Role of PET in the Initial Staging of Cutaneous Malignant Melanoma: Systematic Review

Purpose: To calculate summary estimates of the diagnostic performance of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomographic (PET) imaging in the initial staging of cutaneous malignant melanoma (CMM), following the new American Joint Committee on Cancer (AJCC) staging classification on per-patient and per-lesion bases.

Materials and Methods: MEDLINE, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews databases, and reference lists of reviews and included papers were searched, without any language restrictions, for relevant articles published before March 2007. Two reviewers independently assessed study eligibility and methodologic quality by using the quality assessment of diagnostic accuracy studies checklist. A pooled random effect was estimated and a fixed coefficient regression model was used to explore the existing heterogeneity.

Results: Twenty-eight studies involving 2905 patients met the inclusion criteria. The pooled estimates of FDG PET for the detection of metastasis in the initial staging of CMM were sensitivity, 83% (95% confidence interval [CI]: 81%, 84%); specificity, 85% (95% CI: 83%, 87%); positive likelihood ratio (LR), 4.56 (95% CI: 3.12, 6.64); negative LR, 0.27 (95% CI: 0.18, 0.40); and diagnostic odds ratio, 19.8 (95% CI: 10.8, 36.4). Results from eight studies suggested that FDG PET was associated with 33% disease management changes (range, 15%–64%).

Conclusion: There is good preliminary evidence that FDG PET is useful for the initial staging of patients with CMM, especially as adjunctive role in AJCC stages III and IV, to help detect deep soft-tissue, lymph node, and visceral metastases. FDG PET–computed tomographic imaging seemed to be more precise than PET alone, as suggested by four eligible studies. Further evaluation by using a well-designed prospective study, with clinical outcome–focused measures and cost effectiveness analysis, is needed to clarify the appropriate role of FDG PET in CMM staging.

Supplemental material:

© RSNA, 2008


  • 1 Tsao H, Atkins MB, Sober AJ. Management of cutaneous melanoma. N Engl J Med 2004; 351: 998–1012. Crossref, MedlineGoogle Scholar
  • 2 Balch CM, Soong SJ, Atkins MB, et al. An evidence-based staging system for cutaneous melanoma. CA Cancer J Clin 2004; 54: 131–149. Crossref, MedlineGoogle Scholar
  • 3 Leiter U, Meier F, Schittek B, Garbe C. The natural course of cutaneous melanoma. J Surg Oncol 2004; 86: 172–178. Crossref, MedlineGoogle Scholar
  • 4 Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001; 19: 3635–3648. Crossref, MedlineGoogle Scholar
  • 5 von Schulthess GK, Steinert HC, Hany TF. Integrated PET/CT: current applications and future directions. Radiology 2006; 238: 405–422. LinkGoogle Scholar
  • 6 Larson SM, Schwartz LH. 18F-FDG PET as a candidate for “qualified biomarker”: functional assessment of treatment response in oncology. J Nucl Med 2006; 47: 901–903. MedlineGoogle Scholar
  • 7 Ell PJ. The contribution of PET/CT to improved patient management. Br J Radiol 2006; 79: 32–36. Crossref, MedlineGoogle Scholar
  • 8 Blodgett TM, Meltzer CC, Townsend DW. PET/CT: form and function. Radiology 2007; 242: 360–385. LinkGoogle Scholar
  • 9 Trop I, Stolberg HO, Nahmias C. Estimates of diagnostic accuracy efficacy: how well can this test perform the classification task? Can Assoc Radiol J 2003; 54: 80–86. MedlineGoogle Scholar
