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Validation and clinical utility of prostate cancer biomarkers

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Abstract

To improve future drug development and patient management for patients with castration-resistant prostate cancer (CRPC), surrogate biomarkers that are linked to relevant outcomes are urgently needed. A biomarker must be measurable, reproducible, linked to relevant clinical outcomes, and demonstrate clinical utility. This area is rapidly evolving, with recent trials in patients with CRPC incorporating the detection of circulating tumour cells (CTCs), imaging, and patient-reported outcome biomarkers. We discuss the framework for the development of biomarkers for CRPC, including different categories and contexts of use. We also highlight the requirements of analytical validation, the sequence of trials needed for clinical validation and regulatory approval, and the future outlook for imaging and CTC biomarkers.

Key Points

  • Improving current treatment for patients with castration-resistant prostate cancer requires new biomarkers and surrogate end points for clinical trials

  • Of highest priority are biomarkers that reflect clinical benefit, and predictive biomarkers to guide the selection of treatment most likely to work in the individual patient

  • The development and approval processes for biomarkers are rigorous and lengthy, requiring analytically valid assays and a sequence of trials that support the use of a biomarker in a specific context

  • The investment of resources and time will be recovered by achieving streamlined clinical trials and better selection of new therapies for development

  • Promising emerging biomarkers for castration-resistant prostate cancer include circulating tumour cells and new methods for imaging bone metastases

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Figure 1: Correlation of Log (1+CTC) values for 67 patients plotted using CellSearch® and Flow CTC assays.99
Figure 2: Radionuclide imaging of a patient with castration-resistant prostate cancer
Figure 3: Larson–Fox–Gonen plot showing SUVmax for individual lesions in a patient at baseline and following 1 month of treatment with enzalutamide, a novel anti-androgen.
Figure 4: Identifying CTCs using CellSearch®.

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Change history

  • 12 March 2013

    In the version of this article initially published online, the author contributions statement was incorrect and did not accredit the contribution of Howard I. Scher appropriately. The contributions statement has now been corrected.

References

  1. Kantoff, P. W. et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363, 411–422 (2010).

    Article  CAS  PubMed  Google Scholar 

  2. de Bono, J. S. et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 376, 1147–1154 (2010).

    Article  CAS  PubMed  Google Scholar 

  3. de Bono, J. S. et al. Abiraterone and increased survival in metastatic prostate cancer. N. Engl. J. Med. 364, 1995–2005 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ryan, C. J. et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N. Engl. J. Med. 368, 138–148 (2013).

    Article  CAS  PubMed  Google Scholar 

  5. Scher, H. I. et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N. Engl. J. Med. 367, 1187–1197 (2012).

    Article  CAS  PubMed  Google Scholar 

  6. Fizazi, K. et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377, 813–822 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Scher, H. I. et al. Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer. J. Clin. Oncol. 29, 2191–2198 (2011).

    Article  CAS  PubMed  Google Scholar 

  8. Kelly, W. K. et al. Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401. J. Clin. Oncol. 30, 1534–1540 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Michaelson, M. D. et al. Randomized, placebo-controlled, phase III trial of sunitinib in combination with prednisone (SU+P) versus prednisone (P) alone in men with progressive metastatic castration-resistant prostate cancer (mCRPC) [abstract]. J. Clin. Oncol. 29 (Suppl. 15), a4515 (2011).

    Google Scholar 

  10. Nelson, J. B. et al. Phase 3, randomized, placebo-controlled study of zibotentan (ZD4054) in patients with castration-resistant prostate cancer metastatic to bone. Cancer 118, 5709–5718 (2012).

    Article  CAS  PubMed  Google Scholar 

  11. Petrylak, D. P. et al. A phase 3 study to evaluate the efficacy and safety of docetaxel and prednisone (DP) with or without lenalidomide (LEN) in patients with castrate-resistant prostate cancer (CRPC): the MAINSAIL trial [abstract]. Ann. Oncol. 23 (Suppl. 9), LBA24 (2012).

