Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Concomitant bladder cancer and prostate cancer: challenges and controversies

Nature Reviews Urology volume 14, pages 620–629 (2017)Cite this article

Subjects

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

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Complete slicing of radical cystoprostatectomy (RCP) specimens from patients with concomitant prostate and bladder cancer.
Figure 2: Pathological slices of bladder and prostate cancer prepared using the wholemount technique.
Figure 3: Algorithm for the determination of the clinical significance of concomitant prostate cancer diagnosed at RCP.

Similar content being viewed by others

References

  1. Luchey, A. M. 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).

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

  4. Barbisan, F. 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).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. Winkler, M. H., Livni, N., Mannion, E. M., Hrouda, D. & Christmas, T. Characteristics of incidental prostatic adenocarcinoma in contemporary radical cystoprostatectomy specimens. BJU Int. 99, 554–558 (2007).

    Article  Google Scholar 

  7. Damiano, R. 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).

    Article  Google Scholar 

  8. Revelo, M. P. 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).

    PubMed  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  11. Abbas, F., Hochberg, D., Civantos, F. & Soloway, M. Incidental prostatic adenocarcinoma in patients undergoing radical cystoprostatectomy for bladder cancer. Eur. Urol. 30, 322–326 (1996).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  13. Damiano, R. 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).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Kurahashi, T. 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).

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

  19. Thomas, C. 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).

    Article  Google Scholar 

  20. Conrad, S. 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).

    Article  Google Scholar 

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

    Article  Google Scholar 

  22. Abdelhady, M., Abusamra, A., Pautler, S. E., Chin, J. L. & Izawa, J. I. Clinically significant prostate cancer found incidentally in radical cystoprostatectomy specimens. BJU Int. 99, 326–329 (2007).

    Article  Google Scholar 

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

    Article  Google Scholar 

  24. Nakagawa, T., Kanai, Y., Komiyama, M., Fujimoto, H. & Kakizoe, T. 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).

    Article  CAS  Google Scholar 

  25. Pepe, P. 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).

    Article  Google Scholar 

  26. Fritsche, H. M. 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).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  28. Siadat, F. 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).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  30. Epstein, J. I., Walsh, P. C., Carmichael, M. & Brendler, C. B. Pathologicand clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA 271, 368–374 (1994).

    Article  CAS  Google Scholar 

  31. Iremashvili, V., Lokeshwar, S. D., Jorda, M., Pelaez, L. & Soloway, M. S. Prognostic implications of partial sampling of radical prostatectomy specimens: comparison of 3 methods. J. Urol. 190, 84–90 (2013).

    Article  Google Scholar 

  32. Terris, M. K., Haney, D. J., Johnstone, I. M., McNeal, J. E. & Stamey, T. A. Prediction of prostate cancer volume using prostate-specific antigen levels, transrectal ultrasound, and systematic sextant biopsies. Urology 45, 75–80 (1995).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  37. Ward, J. F. 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).

    Article  CAS  Google Scholar 

  38. Montironi, R. 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).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

  42. Stein, J. P., Hautmann, R. E., Penson, D. & Skinner, D. G. Prostate-sparing cystectomy: A review of the oncologic and functional outcomes. Contraindicated in patients with bladder cancer. Urol. Onc. 27, 466–472 (2009).

    Article  Google Scholar 

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

    Article  Google Scholar 

  44. Kefer, J. C. & Campbell, S. C. Current status of prostate-sparing cystectomy. Urol. Onc. 26, 486–493 (2008).

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

  47. Pepe, P., Dibenedetto, G., Garufi, A., Priolo, G. & Pennisi, M. Multiparametric pelvic MRI accuracy in diagnosing clinically significant prostate cancer in the reevaluation of biopsy microfocal tumor. Anticancer Res. 35, 395–399 (2015).

    PubMed  Google Scholar 

  48. Hankey, B. F. 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).

    Article  CAS  Google Scholar 

  49. Lopez-Beltran, A. & Cheng, L. Histologic variants of urothelial carcinoma: differential diagnosis and clinical implications. Hum. Pathol. 37, 1371–1388 (2006).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  51. Montironi, R. 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).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  53. Gakis, G., Stenz, A. & Renninger, M. Evolution of the concept of androgen-sensitive bladder cancer. Scand. J. Urol. 47, 173–178 (2013).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Google Scholar 

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

    Article  Google Scholar 

  57. De Marzo, A. M. et al. Inflammation in prostate carcinogenesis. Nat. Rev. Cancer. 7, 256–269 (2007).

    Article  CAS  Google Scholar 

  58. Sfanos, K. S. & De Marzo, A. M. Prostate cancer and inflammation: the evidence. Histopathology 60, 199–215 (2012).

    Article  Google Scholar 

  59. Pritchett, T. R. 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).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    PubMed  Google Scholar 

  62. Lopez-Beltran, A., Mikuz, G., Luque, R. J., Mazzucchelli, R. & Montironi, R. Current practice of Gleason grading of prostate carcinoma. Virchows Arch. 448, 111–118 (2006).

    Article  Google Scholar 

  63. Epstein, J. I. 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).

    Article  Google Scholar 

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

    Article  Google Scholar 

  65. Mottet, N. 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).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  68. Flood, T. A. 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).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    Antonio Lopez-Beltran

  2. Champalimaud Clinical Center, Av. de Brasilia, Lisbon, 1400–038, 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, Milan, 20132, 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, Torrette, 60126, Ancona, Italy

    Maria Scarpelli & Rodolfo Montironi

  6. Histopathology and Molecular Diagnostics Service, Careggi University Hospital, Largo Brambilla 3, Florence, 50134, Italy

    Maria R. Raspollini

Authors
  1. Antonio Lopez-Beltran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liang Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francesco Montorsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Scarpelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria R. Raspollini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rodolfo Montironi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.

Corresponding author

Correspondence to Antonio Lopez-Beltran.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lopez-Beltran, A., Cheng, L., Montorsi, F. et al. Concomitant bladder cancer and prostate cancer: challenges and controversies. Nat Rev Urol 14, 620–629 (2017). https://doi.org/10.1038/nrurol.2017.124

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrurol.2017.124

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing