Prostate cancer – from hormonal dependency to castration resistant cancer
Authors:
L. Poláková; D. Pacík; A. Čermák
Published in:
Urol List 2014; 12(2): 29-39
Overview
This article focuses on prostate cancer in its most common form and presents a brief overview of its pathophysiology and diagnostics. The individual strategies of hormonal therapy and chemotherapy are outlined. It highlights the important role of androgen receptors in hormone dependent and resistant cancer treatment, taking into account the quality of life of the patient. For the sake of clarity also novel promising agents are presented, even though their application is currently limited to clinical research.
Key words:
prostate cancer, testosterone, hormonal therapy, hormonal resistance, chemotherapy, novel therapy options
Sources
1. ÚZIS ČR. Uroweb. Dostupné z: www.uroweb.cz.
2. McLeod DG, Iversen P, See WA et al. Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer. BJU Int 2006; 97(2): 247– 254.
3. Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer J Clin 1972; 22(4): 232– 240.
4. Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen‑ dependent growth. Eur Urol 2009; 55(2): 310– 320. doi: 10.1016/ j.eururo.2008.09.024.
5. Kawakami J, Cowan JE, Elkin EP et al. Androgen‑ deprivation therapy as primary treatment for localized prostate cancer: data from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). Cancer 2006; 106(8): 1708– 1714.
6. Studer UE, Whelan P, Albrecht W et al. Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891. J Clin Oncol 2006; 24(12): 1868– 1876.
7. Studer UE, Collette L, Whelan P et al. Which subgroups of patients with newly diagnosed T0– 4 N0– 2 M0 prostate cancer not suitable for local treatment with curative intent (EORTC 30891) are at risk to die from prostate cancer and benefit from immediate androgen deprivation? Eur Urol 2007; 6 (2 Suppl): 27.
8. Messing EM, Manola J, Yao J et al. Immediate versus deferred androgen deprivation treatment in patients with node‑ positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol 2006; 7(6): 472– 479.
9. Palapattu GS, Allaf ME, Trock BJ et al. Prostate specific antigen progression in men with lymph node metastases following radical prostatectomy: results of long‑term followup. J Urol 2004; 172(5 Pt 1): 1860– 1864.
10. Bolla M, Collette L, Blank L et al. Long‑term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet 2002; 360(9327): 103– 106.
11. Pilepich MV, Winter K, Lawton CA et al. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma – long‑term results of phase III RTOG 85– 31. Int J Radiat Oncol Biol Phys 2005; 61(5): 1285– 1290.
12. See WA, Tyrrell CJ. The addition of bicalutamide 150 mg to radiotherapy significantly improves overall survival in men with locally advanced prostate cancer. J Cancer Res Clin Oncol 2006; 132 (Suppl 1): S7– S16.
13. Bolla M, van Tienhoven G, de Reijke TM et al. Concomitant and adjuvant androgen deprivation (ADT) with external beam irradiation (RT) for locally advanced prostate cancer: 6 months versus 3 years ADT – Results of the randomized EORTC Phase III trial 22961. J Clin Oncol 2007; 25 (18 Suppl): 5014.
14. D’Amico AV, Manola J, Loffredo M et al. 6– month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial. JAMA 2004; 292(7): 821– 827.
15. Labrie F, Dupont A, Belanger A. Complete androgen blockade for the treatment of prostate cancer. Important Adv Oncol 1985: 193– 217.
16. Iversen P, Tyrrell CJ, Kaisary AV et al. Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of followup. J Urol 2000; 164(5): 1579– 1582.
17. Nyman CR, Andersen JT, Lodding P et al. The patient’s choice of androgen‑ deprivation therapy in locally advanced prostate cancer: bicalutamide, a gonadotrophin‑releasing hormone analogue or orchidectomy. BJU Int 2005; 96(7): 1014– 1018.
18. Prostate Cancer Trialists’ Collaborative Group. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet 2000; 355(9214): 1491– 1498.
19. Klotz L, Schellhammer P, Carroll K. A re‑assessment of the role of combined androgen blockade for advanced prostate cancer. BJU Int 2004; 93(9): 1177– 1182.
20. Thorpe SC, Azmatullah S, Fellows GJ et al. A prospective, randomised study to compare goserelin acetate (Zoladex) versus cyproterone acetate (Cyprostat) versus a combination of the two in the treatment of metastatic prostatic carcinoma. Eur Urol 1996; 29(1): 47– 54.
21. Iversen P, Tyrrell CJ, Kaisary AV et al. Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer: results from two multicenter randomized trials at a median follow‑up of 4 years. Urology 1998; 51(3): 389– 396.