    Google Scholar 

  12. Parker, C. et al. Overall survival benefit of radium-223 chloride (alpharadin) in the treatment of patients with symptomatic bone metastases in castration-resistant prostate cancer (CRPC): a phase III randomized trial (ALSYMPCA) [abstract]. Eur. J. Cancer 47 (Suppl. 2), a1LBA (2011).

    Google Scholar 

  13. Nilsson, S. et al. Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study. Lancet Oncol. 8, 587–594 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Small, E. J. et al. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J. Clin. Oncol. 22, 1025–1033 (2004).

    Article  CAS  PubMed  Google Scholar 

  15. Saad, E. D. & Buyse, M. Overall survival: patient outcome, therapeutic objective, clinical trial end point, or public health measure? J. Clin. Oncol. 30, 1750–1754 (2012).

    Article  PubMed  Google Scholar 

  16. Scher, H. I. et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J. Clin. Oncol. 26, 1148–1159 (2008).

    Article  PubMed  Google Scholar 

  17. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin. Pharmacol. Ther. 69, 89–95 (2001).

  18. Goodsaid, F. M. & Mendrick, D. L. Translational medicine and the value of biomarker qualification. Sci. Transl. Med. 2, 47ps44 (2010).

    Article  PubMed  Google Scholar 

  19. Khleif, S. N., Doroshow, J. H. & Hait, W. N. AACR-FDA-NCI Cancer Biomarkers Collaborative consensus report: advancing the use of biomarkers in cancer drug development. Clin. Cancer Res. 16, 3299–3318 (2010).

    Article  CAS  PubMed  Google Scholar 

  20. Lin, L. I. A concordance correlation coefficient to evaluate reproducibility. Biometrics 45, 255–268 (1989).

    Article  CAS  PubMed  Google Scholar 

  21. Cummings, J., Raynaud, F., Jones, L., Sugar, R., Dive, C. Fit-for-purpose biomarker method validation for application in clinical trials of anticancer drugs. Br. J. Cancer 103, 1313–1317 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Institute of Medicine of the National Academies. Evidence for clinical utility of molecular diagnostics in oncology: a workshop [online], (2012).

  23. Buyse, M., Sargent, D. J., Grothey, A., Matheson, A. & de Gramont, A. Biomarkers and surrogate end points--the challenge of statistical validation. Nat. Rev. Clin. Oncol. 7, 309–317 (2010).

    Article  PubMed  Google Scholar 

  24. FDA. Draft guidance for industry: Qualification process for drug development tools [online], (2010).

  25. FDA. Draft guidance for industry and FDA staff: In vitro companion diagnostic devices [online], (2011).

  26. Schilsky, R. L., Doroshow, J. H., Leblanc, M. & Conley, B. A. Development and use of integral assays in clinical trials. Clin. Cancer Res. 18, 1540–1546 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Smaletz, O. et al. Nomogram for overall survival of patients with progressive metastatic prostate cancer after castration. J. Clin. Oncol. 20, 3972–3982 (2002).

    Article  PubMed  Google Scholar 

  28. Armstrong, A. J. et al. A contemporary prognostic nomogram for men with hormone-refractory metastatic prostate cancer: a TAX327 study analysis. Clin. Cancer Res. 13, 6396–6403 (2007).

    Article  CAS  PubMed  Google Scholar 

  29. Halabi, S. et al. Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer. J. Clin. Oncol. 21, 1232–1237 (2003).

    Article  PubMed  Google Scholar 

  30. Halabi, S. et al. Progression-free survival as a predictor of overall survival in men with castrate-resistant prostate cancer. J. Clin. Oncol. 27, 2766–2771 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Scher, H. I., Warren, M. & Heller, G. The association between measures of progression and survival in castrate-metastatic prostate cancer. Clin. Cancer Res. 13, 1488–1492 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. Ong, F. S. et al. Personalized medicine and pharmacogenetic biomarkers: progress in molecular oncology testing. Expert Rev. Mol. Diagn. 12, 593–602 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Attard, G. et al. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J. Clin. Oncol. 27, 3742–3748 (2009).