  • 10 Schwimmer J, Essner R, Patel A, et al. A review of the literature for whole-body FDG PET in the management of patients with melanoma. Q J Nucl Med 2000; 44: 153–167. MedlineGoogle Scholar
  • 11 Mijnhout GS, Hoekstra OS, van Tulder MW, Teule GJ, Deville WL. Systematic review of the diagnostic accuracy of (18)F-fluorodeoxyglucose positron emission tomography in melanoma patients. Cancer 2001; 91: 1530–1542. Crossref, MedlineGoogle Scholar
  • 12 Cobben DC, Koopal S, Tiebosch AT, et al. New diagnostic techniques in staging in the surgical treatment of cutaneous malignant melanoma. Eur J Surg Oncol 2002; 28: 692–700. Crossref, MedlineGoogle Scholar
  • 13 Prichard RS, Hill AD, Skehan SJ, O'Higgins NJ. Positron emission tomography for staging and management of malignant melanoma. Br J Surg 2002; 89: 389–396. Crossref, MedlineGoogle Scholar
  • 14 Macapinlac HA. FDG PET and PET/CT imaging in lymphoma and melanoma. Cancer J 2004; 10: 262–270. Crossref, MedlineGoogle Scholar
  • 15 Kumar R, Alavi A. Clinical applications of fluorodeoxyglucose: positron emission tomography in the management of malignant melanoma. Curr Opin Oncol 2005; 17: 154–159. Crossref, MedlineGoogle Scholar
  • 16 Kumar R, Mavi A, Bural G, Alavi A. Fluorodeoxyglucose-PET in the management of malignant melanoma. Radiol Clin North Am 2005; 43: 23–33. Crossref, MedlineGoogle Scholar
  • 17 Friedman KP, Wahl RL. Clinical use of positron emission tomography in the management of cutaneous melanoma. Semin Nucl Med 2004; 34: 242–253. Crossref, MedlineGoogle Scholar
  • 18 Essner R, Belhocine T, Scott AM, Even-Sapir E. Novel imaging techniques in melanoma. Surg Oncol Clin N Am 2006; 15: 253–283. Crossref, MedlineGoogle Scholar
  • 19 Muller SP. Malignant melanoma: PET/CT as a staging procedure. Front Radiat Ther Oncol 2006; 39: 159–170. MedlineGoogle Scholar
  • 20 Mijnhout GS, Riphagen II, Hoekstra OS. Update of the FDG PET search strategy. Nucl Med Commun 2004; 25: 1187–1189. Crossref, MedlineGoogle Scholar
  • 21 Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 2003; 3: 25. Crossref, MedlineGoogle Scholar
  • 22 Whiting PF, Weswood ME, Rutjes AW, Reitsma JB, Bossuyt PN, Kleijnen J. Evaluation of QUADAS, a tool for the quality assessment of diagnostic accuracy studies. BMC Med Res Methodol 2006; 6: 9. Crossref, MedlineGoogle Scholar
  • 23 Clark WH Jr, From L, Bernardino EA, Mihm MC. The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res 1969; 29: 705–727. MedlineGoogle Scholar
  • 24 Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PM. The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol 2003; 56: 1129–1135. Crossref, MedlineGoogle Scholar
  • 25 Deville WL, Buntinx F, Bouter LM, et al. Conducting systematic reviews of diagnostic studies: didactic guidelines. BMC Med Res Methodol 2002; 2: 9. Crossref, MedlineGoogle Scholar
  • 26 Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A. Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol 2006; 6: 31. Crossref, MedlineGoogle Scholar
  • 27 Knottnerus JA, Tugwell P. The standards for reporting of diagnostic accuracy. J Clin Epidemiol 2003; 56: 1029. Crossref, MedlineGoogle Scholar
  • 28 Deeks JJ. Systematic reviews in health care: systematic reviews of evaluations of diagnostic and screening tests. BMJ 2001; 323: 157–162. Crossref, MedlineGoogle Scholar