22. Smith MR, Fallon MA, Goode MJ. Cross‑ sectional study of bone turnover during bicalutamide monotherapy for prostate cancer. Urology 2003; 61(1): 127– 131.
23. Smith MR, Goode M, Zietman AL et al. Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: effects on bone mineral density and body composition. J Clin Oncol 2004; 22(13): 2546– 2553.
24. Bhandari MS, Crook J, Hussain M. Should intermittent androgen deprivation be used in routine clinical practice? J Clin Oncol 2005; 23(32): 8212– 8218.
25. Calais da Silva FE, Calais da Silva F, Gonçalves F et al. Phase III study of intermittent monotherapy versus continuous combined androgen deprivation. J Clin Oncol 2007; 25 (18 Suppl): A5125.
26. Alibhai SM, Gogov S, Allibhai Z. Long‑term side effects of androgen deprivation therapy in men with non‑metastatic prostate cancer: a systematic literature review. Crit Rev Oncol Hematol 2006; 60(3): 201– 215.
27. Braga‑ Basaria M, Dobs AS, Muller DC et al. Metabolic syndrome in men with prostate cancer undergoing long‑term androgen‑ deprivation therapy. J Clin Oncol 2006; 24(24): 3979– 3983.
28. Keating NL, O’Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 2006; 24(27): 4448– 4456.
29. D’Amico AV, Chen MH, Renshaw AA et al. Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA 2008; 299(3): 289– 295. doi: 10.1001/ jama.299.3.289.
30. Efstathiou J, Bae K, Shipley W et al. Cardiovascular mortality following androgen deprivation therapy for locally advanced prostate cancer: Analysis of RTOG 85– 31. Proceedings of Genitourinary Cancers Symposium 2008; (A11): 101.
31. Allain TJ. Prostate cancer, osteoporosis and fracture risk. Gerontology 2006; 52(2): 107– 110.
32. Smith MR, Lee WC, Brandman J et al. Gonadotropin‑releasing hormone agonists and fracture risk: a claims‑based cohort study of men with nonmetastatic prostate cancer. J Clin Oncol 2005; 23(31): 7897– 7903.
33. Holmes‑ Walker DJ, Woo H, Gurney H et al. Maintaining bone health in patients with prostate cancer. Med J Aust 2006; 184(4): 176– 179.
34. Aucoin MW, Wassersug RJ. The sexuality and social performance of androgen‑ deprived (castrated) men throughout history: implications for modern day cancer patients. Soc Sci Med 2006; 63(12): 3162– 3173.
35. Aubert J, Vigouroux V, Doré B. Hot flushes in men after surgical or pharmacologic castration. Prog Urol 1995; 5(4): 507– 509.
36. Gomella LG. Contemporary use of hormonal therapy in prostate cancer: managing complications and addressing quality‑ of‑life issues. BJU Int 2007; 99 (Suppl 1): 25– 29; discussion: 30.
37. Moyad MA. Promoting general health during androgen deprivation therapy (ADT): a rapid 10– step review for your patients. Urol Oncol 2005; 23(1): 56– 64.
38. Alibhai SM, Mohamedali HZ, Gulamhusein H et al. Changes in bone mineral density in men starting androgen deprivation therapy and the protective role of vitamin D. Osteoporos Int 2013; 24(10): 2571– 2579. doi: 10.1007/ s00198‑ 013‑ 2343‑ 4.
39. Botrel TE, Clark O, dos Reis RB et al. Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta‑analysis. BMC Urol 2014; 14: 9. doi: 10.1186/ /1471‑ 2490‑ 14‑ 9.
40. Kratiras Z, Konstantinidis C, Skriapas K. A review of continuous vs intermittent androgen deprivation therapy: redefining the gold standard in the treatment of advanced prostate cancer. Myths, facts and new data on a “perpetual dispute“. Int Braz J Urol 2014; 40(1): 3– 15; discussion: 15. doi: 10.1590/ S1677‑ 5538.IBJU.2014.01.02.
41. Sharifi N, Dahut WL, Steinberg SM et al. A retrospective study of the time to clinical endpoints for advanced prostate cancer. BJU Int 2005; 96(7): 985– 989.
42. Hotte SJ, Saad F. Current management of castrate‑resistant prostate cancer. Current Oncol 2010; 17 (Suppl 2): S72– S79.
43. Mohler JL, Gregory CW, Ford OH 3rd et al. The androgen axis in recurrent prostate cancer. Clin Cancer Res 2004; 10(2): 440– 448.
44. Mostaghel EA, Page ST, Lin DW et al. Intraprostatic androgens and androgen‑ regulated gene expression persist after testosterone suppression: therapeutic implications for castration‑resistant prostate cancer. Cancer Res 2007; 67(10): 5033– 5041.
