1932

Abstract

The therapeutic landscape of prostate cancer has been transformed over the last decade by new therapeutics, advanced functional imaging, next-generation sequencing, and better use of existing therapies in early-stage disease. Until 2004, progression on androgen deprivation therapy for metastatic disease was treated with the addition of secondary hormonal manipulation; in the last decade, six systemic agents have been approved for the treatment of castration-resistant prostate cancer. We review clinical trials and survival benefit for these therapies and assess how the understanding of the disease shifted as these therapies were developed. We also discuss advances in noncastrate disease states, identification of biomarkers for prognosis and treatment selection, and opportunities in locoregional therapy to delay androgen deprivation therapy.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-051517-011947
2019-01-27
2024-10-14
Loading full text...

Full text loading...

/deliver/fulltext/med/70/1/annurev-med-051517-011947.html?itemId=/content/journals/10.1146/annurev-med-051517-011947&mimeType=html&fmt=ahah

Literature Cited

  1. 1.  Howlader N, Noone AM, Krapcho M et al. 2017. SEER Cancer Statistics Review, 19752014 Bethesda, MD: Natl. Cancer Inst http://seer.cancer.gov/csr/1975_2014. Based on November 2016 SEER data submission, posted to SEER web site April 2017
    [Google Scholar]
  2. 2.  Scher HI, Halabi S, Tannock I et al. 2008. 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. 26:1148–59
    [Google Scholar]
  3. 3.  Scher HI, Morris MJ, Stadler WM et al. 2016. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the Prostate Cancer Clinical Trials Working Group 3. J. Clin. Oncol. 34:1402–18
    [Google Scholar]
  4. 4.  Huggins C 1942. Effect of orchiectomy and irradiation on cancer of the prostate. Ann. Surg. 115:1192–200
    [Google Scholar]
  5. 5.  Huggins C 1944. The treatment of cancer of the prostate: the 1943 address in surgery before the royal college of physicians and surgeons of canada. Can. Med. Assoc. J. 50:301–7
    [Google Scholar]
  6. 6.  Caubet JF, Tosteson TD, Dong EW et al. 1997. Maximum androgen blockade in advanced prostate cancer: a meta-analysis of published randomized controlled trials using nonsteroidal antiandrogens. Urology 49:71–78
    [Google Scholar]
  7. 7.  Small EJ, Halabi S, Dawson NA et al. 2004. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J. Clin. Oncol. 22:1025–33
    [Google Scholar]
  8. 8.  Tannock I, Gospodarowicz M, Meakin W et al. 1989. Treatment of metastatic prostatic cancer with low-dose prednisone: evaluation of pain and quality of life as pragmatic indices of response. J. Clin. Oncol. 7:590–97
    [Google Scholar]
  9. 9.  Tannock IF, Osoba D, Stockler MR et al. 1996. 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. 14:1756–64
    [Google Scholar]
  10. 10.  Kantoff PW, Halabi S, Conaway M et al. 1999. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study. J. Clin. Oncol. 17:2506–13
    [Google Scholar]
  11. 11.  Petrylak DP, Tangen CM, Hussain MH et al. 2004. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N. Engl. J. Med. 351:1513–20
    [Google Scholar]
  12. 12.  Tannock IF, de Wit R, Berry WR et al. 2004. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N. Engl. J. Med. 351:1502–12
    [Google Scholar]
  13. 13.  de Bono JS, Oudard S, Ozguroglu M et al. 2010. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 376:1147–54
    [Google Scholar]
  14. 14.  Kantoff PW, Higano CS, Shore ND et al. 2010. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363:411–22
    [Google Scholar]