  • 29 Walter SD. Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data. Stat Med 2002; 21: 1237–1256. Crossref, MedlineGoogle Scholar
  • 30 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557–560. Crossref, MedlineGoogle Scholar
  • 31 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–188. Crossref, MedlineGoogle Scholar
  • 32 Irwig L, Macaskill P, Glasziou P, Fahey M. Meta-analytic methods for diagnostic test accuracy. J Clin Epidemiol 1995; 48: 119–130. Crossref, MedlineGoogle Scholar
  • 33 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 2005; 9: 1–113, iii. Google Scholar
  • 34 Gritters LS, Francis IR, Zasadny KR, Wahl RL. Initial assessment of positron emission tomography using 2-fluorine-18-fluoro-2-deoxy-D-glucose in the imaging of malignant melanoma. J Nucl Med 1993; 34: 1420–1427. MedlineGoogle Scholar
  • 35 Blessing C, Feine U, Geiger L, Carl M, Rassner G, Fierlbeck G. Positron emission tomography and ultrasonography: a comparative retrospective study assessing the diagnostic validity in lymph node metastases of malignant melanoma. Arch Dermatol 1995; 131: 1394–1398. Crossref, MedlineGoogle Scholar
  • 36 Steinert HC, Huch Boni RA, Buck A, et al. Malignant melanoma: staging with whole-body positron emission tomography and 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology 1995; 195: 705–709. LinkGoogle Scholar
  • 37 Holder WD Jr, White RL Jr, Zuger JH, Easton EJ Jr, Greene FL. Effectiveness of positron emission tomography for the detection of melanoma metastases. Ann Surg 1998; 227: 764–769. Crossref, MedlineGoogle Scholar
  • 38 Macfarlane DJ, Sondak V, Johnson T, Wahl RL. Prospective evaluation of 2-[18F]-2-deoxy-D-glucose positron emission tomography in staging of regional lymph nodes in patients with cutaneous malignant melanoma. J Clin Oncol 1998; 16: 1770–1776. Crossref, MedlineGoogle Scholar
  • 39 Rinne D, Baum RP, Hor G, Kaufmann R. Primary staging and follow-up of high risk melanoma patients with whole-body 18F-fluorodeoxyglucose positron emission tomography: results of a prospective study of 100 patients. Cancer 1998; 82: 1664–1671. Crossref, MedlineGoogle Scholar
  • 40 Nguyen AT, Akhurst T, Larson SM, Coit DG, Brady MS. PET scanning with (18)F 2-fluoro-2-deoxy-D-glucose (FDG) in patients with melanoma: benefits and limitations. Clin Positron Imaging 1999; 2: 93–98. Crossref, MedlineGoogle Scholar
  • 41 Crippa F, Leutner M, Belli F, et al. Which kinds of lymph node metastases can FDG PET detect? a clinical study in melanoma. J Nucl Med 2000; 41: 1491–1494. Google Scholar
  • 42 Eigtved A, Andersson AP, Dahlstrom K, et al. Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma. Eur J Nucl Med 2000; 27: 70–75. Crossref, MedlineGoogle Scholar
  • 43 Paquet P, Henry F, Belhocine T, et al. An appraisal of 18-fluorodeoxyglucose positron emission tomography for melanoma staging. Dermatology 2000; 200: 167–169. Crossref, MedlineGoogle Scholar
  • 44 Tyler DS, Onaitis M, Kherani A, et al. Positron emission tomography scanning in malignant melanoma. Cancer 2000; 89: 1019–1025. Crossref, MedlineGoogle Scholar
  • 45 Acland KM, Healy C, Calonje E, et al. Comparison of positron emission tomography scanning and sentinel node biopsy in the detection of micrometastases of primary cutaneous malignant melanoma. J Clin Oncol 2001; 19: 2674–2678. Crossref, MedlineGoogle Scholar
  • 46 Belhocine T, Pierard G, De Labrassinne M, Lahaye T, Rigo P. Staging of regional nodes in AJCC stage I and II melanoma: 18FDG PET imaging versus sentinel node detection. Oncologist 2002; 7: 271–278. Crossref, MedlineGoogle Scholar
  • 47 Swetter SM, Carroll LA, Johnson DL, Segall GM. Positron emission tomography is superior to computed tomography for metastatic detection in melanoma patients. Ann Surg Oncol 2002; 9: 646–653. Crossref, MedlineGoogle Scholar
  • 48 Havenga K, Cobben DC, Oyen WJ, et al. Fluorodeoxyglucose-positron emission tomography and sentinel lymph node biopsy in staging primary cutaneous melanoma. Eur J Surg Oncol 2003; 29: 662–664. Crossref, MedlineGoogle Scholar
  • 49 Fink AM, Holle-Robatsch S, Herzog N, et al. Positron emission tomography is not useful in detecting metastasis in the sentinel lymph node in patients with primary malignant melanoma stage I and II. Melanoma Res 2004; 14: 141–145. Crossref, MedlineGoogle Scholar
  • 50 Finkelstein SE, Carrasquillo JA, Hoffman JM, et al. A prospective analysis of positron emission tomography and conventional imaging for detection of stage IV metastatic melanoma in patients undergoing metastasectomy. Ann Surg Oncol 2004; 11: 731–738. Crossref, MedlineGoogle Scholar
  • 51 Harris MT, Berlangieri SU, Cebon JS, Davis ID, Scott AM. Impact of 2-deoxy-2[F-18]fluoro-D-glucose positron emission tomography on the management of patients with advanced melanoma. Mol Imaging Biol 2005; 7: 304–308. Crossref, MedlineGoogle Scholar
  • 52 Vereecken P, Laporte M, Petein M, Steels E, Heenen M. Evaluation of extensive initial staging procedure in intermediate/high-risk melanoma patients. J Eur Acad Dermatol Venereol 2005; 19: 66–73. Crossref, MedlineGoogle Scholar
  • 53 Wagner JD, Schauwecker D, Davidson D, et al. Inefficacy of F-18 fluorodeoxy-D-glucose-positron emission tomography scans for initial evaluation in early-stage cutaneous melanoma. Cancer 2005; 104: 570–579. Crossref, MedlineGoogle Scholar
  • 54 Brady MS, Akhurst T, Spanknebel K, et al. Utility of preoperative [(18)]F fluorodeoxyglucose-positron emission tomography scanning in high-risk melanoma patients. Ann Surg Oncol 2006; 13: 525–532. Crossref, MedlineGoogle Scholar
  • 55 Clark PB, Soo V, Kraas J, Shen P, Levine EA. Futility of fluorodeoxyglucose F 18 positron emission tomography in initial evaluation of patients with T2 to T4 melanoma. Arch Surg 2006; 141: 284–288. Crossref, MedlineGoogle Scholar
  • 56 Horn J, Lock-Andersen J, Sjostrand H, Loft A. Routine use of FDG-PET scans in melanoma patients with positive sentinel node biopsy. Eur J Nucl Med Mol Imaging 2006; 33: 887–892. Crossref, MedlineGoogle Scholar
  • 57 Bastiaannet E, Hoekstra OS, Oyen WJ, Jager PL, Wobbes T, Hoekstra HJ. Level of fluorodeoxyglucose uptake predicts risk for recurrence in melanoma patients presenting with lymph node metastases. Ann Surg Oncol 2006; 13: 919–926. Crossref, MedlineGoogle Scholar
  • 58 Reinhardt MJ, Joe AY, Jaeger U, et al. Diagnostic performance of whole body dual modality 18F-FDG PET/CT imaging for N- and M-staging of malignant melanoma: experience with 250 consecutive patients. J Clin Oncol 2006; 24: 1178–1187. Crossref, MedlineGoogle Scholar
  • 59 Romer W, Nomayr A, Greess H, et al. Retrospective interactive rigid fusion of (18)F-FDG-PET and CT: additional diagnostic information in melanoma patients. Nuklearmedizin 2006; 45: 88–95. Crossref, MedlineGoogle Scholar
