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Management Options for Biochemically Recurrent Prostate Cancer

  • Genitourinary Cancers (W Oh and M Galsky, Section Editors)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Prostate cancer is the most common solid tumor malignancy in men worldwide. Treatment with surgery and radiation can be curative in organ-confined disease. Unfortunately, about one third of men develop biochemically recurrent disease based only on rising prostate-specific antigen (PSA) in the absence of visible disease on conventional imaging. For these patients with biochemical recurrent prostate cancer, there is no uniform guideline for subsequent management. Based on available data, it seems prudent that biochemical recurrent prostate cancer should initially be evaluated for salvage radiation or prostatectomy, with curative intent. In selected cases, high-intensity focused ultrasound and cryotherapy may be considered in patients that meet very narrow criteria as defined by non-randomized trials. If salvage options are not practical or unsuccessful, androgen deprivation therapy (ADT) is a standard option for disease control. While some patients prefer ADT to manage the disease immediately, others defer treatment because of the associated toxicity. In the absence of definitive randomized data, patients may be followed using PSA doubling time as a trigger to initiate ADT. Based on retrospective data, a PSA doubling time of less than 3–6 months has been associated with near-term development of metastasis and thus could be used signal to initiate ADT. Once treatment is begun, patients and their providers can choose between an intermittent and continuous ADT strategy. The intermittent approach may limit side effects but in patients with metastatic disease studies could not exclude a 20% greater risk of death. In men with biochemical recurrence, large studies have shown that intermittent therapy is non-inferior to continuous therapy, thus making this a reasonable option. Since biochemically recurrent prostate cancer is defined by technological limitations of radiographic detection, as new imaging (i.e., PSMA) strategies are developed, it may alter how the disease is monitored and perhaps managed. Furthermore, patients have no symptoms related to their disease and thus many prefer options that minimize toxicity. For this reason, herbal agents and immunotherapy are under investigation as potential alternatives to ADT and its accompanying side effects. New therapeutic options combined with improved imaging to evaluate the disease may markedly change how biochemically recurrent prostate cancer is managed in the future.

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References and Recommended Readings

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  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30. doi:10.3322/caac.21332.

    Article  PubMed  Google Scholar 

  2. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212–36. doi:10.3322/caac.20121.

    Article  PubMed  Google Scholar 

  3. Amling CL, Blute ML, Bergstralh EJ, Seay TM, Slezak J, Zincke H. Long-term hazard of progression after radical prostatectomy for clinically localized prostate cancer: continued risk of biochemical failure after 5 years. J Urol. 2000;164(1):101–5.

    Article  CAS  PubMed  Google Scholar 

  4. Billis A, Magna LA, Lira MM, Moreira LR, Okamura H, Paz AR, et al. Relationship of age to outcome and clinicopathologic findings in men submitted to radical prostatectomy. International braz j urol: official journal of the Brazilian Society of Urology. 2005;31(6):534–9. discussion 9-40

    Article  Google Scholar 

  5. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281(17):1591–7.

    Article  CAS  PubMed  Google Scholar 

  6. Bruce JY, Lang JM, McNeel DG, Liu G. Current controversies in the management of biochemical failure in prostate cancer. Clinical advances in hematology & oncology: H&O. 2012;10(11):716–22.

    Google Scholar 

  7. Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC, et al. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA. 2005;294(4):433–9. doi:10.1001/jama.294.4.433.

    Article  CAS  PubMed  Google Scholar 

  8. Roehl KA, Han M, Ramos CG, Antenor JA, Catalona WJ. Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3,478 consecutive patients: long-term results. J Urol. 2004;172(3):910–4. doi:10.1097/01.ju.0000134888.22332.bb.

    Article  PubMed  Google Scholar 

  9. Kupelian PA, Mahadevan A, Reddy CA, Reuther AM, Klein EA. Use of different definitions of biochemical failure after external beam radiotherapy changes conclusions about relative treatment efficacy for localized prostate cancer. Urology. 2006;68(3):593–8. doi:10.1016/j.urology.2006.03.075.

    Article  PubMed  Google Scholar 

  10. Thompson IM, Valicenti RK, Albertsen P, Davis BJ, Goldenberg SL, Hahn C, et al. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO Guideline. J Urol. 2013;190(2):441–9. doi:10.1016/j.juro.2013.05.032.

    Article  PubMed  Google Scholar 

  11. Roach 3rd M, Hanks G, Thames Jr H, Schellhammer P, Shipley WU, Sokol GH, et al. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix consensus conference. Int J Radiat Oncol Biol Phys. 2006;65(4):965–74. doi:10.1016/j.ijrobp.2006.04.029.

    Article  PubMed  Google Scholar 

  12. Bolla M, Van Tienhoven G, Warde P, Dubois JB, Mirimanoff RO, Storme G, et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. The Lancet Oncology. 2010;11(11):1066–73. doi:10.1016/s1470-2045(10)70223-0.

    Article  CAS  PubMed  Google Scholar 

  13. Zagars GK, Pollack A. Kinetics of serum prostate-specific antigen after external beam radiation for clinically localized prostate cancer. Radiotherapy and oncology: journal of the European Society for Therapeutic Radiology and Oncology. 1997;44(3):213–21.

    Article  CAS  Google Scholar 

  14. Chade DC, Eastham J, Graefen M, Hu JC, Karnes RJ, Klotz L, et al. Cancer control and functional outcomes of salvage radical prostatectomy for radiation-recurrent prostate cancer: a systematic review of the literature. Eur Urol. 2012;61(5):961–71. doi:10.1016/j.eururo.2012.01.022. Large systematic review in salvage radical prostatectomy literature.

    Article  PubMed  Google Scholar 

  15. Lerner SE, Blute ML, Zincke H. Critical evaluation of salvage surgery for radio-recurrent/resistant prostate cancer. J Urol. 1995;154(3):1103–9.

    Article  CAS  PubMed  Google Scholar 

  16. Yuh B, Ruel N, Muldrew S, Mejia R, Novara G, Kawachi M, et al. Complications and outcomes of salvage robot-assisted radical prostatectomy: a single-institution experience. BJU Int. 2014;113(5):769–76. doi:10.1111/bju.12595.

    Article  PubMed  Google Scholar 

  17. van den Bos W, Muller BG, de Bruin DM, de Castro Abreu AL, Chaussy C, Coleman JA, et al. Salvage ablative therapy in prostate cancer: international multidisciplinary consensus on trial design. Urol Oncol. 2015;33(11):495.e1–7. doi:10.1016/j.urolonc.2015.06.015.

    Article  Google Scholar 

  18. Pearce SM, Richards KA, Patel SG, Pariser JJ, Eggener SE. Population-based analysis of salvage radical prostatectomy with examination of factors associated with adverse perioperative outcomes. Urol Oncol. 2015;33(4):163.e1–6. doi:10.1016/j.urolonc.2015.01.016.

    Article  Google Scholar 

  19. Pokala N, Huynh DL, Henderson AA, Johans C. Survival outcomes in men undergoing radical prostatectomy after primary radiation treatment for adenocarcinoma of the prostate. Clinical genitourinary cancer. 2016;14(3):218–25. doi:10.1016/j.clgc.2015.12.010. Large SEERs data analysis in salvage radical prostatectomy.

    Article  PubMed  Google Scholar 

  20. Matei DV, Ferro M, Jereczek-Fossa BA, Renne G, Crisan N, Bottero D, et al. Salvage radical prostatectomy after external beam radiation therapy: a systematic review of current approaches. Urol Int. 2015;94(4):373–82. doi:10.1159/000371893.

