Multimodal Approach to Imaging and Staging of Bladder Cancer: Diagnostic Standards and Future Trends

The most significant factors influencing the effectiveness of bladder cancer treatment include a tumor subtype, degree of cellular anaplasia, assessment of the invasion depth into the bladder wall, identification of carcinoma in situ, extent of renal function impairment, quality of diagnostic procedures, accurate interpretation of the obtained data, continuity of care among specialists, and the patient’s motivation for treatment. The advent of ultra-high-field magnetic resonance imaging, 640-slice computed tomography, development of new radiopharmaceuticals, and advancements in software technology shape a multimodal approach aimed at identifying optimal diagnostic methods for bladder cancer. The present paper reviews a potential of multiparametric magnetic resonance imaging for determining the degree of neoplastic invasion into the layers of the bladder wall, a value of computed tomography with intravenous contrast enhancement in diagnosing locally advanced forms of the disease, and capabilities of positron emission tomography as a promising method for non-invasive characterization of tumor physiology with sensitivity in the picomolar range. The paper discusses advantages and disadvantages of the imaging modalities used in the diagnosis of urothelial carcinoma. In addition, the study explores the perfusion computed tomography as an alternative imaging technology for evaluating the layers of the bladder wall to be utilized in cases of absolute contraindications to magnetic resonance imaging.

1. Ferlay J., Ervik M., Lam F., Laversanne M., Colombet M., Mery L., et al. Global Cancer Observatory: Cancer Today. Lyon: International Agency for Research on Cancer; 2024. [cited 23 Aug 2024] Available from: https://gco.iarc.who.int/today

2. Clinical guidelines of the Ministry of Health of the Russian Federation. Bladder cancer. Moscow; 2023. [cited 2024 Sep 10] Available from: https://oncology-association.ru/wp-content/uploads/2023/11/rak-mochevogo-puzyrya_23.pdf (In Russ.).

3. Kaprin A.D., Starinsky V.V., Shakhzadova A.O. State of cancer care for population in Russia in 2023. P.A Gertsen Moscow Research Oncology Institute — branch of the National Medical Research Center for Radiology; 2024 (In Russ.).

4. Safiri S., Kolahi A. A., Naghavi M. Global, regional and national burden of bladder cancer and its attributable risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease study 2019. BMJ global health. 2021;6(11):e004128. DOI: 10.1186/s40779-024-00569-w

5. Vlachostergios P.J., Faltas B.M. The molecular limitations of biomarker research in bladder cancer. World J Urol. 2019;37(5):837–48. DOI: 10.1007/s00345-018-2462-9

6. Borgheresi A., Agostini A., Sternardi F., Cesari E., Ventura F., Ottaviani L., et al. Vascular Enlargement as a Predictor of Nodal Involvement in Bladder Cancer. Diagnostics (Basel). 2023;13(13):2227. DOI: 10.3390/diagnostics13132227

7. Babjuk M., Burger M., Capoun O., Cohen D., Compérat E.M., Dominguez Escrig J.L., et al. European Association of Urology Guidelines on non-muscle-invasive bladder cancer (Ta, T1, and carcinoma in situ). Eur Urol. 2022;81(1):75–94. DOI: 10.1016/j.eururo.2021.08.010

8. Alfred Witjes J., Max Bruins H., Carrión A., Cathomas R., Compérat E., Efstathiou J.A., et al. European Association of Urology Guidelines on muscle-invasive and metastatic bladder cancer: Summary of the 2023 Guidelines. Eur Urol. 2024;85(1):17–31. DOI: 10.1016/j.eururo.2023.08.016

9. Gkadkov O.A., Bulychkin P.V., Volkova M.I., Zukov P.A., Matveev V.B., Nosov D.A. Bladder cancer. Malignant tumors. 2023;13(3S2-1):620–39 (In Russ.). DOI: 10.18027/2224-5057-2023-13-3s2-1-620-639

10. Rai A., Hsieh A., Smith A. Contemporary diagnosis and management of pelvi-ureteric junction obstruction. BJU Int. 2022;130(3):285–90. DOI: 10.1111/bju.15689