45. Fossa SD, Slee PH, Brausi M et al. Flutamide versus prednisone in patients with prostate cancer symptomatically progressing after androgen‑ ablative therapy: a phase III study of the European organization for research and treatment of cancer genitourinary group. J Clin Oncol 2001; 19(1): 62– 71.
46. Knudsen KE, Scher HI. Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clin Cancer Res 2009; 15(15): 4792– 4798. doi: 10.1158/ 1078‑ 0432.CCR‑ 08‑ 2660.
47. Petrylak DP, Tangen CM, Hussain MH et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004; 351(15): 1513– 1520.
48. Tannock IF, de Wit R, Berry WR et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004; 351(15): 1502– 1512.
49. Winquist E, Waldron T, Berry S et al. Non‑ hormonal systemic therapy in men with hormone‑ refractory prostate cancer and metastases: a systematic review from the Cancer Care Ontario Program in Evidence‑based Care‘s Genitourinary Cancer Disease Site Group. BMC Cancer 2006; 6: 112.
50. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. [online]. Available from: www.nccn.org/ professionals/ / physician_gls/ PDF/ prostate.pdf.
51. De Bono JS, Oudard S, Ozguroglu M et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration‑resistant prostate cancer progressing after docetaxel treatment: a randomised open‑ label trial. Lancet 2010; 376(9747): 1147– 1154. doi: 10.1016/ S0140‑ -6736(10)61389‑ X.
52. Zhu W, Zhu DS, Madan RA et al. Treatment of castration‑resistant prostate cancer: updates on therapeutics targeting the androgen receptor signaling pathway. Am J Ther 2010; 17(2): 176– 181. doi: 10.1097/ MJT.0b013e3181c6c0b2.
53. Sciarra A, Cardi A, Di Silverio F. Antiandrogen monotherapy: recommendations for the treatment of prostate cancer. Urol Int 2004; 72(2): 91– 98.
54. Cox RL, Crawford ED. Estrogens in the treatment of prostate cancer. J Urol 1995; 154(6): 1991– 1998.
55. Potter GA, Barrie SE, Jarman M et al. Novel steroidal inhibitors of human cytochrome P45017 alpha (17 alpha‑ hydroxylase‑ C17,20– lyase): potential agents for the treatment of prostatic cancer. J Med Chem 1995; 38(13): 2463– 2471.
56. Barrie SE, Potter GA, Goddard PM et al. Pharmacology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha‑ hydroxylase/ C17– 20 lyase). J Steroid Biochem Mol Biol 1994; 50(5– 6): 267– 273.
57. Attard G, Reid AH, A‘Hern R et al. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration‑resistant prostate cancer. J Clin Oncol 2009; 27(23): 3742– 3748. doi: 10.1200/ JCO.2008.20.0642.
58. Danila DC, Morris MJ, de Bono JS et al. Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel‑treated castration‑resistant prostate cancer. J Clin Oncol 2010; 28(9): 1496– 1501. doi: 10.1200/ JCO.2009.25.9259.
59. Ryan CJ, Smith MR, Fong L et al. Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration‑resistant prostate cancer who received prior ketoconazole therapy. J Clin Oncol 2010; 28(9): 1481– 1488. doi: 10.1200/ JCO.2009.24.1281.
60. Saad F, de Bono JS, Haqq CM et al. Abiraterone acetate plus low‑dose prednisone has a favorable safety profile, improves survival and produces PSA a radiographic responses in metastatic castration‑resistant prostate cancer progressing after docetaxel‑based chemotherapy: results from COU‑ AA‑ 301, a randomized, double‑blind, placebo‑ controlled, phase III study. J Urol 2011; 185: e283.
61. Tran C, Ouk S, Clegg NJ et al. Development of a second‑ generation antiandrogen for treatment of advanced prostate cancer. Science 2009; 324(5928): 787– 790. doi: 10.1126/ science.1168175.
62. Scher HI, Beer TM, Higano CS et al. Antitumour activity of MDV3100 in castration‑resistant prostate cancer: a phase 1– 2 study. Lancet 2010; 375(9724): 1437– 1446. doi: 10.1016/ S0140‑- 6736(10)60172‑ 9.
63. George DJ, Halabi S, Shepard TF et al. Prognostic significance of plasma vascular endothelial growth factor levels in patients with hormone‑ refractory prostate cancer treated on Cancer and Leukemia Group B 9480. Clin Cancer Res 2001; 7(7): 1932– 1936.
64. Melnyk O, Zimmerman M, Kim KJ et al. Neutralizing anti‑vascular endothelial growth factor antibody inhibits further growth of established prostate cancer and metastases in a pre‑clinical model. J Urol 1999; 161(3): 960– 963.