    Article  PubMed  Google Scholar 

  21. Warde P, Mason M, Ding K, Kirkbride P, Brundage M, Cowan R, et al. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet. 2011;378(9809):2104–11. doi:10.1016/S0140-6736(11)61095-7. Large phase III randomized clinical trial showing OS benefit with adding local therapy with RT to ADT in locally advanced prostate cancer.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Widmark A, Klepp O, Solberg A, Damber JE, Angelsen A, Fransson P, et al. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet. 2009;373(9660):301–8. doi:10.1016/S0140-6736(08)61815-2.

    Article  CAS  PubMed  Google Scholar 

  23. Stephenson AJ, Shariat SF, Zelefsky MJ, Kattan MW, Butler EB, Teh BS, et al. Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy. JAMA. 2004;291(11):1325–32. doi:10.1001/jama.291.11.1325.

    Article  CAS  PubMed  Google Scholar 

  24. Trock BJ, Han M, Freedland SJ, Humphreys EB, DeWeese TL, Partin AW, et al. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA. 2008;299(23):2760–9. doi:10.1001/jama.299.23.2760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Shipley WU, Seiferheld W, Lukka HR, Major PP, Heney NM, Grignon DJ, et al. Radiation with or without antiandrogen therapy in recurrent prostate cancer. N Engl J Med. 2017;376(5):417–28. doi:10.1056/NEJMoa1607529.

    Article  PubMed  Google Scholar 

  26. Chin JL, Pautler SE, Mouraviev V, Touma N, Moore K, Downey DB. Results of salvage cryoablation of the prostate after radiation: identifying predictors of treatment failure and complications. J Urol. 2001;165(6 Pt 1):1937–41. discussion 41-2

    CAS  PubMed  Google Scholar 

  27. Pisters LL, von Eschenbach AC, Scott SM, Swanson DA, Dinney CP, Pettaway CA, et al. The efficacy and complications of salvage cryotherapy of the prostate. J Urol. 1997;157(3):921–5.

    Article  CAS  PubMed  Google Scholar 

  28. Ismail M, Ahmed S, Kastner C, Davies J. Salvage cryotherapy for recurrent prostate cancer after radiation failure: a prospective case series of the first 100 patients. BJU Int. 2007;100(4):760–4. doi:10.1111/j.1464-410X.2007.07045.x.

    Article  PubMed  Google Scholar 

  29. Izawa JI, Madsen LT, Scott SM, Tran JP, McGuire EJ, Von Eschenbach AC, et al. Salvage cryotherapy for recurrent prostate cancer after radiotherapy: variables affecting patient outcome. J Clin Oncol Off J Am Soc Clin Oncol. 2002;20(11):2664–71.

    Article  Google Scholar 

  30. Bahn DK, Lee F, Silverman P, Bahn E, Badalament R, Kumar A, et al. Salvage cryosurgery for recurrent prostate cancer after radiation therapy: a seven-year follow-up. Clinical prostate cancer. 2003;2(2):111–4.

    Article  PubMed  Google Scholar 

  31. Benoit RM, Cohen JK, Miller Jr RJ. Cryosurgery for prostate cancer: new technology and indications. Current urology reports. 2000;1(1):41–7.

    Article  CAS  PubMed  Google Scholar 

  32. Donnelly BJ, Saliken JC, Ernst DS, Weber B, Robinson JW, Brasher PM, et al. Role of transrectal ultrasound guided salvage cryosurgery for recurrent prostate carcinoma after radiotherapy. Prostate Cancer Prostatic Dis. 2005;8(3):235–42. doi:10.1038/sj.pcan.4500811.

    Article  CAS  PubMed  Google Scholar 

  33. Ghafar MA, Johnson CW, De La Taille A, Benson MC, Bagiella E, Fatal M, et al. Salvage cryotherapy using an argon based system for locally recurrent prostate cancer after radiation therapy: the Columbia experience. J Urol. 2001;166(4):1333–7. discussion 7-8

    Article  CAS  PubMed  Google Scholar 

  34. Pisters LL, Rewcastle JC, Donnelly BJ, Lugnani FM, Katz AE, Jones JS. Salvage prostate cryoablation: initial results from the cryo on-line data registry. J Urol. 2008;180(2):559–63. discussion 63-4 doi:10.1016/j.juro.2008.04.005.

