol. 2017;177(1):134–40.PubMedPubMedCentralCrossRef
3.
Faries MB, Thompson JF, Cochran A, Elashoff R, Glass EC, Mozzillo N, et al. The impact on morbidity and length of stay of early versus delayed complete lymphadenectomy in melanoma: results of the Multicenter Selective Lymphadenectomy Trial (I). Ann Surg Oncol. 2010;17:3324–9.PubMedPubMedCentralCrossRef
4.
Kretschmer L, Thoms K-M, Peeters S, Haenssle H, Bertsch H-P, Emmert S. Postoperative morbidity of lymph node excision for cutaneous melanoma-sentinel lymphonodectomy versus complete regional lymph node dissection. Melanoma Res. 2008;18(1):16–21.PubMedCrossRef
5.
Van Akkooi A, Bouwhuis M, Van Geel A, Hoedemaker R, Verhoef C, Grunhagen D, et al. Morbidity and prognosis after therapeutic lymph node dissections for malignant melanoma. Eur J Surg Oncol. 2007;33(1):102–8.PubMedCrossRef
6.
Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, Zager JS, et al. Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med. 2017;376(23):2211–22.PubMedPubMedCentralCrossRef
7.
Bredbeck BC, Mubarak E, Zubieta DG, Tesorero R, Holmes AR, Dossett LA, et al. Management of the positive sentinel lymph node in the post-MSLT-II era. J Surg Oncol. 2020;122(8):1778–84.PubMedPubMedCentralCrossRef
8.
Broman KK, Hughes T, Dossett L, Sun J, Kirichenko D, Carr MJ, et al. Active surveillance of patients who have sentinel node positive melanoma: an international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy Trial II (MSLT-2). Cancer. 2021;127(13):2251–61.PubMedCrossRef
9.
Montgomery KB, Correya TA, Broman KK. Real-world adherence to nodal surveillance for sentinel lymph node-positive melanoma. Ann Surg Oncol. 2022;29(9):5961–8.PubMedPubMedCentralCrossRef
10.
Campbell JM, Klugar M, Ding S, Carmody DP, Hakonsen SJ, Jadotte YT, White S, Munn Z. Diagnostic test accuracy: methods for systematic review and meta-analysis. JBI Evidence Implementation. 2015;13(3):154-62.
11.
Rutter CM, Gatsonis CA. A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations. Stat Med. 2001;20(19):2865–84.PubMedCrossRef
12.
Dinnes J, Deeks J, Kirby J, Roderick P. A methodological review of how heterogeneity has been examined in systematic reviews of diagnostic test accuracy. Health Technol Assess (Winchester, England). 2005;9(12):1–113 (iii).
13.
Prayer L, Winkelbauer H, Gritzmann N, Winkelbauer F, Helmer M, Pehamberger H. Sonography versus palpation in the detection of regional lymph-node metastases in patients with malignant melanoma. Eur J Cancer Clin Oncol. 1990;26(7):827–30.CrossRef
14.
Nazarian LN, Alexander AA, Rawool NM, Kurtz AB, Maguire HC, Mastrangelo MJ. Malignant melanoma: impact of superficial US on management. Radiology. 1996;199(1):273–7.PubMedCrossRef
15.
Binder M, Kittler H, Steiner A, Dorffner R, Wolff K, Pehamberger H. Lymph node sonography versus palpation for detecting recurrent disease in patients with malignant melanoma. Eur J Cancer. 1997;33(11):1805–8.PubMedCrossRef
16.
Tregnaghi A, De Candia A, Calderone M, Cellini L, Rossi CR, Talenti E, et al. Ultrasonographic evaluation of superficial lymph node metastases in melanoma. Eur J Radiol. 1997;24(3):216–21.PubMedCrossRef
17.
Blum A, Schlagenhauff B, Stroebel W, Breuninger H, Rassner G, Garbe C. Ultrasound examination of regional lymph nodes significantly improves early detection of locoregional metastases during the follow-up of patients with cutaneous melanoma: results of a prospective study of 1288 patients. Cancer Interdiscipl Int J Am Cancer Soc. 2000;88(11):2534–9.