  15. 15.  Parker C, Nilsson S, Heinrich D et al. 2013. Alpha emitter radium-223 and survival in metastatic prostate cancer. N. Engl. J. Med. 369:213–23
    [Google Scholar]
  16. 16.  Smith MR, Saad F, Chowdhury S et al. 2018. Apalutamide treatment and metastasis-free survival in prostate cancer. N. Engl. J. Med. 378:1408–18
    [Google Scholar]
  17. 17.  Scher HI, Fizazi K, Saad F et al. 2012. Increased survival with enzalutamide in prostate cancer after chemotherapy. N. Engl. J. Med. 367:1187–97
    [Google Scholar]
  18. 18.  Beer TM, Armstrong AJ, Rathkopf DE et al. 2014. Enzalutamide in metastatic prostate cancer before chemotherapy. N. Engl. J. Med. 371:424–33
    [Google Scholar]
  19. 19.  James ND, de Bono JS, Spears MR et al. 2017. Abiraterone for prostate cancer not previously treated with hormone therapy. N. Engl. J. Med. 377:338–51
    [Google Scholar]
  20. 20.  Fizazi K, Tran N, Fein L et al. 2017. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N. Engl. J. Med. 377:352–60
    [Google Scholar]
  21. 21.  Mateo J, Carreira S, Sandhu S et al. 2015. DNA-repair defects and olaparib in metastatic prostate cancer. N. Engl. J. Med. 373:1697–708
    [Google Scholar]
  22. 22.  Eisenberger M, Hardy-Bessard AC, Kim CS et al. 2017. Phase III study comparing a reduced dose of cabazitaxel (20 mg/m2) and the currently approved dose (25 mg/m2) in postdocetaxel patients with metastatic castration-resistant prostate cancer—PROSELICA. J. Clin. Oncol. 35:3198–206
    [Google Scholar]
  23. 23.  Oudard S, Fizazi K, Sengelov L et al. 2017. Cabazitaxel versus docetaxel as first-line therapy for patients with metastatic castration-resistant prostate cancer: a randomized phase III trial—FIRSTANA. J. Clin. Oncol. 35:3189–97
    [Google Scholar]
  24. 24.  Antonarakis ES, Tagawa ST, Galletti G et al. 2017. Randomized, noncomparative, phase II trial of early switch from docetaxel to cabazitaxel or vice versa, with integrated biomarker analysis, in men with chemotherapy-naive, metastatic, castration-resistant prostate cancer. J. Clin. Oncol. 35:3181–88
    [Google Scholar]
  25. 25.  Attard G, Reid AH, Yap TA et al. 2008. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J. Clin. Oncol. 26:4563–71
    [Google Scholar]
  26. 26.  de Bono JS, Logothetis CJ, Molina A et al. 2011. Abiraterone and increased survival in metastatic prostate cancer. N. Engl. J. Med. 364:1995–2005
    [Google Scholar]
  27. 27.  Ryan CJ, Smith MR, de Bono JS et al. 2013. Abiraterone in metastatic prostate cancer without previous chemotherapy. N. Engl. J. Med. 368:138–48
    [Google Scholar]
  28. 28.  Ryan CJ, Smith MR, Fizazi K et al. 2015. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 16:152–60
    [Google Scholar]
  29. 29.  Tran C, Ouk S, Clegg NJ et al. 2009. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 324:787–90
    [Google Scholar]
  30. 30.  Collins C, Eary JF, Donaldson G et al. 1993. Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: a phase I/II trial. J. Nucl. Med. 34:1839–44
    [Google Scholar]
  31. 31.  Sartor O, Reid RH, Hoskin PJ et al. 2004. Samarium-153-lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology 63:940–45
    [Google Scholar]
  32. 32.  James ND, Pirrie SJ, Pope AM et al. 2016. Clinical outcomes and survival following treatment of metastatic castrate-refractory prostate cancer with docetaxel alone or with strontium-89, zoledronic acid, or both: the TRAPEZE randomized clinical trial. JAMA Oncol 2:493–99
    [Google Scholar]
  33. 33.  Oosterhof GO, Roberts JT, de Reijke TM et al. 2003. Strontium89 chloride versus palliative local field radiotherapy in patients with hormonal escaped prostate cancer: a phase III study of the European Organisation for Research and Treatment of Cancer, Genitourinary Group. Eur. Urol. 44:519–26
