Introduction: We aimed to assess the diagnostic accuracy of radiolabeled prostate-specific membrane antigen positron emission tomography (PSMA PET) or positron emission tomography/computed tomography (PET/CT) for primary lymph node (LN) staging in newly diagnosed intermediate to high-risk prostate cancer (PCa) patients. Material and Methods: The MEDLINE, PubMed, EMBASE, and Cochrane Library database from the earliest available date of indexing through May 31, 2018, were searched for studies evaluating the diagnostic performance of radiolabeled PSMA PET or PET/CT for primary LN staging in newly diagnosed intermediate to high-risk PCa. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR–), and constructed summary receiver operating characteristic curves. Results: Across 6 studies (298 patients), the pooled sensitivity was 0.71 (95% CI 0.59–0.81) and a pooled specificity of 0.95 (95% CI 0.87–0.99). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 15.6 (95% CI 5.6–43.0) and negative likelihood ratio (LR–) of 0.30 (95% CI 0.21–0.43). The pooled diagnostic odds ratio (DOR) was 51 (95% CI 21–126). Conclusion: Radiolabeled PSMA PET/CT shows a moderate sensitivity and high specificity for the detection of metastatic LNs in patients with newly diagnosed intermediate to high-risk PCa.

1.
Brawley OW: Prostate cancer epidemiology in the United States. World J Urol 2012; 30: 195–200.
2.
Siegel RL, Miller KD, Jemal A: Cancer statistics, 2017. CA Cancer J Clin 2017; 67: 7–30.
3.
Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, Mason M, Matveev V, Wiegel T, Zattoni F, Mottet N; European Association of Urology: EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 2014; 65: 467–479.
4.
Carter HB: American Urological Association (AUA) guideline on prostate cancer detection: process and rationale. BJU Int 2013; 112: 543–547.
5.
Gakis G, Boorjian SA, Briganti A, Joniau S, Karazanashvili G, Karnes RJ, Mattei A, Shariat SF, Stenzl A, Wirth M, Stief CG: The role of radical prostatectomy and lymph node dissection in lymph node-positive prostate cancer: a systematic review of the literature. Eur Urol 2013; 22:S0302–S2838.
6.
Briganti A, Abdollah F, Nini A, Suardi N, Gallina A, Capitanio U, Bianchi M, Tutolo M, Passoni NM, Salonia A, Colombo R, Freschi M, Rigatti P, Montorsi F: Performance characteristics of computed tomography in detecting lymph node metastases in contemporary patients with prostate cancer treated with extended pelvic lymph node dissection. Eur Urol 2012; 61: 1132–1138.
7.
Budiharto T, Joniau S, Lerut E, Van den Bergh L, Mottagy F, Deroose CM, Oyen R, Ameye F, Bogaerts K, Haustermans K, Van Poppel H: Prospective evaluation of C-11-choline positron emission tomography/computed tomography and diffusion weighted magnetic resonance imaging for the nodal staging of prostate cancer with a high risk lymph node metastases. Eur Urol 2011; 60: 125–130.
8.
Perner S, Hofer MD, Kim R, Shah RB, Li H, Möller P, Hautmann RE, Gschwend JE, Kuefer R, Rubin MA: Prostate-specific membrane antigen expression as a predictor of prostate cancer progression. Hum Pathol 2007; 38: 696–701.
9.
Wright GL Jr, Grob BM, Haley C, Grossman K, Newhall K, Petrylak D, Troyer J, Konchuba A, Schellhammer PF, Moriarty R: Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology 1996; 48: 326–334.
10.
Eder M, Schafer M, Baeder-Wüst U, Hull WE, Wangler C, Mier W, Haberkorn U, Eisenhut M: 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Biconjug Chem 2012; 23: 688–697.
11.
Eder M, Schafer M, Bauder-Wüst U, Haberkorn U, Eisenhut M, Kopka K: Preclinical evaluation of a bispecific low-molecular heterodimer targeting both PSMA and GRPR for improved PET imaging and therapy of prostate cancer. Prostate 2014; 74: 659–668.
12.
Afshar-Oromieh A, Zechmann CM, Malcher A, Eder M, Eisenhut M, Linhart HG, Holland-Letz T, Hadaschik BA, Giesel FL, Debus J, Haberkorn U: Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2014; 41: 11–20.
13.
Morigi JJ, Stricker PD, Van Leeuwen PJ, Tang R, Ho B, Nguyen Q, Hruby G, Fogarty G, Jagavkar R, Kneebone A, Hickey A, Fanti S, Tarlinton L, Emmett L: Prospective comparison of 18F-Fluoromethylcholine versus 68Ga-PSMA PET/CT in prostate cancer patients who have rising PSA after curative treatment and are being considered for targeted therapy. J Nucl Med 2015; 56: 1185–1190.
14.
Zang S, Shao G, Cui C, Li TN, Huang Y, Yao X, Fan Q, Chen Z, Du J, Jia R, Sun H, Hua Z, Tang J, Wang F: 68Ga-PSMA-11 PET/CT for prostate cancer staging and risk stratification in Chinese patients. Oncotarget 2017; 8: 12247–12258.