  • 60 Iagaru A, Quon A, Johnson D, Gambhir SS, McDougall IR. 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography/computed tomography in the management of melanoma. Mol Imaging Biol 2007; 9: 50–57. Crossref, MedlineGoogle Scholar
  • 61 Pfannenberg C, Aschoff P, Schanz S, et al. Prospective comparison of 18F-fluorodeoxyglucose positron emission tomography/computed tomography and whole-body magnetic resonance imaging in staging of advanced malignant melanoma. Eur J Cancer 2007; 43: 557–564. Crossref, MedlineGoogle Scholar
  • 62 Bastiaannet E, Oyen WJ, Meijer S, et al. Impact of [18F]fluorodeoxyglucose positron emission tomography on surgical management of melanoma patients. Br J Surg 2006; 93: 243–249. Crossref, MedlineGoogle Scholar
  • 63 Boni R, Huch-Boni RA, Steinert H, von Schulthess GK, Burg G. Early detection of melanoma metastasis using fludeoxyglucose F 18 positron emission tomography. Arch Dermatol 1996; 132: 875–876. Crossref, MedlineGoogle Scholar
  • 64 Fuster D, Chiang S, Johnson G, Schuchter LM, Zhuang H, Alavi A. Is 18F-FDG PET more accurate than standard diagnostic procedures in the detection of suspected recurrent melanoma? J Nucl Med 2004; 45: 1323–1327. MedlineGoogle Scholar
  • 65 Loffler M, Weckesser M, Franzius C, Nashan D, Schober O. Malignant melanoma and (18)F-FDG-PET: should the whole body scan include the legs? Nuklearmedizin 2003; 42: 167–172. Crossref, MedlineGoogle Scholar
  • 66 Mijnhout GS, Pijpers R, Hoekstra OS, Teule GJ, Borgstein PJ, Meijer S. Primary staging and follow-up of high risk melanoma patients with whole-body 18F-fluorodeoxyglucose positron emission tomography: results of a prospective study of 100 patients. Cancer 1999; 85: 1199–1201. Crossref, MedlineGoogle Scholar
  • 67 Mottaghy FM, Sunderkotter C, Schubert R, et al. Direct comparison of [(18)F]FDG PET/CT with PET alone and with side-by-side PET and CT in patients with malignant melanoma. Eur J Nucl Med Mol Imaging 2007; 34: 1355–1364. Crossref, MedlineGoogle Scholar
  • 68 Nieweg O, Valdes Olmos R. Routine use of FDG-PET scans in melanoma patients with positive sentinel node biopsy. Eur J Nucl Med Mol Imaging 2007; 34: 602. Crossref, MedlineGoogle Scholar
  • 69 Paquet P, Hustinx R, Rigo P, Pierard GE. Malignant melanoma staging using whole-body positron emission tomography. Melanoma Res 1998; 8: 59–62. Crossref, MedlineGoogle Scholar
  • 70 Steinert HC, Voellmy DR, Trachsel C, et al. Planar coincidence scintigraphy and PET in staging malignant melanoma. J Nucl Med 1998; 39: 1892–1897. MedlineGoogle Scholar
  • 71 Damian DL, Fulham MJ, Thompson E, Thompson JF. Positron emission tomography in the detection and management of metastatic melanoma. Melanoma Res 1996; 6: 325–329. Crossref, MedlineGoogle Scholar
  • 72 Dietlein M, Krug B, Groth W, et al. Positron emission tomography using 18F-fluorodeoxyglucose in advanced stages of malignant melanoma: a comparison of ultrasonographic and radiological methods of diagnosis. Nucl Med Commun 1999; 20: 255–261. Crossref, MedlineGoogle Scholar
  • 73 Falk MS, Truitt AK, Coakley FV, Kashani-Sabet M, Hawkins RA, Franc B. Interpretation, accuracy and management implications of FDG PET/CT in cutaneous malignant melanoma. Nucl Med Commun 2007; 28: 273–280. Crossref, MedlineGoogle Scholar
