Review Article | Published:

Concomitant bladder cancer and prostate cancer: challenges and controversies

Nature Reviews Urology volume 14, pages 620629 (2017) | Download Citation


Radical cystoprostatectomy (RCP) followed by bilateral pelvic lymphadenectomy and urinary diversion remains the gold-standard therapy for men with localized muscle-invasive bladder cancer (MIBC). Prostate cancer might be incidentally detected at the time of RCP with a reported prevalence of 24–51%. Typically, these patients are considered to have clinically insignificant disease, but data from emerging series challenge this assumption and suggest that some of these tumours might be aggressive, or somehow increase the aggressiveness of the associated MIBC, and can negatively influence the patient's overall survival outcomes. Furthermore, the potential use of prostate-sparing cystectomy in patients with less-aggressive MIBC might lead to newly diagnosed incidental cases of prostate cancer, with characteristics suggestive of clinically significant disease, requiring a specific, separate workup. The development of evidence-based, validated protocols to define the necessary steps for diagnosis of prostate cancer in these patients, including the role of serum PSA testing, digital rectal examination, the role of imaging methods and the indication and type of biopsy protocol, is of major importance to the multidisciplinary management of patients with urological cancer. Finally, the retrospective nature of the available data account for much of the variability in the prevalence of coexisting bladder and prostate cancer and emphasizes the need for randomized trials in this controversial area of urological oncology.

Key points

  • Pathological evaluations of the prostate variably reveal incidental prostate cancer in 24–51% of patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystoprostatectomy (RCP)

  • The reported incidence of prostate cancer in RCP specimens is highly variable, mostly owing to differences in the histopathological analysis techniques used to investigate the samples

  • Most available data suggest that incidentally diagnosed prostate cancer is clinically insignificant; however, emerging data suggest that a subset of these patients could indeed have clinically significant disease

  • A subset of incidentally diagnosed prostate cancers in patients >60 years of age with Gleason ≥7 disease might negatively influence patients' overall survival outcomes, indicating a need for intervention in this subset of patients

  • Preoperative serum PSA levels and digital rectal examination (DRE) results mostly fail to indicate asymptomatic, incidental prostate cancer; however, the introduction of imaging methods such as MRI might assist in detecting such cases

  • The retrospective nature of the available data on prostate cancer aggressiveness in patients undergoing RCP for MIBC, in addition to a lack of prospective data on the risk of clinically significant prostate cancer, all preclude the optimal treatment of such patients

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  1. 1.

    et al. Implications of definitive prostate cancer therapy on soft tissue margins and survival in patients undergoing radical cystectomy for bladder urothelial cancer. J. Urol. 194, 1220–1225 (2015).

  2. 2.

    et al. Cystectomy with prostate sparing for bladder cancer in 100 patients: 10 year experience. J. Urol. 168, 2413–2417 (2002).

  3. 3.

    et al. Synchronous primary malignancies of the male urogenital tract. Can. Urol. Assoc. J. 8, E353–E355 (2014).

  4. 4.

    et al. Urothelial and incidental prostate carcinoma in prostates from cystoprostatectomies for bladder cancer: is there a relationship between urothelial and prostate cancer? BJU Int. 103, 1058–1063 (2009).

  5. 5.

    et al. Active surveillance for prostate cancer: a narrative review of clinical guidelines. Nat. Rev. Urol. 13, 151–167 (2016)

  6. 6.

    , , , & Characteristics of incidental prostatic adenocarcinoma in contemporary radical cystoprostatectomy specimens. BJU Int. 99, 554–558 (2007).

  7. 7.

    et al. Clinicopathologic features of prostate adenocarcinoma incidentally discovered at the time of radical cystectomy: an evidence-based analysis. Eur. Urol. 52, 648–657 (2007).

  8. 8.

    et al. Incidence and location of prostate and urothelial carcinoma in prostates from cystoprostatectomies: implication for possible apical sparing surgery. J. Urol. 179 (Suppl. 5) S27–S32 (2008).