15.
Schwenck J, Rempp H, Reischl G, Kruck S, Stenzl A, Nikolaou K, Pfannenberg C, la Fougère C: Comparison of 68Ga-labelled PSMA-11 and 11C-choline in the detection of prostate cancer metastases by PET/CT. Eur J Nucl Med Mol Imaging 2017; 44: 92–101.
16.
Freitag MT, Radtke JP, Hadaschik BA, Kopp-Schneider A, Eder M, Kopka K, Haberkorn U, Roethke M, Schlemmer HP, Afshar-Oromieh A: Comparison of hybrid (68)Ga-PSMA PET/MRI and (68)Ga-PSMA PET/CT in the evaluation of lymph node and bone metastases of prostate cancer. Eur J Nucl Med Mol Imaging 2016; 43: 70–83.
17.
Cantiello F, Gangemi V, Cascini GL, Calabria F, Moschini M, Ferro M, Musi G, Butticè S, Salonia A, Briganti A, Damiano R: Diagnostic accuracy of 64Copper prostate-specific membrane antigen positron emission tomography/computed tomography for primary lymph node staging of intermediate- to high-risk prostate cancer: our preliminary experience. Urology 2017:pii:S0090-4295(17)30385-0.
18.
van Leeuwen PJ, Emmett L, Ho B, Delprado W, Ting F, Nguyen Q, Stricker PD: Prospective evaluation of 68Gallium-prostate-specific membrane antigen positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer. BJU Int 2017; 119: 209–215.
19.
Öbek C, Doğanca T, Demirci E, Ocak M, Kural AR, Yıldırım A, Yücetaş U, Demirdağ Ç, Erdoğan SM, Kabasakal L; Members of Urooncology Association, Turkey: The accuracy of 68Ga-PSMA PET/CT in primary lymph node staging in high-risk prostate cancer. Eur J Nucl Med Mol Imaging 2017, Epub ahead of print.
20.
Budäus L, Leyh-Bannurah SR, Salomon G, Michl U, Heinzer H, Huland H, Graefen M, Steuber T, Rosenbaum C: Initial experience of 68Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol 2016; 69: 393–396.
21.
Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, Wester HJ, Heck M, Kübler H, Beer AJ, Schwaiger M, Eiber M: Diagnostic efficacy of 68Gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol 2016; 195: 1436–1443.
22.
Herlemann A, Wenter V, Kretschmer A, Thierfelder KM, Bartenstein P, Faber C, Gildehaus FJ, Stief CG, Gratzke C, Fendler WP: 68Ga-PSMA positron emission tomography/computed tomography provides accurate staging of lymph node regions prior to lymph node dissection in patients with prostate cancer. Eur Urol 2016; 70: 553–557.
23.
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: 25–37.
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.
25.
Thompson SG: Why sources of heterogeneity in meta-analysis should be investigated. BMJ 1994; 309: 1351–1355.
26.
Deeks JJ, Macaskill P, Irwig L: The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 2005; 58: 882–893.
27.
Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH: Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol 2005; 58: 982–990.
28.
Hamza TH, van Houwelingen HC, Stijnen T: The binomial distribution of meta-analysis was preferred to model within-study variability. J Clin Epidemiol 2008; 61: 41–51.
29.
Rutter CM, Gatsonis CA: A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations. Stat Med 2001; 20: 2865–2884.
30.
Lijmer JG, Mol BW, Heisterkamp S, Bonsel GJ, Prins MH, van der Meulen JH, Bossuyt PM: Empirical evidence of design-related bias in studies of diagnostic tests. JAMA 1999; 282: 1061–1066.
31.
Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C: Prostate specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 1997; 3: 81–85.
32.
Bostwick DG, Pacelli A, Blute M, Roche P, Murphy GP: Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer 1998; 82: 2256–2261.
33.
Sweat SD, Pacelli A, Murphy GP, Bostwick DG: Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology 1998; 52: 637–640.
34.
Mannweiler S, Amersdorfer P, Trajanoski S, Terrett JA, King D, Mehes G: Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis. Pathol Oncol Res 2009; 15: 167–172.
35.
NCCN Guidelines: Prostate Cancer. Fort Washington, PA, National Comprehensive Cancer Network, 2015.
36.
Hovels AM, Heesakkers RA, Adang EM, Jager GJ, Strum S, Hoogeveen YL, Severens JL, Barentsz JO: The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin Radiol 2008; 63: 387–395.
37.
Rauscher I, Maurer T, Beer AJ, Graner FP, Haller B, Weirich G, Doherty A, Gschwend JE, Schwaiger M, Eiber M: Value of 68Ga-PSMA HBED-CC PET for the assessment of lymph node metastases in prostate cancer patients with biochemical recurrence: comparison with histopathology after salvage lymphadenectomy. J Nucl Med 2016; 57: 1713–1719.
38.
Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, Bolton D, Lawrentschuk N: Sensitivity, specificity, and predictors of positive 68Ga-prostatespecific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis. Eur Urol 2016; 70: 926–937.
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