    Article  CAS  PubMed  Google Scholar 

  34. Tomlins, S. A. et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310, 644–648 (2005).

    Article  CAS  PubMed  Google Scholar 

  35. Baca, S. C. & Garraway, L. A. The genomic landscape of prostate cancer. Front. Endocrinol. (Lausanne) 3, 69 (2012).

    Article  Google Scholar 

  36. Prensner, J. R., Rubin, M. A., Wei, J. T. & Chinnaiyan, A. M. Beyond PSA: the next generation of prostate cancer biomarkers. Sci. Transl. Med. 4, 127rv3 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Taylor, B. S. et al. Integrative genomic profiling of human prostate cancer. Cancer Cell 18, 11–22 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Carver, B. S. et al. Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell 19, 575–586 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Scher, H. I., Morris, M. J., Kelly, W. K., Schwartz, L. H. & Heller, G. Prostate cancer clinical trial end points: “RECIST”ing a step backwards. Clin. Cancer Res. 11, 5223–5232 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Gignac, G. A., Morris, M. J., Heller, G., Schwartz, L. H. & Scher, H. I. Assessing outcomes in prostate cancer clinical trials: a twenty-first century tower of Babel. Cancer 113, 966–974 (2008).

    Article  PubMed  Google Scholar 

  41. Tannock, I. F. et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J. Clin. Oncol. 14, 1756–1764 (1996).

    Article  CAS  PubMed  Google Scholar 

  42. Berthold, D. R. et al. Treatment of hormone-refractory prostate cancer with docetaxel or mitoxantrone: relationships between prostate-specific antigen, pain, and quality of life response and survival in the TAX-327 study. Clin. Cancer Res. 14, 2763–2767 (2008).

    Article  CAS  PubMed  Google Scholar 

  43. Sartor, O. et al. Samarium-153-lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology 63, 940–945 (2004).

    Article  PubMed  Google Scholar 

  44. Logothetis, C. J. et al. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol. 13, 1210–1217 (2012).

    Article  CAS  PubMed  Google Scholar 

  45. Atkinson, T. M. et al. The Brief Pain Inventory and its “pain at its worst in the last 24 hours” item: clinical trial endpoint considerations. Pain Med. 11, 337–346 (2010).

    Article  PubMed  Google Scholar 

  46. Osoba, D., Tannock, I. F., Ernst, D. S. & Neville, A. J. Health-related quality of life in men with metastatic prostate cancer treated with prednisone alone or mitoxantrone and prednisone. J. Clin. Oncol. 17, 1654–1663 (1999).

    Article  CAS  PubMed  Google Scholar 

  47. Sternberg, C. N. et al. Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial. J. Clin. Oncol. 27, 5431–5438 (2009).

    Article  CAS  PubMed  Google Scholar 

  48. Smith, D. C. et al. Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. J. Clin. Oncol. 31, 412–419 (2013).

    Article  CAS  PubMed  Google Scholar 

  49. US National Library of Medicine. ClinicalTrials.gov [online], (2013).

  50. US National Library of Medicine. ClinicalTrials.gov [online], (2012).

  51. Lakhal, L., Rivest, L.-P. & Beaudoin, D. IPCW estimator for Kendall's Tau under bivariate censoring. Int. J. Biostat. 5, 8 (2009).

    Article  Google Scholar 

  52. Prentice, R. L. Surrogate endpoints in clinical trials: definition and operational criteria. Stat. Med. 8, 431–440 (1989).