    [Google Scholar]
  34. 34.  Nilsson S, Franzen L, Parker C et al. 2007. Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study. Lancet Oncol 8:587–94
    [Google Scholar]
  35. 35.  Nilsson S, Strang P, Aksnes AK et al. 2012. A randomized, dose-response, multicenter phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostate cancer. Eur. J. Cancer 48:678–86
    [Google Scholar]
  36. 36.  Mirski D 2017. Xofigo® (radium Ra 223 dichloride): important safety information update regarding increased incidence of deaths and fractures in an investigational Phase III clinical trial with Xofigo used in combination with abiraterone acetate and prednisolone/prednisone Bayer Important Drug Warning. https://hcp.xofigo-us.com/downloads/pdf/PP-600-US-3282%20Xofigo%20November%202017%20DHCP%20Letter%20-%20Digital%20Version.pdf
    [Google Scholar]
  37. 37.  Small EJ, Schellhammer PF, Higano CS et al. 2006. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J. Clin. Oncol. 24:3089–94
    [Google Scholar]
  38. 38.  George DJ, Nabhan C, DeVries T et al. 2015. Survival outcomes of sipuleucel-T phase III studies: impact of control-arm cross-over to salvage immunotherapy. Cancer Immunol. Res. 3:1063–69
    [Google Scholar]
  39. 39.  Higano CS, Schellhammer PF, Small EJ et al. 2009. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer 115:3670–79
    [Google Scholar]
  40. 40.  Pritchard CC, Mateo J, Walsh MF et al. 2016. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N. Engl. J. Med. 375:443–53
    [Google Scholar]
  41. 41.  Abida W, Armenia J, Gopalan A et al. 2017. Prospective genomic profiling of prostate cancer across disease states reveals germline and somatic alterations that may affect clinical decision making. J. Clin. Oncol. Precision Oncol. https://doi.org/10.1200/PO.17.00029
    [Crossref] [Google Scholar]
  42. 42.  Beer TM, Kwon ED, Drake CG et al. 2017. Randomized, double-blind, phase III trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naive castration-resistant prostate cancer. J. Clin. Oncol. 35:40–47
    [Google Scholar]
  43. 43.  Kwon ED, Drake CG, Scher HI et al. 2014. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184–043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 15:700–12
    [Google Scholar]
  44. 44.  Topalian SL, Hodi FS, Brahmer JR et al. 2012. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366:2443–54
    [Google Scholar]
  45. 45.  Patnaik A, Kang SP, Rasco D et al. 2015. Phase I study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in patients with advanced solid tumors. Clin. Cancer Res. 21:4286–93
    [Google Scholar]
  46. 46.  Graff JN, Alumkal JJ, Drake CG et al. 2016. Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Oncotarget 7:52810–17
    [Google Scholar]
  47. 47.  De Bono JS, Goh JCH, Ojamaa K et al. 2018. KEYNOTE-199: Pembrolizumab (pembro) for docetaxel-refractory metastatic castration-resistant prostate cancer (mCRPC). J. Clin. Oncol. 36:Suppl. 155007
    [Google Scholar]
  48. 48.  Le DT, Durham JN, Smith KN et al. 2017. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357:409–13
    [Google Scholar]
  49. 49.  Pritchard CC, Morrissey C, Kumar A et al. 2014. Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer. Nat. Commun. 25:4988
    [Google Scholar]
  50. 50.  Abida W, Cheng ML, Amernia J et al. 2018. Microsatellite instability in prostate cancer and response to immune checkpoint blockade. J. Clin. Oncol. 36:5020
    [Google Scholar]
  51. 51.  Wu YM, Cieslik M, Lonigro RJ et al. 2018. Inactivation of CDK12 delineates a distinct immunogenic class of advanced prostate cancer. Cell 173:170–82
