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Biomarker research in prostate cancer—towards utility, not futility

Nature Reviews Urology volume 8, pages 131–138 (2011)Cite this article

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Abstract

The identification of an appropriate clinical question is critical for any biomarker project. Despite rapid advances in technology, few biomarkers have been forthcoming for prostate cancer. This could be because the clinical questions under investigation have not actually originated from clinical practice. These clinical questions are difficult to identify in the complex and heterogeneous pathogenesis of prostate cancer. In this Review, we have developed a prostate cancer 'roadmap' to identify the aspects of prostate cancer that may be amenable to biomarker discovery and serve as a guide for future projects in prostate cancer biomarker research.

Key Points

  • Biomarker research should be informed by clinical need and not because of the ability of 'omics' technology to generate large datasets

  • Developing a 'roadmap' to identify the key clinical questions for biomarker discovery efforts can serve as a guide for researching biomarkers in prostate cancer

  • Biomarkers for low-risk cancer, pathological grade and cancer stage could have a pivotal role in determining the appropriate management approach for patients with prostate cancer

  • The development of similar roadmaps for biomarker research in other diseases will increase the likelihood of biomarkers entering clinical utility, and not futility

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Figure 1: Milestone 1: biomarkers for cancer detection.
Figure 2: Milestone 2: Biomarkers for cancer staging.
Figure 3: Milestone 3: biomarkers for cancer grading.
Figure 4: Milestone 4: biomarkers for determining clinical significance.
Figure 5: Milestone 5: biomarkers in cancer recurrence.

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References

  1. Oliver, S. E., May, M. T. & Gunnell, D. International trends in prostate-cancer mortality in the “PSA era”. Int. J. Cancer 92, 893–898 (2001).

    Article  CAS  Google Scholar 

  2. Baade, P. D., Coory, M. D. & Aitken, J. F. International trends in prostate-cancer mortality: the decrease is continuing and spreading. Cancer Causes Control 15, 237–241 (2004).

    Article  CAS  Google Scholar 

  3. Baker, M. In biomarkers we trust? Nat. Biotechnol. 23, 297–304 (2005).

    Article  CAS  Google Scholar 

  4. Partin, A. W. et al. The use of prostate specific antigen, clinical stage and Gleason score to predict pathological stage in men with localized prostate cancer. J. Urol. 150, 110–114 (1993).

    Article  CAS  Google Scholar 

  5. Partin, A. W. et al. Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer: a multi-institutional update. JAMA 277, 1445–1451 (1997).

    Article  CAS  Google Scholar 

  6. Partin, A. W. et al. Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology 58, 843–848 (2001).

    Article  CAS  Google Scholar 

  7. Makarov, D. V. et al. Updated nomogram to predict pathologic stage of prostate cancer given prostate-specific antigen level, clinical stage, and biopsy Gleason score (Partin tables) based on cases from 2000 to 2005. Urology 69, 1095–1101 (2007).

    Article  Google Scholar 

  8. Gleason, D. F. Classification of prostatic carcinomas. Cancer Chemother. Rep. 50, 125–128 (1966).

    CAS  PubMed  Google Scholar 

  9. Epstein, J. I., Allsbrook, W. C. Jr, Amin, M. B., Egevad, L. L. & ISUP Grading Committee. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason grading of prostatic carcinoma. Am. J. Surg. Pathol. 29, 1228–1242 (2005).

    Article  Google Scholar 

  10. Brewster, S., Turkeri, L., Brausi, M., Ravery, V. & Djavan, B. 5A prospective survey of current prostate biopsy practices among oncological urologists. Can. J. Urol. 17, 5071–5076 (2010).

    PubMed  Google Scholar 

  11. Thompson, I. M. Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower. JAMA 294, 66–70 (2005).

    Article  CAS  Google Scholar 

  12. Thompson, I. M. et al. Prevalence of prostate cancer among men with a prostate-specific antigen level ≤4.0 ng/ml. N. Engl. J. Med. 350, 2239–2246 (2004).

    Article  CAS  Google Scholar 

  13. Pinsky, P. F. et al. Prostate volume and prostate-specific antigen levels in men enrolled in a large screening trial. Urology 68, 352–356 (2006).

    Article  Google Scholar 

  14. Schröder, F. H. et al. Screening and prostate-cancer mortality in a randomized European study. N. Engl. J. Med. 360, 1320–1328 (2009).

    Article  Google Scholar 

  15. Andriole, G. L. et al. Mortality results from a randomized prostate-cancer screening trial. N. Engl. J. Med. 360, 1310–1319 (2009).