11. Li C., Gu Z., Ni P., Zhang W., Yang F., Li W., et al. The value of contrast-enhanced ultrasound and magnetic resonance imaging in the diagnosis of bladder cancer. J Cancer Res Ther. 2021;17(5):1179–85. DOI: 10.4103/jcrt.jcrt_1056_21

12. Berce V., Rataj N., Dorič M., Zorko A., Kolarič T. Association between the clinical, laboratory and ultrasound characteristics and the etiology of peripheral lymphadenopathy in children. Children (Basel). 2023;10(10):1589. DOI: 10.3390/children10101589

13. Xu C., Zhang Z., Wang H., Song Q., Wei R., Yu Y., et al. A new tool for distinguishing muscle invasive and non-muscle invasive bladder cancer: the initial application of flexible ultrasound bronchoscope in bladder tumor staging. PLoS One. 2014;9(4):e92385. DOI: 10.1371/journal.pone.0092385

14. Russell G., Strnad B.S., Ludwig D.R., Middleton W.D., Itani M., Khot R., et al. Contrast-Enhanced Ultrasound for Image-Guided Procedures. Tech Vasc Interv Radiol. 2023;26(3):100913. DOI: 10.1016/j.tvir.2023.100913

15. Feng Y., Hao Y., Wang Y., Song W., Zhang S., Ni D., et al. Ultrasound molecular imaging of bladder cancer via extradomain B fibronectin-targeted biosynthetic GVs. Int J Nanomedicine. 2023;18:4871–84. DOI: 10.2147/IJN.S412422

16. Fournier L., de La Taille T., Chauvierre C. Microbubbles for human diagnosis and therapy. Biomaterials. 2023;294:122025. DOI: 10.1016/j.biomaterials.2023.122025

17. Panebianco V. VI-RADS for the diagnosis and management of urinary bladder cancer. Eur Radiol. 2023;33(10):7209–11. DOI: 10.1007/s00330-023-09677-y

18. Del Giudice F., Flammia R.S., Pecoraro M., Moschini M., D’Andrea D., Messina E., et al. The accuracy of Vesical Imaging-Reporting and Data System (VI-RADS): an updated comprehensive multi-institutional, multi-readers systematic review and meta-analysis from diagnostic evidence into future clinical recommendations. World J Urol. 2022;40(7):1617–28. DOI: 10.1007/s00345-022-03969-6

19. Grigoriev E.G., Frolova I.G., Usynin E.A., Usova A.V., Tabakaev S.A. Volumetric tumor segmentation according to diffusion-weighted MRI data in predicting and evaluating the response to chemotherapy in bladder cancer. Siberian journal of oncology. 2023;22(3):25–35 (In Russ.). DOI: 10.21294/1814-4861-2023-22-3-25-35

20. Cressoni M., Cozzi A., Schiaffino S., Cadringher P., Vitali P., Basso G., et al. Computation of contrast-enhanced perfusion using only two CT scan phases: a proof-of-concept study on abdominal organs. Eur Radiol Exp. 2022;6(1):37. DOI: 10.1186/s41747-022-00292-y

21. Lomonosova E.V., Golbits A.B., Rubtsova N.A., Alekseev B.Ya., Kaprin A.D. Application of perfusion computed tomography in renal diseases (review of literature). Medical Visualization. 2023;27(2):85–98 (In Russ.). DOI: 10.24835/1607-0763-1220

22. Oprea-Lager D.E., MacLennan S., Bjartell A., Briganti A., Burger I.A., de Jong I., et al. European Association of Nuclear Medicine Focus 5: consensus on molecular imaging and theranostics in prostate cancer. Eur Urol. 2024;85(1):49–60. DOI: 10.1016/j.eururo.2023.09.003

23. El-Kawy O.A., Abdelaziz G. Preparation, characterization and evaluation of [125I]-pirarubicin: A new therapeutic agent for urinary bladder cancer with potential for use as theranostic agent. Applied radiation and isotopes: including data, instrumentation and methods for use in agriculture, industry and medicine. 2022;179:110007. DOI: 10.1016/j.apradiso.2021.110007