    [Google Scholar]
  52. 52.  Annala M, Vandekerkhove G, Khalaf D et al. 2018. Circulating tumor DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer. Cancer Discov 8:444–57
    [Google Scholar]
  53. 53.  Sundi D, Wang VM, Pierorazio PM et al. 2014. Very-high-risk localized prostate cancer: definition and outcomes. Prostate Cancer Prostatic. Dis. 17:57–63
    [Google Scholar]
  54. 54.  Antonarakis ES, Feng Z, Trock BJ et al. 2012. The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term follow-up. BJU Int 109:32–39
    [Google Scholar]
  55. 55.  Pound CR, Partin AW, Eisenberger MA et al. 1999. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 281:1591–97
    [Google Scholar]
  56. 56.  Crook JM, O'Callaghan CJ, Duncan G et al. 2012. Intermittent androgen suppression for rising PSA level after radiotherapy. N. Engl. J. Med. 367:895–903
    [Google Scholar]
  57. 57.  Smith MR, Saad F, Oudard S et al. 2013. Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time. J. Clin. Oncol. 31:3800–6
    [Google Scholar]
  58. 58.  Hussain M, Fizazi K, Saad F et al. 2018. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N. Engl. J. Med. 378:2465–74
    [Google Scholar]
  59. 59.  Xie W, Regan MM, Buyse M et al. 2017. Metastasis-free survival is a strong surrogate of overall survival in localized prostate cancer. J. Clin. Oncol. 35:3097–104
    [Google Scholar]
  60. 60.  Choline C 11 Injection [package insert]. Rochester, MN: Mayo Clinic 2012. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203155s000lbl.pdf
  61. 61.  AXUMIN (fluciclovine F 18) injection [package insert].. Oxford, UK: Blue Earth Diagnostics LTD 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208054s000lbl.pdf
  62. 62.  Sweeney CJ, Chen YH, Carducci M et al. 2015. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N. Engl. J. Med. 373:737–46
    [Google Scholar]
  63. 63.  Kyriakopoulos CE, Chen YH, Carducci MA et al. 2018. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J. Clin. Oncol. 36:1080–87
    [Google Scholar]
  64. 64.  James ND, Sydes MR, Clarke NW et al. 2016. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 387:1163–77
    [Google Scholar]
  65. 65.  Gravis G, Fizazi K, Joly F et al. 2013. Androgen-deprivation therapy alone or with docetaxel in noncastrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol 14:149–58
    [Google Scholar]
  66. 66.  Gravis G, Boher JM, Joly F et al. 2015. Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 trial. Eur. Urol. 70:256–62
    [Google Scholar]
  67. 67.  Sydes MR, Spears MR, Mason MD et al. 2018. Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol. Ann. Oncol. 29:1235–48
    [Google Scholar]
  68. 68.  Strimbu K, Tavel JA 2010. What are biomarkers?. Curr. Opin. HIV AIDS 5:463–66
    [Google Scholar]
  69. 69.  Antonarakis ES, Lu C, Wang H et al. 2014. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N. Engl. J. Med. 371:1028–38
    [Google Scholar]
  70. 70.  Antonarakis ES, Lu C, Luber B et al. 2015. Androgen receptor splice variant 7 and efficacy of taxane chemotherapy in patients with metastatic castration-resistant prostate cancer. JAMA Oncol 1:582–91
    [Google Scholar]
  71. 71.  Conteduca V, Wetterskog D, Sharabiani MTA et al. 2017. Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study. Ann. Oncol. 28:1508–16
    [Google Scholar]
  72. 72.  Hussain M, Daignault-Newton S, Twardowski PW et al. 2018. Targeting androgen receptor and DNA repair in metastatic castration-resistant prostate cancer: results from NCI 9012. J. Clin. Oncol. 36:991–99
    [Google Scholar]