18.
Rossi C, Scagnet B, Vecchiato A, Mocellin S, Pilati P, Foletto M, et al. Sentinel node biopsy and ultrasound scanning in cutaneous melanoma: clinical and technical considerations. Eur J Cancer. 2000;36(7):895–900.PubMedCrossRef
19.
Voit C, Mayer T, Kron M, Schoengen A, Sterry W, Weber L, et al. Efficacy of ultrasound B-scan compared with physical examination in follow-up of melanoma patients. Cancer. 2001;91(12):2409–16.PubMedCrossRef
20.
Hofmann U, Szedlak M, Rittgen W, Jung E, Schadendorf D. Primary staging and follow-up in melanoma patients–monocenter evaluation of methods, costs and patient survival. Br J Cancer. 2002;87(2):151–7.PubMedPubMedCentralCrossRef
21.
Uren RF, Howman-Giles R, Thompson JF, Shaw HM, Roberts JM, Bernard E, et al. High-resolution ultrasound to diagnose melanoma metastases in patients with clinically palpable lymph nodes. Australas Radiol. 1999;43(2):148–52.PubMedCrossRef
22.
Brountzos EN, Panagiotou IE, Bafaloukos DI, Kelekis DA. Ultrasonographic detection of regional lymph node metastases in patients with intermediate or thick malignant melanoma. Oncol Rep. 2003;10(2):505–10.PubMed
23.
Klebl FH, Gelbmann CM, Lammert I, Bogenrieder T, Stolz W, Schlmerich J, et al. Palpatorische und sonographische Detektion von Lymphknotenmetastasen bei lokal fortgeschrittenem malignen Melanom. Medizinische Klinik-Intensivmedizin und Notfallmedizin. 2003;12(98):783–7.
24.
Garbe C, Paul A, Kohler-Späth H, Ellwanger U, Stroebel W, Schwarz M, et al. Prospective evaluation of a follow-up schedule in cutaneous melanoma patients: recommendations for an effective follow-up strategy. J Clin Oncol. 2003;21(3):520–9.PubMedCrossRef
25.
Schmid-Wendtner M-H, Paerschke G, Baumert J, Plewig G, Volkenandt M. Value of ultrasonography compared with physical examination for the detection of locoregional metastases in patients with cutaneous melanoma. Melanoma Res. 2003;13(2):183–8.PubMedCrossRef
26.
Machet L, Nemeth-Normand F, Giraudeau B, Perrinaud A, Tiguemounine J, Ayoub J, et al. Is ultrasound lymph node examination superior to clinical examination in melanoma follow-up? A monocentre cohort study of 373 patients. Br J Dermatol. 2005;152(1):66–70.PubMedCrossRef
27.
Saiag P, Bernard M, Beauchet A, Bafounta M-L, Bourgault-Villada I, Chagnon S. Ultrasonography using simple diagnostic criteria vs palpation for the detection of regional lymph node metastases of melanoma. Arch Dermatol. 2005;141(2):183–9.PubMedCrossRef
28.
Starritt EC, Uren RF, Scolyer RA, Quinn MJ, Thompson JF. Ultrasound examination of sentinel nodes in the initial assessment of patients with primary cutaneous melanoma. Ann Surg Oncol. 2005;12:18–23.PubMedCrossRef
29.
Testori A, Lazzaro G, Baldini F, Tosti G, Mosconi M, Lovati E, et al. The role of ultrasound of sentinel nodes in the pre-and post-operative evaluation of stage I melanoma patients. Melanoma Res. 2005;15(3):191–8.PubMedCrossRef
30.
Hengge UR, Wallerand A, Stutzki A, Kockel N. Cost-effectiveness of reduced follow-up in malignant melanoma. J Dtsch Dermatol Ges. 2007;5(10):898–907.PubMedCrossRef
31.
