Genitourinary Tumors

  • Marie-Lisa Eich
  • George J. NettoEmail author


Neoplasms of the prostate and bladder are among the most common solid tumors. Recent genomic advances have contributed to our understanding of the key driver genetic alterations in these malignancies offering new opportunities for targeted therapy. Novel molecular classifications have been suggested.

This chapter lists salient predictive and prognostic biomarkers in prostate cancer and urothelial neoplasms as well as molecular approaches examining eligibility for therapeutic targets and novel immunotherapy strategies. A summary of noninvasive urine-based assays for early detection and surveillance of urothelial carcinoma is forwarded. The potential practical implications of a recently proposed genomic-based taxonomy for bladder cancer is discussed. Practice-based take-home messages are emphasized.


Prostate adenocarcinoma Urothelial carcinoma Bladder TCGA Classification Targeted therapy Biomarkers Immunotherapy 


  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7–30.CrossRefGoogle Scholar
  2. 2.
    Weier C, Haffner MC, Mosbruger T, Esopi DM, Hicks J, Zheng Q, et al. Nucleotide resolution analysis of TMPRSS2 and ERG rearrangements in prostate cancer. J Pathol. 2013;230:174–83.CrossRefGoogle Scholar
  3. 3.
    Netto GJ. Clinical applications of recent molecular advances in urologic malignancies: no longer chasing a “mirage”? Adv Anat Pathol. 2013;20:175–203.CrossRefGoogle Scholar
  4. 4.
    Kote-Jarai Z, Mikropoulos C, Leongamornlert DA, Dadaev T, Tymrakiewicz M, Saunders EJ, et al. Prevalence of the HOXB13 G84E germline mutation in British men and correlation with prostate cancer risk, tumour characteristics and clinical outcomes. Ann Oncol. 2015;26:756–61.CrossRefGoogle Scholar
  5. 5.
    Bryant HE. The clinical impact of BRCA2 loss in prostate cancer. Eur Urol. 2016;69:996–7.CrossRefGoogle Scholar
  6. 6.
    Ryan S, Jenkins MA, Win AK. Risk of prostate cancer in Lynch syndrome: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2014;23:437–49.CrossRefGoogle Scholar
  7. 7.
    Network NCC. National Comprehensive Cancer Network (NCCN): prostate. Cancer. 2018.
  8. 8.
    Cuzick J, Swanson GP, Fisher G, Brothman AR, Berney DM, Reid JE, et al. Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study. Lancet Oncol. 2011;12:245–55.CrossRefGoogle Scholar
  9. 9.
    Knezevic D, Goddard AD, Natraj N, Cherbavaz DB, Clark-Langone KM, Snable J, et al. Analytical validation of the Oncotype DX prostate cancer assay – a clinical RT-PCR assay optimized for prostate needle biopsies. BMC Genomics. 2013;14:690.CrossRefGoogle Scholar
  10. 10.
    Erho N, Crisan A, Vergara IA, Mitra AP, Ghadessi M, Buerki C, et al. Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS One. 2013;8:e66855.CrossRefGoogle Scholar
  11. 11.
    Karnes RJ, Bergstralh EJ, Davicioni E, Ghadessi M, Buerki C, Mitra AP, et al. Validation of a genomic classifier that predicts metastasis following radical prostatectomy in an at risk patient population. J Urol. 2013;190:2047.CrossRefGoogle Scholar
  12. 12.
    Blume-Jensen P, Berman DM, Rimm DL, Shipitsin M, Putzi M, Nifong TP, et al. Development and clinical validation of an in situ biopsy-based multimarker assay for risk stratification in prostate cancer. Clin Cancer Res. 2015;21:2591–600.CrossRefGoogle Scholar
  13. 13.
    Network CGAR. The molecular taxonomy of primary prostate cancer. Cell. 2015;163:1011–25.CrossRefGoogle Scholar
  14. 14.
    Abida W, Armenia J, Gopalan A, Brennan R, Walsh M, Barron D, et al. Prospective genomic profiling of prostate cancer across disease states reveals germline and somatic alterations that may affect clinical decision making. JCO Precis Oncol. 2017;2017
  15. 15.
    Antonarakis ES, Lu C, Luber B, Liang C, Wang H, Chen Y, et al. Germline DNA-repair gene mutations and outcomes in men with metastatic castration-resistant prostate cancer receiving first-line abiraterone and enzalutamide. Eur Urol. 2018;74:218–25.CrossRefGoogle Scholar
  16. 16.
    Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med. 2016;375:443–53.CrossRefGoogle Scholar
  17. 17.
    Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;162:454.CrossRefGoogle Scholar
  18. 18.
    Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmana J, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015;33:244–50.CrossRefGoogle Scholar
  19. 19.
    Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–13.CrossRefGoogle Scholar
  20. 20.
    Imyanitov EN, Moiseyenko VM. Drug therapy for hereditary cancers. Hered Cancer Clin Pract. 2011;9:5.CrossRefGoogle Scholar
  21. 21.
    Chamie K, Litwin MS, Bassett JC, Daskivich TJ, Lai J, Hanley JM, et al. Recurrence of high-risk bladder cancer: a population-based analysis. Cancer. 2013;119:3219–27.CrossRefGoogle Scholar
  22. 22.
    Millan-Rodriguez F, Chechile-Toniolo G, Salvador-Bayarri J, Palou J, Algaba F, Vicente-Rodriguez J. Primary superficial bladder cancer risk groups according to progression, mortality and recurrence. J Urol. 2000;164:680–4.CrossRefGoogle Scholar
  23. 23.
    Babjuk M, Bohle A, Burger M, Capoun O, Cohen D, Comperat EM, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol. 2017;71:447–61.CrossRefGoogle Scholar
  24. 24.
    Chang SS, Boorjian SA, Chou R, Clark PE, Daneshmand S, Konety BR, Pruthi R, Quale DZ, Ritch CR, Seigne JD, Skinner EC, Smith ND, McKiernan JM. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO Joint Guideline. 2016.
  25. 25.
    Network NCC. NCCN Clinical Practice Guidelines in Oncology. Bladder Cancer. 2018.
  26. 26.
    Chang SS, Bochner BH, Chou R, Dreicer R, Kamat AM, Lerner SP, Lotan Y, Meeks JJ, Michalski JM, Morgan TM, Quale DZ, Rosenberg JE, Zietman AL, Holzbeierlein JM. Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO Guideline. 2017.
  27. 27.
    Witjes JA (Chair), Bruins M, Compérat E, Cowan NC, Gakis G, Hernández V, Lebret T, Lorch A, Ribal MJ (Vice-chair), van der Heijden AG, Veskimäe E. European Association of Urology (EAU) Guideline: muscle-invasive and metastatic bladder cancer. 2018.
  28. 28.
    Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. New Engl J Med. 2017;376:1015–26.CrossRefGoogle Scholar
  29. 29.
    Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389:67–76.CrossRefGoogle Scholar
  30. 30.
    Balar AV, Castellano D, O’Donnell PH, Grivas P, Vuky J, Powles T, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017;18:1483–92.CrossRefGoogle Scholar
  31. 31.
    Lokeshwar VB, Habuchi T, Grossman HB, Murphy WM, Hautmann SH, Hemstreet GP 3rd, et al. Bladder tumor markers beyond cytology: International Consensus Panel on bladder tumor markers. Urology. 2005;66:35–63.CrossRefGoogle Scholar
  32. 32.
    Guo A, Wang X, Gao L, Shi J, Sun C, Wan Z. Bladder tumour antigen (BTA stat) test compared to the urine cytology in the diagnosis of bladder cancer: a meta-analysis. Can Urol Assoc J. 2014;8:E347–52.CrossRefGoogle Scholar
  33. 33.
    Chou R, Gore JL, Buckley D, Fu R, Gustafson K, Griffin JC, et al. Urinary biomarkers for diagnosis of bladder cancer: a systematic review and meta-analysis. Ann Intern Med. 2015;163:922–31.CrossRefGoogle Scholar
  34. 34.
    Smith ZL, Guzzo TJ. Urinary markers for bladder cancer. F1000Prime Rep. 2013;5:21.CrossRefGoogle Scholar
  35. 35.
    O’Sullivan P, Sharples K, Dalphin M, Davidson P, Gilling P, Cambridge L, et al. A multigene urine test for the detection and stratification of bladder cancer in patients presenting with hematuria. J Urol. 2012;188:741–7.CrossRefGoogle Scholar
  36. 36.
    Wang Z, Que H, Suo C, Han Z, Tao J, Huang Z, et al. Evaluation of the NMP22 BladderChek test for detecting bladder cancer: a systematic review and meta-analysis. Oncotarget. 2017;8:100648–56.PubMedPubMedCentralGoogle Scholar
  37. 37.
    He H, Han C, Hao L, Zang G. ImmunoCyt test compared to cytology in the diagnosis of bladder cancer: a meta-analysis. Oncol Lett. 2016;12:83–8.CrossRefGoogle Scholar
  38. 38.
    Lavery HJ, Zaharieva B, McFaddin A, Heerema N, Pohar KS. A prospective comparison of UroVysion FISH and urine cytology in bladder cancer detection. BMC Cancer. 2017;17:247.CrossRefGoogle Scholar
  39. 39.
    Feber A, Dhami P, Dong L, de Winter P, Tan WS, Martinez-Fernandez M, et al. UroMark-a urinary biomarker assay for the detection of bladder cancer. Clin Epigenetics. 2017;9:8.CrossRefGoogle Scholar
  40. 40.
    Lotan Y, O’Sullivan P, Raman JD, Shariat SF, Kavalieris L, Frampton C, et al. Clinical comparison of noninvasive urine tests for ruling out recurrent urothelial carcinoma. Urol Oncol. 2017;35:531.e15–22.CrossRefGoogle Scholar
  41. 41.
    Springer SU, Chen CH, Rodriguez Pena MDC, Li L, Douville C, Wang Y, et al. Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy. Elife. 2018;7. pii: e32143.Google Scholar
  42. 42.
    Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G, Cherniack AD, et al. Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell. 2017;171:540–56 e25.CrossRefGoogle Scholar
  43. 43.
    Netto GJ, Tafe LJ. Emerging bladder cancer biomarkers and targets of therapy. Urol Clin North Am. 2016;43:63–76.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of PathologyThe University of Alabama at BirminghamBirminghamUSA

Personalised recommendations