  9. 9.

    et al. Is incidentally detected prostate cancer in patients undergoing radical cystoprostatectomy clinically significant? Am. J. Clin. Pathol. 131, 279–283 (2009).

  10. 10.

    Coincidence of bladder and prostate cancer. J. Urol. 157, 65–67 (1997).

  11. 11.

    , , & Incidental prostatic adenocarcinoma in patients undergoing radical cystoprostatectomy for bladder cancer. Eur. Urol. 30, 322–326 (1996).

  12. 12.

    & Clinicopathologic features of incidental prostatic adenocarcinoma in radical cystoprostatectomy specimens. World J. Surg. Oncol. 9, 81 (2011).

  13. 13.

    et al. Clinicopathologic features of prostate adenocarcinoma incidentally discovered at the time of radical cystectomy: an evidence-based analysis. Eur. Urol. 52, 648–657 (2007).

  14. 14.

    et al. The incidence and relevance of prostate cancer in radial cystoprostatectomy specimens. Int. Urol. Nephrol. 44, 1705–1710 (2012).

  15. 15.

    et al. Characterization of prostate cancer incidentally detected in radical cystoprostatectomy specimens from Japanese men with bladder cancer. Int. Urol. Nephrol. 42, 73–79 (2010).

  16. 16.

    et al. Clinicopathological characteristics of incidental prostate cancer discovered from radical cystoprostatectomy specimen: a multicenter French study. Ann. Surg Oncol. 21, 684–690 (2014).

  17. 17.

    et al. Incidental prostate cancer in patients with bladder urothelial carcinoma: comprehensive analysis of 1476 radical cystoprostatectomy specimen. J. Urol. 109, 1704–1709 (2013).

  18. 18.

    et al. Characterization and risk stratification of prostate cancer in patients undergoing radical cystoprostatectomy. Int. J. Urol. 20, 866–871 (2013).

  19. 19.

    et al. Concomitant Gleason Score ≥7 prostate cancer is an independent prognosticator for poor survival in nonmetastatic bladder cancer patients undergoing radical Cystoprostatectomy. Int. Urol. Nephrol. 47, 1789–1796 (2015).

  20. 20.

    et al. Detection and characterization of early prostate cancer by six systematic biopsies and fine needleaspiration cytology in prostates from bladder cancer patients. Eur. Urol. 39 (Suppl. 4) 25–29 (2001).

  21. 21.

    et al. Outcome of patients with fortuitous prostate cancer after radical cystoprostatectomy for bladder cancer. Eur. Urol. 48, 946–950 (2005).

  22. 22.

    , , , & Clinically significant prostate cancer found incidentally in radical cystoprostatectomy specimens. BJU Int. 99, 326–329 (2007).

  23. 23.

    et al. Incidental prostate cancer in radical cystoprostatectomy specimens. Asian J. Androl. 10, 809–814 (2008).

  24. 24.

    , , , & Characteristics of prostate cancers found in specimens removed by radical cystoprostatectomy for bladder cancer and their relationship with serum prostate-specific antigen level. Cancer Sci. 100, 1880–1884 (2009).

  25. 25.

    et al. Preoperative findings, pathological stage PSA recurrence in men with prostate cancer incidentally detected at radical cystectomy: our experience in 242 cases. Int. Urol. Nephrol. 46, 1325–1328 (2014).

  26. 26.

    et al. Potentially clinically relevant prostate cancer is found frequently after complete than after partial histopathological processing of radical cystoprostatectomy specimen. Virchows Arch. 461, 655–661 (2012).

  27. 27.

    et al. Preservation of prostate during radical cystectomy: evaluation of prevalence of prostate cancer associated with bladder cancer. Urology 65, 703–707 (2005).

  28. 28.

    et al. Not all Gleason pattern 4 prostate cancers are created equal: A study of latent prostatic carcinomas in a cystoprostatectomy and autopsy series. Prostate. 75, 1277–1284 (2015).

  29. 29.

    et al. Localized prostate cancer. Relationship of tumor volume to clinical significance for treatment of prostate cancer. Cancer 71(Suppl. 3) 933–938 (1993).