    Article  CAS  PubMed  Google Scholar 

  53. Fox, J. J., Morris, M. J., Larson, S. M., Schöder, H. & Scher, H. I. Developing imaging strategies for castration resistant prostate cancer. Acta Oncol. 50 (Suppl. 1), 39–48 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Logothetis, C. J. et al. Doxorubicin, mitomycin-C, and 5-fluorouracil (DMF) in the treatment of metastatic hormonal refractory adenocarcinoma of the prostate, with a note on the staging of metastatic prostate cancer. J. Clin. Oncol. 1, 368–379 (1983).

    Article  CAS  PubMed  Google Scholar 

  55. Soloway, M. S. et al. Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. Cancer 61, 195–202 (1988).

    Article  CAS  PubMed  Google Scholar 

  56. Rigaud, J. et al. Prognostic value of bone scan in patients with metastatic prostate cancer treated initially with androgen deprivation therapy. J. Urol. 168, 1423–1426 (2002).

    Article  PubMed  Google Scholar 

  57. Morris, M. J. et al. The Prostate Cancer Clinical Trials Consortium (PCCTC) bone scan data capture tool for clinical trials using Prostate Cancer Working Group 2 (PCWG2) criteria: Effect on data accuracy and workload [abstract]. J. Clin. Oncol. 29 (Suppl. 7), a121 (2011).

    Article  Google Scholar 

  58. Ryan, C. J. et al. Association of radiographic progression-free survival (rPFS) adapted from Prostate Cancer Working Group 2 (PCWG2) consensus criteria (APCWG2) with overall survival (OS) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): results from COU-AA-302 [abstract]. Ann. Oncol. 23 (Suppl. 9), a8940 (2012).

    Google Scholar 

  59. FDA. FDA expands Zytiga's use for late-stage prostate cancer: drug can now be used before treatment with chemotherapy [online], (2012).

  60. Imbriaco, M. et al. A new parameter for measuring metastatic bone involvement by prostate cancer: the Bone Scan index. Clin. Cancer Res. 4, 1765–1772 (1998).

    CAS  PubMed  Google Scholar 

  61. Dennis, E. R. et al. Bone scan index: a quantitative treatment response biomarker for castration-resistant metastatic prostate cancer. J. Clin. Oncol. 30, 519–524 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Ulmert, D. et al. A novel automated platform for quantifying the extent of skeletal tumour involvement in prostate cancer patients using the Bone Scan Index. Eur. Urol. 62, 78–84 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Brown, M. S. et al. Computer-aided quantitative bone scan assessment of prostate cancer treatment response. Nucl. Med. Commun. 33, 384–394 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  64. US National Library of Medicine. ClinicalTrials.gov [online], (2013).

  65. Yeh, S. D. et al. Detection of bony metastases of androgen-independent prostate cancer by PET-FDG. Nucl. Med. Biol. 23, 693–697 (1996).

    Article  CAS  PubMed  Google Scholar 

  66. Meirelles, G. S. et al. Prognostic value of baseline [18F] fluorodeoxyglucose positron emission tomography and 99mTc-MDP bone scan in progressing metastatic prostate cancer. Clin. Cancer Res. 16, 6093–6099 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Morris, M. J. et al. Fluorinated deoxyglucose positron emission tomography imaging in progressive metastatic prostate cancer. Urology 59, 913–918 (2002).

    Article  PubMed  Google Scholar 

  68. US National Library of Medicine. ClinicalTrials.gov [online], (2012).

  69. Wahl, R. L., Jacene, H., Kasamon, Y. & Lodge, M. A. From RECIST to PERCIST: Evolving considerations for PET response criteria in solid tumors. J. Nucl. Med. 50 (Suppl. 1), 122S–150S (2009).

    Article  CAS  PubMed  Google Scholar 

  70. Morris, M. J. et al. Pretreatment fluorodeoxyglucose (FDG) PET and survival for castration-resistant metastatic prostate cancer (CRMPC) [abstract]. ASCO Genitourinary Cancers Symp. a108 (2010).