Voit C, Van Akkooi AC, Schäfer-Hesterberg G, Schöngen A, Kowalczyk K, Röwert JC, et al. Ultrasound morphology criteria predict metastatic disease of the sentinel nodes in patients with melanoma. J Clin Oncol. 2010;28(5):847–52.PubMedCrossRef
32.
Krüger U, Kretschmer L, Thoms K-M, Padeken M, Bertsch HP, Schön MP, et al. Lymph node ultrasound during melanoma follow-up significantly improves metastasis detection compared with clinical examination alone: a study on 433 patients. Melanoma Res. 2011;21(5):457–63.PubMedCrossRef
33.
Livingstone E, Krajewski C, Eigentler T, Windemuth-Kieselbach C, Benson S, Elsenbruch S, et al. Prospective evaluation of follow-up in melanoma patients in Germany–results of a multicentre and longitudinal study. Eur J Cancer. 2015;51(5):653–67.PubMedCrossRef
34.
Hayes A, Moskovic E, O’meara K, Smith H, Pope R, Larkin J, et al. Prospective cohort study of ultrasound surveillance of regional lymph nodes in patients with intermediate-risk cutaneous melanoma. J Br Surg. 2019;106(6):729–34.CrossRef
35.
Ipenburg NA, Thompson JF, Uren RF, Chung D, Nieweg OE. Focused ultrasound surveillance of lymph nodes following lymphoscintigraphy without sentinel node biopsy: a useful and safe strategy in elderly or frail melanoma patients. Ann Surg Oncol. 2019;26:2855–63.PubMedPubMedCentralCrossRef
36.
Bartlett E, Lee A, Spanheimer P, Bello D, Brady M, Ariyan C, et al. Nodal and systemic recurrence following observation of a positive sentinel lymph node in melanoma. J Br Surg. 2020;107(11):1480–8.CrossRef
37.
Pozsgai M, Németh K, Oláh P, Gyulai R, Lengyel Z. The significance of imaging examinations during follow-up for malignant melanoma. Eur J Dermatol. 2021;31:357–63.PubMedCrossRef
38.
Thompson JF, Haydu LE, Uren RF, Andtbacka RH, Zager JS, Beitsch PD, et al. Preoperative ultrasound assessment of regional lymph nodes in melanoma patients does not provide reliable nodal staging: results from a large multicenter trial. Ann Surg. 2021;273(4):814–20.PubMedCrossRef
39.
Nadelman DA, Ahn JW, VanKoevering KK, Smith NR, Hughes TM, Bichakjian CK, et al. A single institution’s review of patterns of compliance with melanoma ultrasound surveillance recommendations. J Am Acad Dermatol. 2022;86(1):207–8.PubMedCrossRef
40.
Toia F, Cajozzo M, Rosatti F, Di Lorenzo S, Rinaldi G, Mazzucco W, et al. Effectiveness of clinical and instrumental follow-up for cutaneous melanoma. Surg Oncol. 2022;44: 101821.PubMedCrossRef
41.
Parvez E, Khosrow-Khavar F, Dumitra T, Nessim C, Bernard-Bédard É, Rivard J, et al. Multicenter adoption and outcomes of nodal observation for patients with melanoma and sentinel lymph node metastases. Ann Surg Oncol. 2023;30(2):1195–205.PubMedCrossRef
42.
Vassallo P, Wernecke K, Roos N, Peters PE. Differentiation of benign from malignant superficial lymphadenopathy: the role of high-resolution US. Radiology. 1992;183(1):215–20.PubMedCrossRef
43.
Machet L, Belot V, Naouri M, Boka M, Mourtada Y, Giraudeau B, et al. Preoperative measurement of thickness of cutaneous melanoma using high-resolution 20 MHz ultrasound imaging: a monocenter prospective study and systematic review of the literature. Ultrasound Med Biol. 2009;35(9):1411–20.PubMedCrossRef
44.