  73. 73.  Annala M, Struss WJ, Warner EW et al. 2017. Treatment outcomes and tumor loss of heterozygosity in germline DNA repair-deficient prostate cancer. Eur. Urol. 72:34–42
    [Google Scholar]
  74. 74.  Robinson D, Van Allen EM, Wu YM et al. 2015. Integrative clinical genomics of advanced prostate cancer. Cell 161:1215–28
    [Google Scholar]
  75. 75.  Aus G, Robinson D, Rosell J, Sandblom G et al. 2005. Survival in prostate carcinoma—outcomes from a prospective, population-based cohort of 8887 men with up to 15 years of follow-up: results from three countries in the population-based National Prostate Cancer Registry of Sweden. Cancer 103:943–51
    [Google Scholar]
  76. 76.  Heidenreich A, Pfister D, Porres D 2015. Cytoreductive radical prostatectomy in patients with prostate cancer and low volume skeletal metastases: results of a feasibility and case-control study. J. Urol. 193:832–38
    [Google Scholar]
  77. 77.  Sooriakumaran P, Karnes J, Stief C et al. 2016. A multi-institutional analysis of perioperative outcomes in 106 men who underwent radical prostatectomy for distant metastatic prostate cancer at presentation. Eur. Urol. 69:788–94
    [Google Scholar]
  78. 78.  Antwi S, Everson TM 2014. Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: a population-based, propensity score analysis. Cancer Epidemiol 38:435–41
    [Google Scholar]
  79. 79.  Culp SH, Schellhammer PF, Williams MB 2014. Might men diagnosed with metastatic prostate cancer benefit from definitive treatment of the primary tumor? A SEER-based study. Eur. Urol. 65:1058–66
    [Google Scholar]
  80. 80.  Rusthoven CG, Jones BL, Flaig TW et al. 2016. Improved survival with prostate radiation in addition to androgen deprivation therapy for men with newly diagnosed metastatic prostate cancer. J. Clin. Oncol. 34:2835–42
    [Google Scholar]
  81. 81.  Perez-Lopez R, Lorente D, Blackledge MD et al. 2016. Volume of bone metastasis assessed with whole-body diffusion-weighted imaging is associated with overall survival in metastatic castration-resistant prostate cancer. Radiology 280:151–60
    [Google Scholar]
  82. 82.  Vargas HA, Wassberg C, Fox JJ et al. 2014. Bone metastases in castration-resistant prostate cancer: associations between morphologic CT patterns, glycolytic activity, and androgen receptor expression on PET and overall survival. Radiology 271:220–29
    [Google Scholar]
  83. 83.  Pasqualetti F, Panichi M, Sainato A et al. 2016. [18F]Choline PET/CT and stereotactic body radiotherapy on treatment decision making of oligometastatic prostate cancer patients: preliminary results. Radiat Oncol 11:9
    [Google Scholar]
  84. 84.  Decaestecker K, De Meerleer G, Lambert B et al. 2014. Repeated stereotactic body radiotherapy for oligometastatic prostate cancer recurrence. Radiat Oncol 9:135
    [Google Scholar]
  85. 85.  Ost P, Jereczek-Fossa BA, As NV et al. 2016. Progression-free survival following stereotactic body radiotherapy for oligometastatic prostate cancer treatment-naive recurrence: a multi-institutional analysis. Eur. Urol. 69:9–12
    [Google Scholar]
  86. 86.  Ost P, Reynders D, Decaestecker K et al. 2018. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, multicenter phase II trial. J. Clin. Oncol. 36:446–53
    [Google Scholar]
  87. 87.  O'Shaughnessy MJ, McBride SM, Vargas HA et al. 2016. A pilot study of a multimodal treatment paradigm to accelerate drug evaluations in early stage metastatic prostate cancer. Urology 102:164–72
    [Google Scholar]
/content/journals/10.1146/annurev-med-051517-011947
Loading
/content/journals/10.1146/annurev-med-051517-011947
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error