  71. Morris, M. J. et al. Fluorodeoxyglucose positron emission tomography as an outcome measure for castrate metastatic prostate cancer treated with antimicrotubule chemotherapy. Clin. Cancer Res. 11, 3210–3216 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Fox, J. J. et al. Practical approach for comparative analysis of multilesion molecular imaging using a semiautomated program for PET/CT. J. Nucl. Med. 52, 1727–1732 (2011).

    Article  PubMed  Google Scholar 

  73. Pantel, K. & Alix-Panabieres, C. Circulating tumour cells in cancer patients: challenges and perspectives. Trends Mol. Med. 16, 398–406 (2010).

    Article  PubMed  Google Scholar 

  74. Yu, M., Stott, S., Toner, M., Maheswaran, S. & Haber, D. A. Circulating tumor cells: approaches to isolation and characterization. J. Cell Biol. 192, 373–382 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Danila, D. C., Pantel, K., Fleisher, M. & Scher, H. I. Circulating tumors cells as biomarkers: progress toward biomarker qualification. Cancer J. 17, 438–450 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Gleghorn, J. P. et al. Capture of circulating tumor cells from whole blood of prostate cancer patients using geometrically enhanced differential immunocapture (GEDI) and a prostate-specific antibody. Lab. Chip 10, 27–29 (2010).

    Article  CAS  PubMed  Google Scholar 

  77. Tan, S. J. et al. Versatile label free biochip for the detection of circulating tumor cells from peripheral blood in cancer patients. Biosens. Bioelectron. 26, 1701–1705 (2010).

    Article  CAS  PubMed  Google Scholar 

  78. Tan, S. J. et al. Microdevice for the isolation and enumeration of cancer cells from blood. Biomed. Microdevices 11, 883–892 (2009).

    Article  PubMed  Google Scholar 

  79. Alix-Panabieres, C. et al. Detection of circulating prostate-specific antigen-secreting cells in prostate cancer patients. Clin. Chem. 51, 1538–1541 (2005).

    Article  CAS  PubMed  Google Scholar 

  80. Katz, R. L. et al. Genetically abnormal circulating cells in lung cancer patients: an antigen-independent fluorescence in situ hybridization-based case-control study. Clin. Cancer Res. 16, 3976–3987 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Marrinucci, D. et al. Circulating tumor cells from well-differentiated lung adenocarcinoma retain cytomorphologic features of primary tumor type. Arch. Pathol. Lab. Med. 133, 1468–1471 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Pantel, K., Brakenhoff, R. H. & Brandt, B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat. Rev. Cancer 8, 329–340 (2008).

    Article  CAS  PubMed  Google Scholar 

  83. Willipinski-Stapelfeldt, B. et al. Changes in cytoskeletal protein composition indicative of an epithelial-mesenchymal transition in human micrometastatic and primary breast carcinoma cells. Clin. Cancer Res. 11, 8006–8014 (2005).

    Article  CAS  PubMed  Google Scholar 

  84. FDA. CellSearch(TM) Circulating Tumor Cell Kit. Premarket notification - expanded indications for use - metastatic prostate cancer [online], (2008).

  85. Shaffer, D. R. et al. Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer. Clin. Cancer Res. 13, 2023–2029 (2007).

    Article  CAS  PubMed  Google Scholar 

  86. Cristofanilli, M. et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N. Engl. J. Med. 351, 781–791 (2004).

    Article  CAS  PubMed  Google Scholar 

  87. Cohen, S. J. et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J. Clin. Oncol. 26, 3213–3221 (2008).

    Article  PubMed  Google Scholar 

  88. de Bono, J. S. et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin. Cancer Res. 14, 6302–6309 (2008).