    Article  PubMed  Google Scholar 

  35. Zacharakis E, Ahmed HU, Ishaq A, Scott R, Illing R, Freeman A, et al. The feasibility and safety of high-intensity focused ultrasound as salvage therapy for recurrent prostate cancer following external beam radiotherapy. BJU Int. 2008;102(7):786–92. doi:10.1111/j.1464-410X.2008.07775.x.

    Article  PubMed  Google Scholar 

  36. de Castro Abreu AL, Bahn D, Leslie S, Shoji S, Silverman P, Desai MM, et al. Salvage focal and salvage total cryoablation for locally recurrent prostate cancer after primary radiation therapy. BJU Int. 2013;112(3):298–307. doi:10.1111/bju.12151. A study that directly compared focal therapy to whole gland salvage cryotherapy.

    Article  PubMed  Google Scholar 

  37. Messing EM, Manola J, Yao J, Kiernan M, Crawford D, Wilding G, 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):472–9. doi:10.1016/S1470-2045(06)70700-8.

    Article  CAS  PubMed  Google Scholar 

  38. Duchesne GM, Woo HH, Bassett JK, Bowe SJ, D’Este C, Frydenberg M, et al. Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial. The Lancet Oncology. 2016;17(6):727–37. doi:10.1016/s1470-2045(16)00107-8. First and the only phase III trial that investigated the timing of ADT with subgroup of patients with BCR prostate cancer.

    Article  CAS  PubMed  Google Scholar 

  39. Antonarakis ES, Chen Y, Elsamanoudi SI, Brassell SA, Da Rocha MV, Eisenberger MA, et al. Long-term overall survival and metastasis-free survival for men with prostate-specific antigen-recurrent prostate cancer after prostatectomy: analysis of the Center for Prostate Disease Research National Database. BJU Int. 2011;108(3):378–85. doi:10.1111/j.1464-410X.2010.09878.x.

    Article  PubMed  Google Scholar 

  40. Antonarakis ES, Feng Z, Trock BJ, Humphreys EB, Carducci MA, Partin AW, et al. The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term follow-up. BJU Int. 2012;109(1):32–9. doi:10.1111/j.1464-410X.2011.10422.x. OS and MFS retrospective data in BCRPC post prostatectomy based on the PSADT.

    Article  CAS  PubMed  Google Scholar 

  41. Keizman D, Huang P, Antonarakis ES, Sinibaldi V, Carducci MA, Denmeade S, et al. The change of PSA doubling time and its association with disease progression in patients with biochemically relapsed prostate cancer treated with intermittent androgen deprivation. Prostate. 2011;71(15):1608–15. doi:10.1002/pros.21377.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Antonarakis ES, Zahurak ML, Lin J, Keizman D, Carducci MA, Eisenberger MA. Changes in PSA kinetics predict metastasis- free survival in men with PSA-recurrent prostate cancer treated with nonhormonal agents: combined analysis of 4 phase II trials. Cancer. 2012;118(6):1533–42. doi:10.1002/cncr.26437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kim-Sing C, Pickles T. Intervention after PSA failure: examination of intervention time and subsequent outcomes from a prospective patient database. Int J Radiat Oncol Biol Phys. 2004;60(2):463–9. doi:10.1016/j.ijrobp.2004.03.004.

    Article  PubMed  Google Scholar 

  44. Okotie OT, Aronson WJ, Wieder JA, Liao Y, Dorey F, De KJ, et al. Predictors of metastatic disease in men with biochemical failure following radical prostatectomy. J Urol. 2004;171(6 Pt 1):2260–4.

