INTRODUCTION: Lymph node (LN) involvement is a crucial determinant of prognosis for patients with bladder cancer, and an accurate staging is of utmost importance to better identify timely and appropriate therapeutic strategies. To improve the accuracy of LN detection, as an alternative to traditional methods such as CT or MRI, 18F-FDG PET/CT has been increasingly used. 18F-FDG PET/CT is also used in post-treatment restaging after neoadjuvant chemotherapy. The aim of this narrative literature review is to provide an overview of the current evidence on the use of 18F-FDG PET/CT in the diagnosis, staging, and restaging of bladder cancer, with a particular focus on its sensitivity and specificity for the detection of LN metastasis. We aim to provide clinicians with a better understanding of 18F-FDG PET/CT's potential benefits and limitations in clinical practice. MATERIALS AND METHODS: We designed a narrative review starting from a wide search in the PubMed/MEDLINE and Embase databases, selecting full-text English articles that have examined the sensibility and specificity of PET/CT for nodal staging or restaging after neoadjuvant therapy in patients with bladder cancer. The extracted data were analyzed and synthesized using a narrative synthesis approach. The results are presented in a tabular format, with a summary of the main findings of each study. RESULTS: Twenty-three studies met the inclusion criteria: fourteen studies evaluated 18F-FDG PET/CT for nodal staging, six studies examined its accuracy for restaging after neoadjuvant therapy, and three studies evaluated both applications. To date, the use of F-18 FDG PET/TC for detection of LN metastasis in bladder cancer is controversial and uncertain: some studies showed low accuracy rates, but over the years other studies have reported evidence of high sensitivity and specificity. CONCLUSIONS: 18F-FDG PET/CT provides important incremental staging and restaging information that can potentially influence clinical management in MIBC patients. Standardization and development of a scoring system are necessary for its wider adoption. Well-designed randomized controlled trials in larger populations are necessary to provide consistent recommendations and consolidate the role of 18F-FDG PET/CT in the management of bladder cancer patients.

Comprehensive Cancer Center Department of Urology Medical University of Vienna Vienna General Hospital Währinger Gürtel 18 20 1090 Vienna Austria

Department of Maternal Infant and Urological Sciences Policlinico Umberto 1 Hospital Sapienza University of Rome 00185 Rome Italy

Department of Minimally Invasive and Robotic Urology Wrocław Medical University 50 367 Wroclaw Poland

Department of Urology 2nd Faculty of Medicine Charles University 15006 Prague Czech Republic

Department of Urology and Division of Experimental Oncology URI Urological Research Institute IRCCS San Raffaele Scientific Institute 20132 Milan Italy

Department of Urology La Croix du Sud Hôpital Quint Fonsegrives 31000 Toulouse France

Department of Urology The Netherlands Cancer Institute 1066 Amsterdam The Netherlands

Department of Urology University of Texas Southwestern Medical Center Dallas TX 75390 USA

Department of Urology Weill Cornell Medical College New York NY 10065 USA

Hourani Center for Applied Scientific Research Al Ahliyya Amman University Amman 19328 Jordan

Institute for Urology and Reproductive Health Sechenov University 119435 Moscow Russia

Karl Landsteiner Institute of Urology and Andrology 1090 Vienna Austria

Oncologic Minimally Invasive Urology and Andrology Unit Department of Experimental and Clinical Medicine Careggi Hospital University of Florence 50121 Florence Italy

Zobrazit více v PubMed

Chang S.S., Bochner B.H., Chou R., Dreicer R., Kamat A.M., Lerner S.P., Lotan Y., Meeks J.J., Michalski J.M., Morgan T.M., et al. Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline. J. Urol. 2017;198:552–559. doi: 10.1016/j.juro.2017.04.086. PubMed DOI PMC

Josephson D., Pasin E., Stein J.P. Superficial bladder cancer: Part 2. Management. Expert Rev. Anticancer Ther. 2007;7:567–581. doi: 10.1586/14737140.7.4.567. PubMed DOI

Rieken M., Shariat S.F., Kluth L., Crivelli J.J., Abufaraj M., Foerster B., Mari A., Ilijazi D., Karakiewicz P.I., Babjuk M., et al. Comparison of the EORTC tables and the EAU categories for risk stratification of patients with nonmuscle-invasive bladder cancer. Urol. Oncol. Semin. Orig. Investig. 2018;36:8. doi: 10.1016/j.urolonc.2017.08.027. PubMed DOI PMC

Mari A., Kimura S., Foerster B., Abufaraj M., D’Andrea D., Gust K.M., Shariat S.F. A systematic review and meta-analysis of lymphovascular invasion in patients treated with radical cystectomy for bladder cancer. Urol. Oncol. Semin. Orig. Investig. 2018;36:293–305. doi: 10.1016/j.urolonc.2018.03.018. PubMed DOI

Omorphos N.P., Ghose A., Hayes J.D., Kandala A., Dasgupta P., Sharma A., Vasdev N. The increasing indications of FDG-PET/CT in the staging and management of Invasive Bladder Cancer. Urol. Oncol. Semin. Orig. Investig. 2022;40:434–441. doi: 10.1016/j.urolonc.2022.05.017. PubMed DOI

Mari A., D’andrea D., Abufaraj M., Foerster B., Kimura S., Shariat S.F. Genetic determinants for chemo- and radiotherapy resistance in bladder cancer. Transl. Androl. Urol. 2017;6:1081–1089. doi: 10.21037/tau.2017.08.19. PubMed DOI PMC

González-Del-Alba A., Conde-Moreno A.J., Vicente A.M.G., González-Peramato P., Linares-Espinós E., Climent M.Á. Management of Patients with Metastatic Bladder Cancer in the Real-World Setting from the Multidisciplinary Team: Current Opinion of the SOGUG Multidisciplinary Working Group. Cancers. 2022;14:1130. doi: 10.3390/cancers14051130. PubMed DOI PMC

Cacciamani G.E., Ghodoussipour S., Mari A., Gill K.S., Desai M., Artibani W., Shariat S.F., Djaladat H. Association between Smoking Exposure, Neoadjuvant Chemotherapy Response and Survival Outcomes following Radical Cystectomy: Systematic Review and Meta-Analysis. J. Urol. 2020;204:649–660. doi: 10.1097/JU.0000000000000813. PubMed DOI

Siles M.G., López-Beltran A., Pelechano P., Vicente A.M.G., Sarrió R.G., Peña E.G.-H., Antolín A.R., Zapatero A., Arranz J., Climent M. Advances in Transversal Topics Applicable to the Care of Bladder Cancer Patients in the Real-World Setting. Cancers. 2022;14:3968. doi: 10.3390/cancers14163968. PubMed DOI PMC

Girard A., Rouanne M., Taconet S., Radulescu C., Neuzillet Y., Girma A., Beaufrere A., Lebret T., Le Stanc E., Grellier J.-F. Integrated analysis of 18F-FDG PET/CT improves preoperative lymph node staging for patients with invasive bladder cancer. Eur. Radiol. 2019;29:4286–4293. doi: 10.1007/s00330-018-5959-0. PubMed DOI

Drieskens O., Oyen R., Van Poppel H., Vankan Y., Flamen P., Mortelmans L. FDG-PET for preoperative staging of bladder cancer. Eur. J. Nucl. Med. Mol. Imaging. 2005;32:1412–1417. doi: 10.1007/s00259-005-1886-9. PubMed DOI

Dos Anjos D.A., Etchebehere E., Ramos C.D., Santos A., Albertotti C., Camargo E.E. 18F-FDG PET/CT Delayed Images After Diuretic for Restaging Invasive Bladder Cancer. J. Nucl. Med. 2007;48:764–770. doi: 10.2967/jnumed.106.036350. PubMed DOI

Jadvar H., Quan V., Henderson R.W., Conti P.S. [F-18]-Fluorodeoxyglucose PET and PET-CT in diagnostic imaging evaluation of locally recurrent and metastatic bladder transitional cell carcinoma. Int. J. Clin. Oncol. 2008;13:42–47. doi: 10.1007/s10147-007-0720-8. PubMed DOI PMC

Swinnen G., Maes A., Pottel H., Vanneste A., Billiet I., Lesage K., Werbrouck P. FDG-PET/CT for the Preoperative Lymph Node Staging of Invasive Bladder Cancer. Eur. Urol. 2010;57:641–647. doi: 10.1016/j.eururo.2009.05.014. PubMed DOI

Kibel A.S., Dehdashti F., Katz M.D., Klim A.P., Grubb R.L., Humphrey P.A., Siegel C., Cao D., Gao F., Siegel B.A. Prospective Study of [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Staging of Muscle-Invasive Bladder Carcinoma. J. Clin. Oncol. 2009;27:4314–4320. doi: 10.1200/JCO.2008.20.6722. PubMed DOI PMC