De Langen AJ, Raijmakers P, Riphagen I, Paul MA, Hoekstra OS. The size of mediastinal lymph nodes and its relation with metastatic involvement: a meta-analysis. Eur J Cardiothorac Surg. 2006;29(1):26–9.PubMedCrossRef
45.
Biele G, Gustavson K, Czajkowski NO, Nilsen RM, Reichborn-Kjennerud T, Magnus PM, et al. Bias from self selection and loss to follow-up in prospective cohort studies. Eur J Epidemiol. 2019;34:927–38.PubMedCrossRef
46.
Ribero S, Podlipnik S, Osella-Abate S, Sportoletti-Baduel E, Manubens E, Barreiro A, et al. Ultrasound-based follow-up does not increase survival in early-stage melanoma patients: A comparative cohort study. Eur J Cancer. 2017;85:59–66.PubMedCrossRef
47.
Bafounta M-L, Beauchet A, Chagnon S, Saiag P. Ultrasonography or palpation for detection of melanoma nodal invasion: a meta-analysis. Lancet Oncol. 2004;5(11):673–80.PubMedCrossRef
48.
Speijers MJ, Francken AB, Hoekstra-Weebers JE, Bastiaannet E, Kruijff S, Hoekstra HJ. Optimal follow-up for melanoma. Expert Rev Dermatol. 2010;5(4):461–78.CrossRef
49.
Howard MD. Focus: skin: melanoma radiological surveillance: a review of current evidence and clinical challenges. Yale J Biol Med. 2020;93(1):207.PubMedPubMedCentral
50.
Mitra D, Ologun G, Keung EZ, Goepfert RP, Amaria RN, Ross MI, et al. Nodal recurrence is a primary driver of early relapse for patients with sentinel lymph node-positive melanoma in the modern therapeutic era. Ann Surg Oncol. 2021;28(7):3480–9.PubMedPubMedCentralCrossRef
51.
Reticker-Flynn NE, Zhang W, Belk JA, Basto PA, Escalante NK, Pilarowski GO, et al. Lymph node colonization induces tumor-immune tolerance to promote distant metastasis. Cell. 2022;185(11):1924-42.e23.PubMedPubMedCentralCrossRef
52.
53.
Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Nieweg OE, Roses DF, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370(7):599–609.PubMedPubMedCentralCrossRef
54.
Groen LC, Lazarenko SV, Schreurs HW, Richir MC. Evaluation of PET/CT in patients with stage III malignant cutaneous melanoma. Am J Nucl Med Mol Imaging. 2019;9(2):168–75.PubMedPubMedCentral
55.
Shung KK. Diagnostic ultrasound: past, present, and future. J Med Biol Eng. 2011;31(6):371–4.CrossRef
56.
Beach KW. 1975–2000: a quarter century of ultrasound technology. Ultrasound Med Biol. 1992;18(4):377–88.PubMedCrossRef
57.
Nieweg OE, Uren RF, Thompson JF. The history of sentinel lymph node biopsy. Cancer J. 2015;21(1):3–6.PubMedCrossRef
58.
Leong SP, Steinmetz I, Habib FA, McMillan A, Gans JZ, Allen RE Jr, et al. Optimal selective sentinel lymph node dissection in primary malignant melanoma. Arch Surg. 1997;132(6):666–72 (discussion 73).PubMedCrossRef
Metadata
Title
Ultrasound Surveillance in Melanoma Management: Bridging Diagnostic Promise with Real-World Adherence: A Systematic Review and Meta-Analysis
Authors
Zhao Feng Liu
Amy Sylivris
Johnny Wu
Darren Tan
Samuel Hong
Lawrence Lin
Michael Wang
Christopher Chew
Publication date
18-04-2024
Publisher
Springer International Publishing
Published in
American Journal of Clinical Dermatology
Print ISSN: 1175-0561
Electronic ISSN: 1179-1888
DOI
https://doi.org/10.1007/s40257-024-00862-3