  • 74 Gulec SA, Faries MB, Lee CC, et al. The role of fluorine-18 deoxyglucose positron emission tomography in the management of patients with metastatic melanoma: impact on surgical decision making. Clin Nucl Med 2003; 28: 961–965. Crossref, MedlineGoogle Scholar
  • 75 Jadvar H, Johnson DL, Segall GM. The effect of fluorine-18 fluorodeoxyglucose positron emission tomography on the management of cutaneous malignant melanoma. Clin Nucl Med 2000; 25: 48–51. Crossref, MedlineGoogle Scholar
  • 76 Krug B, Dietlein M, Groth W, et al. Fluor-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in malignant melanoma: diagnostic comparison with conventional imaging methods. Acta Radiol 2000; 41: 446–452. MedlineGoogle Scholar
  • 77 Longo MI, Lazaro P, Bueno C, Carreras JL, Montz R. Fluorodeoxyglucose-positron emission tomography imaging versus sentinel node biopsy in the primary staging of melanoma patients. Dermatol Surg 2003; 29: 245–248. Crossref, MedlineGoogle Scholar
  • 78 Maubec E, Lumbroso J, Masson F, et al. F-18 fluorodeoxy-D-glucose positron emission tomography scan in the initial evaluation of patients with a primary melanoma thicker than 4 mm. Melanoma Res 2007; 17: 147–154. Crossref, MedlineGoogle Scholar
  • 79 Schafer A, Herbst RA, Beiteke U, et al. Sentinel lymph node excision (SLNE) and positron emission tomography in the staging of stage I-II melanoma patients [in German]. Hautarzt 2003; 54: 440–447. Crossref, MedlineGoogle Scholar
  • 80 Hafner J, Schmid MH, Kempf W, et al. Baseline staging in cutaneous malignant melanoma. Br J Dermatol 2004; 150: 677–686. Crossref, MedlineGoogle Scholar
  • 81 Acland KM, O'Doherty MJ, Russell-Jones R. The value of positron emission tomography scanning in the detection of subclinical metastatic melanoma. J Am Acad Dermatol 2000; 42: 606–611. Crossref, MedlineGoogle Scholar
  • 82 Boni R, Boni RA, Steinert H, et al. Staging of metastatic melanoma by whole-body positron emission tomography using 2-fluorine-18-fluoro-2-deoxy-D-glucose. Br J Dermatol 1995; 132: 556–562. MedlineGoogle Scholar
  • 83 Wagner JD, Schauwecker D, Davidson D, et al. Prospective study of fluorodeoxyglucose-positron emission tomography imaging of lymph node basins in melanoma patients undergoing sentinel node biopsy. J Clin Oncol 1999; 17: 1508–1515. Crossref, MedlineGoogle Scholar
  • 84 Wagner JD, Schauwecker D, Hutchins G, Coleman JJ 3rd. Initial assessment of positron emission tomography for detection of nonpalpable regional lymphatic metastases in melanoma. J Surg Oncol 1997; 64: 181–189. Crossref, MedlineGoogle Scholar
  • 85 Choi EA, Gershenwald JE. Imaging studies in patients with melanoma. Surg Oncol Clin N Am 2007; 16: 403–430. Crossref, MedlineGoogle Scholar
  • 86 Reid MC, Lachs MS, Feinstein AR. Use of methodological standards in diagnostic test research: getting better but still not good. JAMA 1995; 274: 645–651. Crossref, MedlineGoogle Scholar
  • 87 Lijmer JG, Bossuyt PM, Heisterkamp SH. Exploring sources of heterogeneity in systematic reviews of diagnostic tests. Stat Med 2002; 21: 1525–1537. Crossref, MedlineGoogle Scholar
  • 88 Bossuyt PM, Reitsma JB, Bruns DE, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. BMJ 2003; 326: 41–44. Crossref, MedlineGoogle Scholar
  • 89 Hofmann U, Szedlak M, Rittgen W, Jung EG, Schadendorf D. Primary staging and follow-up in melanoma patients: monocenter evaluation of methods, costs and patient survival. Br J Cancer 2002; 87: 151–157. Crossref, MedlineGoogle Scholar

Article History

Published in print: 2008