24. Tumedei M.M., Ravaioli S., Matteucci F., Celli M., De Giorgi U., Gunelli R., et al. Spotlight on PSMA as a new theranostic biomarker for bladder cancer. Sci Rep. 2021;11(1):9777. DOI: 10.1038/s41598-021-89160-0

25. Sadulaeva T.A., Edilgireeva L.A., Bimurzaeva M.B., Morozov A.O. Use of artificial intelligence in diagnostic cystoscopy of bladder cancer. Cancer Urology. 2023;19(2):146–52 (In Russ.). DOI: 10.17650/1726-9776-2023-19-2-148-152

26. Bouchelouche K. PET/CT in bladder cancer: an update. Semin Nucl Med, 2022;52(4):475–85. DOI: 10.1053/j.semnuclmed.2021.12.004

27. Zhan Y., Zhang G., Li M., Zhou X. Whole-body MRI vs. PET/CT for the detection of bone metastases in patients with prostate cancer: a systematic review and meta-analysis. Front Oncol. 2021;11:633833. DOI: 10.3389/fonc.2021.633833

28. Pavlov V.N., Urmantsev M.F., Bakeev M.R. The success of robot-assisted cystectomy in the treatment of muscle-invasive bladder cancer. Cancer Urology. 2022;18(2):123–8 (In Russ.). DOI: 10.17650/1726-9776-2022-18-2-123-128

29. Pavlov V.N., Urmantsev M.F., Bakeev M.R. Survival in patients with muscle-invasive bladder cancer after robot-assisted radical cystectomy with intracorporeal urinary derivation. Creative surgery and oncology. 2024;14(1):5–12 (In Russ.). DOI: 10.24060/2076-3093-2024-14-1-5-12

30. Kaprin A.D., Rubtsova N.A., Kabanov D.O., Golbits A.B., Vorobyev N.V., Pilchuk P.S. Experience in using the VI-RADS system in assessing the depth of invasion of bladder tumors. Medical Visualization. 2023;27(3):118–29 (In Russ.). DOI: 10.24835/1607-0763-1242

31. Zhang H.P., Liang R.X., Lin X.Y., Xue E.S., Ye Q., Zhu Y.F. Application of contrast-enhanced ultrasound in diagnosis and grading of bladder urothelial carcinoma. BMC Med Imaging. 2024;24(1):26. DOI: 10.1186/s12880-024-01199-3

32. Mo X., Cui Y., Yuan J., Hang Z., Jiang X., Duan G., et al. Study on a new “One-stop-shop” scan protocol combining brain CT perfusion and head-and-neck CT angiography by using 256-detector CT for stroke patients. Eur J Radiol. 2022;154:110426. DOI: 10.1016/j.ejrad.2022.110426

33. Ronot M., Leporq B., Van Beers B.E., Vilgrain V. CT and MR perfusion techniques to assess diffuse liver disease. Abdom Radiol (NY). 2020;45(11):3496–506. DOI: 10.1007/s00261-019-02338-z

34. Li W., Su Z.Z., Kang J.H., Xie X.Y., Xie X.H., Zhuang B.W. Application of contrast-enhanced ultrasonography for large cell neuroendocrine carcinoma in the urinary bladder: a case report. BMC Med Imaging. 2020;20(1):46. DOI: 10.1186/s12880-020-00447-6

35. Dietrich C.F., Nolsøe C.P., Barr R.G., Berzigotti A., Burns P.N., Cantisani V., et al. Guidelines and good clinical practice recommendations for Contrast Enhanced Ultrasound (CEUS) in the Liver — Update 2020 — WFUMB in cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS. Ultraschall Med. 2020;41(5):562–85. DOI: 10.1055/a-1177-0530

36. Golemati S., Cokkinos D.D. Recent advances in vascular ultrasound imaging technology and their clinical implications. Ultrasonics. 2022;119:106599. DOI: 10.1016/j.ultras.2021.106599