Lodde M., Lacombe L., Friede J., Morin F., Saourine A., Fradet Y. Evaluation of fluorodeoxyglucose positron-emission tomography with computed tomography for staging of urothelial carcinoma. BJU Int. 2010;106:658–663. doi: 10.1111/j.1464-410X.2010.09212.x. PubMed DOI

Harkirat S., Anand S., Jacob M. Forced diuresis and dual-phase 18F-fluorodeoxyglucose-PET/CT scan for restaging of urinary bladder cancers. Indian J. Radiol. Imaging. 2010;20:13–19. doi: 10.4103/0971-3026.59746. PubMed DOI PMC

Apolo A.B., Riches J., Schöder H., Akin O., Trout A., Milowsky M.I., Bajorin D.F. Clinical Value of Fluorine-18 2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography in Bladder Cancer. J. Clin. Oncol. 2010;28:3973–3978. doi: 10.1200/JCO.2010.28.7052. PubMed DOI PMC

Jensen T.K., Holt P., Gerke O., Riehmann M., Svolgaard B., Marcussen N., Bouchelouche K. Preoperative lymph-node staging of invasive urothelial bladder cancer with 18F-fluorodeoxyglucose positron emission tomography/computed axial tomography and magnetic resonance imaging: Correlation with histopathology. Scand. J. Urol. Nephrol. 2011;45:122–128. doi: 10.3109/00365599.2010.544672. PubMed DOI

Mertens L.S., Fioole-Bruining A., Van Rhijn B.W., Kerst J.M., Bergman A.M., Vogel W.V., Vegt E., Horenblas S. FDG-Positron Emission Tomography/Computerized Tomography for Monitoring the Response of Pelvic Lymph Node Metastasis to Neoadjuvant Chemotherapy for Bladder Cancer. J. Urol. 2013;189:1687–1691. doi: 10.1016/j.juro.2012.11.009. PubMed DOI

Hitier-Berthault M., Ansquer C., Branchereau J., Renaudin K., Bodere F., Bouchot O., Rigaud J. 18F-fluorodeoxyglucose positron emission tomography-computed tomography for preoperative lymph node staging in patients undergoing radical cystectomy for bladder cancer: A prospective study. Int. J. Urol. 2013;20:788–796. doi: 10.1111/iju.12045. PubMed DOI

Goodfellow H., Viney Z., Hughes P., Rankin S., Rottenberg G., Hughes S., Evison F., Dasgupta P., O’Brien T., Khan M.S. Role of fluorodeoxyglucose positron emission tomography (FDG PET)-computed tomography (CT) in the staging of bladder cancer. BJU Int. 2014;114:389–395. doi: 10.1111/bju.12608. PubMed DOI

Nayak B., Dogra P.N., Naswa N., Kumar R. Diuretic 18F-FDG PET/CT imaging for detection and locoregional staging of urinary bladder cancer: Prospective evaluation of a novel technique. Eur. J. Nucl. Med. Mol. Imaging. 2013;40:386–393. doi: 10.1007/s00259-012-2294-6. PubMed DOI

Jeong I.G., Hong S., You D., Hong J.H., Ahn H., Kim C.-S. FDG PET–CT for Lymph Node Staging of Bladder Cancer: A Prospective Study of Patients with Extended Pelvic Lymphadenectomy. Ann. Surg. Oncol. 2015;22:3150–3156. doi: 10.1245/s10434-015-4369-7. PubMed DOI

Aljabery F., Lindblom G., Skoog S., Shabo I., Olsson H., Rosell J., Jahnson S. PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer. BMC Urol. 2015;15:87. doi: 10.1186/s12894-015-0080-z. PubMed DOI PMC

Pichler R., De Zordo T., Fritz J., Kroiss A., Aigner F., Heidegger I., Virgolini I., Horninger W., Uprimny C. Pelvic Lymph Node Staging by Combined 18 F-FDG-PET/CT Imaging in Bladder Cancer Prior to Radical Cystectomy. Clin. Genitourin. Cancer. 2017;15:e387–e395. doi: 10.1016/j.clgc.2016.08.009. PubMed DOI

Mete U.K., Nayak P., Bhattacharya A., Kakkar N., Mandal A. Is [F-18]-fluorodeoxyglucose FDG-PET/CT better than ct alone for the preoperative lymph node staging of muscle invasive bladder cancer? Int. braz j urol. 2016;42:234–241. doi: 10.1590/s1677-5538.ibju.2014.0579. PubMed DOI PMC