    Article  CAS  Google Scholar 

  16. Eckersberger, E. et al. Screening for prostate cancer: a review of the ERSPC and PLCO trials. Rev. Urol. 11, 127–133 (2009).

    PubMed  PubMed Central  Google Scholar 

  17. Chodak, G. W., Keller, P. & Schoenberg, H. W. Assessment of screening for prostate cancer using the digital rectal examination. J. Urol. 141, 1136–1138 (1989).

    Article  CAS  Google Scholar 

  18. Gosselaar, C., Kranse, R., Roobol, M. J., Roemeling, S. & Schröder, F. H. The interobserver variability of digital rectal examination in a large randomized trial for the screening of prostate cancer. Prostate 68, 985–993 (2008).

    Article  CAS  Google Scholar 

  19. Mistry, K. & Cable, G. Meta-analysis of prostate-specific antigen and digital rectal examination as screening tests for prostate carcinoma. J. Am. Board Fam. Pract. 16, 95–101 (2003).

    Article  Google Scholar 

  20. Chodak, G. W., Keller, P. & Schoenberg, H. W. Assessment of screening for prostate cancer using the digital rectal examination. J. Urol. 141, 1136–1138 (1989).

    Article  CAS  Google Scholar 

  21. Heidenreich, A. et al. European Association of Urology Guidelines on Prostate Cancer [online], (2011).

    Google Scholar 

  22. Hendrikx, A., Safarik, L. & Hammerer, P. TRUS and biopsy: practical aspects. Eur. Urol. 41, 581–704 (2002).

    Article  Google Scholar 

  23. Schröder, F. H. et al. Eleven year outcome of patients with prostate cancers diagnosed during screening after initial negative sextant biopsies. Eur. Urol. 57, 256–266 (2010).

    Article  Google Scholar 

  24. Edge, S. B. et al. AJCC Cancer Staging Manual 7th edition 457–468 (Springer, New York, 2010).

    Google Scholar 

  25. Engelbrecht, M. R. et al. Prostate cancer staging using imaging. BJU Int. 86, 123–134 (2000).

    Article  Google Scholar 

  26. Stratton, K. L. & Chang, S. S. Locally advanced prostate cancer: the role of surgical management. BJU Int. 104, 449–454 (2009).

    Article  Google Scholar 

  27. Ward, J. F., Slezak, J. M., Blute, M. L., Bergstralh, E. J. & Zincke, H. Radical prostatectomy for clinically advanced (cT3) prostate cancer since the advent of prostate-specific antigen testing: 15 year outcome. BJU Int. 95, 751–756 (2005).

    Article  Google Scholar 

  28. Hsu, C. Y., Joniau, S., Oyen, R., Roskams, T. & Van Poppel, H. Outcome of surgery for clinical unilateral T3a prostate cancer: a single-institution experience. Eur. Urol. 51, 121–128 (2007).

    Article  Google Scholar 

  29. Eisenberg, M. L., Cowan, J. E., Davies, B. J., Carroll, P. R. & Shinohara, K. The importance of tumor palpability and transrectal ultrasonographic appearance in the contemporary clinical staging of prostate cancer. Urol. Oncol. doi: 10.1016/j.urolonc.2009.01.005.

  30. Wieder, J. A. & Soloway, M. S. Incidence, etiology, location, prevention and treatment of positive surgical margins after radical prostatectomy for prostate cancer. J. Urol. 160, 299–315 (1998).

    Article  CAS  Google Scholar 

  31. Joniau, S. et al. A pretreatment table for the prediction of final histopathology after radical prostatectomy in clinical unilateral T3a prostate cancer. Eur. Urol. 51, 388–389 (2007).

    Article  CAS  Google Scholar 

  32. Van Poppel, H. et al. Radical prostatectomy for locally advanced prostate cancer: results of a feasibility study (EORTC 30001). Eur. J. Cancer 42, 1062–1067 (2006).

    Article  CAS  Google Scholar 

  33. Touma, N. J., Izawa, J. I. & Chin, J. L. Current status of local salvage therapies following radiation failure for prostate cancer. J. Urol. 173, 373–379 (2005).

    Article  Google Scholar 

  34. Villari, D. et al. Radical retropubic prostatectomy for prostate cancer with microscopic bladder neck involvement: survival and prognostic implications. BJU Int. 105, 946–950 (2010).

    Article  Google Scholar 

  35. Hövels, A. M. et al. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin. Radiol. 63, 387–395 (2008).

    Article  Google Scholar 

  36. Ordon, M. & Nam, R. K. Lymph node assessment and lymphadenectomy in prostate cancer. J. Surg. Oncol. 99, 215–224 (2009).