  30. 30.

    , , & Pathologicand clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA 271, 368–374 (1994).

  31. 31.

    , , , & Prognostic implications of partial sampling of radical prostatectomy specimens: comparison of 3 methods. J. Urol. 190, 84–90 (2013).

  32. 32.

    , , , & Prediction of prostate cancer volume using prostate-specific antigen levels, transrectal ultrasound, and systematic sextant biopsies. Urology 45, 75–80 (1995).

  33. 33.

    et al. Indications for preoperative prostate biopsy in patients undergoing radical cystoprostatectomy for bladder cancer. J. Urol. 180, 1938–1941 (2008).

  34. 34.

    et al. Incidental prostate cancer at radical cystoprostatectomy: implications for apex-sparing surgery. BJU Int. 105, 468–471 (2009).

  35. 35.

    et al. Should prostate cancer status be determined in patients undergoing radical cystoprostatectomy? Urol. Int. 77, 307–310 (2006).

  36. 36.

    et al. Incidental prostate cancer prevalence at radical cystoprostatectomy, importance of histopathological work-up. Virchows Arch. 465, 629–636 (2014).

  37. 37.

    et al. Pathologic characterization of prostate cancers with a very low serum prostate specific antigen (0–2 ng/mL) incidental to cystoprostatectomy: is PSA a useful indicator of clinical significance? Urol. Oncol. 22, 40–47 (2004).

  38. 38.

    et al. Critical evaluation of the prostate from cystoprostatectomies for bladder cancer: insights from a complete sampling with the whole mount technique. Eur. Urol. 55, 1305–1309 (2009).

  39. 39.

    et al. Transitional cell carcinoma involving the prostate with proposed staging classification for stromal invasion. J. Urol. 156, 1071–1076 (1996).

  40. 40.

    , & Rouprêt, M. Prostate-sparing cystectomy for bladder cancer: A step toward a deade-end. Urology 76, 260–263 (2010).

  41. 41.

    et al. Prostate capsule and seminal-sparing cystectomy for bladder carcinoma: initial results for selected patients. BJU Int. 94, 1021–1025 (2004).

  42. 42.

    , , & Prostate-sparing cystectomy: A review of the oncologic and functional outcomes. Contraindicated in patients with bladder cancer. Urol. Onc. 27, 466–472 (2009).

  43. 43.

    et al. Risk assessment of prostatic pathology in patients undergoing radical cystoprostatectomy. Eur. Urol. 53, 370–375 (2008).

  44. 44.

    & Current status of prostate-sparing cystectomy. Urol. Onc. 26, 486–493 (2008).

  45. 45.

    et al. Oncological evaluation of prostate sparing cystectomy: The Montsouris long-term results. J. Urol. 179, 2170–2175 (2008).

  46. 46.

    et al. Preoperative nomograms incorporating magnetic resonance imaging and spectroscopy for prediction of insignificant prostate cancer. BJU Int. 109, 1315–1322 (2012).

  47. 47.

    , , , & Multiparametric pelvic MRI accuracy in diagnosing clinically significant prostate cancer in the reevaluation of biopsy microfocal tumor. Anticancer Res. 35, 395–399 (2015).

  48. 48.

    et al. Cancer surveillance series: interpreting trends in prostate cancer—part I: Evidence of the effects of screening in recent prostate cancer incidence, mortality, and survival rates. J. Natl Cancer Inst. 91, 1017–1024 (1999).

  49. 49.

    & Histologic variants of urothelial carcinoma: differential diagnosis and clinical implications. Hum. Pathol. 37, 1371–1388 (2006).

  50. 50.

    et al. Partial sampling of radical prostatectomy specimens: detection of positive margins and extraprostatic extension. Am. J. Surg. Pathol. 37, 219–225 (2013)

  51. 51.

    et al. HER2 expression and gene amplification in pT2a Gleason score 6 prostate cancer incidentally detected in cystoprostatectomies: comparison with clinically detected androgen-dependent and androgenindependent cancer. Hum. Pathol. 37, 1137–1144 (2006).

  52. 52.

    et al. α-methylacylcoenzyme A racemase, Ki-67, and topoisomerase IIα incystoprostatectomies with incidental prostate cancer. Am. J. Clin. Pathol. 128, 657–666 (2007).

  53. 53.

    , & Evolution of the concept of androgen-sensitive bladder cancer. Scand. J. Urol. 47, 173–178 (2013).

  54. 54.

    et al. Promotion of bladder cancer development and progression by androgen receptor signals. J. Natl Cancer Inst. 99, 558–568 (2007).

  55. 55.

    et al. Androgen deprivation therapy prevents bladder cancer recurrence. Oncotarget 30, 12665–12674 (2014).

  56. 56.

    et al. Is bladder tumor location associated with prostate cancer detection after intravesical bacillus Calmette–Guerin instillation? PLoS ONE 9, e103791 (2014).

  57. 57.

    et al. Inflammation in prostate carcinogenesis. Nat. Rev. Cancer. 7, 256–269 (2007).

  58. 58.

    & Prostate cancer and inflammation: the evidence. Histopathology 60, 199–215 (2012).

  59. 59.

    et al. Unsuspected prostatic adenocarcinoma in patients who have undergone radical cystoprostatectomy for transitional cell carcinoma of the bladder. J. Urol. 139, 1214–1216 (1988).

  60. 60.

    et al. Comparison of incidentally detected prostate cancer with screen-detected prostate cancer treated by prostatectomy. Prostate 72, 108–115 (2012).

  61. 61.

    et al. Prostatic and urothelial metastasis in the same lymph node: a case report. Anal. Quant. Cytopathol. Histpathol. 37, 139–143 (2015).

  62. 62.

    , , , & Current practice of Gleason grading of prostate carcinoma. Virchows Arch. 448, 111–118 (2006).

  63. 63.

    et al. The 2005 International Society of Urological Pathology (ISUP) consensus conference of Gleason grading of prostatic carcinoma. Am. J. Surg. Pathol. 29, 1228 (2005).

  64. 64.

    et al. Incidental prostate cancer diagnosed at radical cystoprostatectomy for bladder cancer: disease-specific outcomes and survival. Prostate Int. 4, 107–112 (2016).

  65. 65.

    et al. EAU-ESTRO-SIOG guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent. Eur. Urol. 71, 618–629 (2017).

  66. 66.

    et al. Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur. Urol. 71, 462–475 (2017).

  67. 67.

    et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur. Urol. 71, 447–461 (2017).

  68. 68.

    et al. Utility of Gleason pattern 4 morphologies detected on transrectal ultrasound (TRUS)-guided biopsies for prediction of upgrading or upstaging in Gleason score 3 + 4 = 7 prostate cancer. Virchows Arch. 469, 313–319 (2017).

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Author information


  1. Unit of Anatomical Pathology, Department of Surgery and Pathology, Cordoba University Medical School, Cordoba University, E-14004 Cordoba, Spain.

    • Antonio Lopez-Beltran
  2. Champalimaud Clinical Center, Av. de Brasilia, 1400–038 Lisbon, Portugal.

    • Antonio Lopez-Beltran
  3. Departments of Pathology and Urology, Indiana University School of Medicine, 350 West 11th street, Indianapolis, Indiana, USA.

    • Liang Cheng
  4. Department of Urology, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy.

    • Francesco Montorsi
  5. Institute of Pathological Anatomy and Histopathology, Polytechnic University of the Marche Region (Ancona), School of Medicine, United Hospitals, Via Conca 71, 60126 Torrette, Ancona, Italy.

    • Maria Scarpelli
    •  & Rodolfo Montironi
  6. Histopathology and Molecular Diagnostics Service, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy.

    • Maria R. Raspollini


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A. L.–B., M.S., M.R.R. and R.M. researched data for this article, all authors made a substantial contribution to discussions of content, A. L.–B. wrote the manuscript, and all authors reviewed and/or edited the manuscript prior to submission.

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The authors declare no competing financial interests.

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Correspondence to Antonio Lopez-Beltran.

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