Soubra A., Hayward D., Dahm P., Goldfarb R., Froehlich J., Jha G., Konety B.R. The diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography and computed tomography in staging bladder cancer: A single-institution study and a systematic review with meta-analysis. World J. Urol. 2016;34:1229–1237. doi: 10.1007/s00345-016-1772-z. PubMed DOI

Alongi P., Caobelli F., Gentile R., Stefano A., Russo G., Albano D., Baldari S., Gilardi M.C., Midiri M. Recurrent bladder carcinoma: Clinical and prognostic role of 18 F-FDG PET/CT. Eur. J. Nucl. Med. Mol. Imaging. 2017;44:224–233. doi: 10.1007/s00259-016-3500-8. PubMed DOI

Kollberg P., Almquist H., Bläckberg M., Cwikiel M., Gudjonsson S., Lyttkens K., Patschan O., Liedberg F. [18F]Fluorodeoxyglucose-positron emission tomography/computed tomography response evaluation can predict histological response at surgery after induction chemotherapy for oligometastatic bladder cancer. Scand. J. Urol. 2017;51:308–313. doi: 10.1080/21681805.2017.1321579. PubMed DOI

Zattoni F., Incerti E., Colicchia M., Castellucci P., Panareo S., Picchio M., Fallanca F., Briganti A., Moschini M., Gallina A., et al. Comparison between the diagnostic accuracies of 18F-fluorodeoxyglucose positron emission tomography/computed tomography and conventional imaging in recurrent urothelial carcinomas: A retrospective, multicenter study. Abdom. Radiol. 2018;43:2391–2399. doi: 10.1007/s00261-017-1443-6. PubMed DOI

Higashiyama A., Komori T., Juri H., Inada Y., Azuma H., Narumi Y. Detectability of residual invasive bladder cancer in delayed 18F-FDG PET imaging with oral hydration using 500 mL of water and voiding-refilling. Ann. Nucl. Med. 2018;32:561–567. doi: 10.1007/s12149-018-1280-x. PubMed DOI

Antoch G., Saoudi N., Kuehl H., Dahmen G., Mueller S.P., Beyer T., Bockisch A., Debatin J.F., Freudenberg L.S. Accuracy of Whole-Body Dual-Modality Fluorine-18–2-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography and Computed Tomography (FDG-PET/CT) for Tumor Staging in Solid Tumors: Comparison With CT and PET. J. Clin. Oncol. 2004;22:4357–4368. doi: 10.1200/JCO.2004.08.120. PubMed DOI

Lu Y.-Y., Chen J.-H., Liang J.-A., Wang H.-Y., Lin C.-C., Lin W.-Y., Kao C.-H. Clinical value of FDG PET or PET/CT in urinary bladder cancer: A systemic review and meta-analysis. Eur. J. Radiol. 2012;81:2411–2416. doi: 10.1016/j.ejrad.2011.07.018. PubMed DOI

Civelek A.C., Niglio S.A., Malayeri A.A., Lin J., Gurram S., Chalfin H.J., Turkbey B., Valera V., Steinberg S.M., Apolo A.B. Clinical value of 18FDG PET/MRI in muscle-invasive, locally advanced, and metastatic bladder cancer. Urol. Oncol. Semin. Orig. Investig. 2021;39:787. doi: 10.1016/j.urolonc.2021.04.024. PubMed DOI PMC

Zattoni F., Incerti E., Moro F.D., Moschini M., Castellucci P., Panareo S., Picchio M., Fallanca F., Briganti A., Gallina A., et al. 18F-FDG PET/CT and Urothelial Carcinoma: Impact on Management and Prognosis—A Multicenter Retrospective Study. Cancers. 2019;11:700. doi: 10.3390/cancers11050700. PubMed DOI PMC

Voskuilen C.S., van Gennep E.J., Einerhand S.M., Vegt E., Donswijk M.L., Bruining A., van der Poel H.G., Horenblas S., Hendricksen K., van Rhijn B.W., et al. Staging 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Changes Treatment Recommendation in Invasive Bladder Cancer. Eur. Urol. Oncol. 2022;5:366–369. doi: 10.1016/j.euo.2021.01.005. PubMed DOI

Sinha A., West A., Hayes J., Teoh J., Decaestecker K., Vasdev N. Methods of Sentinel Lymph Node Detection and Management in Urinary Bladder Cancer—A Narrative Review. Curr. Oncol. 2022;29:1335–1348. doi: 10.3390/curroncol29030114. PubMed DOI PMC