65. Picus J, Halabi S, Kelly WK et al. A phase 2 study of estramustine, docetaxel, and bevacizumab in men with castrate‑resistant prostate cancer: results from Cancer and Leukemia Group B Study 90006. Cancer 2011; 117(3): 526– 533. doi: 10.1002/cncr.25421.
66. Kelly WK, Halabi S, Carducci MA et al. A randomized, double‑blind, placebo‑ controlled phase III trial comparing docetaxel, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with metastatic castration‑resistant prostate cancer (mCRPC): Survival results of CALGB 90401. J Clin Oncol 2010; 28: LBA4511.
67. Verheul HM, Hammers H, van Erp K et al. Vascular endothelial growth factor trap blocks tumor growth, metastasis formation, and vascular leakage in an orthotopic murine renal cell cancer model. Clin Cancer Res 2007; 13(14): 4201– 4208.
68. Tannock IF, Fizazi K, Ivanov S et al. Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration‑resistant prostate cancer (VENICE): a phase 3, double‑blind randomised trial. Lancet Oncol 2013; 14(8): 760– 768. doi: 10.1016/ S1470‑ 2045(13)70184‑ 0.
69. Kantoff PW, Higano CS, Shore ND et al. Sipuleucel‑ T immunotherapy for castration‑resistant prostate cancer. N Engl J Med 2010; 363(5): 411– 422. doi: 10.1056/ NEJMoa1001294.
70. Small EJ, Schellhammer PF, Higano CS et al. Placebo‑ controlled phase III trial of immunologic therapy with sipuleucel‑ T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 2006; 24(19): 3089– 3094.
71. Higano CS, Schellhammer PF, Small EJ et al. Integrated data from 2 randomized, double‑blind, placebo‑ controlled, phase 3 trials of active cellular immunotherapy with sipuleucel‑ T in advanced prostate cancer. Cancer 2009; 115(16): 3670– 3679. doi: 10.1002/ cncr.24429.
72. Madan RA, Arlen PM, Mohebtash M et al. Prostvac‑ VF: a vector‑based vaccine targeting PSA in prostate cancer. Expert Opin Investig Drugs 2009; 18(7): 1001– 1011. doi: 10.1517//13543780902997928.
73. Kantoff PW, Schuetz TJ, Blumenstein BA et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral‑based PSA‑ targeted immunotherapy in metastatic castration‑resistant prostate cancer. J Clin Oncol 2010; 28(7): 1099– 1105. doi: 10.1200/ JCO.2009.25.0597.
74. Antonarakis ES, Carducci MA, Eisenberger MA. Novel targeted therapeutics for metastatic castration‑resistant prostate cancer. Cancer Lett 2010; 291(1): 1– 13. doi: 10.1016/ j.canlet.2009.08.012.
75. Weinfurt KP, Li Y, Castel LD et al. The significance of skeletal‑related events for the health‑related quality of life of patients with metastatic prostate cancer. Ann Oncol 2005; 16(4): 579– 584.
76. Diamond TH, Higano CS, Smith MR et al. Osteoporosis in men with prostate carcinoma receiving androgen‑ deprivation therapy: recommendations for diagnosis and therapies. Cancer 2004; 100(5): 892– 899.
77. Preston DM, Torrens JI, Harding P et al. Androgen deprivation in men with prostate cancer is associated with an increased rate of bone loss. Prostate Cancer Prostatic Dis 2002; 5(4): 304– 310.
78. Smith MR, McGovern FJ, Zietman AL et al. Pamidronate to prevent bone loss during androgen‑ deprivation therapy for prostate cancer. N Engl J Med 2001; 345(13): 948– 955.
79. Smith MR, Eastham J, Gleason DM et al. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol 2003; 169(6): 2008– 2012.
80. Saad F, Gleason DM, Murray R et al. Long‑term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone‑ refractory prostate cancer. J Natl Cancer Inst 2004; 96(11): 879– 882.
81. Ullén A, Lennartsson L, Harmenberg U et al. Additive/ synergistic antitumoral effects on prostate cancer cells in vitro following treatment with a combination of docetaxel and zoledronic acid. Acta Oncol 2005; 44(6): 644– 650.
82. Boyce BF, Xing L. Functions of RANKL/ RANK/ OPG in bone modeling and remodeling. Arch Biochem Biophys 2008; 473(2): 139– 146. doi: 10.1016/ j.abb.2008.03.018.
83. Fizazi K, Carducci M, Smith M et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration‑resistant prostate cancer: a randomised, double‑blind study. Lancet 2011; 377(9768): 813– 822. doi: 10.1016/ S0140‑ 6736(10)62344‑ 6.
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