37. Liu X., Liu D., Long M., Chen F. Application value of ultrasonic contrast imaging and ultrasonic parameters in post-transplant renal surgery. Front Med (Lausanne). 2024;11:1397884. DOI: 10.3389/fmed.2024.1397884

38. Oglat A.A. A review of ultrasound contrast media. F1000Res. 2024;12:1444. DOI: 10.12688/f1000research.140131.2

39. Deng XH, Du ZS, Wu ZG, Chen Y, Wu XY, Tang LN. The Value of Contrast-Enhanced Ultrasound in the Detection of Sentinel Lymph Nodes in Malignant Melanoma. J Ultrasound Med. 2023 May;42(5):1015–22. DOI: 10.1002/jum.16110

40. Galiya R, Stanislav K, Jawdat J, Benjamin H, Boris C. Pediatric urothelial bladder neoplasm. J Pediatr Urol. 2022 Dec;18(6):833.e1–e4. DOI: 10.1016/j.jpurol.2022.06.026

41. Ng K., Stenzl A., Sharma A., Vasdev N. Urinary biomarkers in bladder cancer: A review of the current landscape and future directions. Urol Oncol. 2021;39(1):41–51. DOI: 10.1016/j.urolonc.2020.08.016

42. Muin D., Laukhtina E., Hacker M., Shariat S.F. PET in bladder cancer imaging. Curr Opin Urol. 2023;33(3):206–10. DOI: 10.1097/MOU.0000000000001090

43. Kozikowski M, Suarez-Ibarrola R, Osiecki R, Bilski K, Gratzke C, Shariat SF, Miernik A, Dobruch J. Role of Radiomics in the Prediction of Muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis. Eur Urol Focus. 2022 May;8(3):728–38. DOI: 10.1016/j.euf.2021.05.005

44. Qureshi T.A., Chen X., Xie Y., Sakatani T., Kita Y., Kobayashi T. et al. MRI/RNA-Seq-Based Radiogenomics and Artificial Intelligence for More Accurate Staging of Muscle-Invasive Bladder Cancer. Int J Mol Sci. 2023;25(1):88. DOI: 10.3390/ijms25010088

45. Panebianco V., Briganti A., Boellaard T.N., Catto J., Comperat E., Efstathiou J., et al. Clinical application of bladder MRI and the Vesical Imaging-Reporting and Data System. Nat Rev Urol. 2024;21(4):243–51. DOI: 10.1038/s41585-023-00830-2

46. Mertens L.S., Meijer R.P., Alfred Witjes J. Positron emission tomography/computed tomography for staging of bladder cancer: a continuing clinical controversy. Eur Urol. 2023;83(2):95–6. DOI: 10.1016/j.eururo.2022.09.017

47. Liang H., Yang Q., Sun H., Xu Y., Wang J., Huang W., et al. The vascular and morphological characteristics of tumors under narrow-band imaging as predictors for the grade and stage of bladder cancer: a prospective and multi-center study. Ann Med. 2023;55(2):2281656. DOI: 10.1080/07853890.2023.2281656

48. Jin Y.H., Zeng X.T., Liu T.Z., Bai Z.M., Dou Z.L., Ding D.G., et al. Treatment and surveillance for non-muscle-invasive bladder cancer: a clinical practice guideline (2021 edition). Mil Med Res. 2022;9(1):44. DOI: 10.1186/s40779-022-00406-y

49. Lenis A.T., Lec P.M., Chamie K. Bladder cancer: a review. JAMA. 2020;324(19):1980–91. DOI: 10.1001/jama.2020.17598

50. Contieri R., Pichler R., Del Giudice F., Marcq G., Gallioli A., Albisinni S., et al. Variation in follow-up after radical cystectomy for bladder cancer-an inventory roundtable and literature review. J Clin Med. 2024;13(9):2637. DOI: 10.3390/jcm13092637

51. Ghoreifi A., Allgood E., Whang G., Douglawi A., Yu W., Cai J., et al. Risk factors and natural history of parastomal hernia after radical cystectomy and ileal conduit. BJU Int. 2022;130(3):381–8. DOI: 10.1111/bju.15658