    Article  Google Scholar 

  37. Heidenrich, A., Varga, Z. & Von Knobloch, R. Extended pelvic lymphadenectomy in patients undergoing radical prostatectomy: high incidence of lymph node metastases. J. Urol. 167, 1681–1686 (2002).

    Article  Google Scholar 

  38. Bader, P., Burkhard, F. C., Markwalder, R. & Studer, U. E. Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure? J. Urol. 169, 849–854 (2003).

    Article  Google Scholar 

  39. Briganti, A. et al. Complications and other surgical outcomes associated with extended pelvic lymphadenectomy in men with localized prostate cancer. Eur. Urol. 50, 1006–1013 (2006).

    Article  Google Scholar 

  40. Briganti, A. et al. Pelvic lymph node dissection in prostate cancer. Eur. Urol. 55, 1251–1265 (2009).

    Article  Google Scholar 

  41. De la Taille, A. et al. Perineural invasion on prostate needle biopsy: an independent predictor of final pathologic stage. Urology 54, 1039–1043 (1999).

    Article  CAS  Google Scholar 

  42. Sebo, T. J. et al. Predicting prostate carcinoma volume and stage at radical prostatectomy by assessing needle biopsy specimens for percent surface area and cores positive for carcinoma, perineural invasion, Gleason score, DNA ploidy and proliferation, and preoperative serum prostate specific antigen: a report of 454 cases. Cancer 91, 2196–2204 (2001).

    Article  CAS  Google Scholar 

  43. Yu, J. B. et al. Validation of the Partin nomogram for prostate cancer in a national sample. J. Urol. 183, 105–111 (2010).

    Article  Google Scholar 

  44. Bhojani, N. et al. Partin tables cannot accurately predict the pathological stage at radical prostatectomy. Eur. J. Surg. Oncol. 35, 123–128 (2009).

    Article  CAS  Google Scholar 

  45. Bhojani, N. et al. External validation of the updated Partin tables in a cohort of French and Italian men. Int. J. Radiat. Oncol. Biol. Phys. 73, 347–352 (2009).

    Article  Google Scholar 

  46. Fanning, D. M., Yue, F., Fitzpatrick, J. M. & Watson, R. W. Novel predictive tools for Irish radical prostatectomy pathological outcomes: development and validation. Ir. J. Med. Sci. 179, 187–195 (2010).

    Article  CAS  Google Scholar 

  47. Helpap, B. & Egevad, L. Modified Gleason grading. An updated review. Histol. Histopathol. 24, 661–666 (2009).

    PubMed  Google Scholar 

  48. Chan, T. Y., Partin, A. W., Walsh, P. C. & Epstein, J. I. Prognostic significance of Gleason Score 3+4 versus Gleason Score 4+3 tumor at radical prostatectomy. Urology 56, 823–827 (2000).

    Article  CAS  Google Scholar 

  49. Epstein, J. I. An update of the Gleason grading system. J. Urol. 183, 433–440 (2010).

    Article  Google Scholar 

  50. Lau, W. K. et al. Prognostic factors for survival of patients with pathological Gleason score 7 prostate cancer: differences in outcome between 3 and 4. J. Urol. 166, 1692–1697 (2001).

    Article  CAS  Google Scholar 

  51. Stark, J. R. et al. Gleason score and lethal prostate cancer: does 3 + 4 = 4 + 3? J. Clin. Oncol. 27, 3459–3464 (2009).

    Article  Google Scholar 

  52. Wright, J. L. et al. Prostate cancer specific mortality and Gleason 7 disease differences in prostate cancer outcomes between cases with Gleason 4 + 3 and Gleason 3 + 4 tumors in a population based cohort. J. Urol. 182, 2702–2707 (2009).

    Article  Google Scholar 

  53. Sakr, W. A. et al. Gleason score 7 prostate cancer: a heterogenous entity? Correlation with pathologic parameters and disease free survival. Urology 56, 730–734 (2000).

    Article  CAS  Google Scholar 

  54. Gleason, D. F. Classification of prostatic carcinomas. Cancer Chemother. Rep. 50, 125–128 (1966).

    CAS  PubMed  Google Scholar 

  55. Glaessgen, A. et al. Interobserver reproducibility of percent Gleason grade 4/5 in total prostatectomy specimens. J. Urol. 168, 2006–2010 (2002).

    Article  Google Scholar 

  56. Helpap, B. & Egevad, L. The significance of modified Gleason grading of prostatic adenocarcinoma by combined histological grading and clinical staging. Virchows Arch. 449, 622–627 (2006).

