Abstract
Objective
We aimed to assess the diagnostic accuracy of C-11 choline and C-11 acetate positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging in bladder cancer (BC) patients through a systematic review and meta-analysis.
Methods
The MEDLINE, EMBASE, and Cochrane Library database, from the earliest available date of indexing through June 30, 2017, were searched for studies evaluating the diagnostic performance of C-11 choline and C-11 acetate PET/CT for LN staging in BC. 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 10 studies (282 patients), the pooled sensitivity was 0.66 (95% CI 0.54–0.75) without heterogeneity (χ2 = 12.4, p = 0.19) and a pooled specificity of 0.89 (95% CI 0.76–0.95) with heterogeneity (χ2 = 29.1, p = 0.00). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 5.8 (95% CI 2.7–12.7) and negative likelihood ratio (LR−) of 0.39 (95% CI 0.28–0.53). The pooled diagnostic odds ratio (DOR) was 15 (95% CI 6–38). In meta-regression analysis, the study design (prospective vs retrospective) was the source of the study heterogeneity.
Conclusion
C-11 choline and C-11 acetate PET/CT shows a low sensitivity and moderate specificity for the detection of metastatic LNs in patients with BC. Moreover, heterogeneity among the studies should be considered a limitation. Further large multicenter studies would be necessary to substantiate the diagnostic accuracy of C-11 choline and C-11 acetate PET/CT for this purpose.
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References
Siegel RL et al (2017) Cancer Statistics, 2017. CA Cancer J Clin 67(1):7–30
Amin MB et al (2013) ICUD-EAU international consultation on bladder cancer 2012: pathology. Eur Urol 63(1):16–35
Paik ML et al (2000) Limitations of computerized tomography in staging invasive bladder cancer before radical cystectomy. J Urol 163(6):1693–1696
Herr HW et al (2007) Defining optimal therapy for muscle invasive bladder cancer. J Urol 177(2):437–443
Stein JP et al (2001) Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 19(3):666–675
Nishiyama H et al (2004) Clinical outcome of a large-scale multi-institutional retrospective study for locally advanced bladder cancer: a survey including 1131 patients treated during 1990–2000 in Japan. Eur Urol 45(2):176–181
Palmieri F et al (2010) Prognostic value of lymphovascular invasion in bladder cancer in patients treated with radical cystectomy. Anticancer Res 30(7):3–6
Zehnder P et al (2011) Super extended versus extended pelvic lymph node dissection in patients undergoing radical cystectomy for bladder cancer: a comparative study. J Urol 186(4):1261–1268
Schiavina R et al (2013) Perioperative complications and mortality after radical cystectomy when using a standardized reporting methodology. Clin Genitourin Cancer 11(2):189–197
Husband JE (1995) Computer tomography and magnetic resonance imaging in the evaluation of bladder cancer. J Belge Radiol 78(6):350–355
Blodgett TM et al (2007) PET/CT: form and function. Radiology 242(2):360–385
Czernin J et al (2007) Improvements in cancer staging with PET/CT: literature-based evidence as of September 2006. J Nucl Med 48(Suppl 1):78S–88S
Kibel AS et al (2009) Prospective study of [18F] fluorodeoxyglucose positron emission tomography/computed tomography for staging of muscle-invasive bladder carcinoma. J Clin Oncol 27(26):4314–4320
Lodde M et al (2010) Evaluation of fluorodeoxyglucose positron-emission tomography with computed tomography for staging of urothelial carcinoma. BJU Int 106(5):658–663
Swinnen G et al (2010) FDG-PET/CT for the preoperative lymph node staging of invasive bladder cancer. Eur Urol 57(4):641–647
Vind-Kezunovic S et al (2017) Detection of lymph node metastasis in patients with bladder cancer using maximum standardised uptake value and 18F-fluorodeoxyglucose positron emission tomography/computed tomography: results from a high-volume centre including long-term follow-up. Eur Urol Focus. https://doi.org/10.1016/j.euf.2017.06.005 (Epub ahead of print)
Golan S et al (2011) Comparison of 11C-choline with 18F-FDG in positron emission tomography/computerized tomography for staging urothelial carcinoma: a prospective study. J Urol 186(2):436–441
Vargas HA et al (2012) Prospective evaluation of MRI, 11C-acetate PET/CT and contrast-enhanced CT for staging of bladder cancer. Eur J Radiol 81(12):4131–4137
Whiting PF et al (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155(8):529–536
Glas AS et al (2003) The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol 56(11):1129–1135
Thompson SG (1994) Why sources of heterogeneity in meta-analysis should be investigated. BMJ 309(6965):1351–1355
Deeks JJ et al (2005) The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 58(9):882–893
Reitsma JB et al (2005) Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol 58(10):982–990
Hamza TH et al (2008) The binomial distribution of meta-analysis was preferred to model within-study variability. J Clin Epidemiol 61(1):41–51
Rutter CM et al (2001) A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations. Stat Med 20(19):2865–2884
Lijmer JG et al (1999) Empirical evidence of design-related bias in studies of diagnostic tests. JAMA 282(11):1061–1066
Brunocilla E et al (2014) Diagnostic accuracy of 11C-choline PET/CT in preoperative lymph node staging of bladder cancer: a systematic comparison with contrast-enhanced CT and histologic findings. Clin Nucl Med 39(5):e308–e312
Ceci F et al (2015) 11C-choline PET/CT and bladder cancer: lymph node metastasis assessment with pathological specimens as reference standard. Clin Nucl Med 40(2):e124–e128
Gofrit ON et al (2006) Contribution of 11C-choline positron emission tomography/computerized tomography to preoperative staging of advanced transitional cell carcinoma. J Urol 176(3):940–944
de Jong IJ et al (2002) Visualisation of bladder cancer using 11C-choline PET: first clinical experience. Eur J Nucl Med Mol Imaging 29(10):1283–1288
Graziani T et al (2015) 11C-choline PET/CT for restaging of bladder cancer. Clin Nucl Med 40(1):e1–e5
Maurer T et al (2012) Diagnostic efficacy of [11C]choline positron emission tomography/computed tomography compared with conventional computed tomography in lymph node staging of patients with bladder cancer prior to radical cystectomy. Eur Urol 61(5):1031–1038
Picchio M et al (2006) Value of 11C-choline PET and contrast-enhanced CT for staging of bladder cancer: correlation with histopathologic findings. J Nucl Med 47(6):938–944
Schöder H et al (2012) Initial results with 11C-acetate positron emission tomography/computed tomography (PET/CT) in the staging of urinary bladder cancer. Mol Imaging Biol 14(2):245–251
Treiber U et al (2005) Diagnostic efficacy of 11C-choline positron emission tomography in patients scheduled for cystectomy. Eur Urol Suppl 4(3):161
Brunocilla E et al (2011) The role of pelvic lymph node dissection during radical cystectomy for bladder cancer. Anticancer Res 31(1):271–275
Shvarts O et al (2002) Positron emission tomography in urologic oncology. Cancer Control 9(4):335–342
Farsad M et al (2008) Positron-emission tomography in imaging and staging prostate cancer. Cancer Biomark 4(4–5):277–284
Nanni C et al (2013) Comparison of 18F-FACBC and 11C-choline PET/CT in patients with radically treated prostate cancer and biochemical relapse: preliminary results. Eur J Nucl Med Mol Imaging 40(Suppl 1):S11–S17
Lu YY et al (2012) Clinical value of FDG PET or PET/CT in urinary bladder cancer: a systemic review and meta-analysis. Eur J Radiol 81(9):2411–2416
Kates AM et al (2003) Impact of aging on substrate metabolism by the human heart. J Am Coll Cardiol 41(2):293–299
Oyama N et al (2003) 11C-acetate PET imaging of prostate cancer: detection of recurrent disease at PSA relapse. J Nucl Med 44(4):549–555
Sandblom G et al (2006) Positron emission tomography with C11-acetate for tumor detection and localization in patients with prostate-specific antigen relapse after radical prostatectomy. Urology 67(5):996–1000
Yoshimoto M et al (2001) Characterization of acetate metabolism in tumor cells in relation to cell proliferation: acetate metabolism in tumor cells. Nucl Med Biol 28(2):117–122
Vavere AL et al (2008) 11C-acetate as a PET radiopharmaceutical for imaging fatty acid synthase expression in prostate cancer. J Nucl Med 49(2):327–334
Menendez JA et al (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 7(10):763–777
Brusselmans K et al (2005) RNA interference-mediated silencing of the acetyl-CoA-carboxylase alpha gene induces growth inhibition and apoptosis of prostate cancer cells. Cancer Res 65(15):6719–6725
Boellaard R (2012) Mutatis mutandis: harmonize the standard! J Nucl Med 53(1):1–3
Boellaard R et al (2008) The Netherlands protocol for standardisation and quantification of FDG whole body PET studies in multi-centre trials. Eur J Nucl Med Mol Imaging 35(12):2320–2333
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Protocol/project development: KSJ. Data collection or management: KSJ and PJK. Data analysis: KSJ and PJK. Manuscript writing/editing; KSJ and PJK.
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The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.
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Institutional review board approval was not required because we only performed data analysis based on the published studies.
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Written informed consent was not required for this study because it is a meta-analysis based on the studies that have been published.
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Kim, SJ., Koo, P.J., Pak, K. et al. Diagnostic accuracy of C-11 choline and C-11 acetate for lymph node staging in patients with bladder cancer: a systematic review and meta-analysis. World J Urol 36, 331–340 (2018). https://doi.org/10.1007/s00345-017-2168-4
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DOI: https://doi.org/10.1007/s00345-017-2168-4