    Article  CAS  PubMed  Google Scholar 

  89. Danila, D. C. et al. Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin. Cancer Res. 13, 7053–7058 (2007).

    Article  CAS  PubMed  Google Scholar 

  90. Reid, A. H. et al. Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. J. Clin. Oncol. 28, 1489–1495 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Olmos, D. et al. Baseline circulating tumor cell counts significantly enhance a prognostic score for patients participating in phase I oncology trials. Clin. Cancer Res. 17, 5188–5196 (2011).

    Article  CAS  PubMed  Google Scholar 

  92. Scher, H. I. et al. Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncol. 10, 233–239 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Goodman, O. B. Jr et al. Circulating tumor cells in patients with castration-resistant prostate cancer baseline values and correlation with prognostic factors. Cancer Epidemiol. Biomarkers Prev. 18, 1904–1913 (2009).

    Article  CAS  PubMed  Google Scholar 

  94. Olmos, D. et al. Circulating tumour cell (CTC) counts as intermediate end points in castration-resistant prostate cancer (CRPC): a single-centre experience. Ann. Oncol. 20, 27–33 (2009).

    Article  CAS  PubMed  Google Scholar 

  95. Danila, D. C. et al. Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer. J. Clin. Oncol. 28, 1496–1501 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Scher, H. I. et al. Evaluation of circulating tumor cell (CTC) enumeration as an efficacy response biomarker of overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC): planned final analysis (FA) of COU-AA-301, a randomized double-blind, placebo-controlled phase III study of abiraterone acetate (AA) plus low-dose prednisone (P) post docetaxel [abstract]. J. Clin. Oncol. 29 (Suppl. 18), LBA4517 (2011).

    Google Scholar 

  97. Buyse, M. & Molenberghs, G. Criteria for the validation of surrogate endpoints in randomized experiments. Biometrics 54, 1014–1029 (1998).

    Article  CAS  PubMed  Google Scholar 

  98. Burzykowski, T., Molenberghs, G., Buyse, M., Geys, H. & Renard, D. Validation of surrogate endpoints in multiple randomized clinical trials with failure-time endpoints. Appl. Stat. 50, 405–422 (2001).

    Google Scholar 

  99. Shaffer, D. R. et al. Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer. Clin. Cancer Res. 13, 2023–2029 (2007).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The work in this article was supported by: The Sidney Kimmel Center for Prostate and Urologic Cancers. Supported in part by the MSKCC SPORE in Prostate Cancer (P50 CA92629), the Department of Defense Prostate Cancer Research Program (PC051382), The Research and Therapeutics Program for Prostate Cancer, The Prostate Cancer Foundation, William H. and Alice Goodwin and the Commonwealth Foundation for Cancer Research and the Experimental Therapeutics Center of Memorial Sloan–Kettering Cancer Center (MSKCC). In addition, S. Larson was supported by P50 CA85438. We thank Amy Plofker, MSKCC editor, for manuscript editing.

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H. I. Scher devised the concept of the article, researched the data for the article, and co-wrote the article with M. J. Morris, S. Larson and G. Heller. All authors made a substantial contribution to discussion of the content, reviewed and edited the manuscript prior to submission, and revised the article after peer review.

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Correspondence to Howard I. Scher.

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Competing interests

H. I. Scher is a consultant for Bristol-Myers Squibb, Dendreon, Endo/Orion Pharmaceuticals, Genentech, Novartis, Ortho Biotech Oncology Research & Development, and Sanofi Aventis. He receives research funding from Aragon, Bristol-Myers Squibb, Exelixis, Janssen Research & Development, Janssen Services, and Medivation. M. J. Morris is a consultant for Millennium. He receives research funding from Agensys, Algeta, Bayer, Genta, Medivation, and Sanofi Aventis. S. Larson is a consultant for ImaginAb, Perceptive, and Progenics. He receives research funding from GE Medical Systems. G. Heller declares no competing interests.

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Scher, H., Morris, M., Larson, S. et al. Validation and clinical utility of prostate cancer biomarkers. Nat Rev Clin Oncol 10, 225–234 (2013). https://doi.org/10.1038/nrclinonc.2013.30

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