    Article  Google Scholar 

  57. 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 

  58. Uemura, H. et al. Usefulness of the 2005 International Society of Urologic Pathology Gleason grading system in prostate biopsy and radical prostatectomy specimens. BJU Int. 103, 1190–1194 (2009).

    Article  Google Scholar 

  59. Rullis, I., Schaeffer, J. A. & Lilien, O. M. Incidence of prostatic carcinoma in the elderly. Urology 6, 295–297 (1975).

    Article  CAS  Google Scholar 

  60. Albertsen, P. C., Fryback, D. G., Storer, B. E., Kolon, T. F. & Fine, J. Long-term survival among men with conservatively treated localized prostate cancer. JAMA 274, 626–631 (1995).

    Article  CAS  Google Scholar 

  61. Parkin, D. M., Bray, F. I. & Devesa, S. S. Cancer burden in the year 2000. The global picture. Eur. J. Cancer 37, S4–S66 (2001).

    Article  Google Scholar 

  62. Dall'Era, M. A. et al. Active surveillance for early-stage prostate cancer: review of the current literature. Cancer 112, 1650–1659 (2008).

    Article  Google Scholar 

  63. Shariat, S. F., Karakiewicz, P. I., Roehrborn, C. G. & Kattan, M. W. An updated catalog of prostate cancer predictive tools. Cancer 113, 3075–3099 (2008).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  65. Jeldres, C. et al. Validation of the contemporary Epstein criteria for insignificant prostate cancer in European men. Eur. Urol. 54, 1306–1313 (2008).

    Article  Google Scholar 

  66. Lee, M. C. et al. The Epstein Criteria Predict for organ-confined but not insignificant disease and a high likelihood of cure at radical prostatectomy. Eur. Urol. 8, 90–95 (2010).

    Article  Google Scholar 

  67. Hekal, I. A. et al. Validation of Epstein criteria of insignificant prostate cancer in Middle East patients. Int. Urol. Nephrol. 42, 667–671 (2009).

    Article  Google Scholar 

  68. Lee, S. E. et al. Application of the Epstein criteria for prediction of clinically insignificant prostate cancer in Korean men. BJU Int. 105, 1526–1530 (2010).

    Article  Google Scholar 

  69. Louie-Johnsun, M., Neill, M., Treurnicht, K., Jarmulowicz, M. & Eden, C. Final outcomes of patients with low-risk prostate cancer suitable for active surveillance but treated surgically. BJU Int. 104, 1501–1504 (2009).

    Article  Google Scholar 

  70. Kattan, M. W., Eastham, J. A., Stapleton, A. M., Wheeler, T. M. & Scardino, P. T. A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. J. Natl Cancer Inst. 90, 766–771 (1998).

    Article  CAS  Google Scholar 

  71. Rouprêt, M. et al. Cross-cultural validation of a prognostic tool: example of the Kattan preoperative nomogram as a predictor of prostate cancer recurrence after radical prostatectomy. BJU Int. 104, 813–817 (2009).

    Article  Google Scholar 

  72. Zagars, G. K. & Pollack, A. Kinetics of serum prostate-specific antigen after external beam radiation for clinically localized prostate cancer. Radiother. Oncol. 44, 213–221 (1997).

    Article  CAS  Google Scholar 

  73. Naito, S. Evaluation and management of prostate-specific antigen recurrence after radical prostatectomy for localized prostate cancer. Jpn J. Clin. Oncol. 35, 365–374 (2005).

    Article  Google Scholar 

  74. Pound, C. R. et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 281, 1591–1597 (1999).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by The Urological Foundation, the Royal College of Surgeons in Ireland, Science Foundation Ireland, the Higher Education Authority and the Prostate Cancer Research Consortium, funded by the Irish Cancer Society.

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Authors and Affiliations

  1. UCD School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, 4, Dublin, Ireland

    Sheng Fei Oon, Stephen R. Pennington & R. William G. Watson

  2. Department of Urology, Mater Misericordae University Hospital, 47 Eccles Street, 7, Dublin, Ireland

    John M. Fitzpatrick

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S. F. Oon researched data for, and wrote, the article. S. F. Oon, S. R. Pennington, J. M. Fitzpatrick and R. W. G. Watson contributed to discussions of content, and reviewed and edited the article before submission.

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Correspondence to Sheng Fei Oon.

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Oon, S., Pennington, S., Fitzpatrick, J. et al. Biomarker research in prostate cancer—towards utility, not futility. Nat Rev Urol 8, 131–138 (2011). https://doi.org/10.1038/nrurol.2011.11

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