    Article  PubMed  Google Scholar 

  45. Patel A, Dorey F, Franklin J. deKernion JB. Recurrence patterns after radical retropubic prostatectomy: clinical usefulness of prostate specific antigen doubling times and log slope prostate specific antigen. J Urol. 1997;158(4):1441–5.

    Article  CAS  PubMed  Google Scholar 

  46. Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC, et al. Death in patients with recurrent prostate cancer after radical prostatectomy: prostate-specific antigen doubling time subgroups and their associated contributions to all-cause mortality. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25(13):1765–71. doi:10.1200/jco.2006.08.0572.

    Article  Google Scholar 

  47. D’Amico AV, Cote K, Loffredo M, Renshaw AA, Schultz D. Determinants of prostate cancer specific survival following radiation therapy during the prostate specific antigen era. J Urol. 2003;170(6 Pt 2):S42–6. discussion S6-7 doi:10.1097/01.ju.0000094800.63501.15.

    Article  PubMed  Google Scholar 

  48. D’Amico AV, Moul JW, Carroll PR, Sun L, Lubeck D, Chen MH. Surrogate end point for prostate cancer-specific mortality after radical prostatectomy or radiation therapy. J Natl Cancer Inst. 2003;95(18):1376–83.

    Article  PubMed  Google Scholar 

  49. Hanlon AL, Diratzouian H, Hanks GE. Posttreatment prostate-specific antigen nadir highly predictive of distant failure and death from prostate cancer. Int J Radiat Oncol Biol Phys. 2002;53(2):297–303.

    Article  PubMed  Google Scholar 

  50. Buyyounouski MK, Hanlon AL, Horwitz EM, Pollack A. Interval to biochemical failure highly prognostic for distant metastasis and prostate cancer-specific mortality after radiotherapy. Int J Radiat Oncol Biol Phys. 2008;70(1):59–66. doi:10.1016/j.ijrobp.2007.05.047.

    Article  CAS  PubMed  Google Scholar 

  51. Crook JM, O’Callaghan CJ, Duncan G, Dearnaley DP, Higano CS, Horwitz EM, et al. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med. 2012;367(10):895–903. doi:10.1056/NEJMoa1201546. The only large randomized phase III trials comparing intermittent vs continuous ADT, in biochemical recurrent prostate cancer patients.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–22. doi:10.1056/NEJMoa1001294.

    Article  CAS  PubMed  Google Scholar 

  53. Emmanuel S. Antonarakis ASK, George Adams, Lawrence Ivan Karsh, Aymen Elfiky, Neal D. Shore, Nicholas J. Vogelzang, John M. Corman, Robert Claude Tyler, Candice McCoy, Yang Wang, Nadeem A. Sheikh, Charles G. Drake; A randomized phase II study evaluating the optimal sequencing of sipuleucel-T and androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC): immune results. ASCO anual meeting; 2013; Chicago: J Clin Oncol p. suppl; abstr 5016.

  54. DiPaola RS, Chen YH, Bubley GJ, Stein MN, Hahn NM, Carducci MA, et al. A national multicenter phase 2 study of prostate-specific antigen (PSA) pox virus vaccine with sequential androgen ablation therapy in patients with PSA progression: ECOG 9802. Eur Urol. 2015;68(3):365–71. doi:10.1016/j.eururo.2014.12.010.

    Article  CAS  PubMed  Google Scholar 

  55. Pantuck AJ, Pettaway CA, Dreicer R, Corman J, Katz A, Ho A, et al. A randomized, double-blind, placebo-controlled study of the effects of pomegranate extract on rising PSA levels in men following primary therapy for prostate cancer. Prostate Cancer Prostatic Dis. 2015;18(3):242–8. doi:10.1038/pcan.2015.32.

    Article  CAS  PubMed  Google Scholar 

  56. Paller CJ, Ye X, Wozniak PJ, Gillespie BK, Sieber PR, Greengold RH, et al. A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer. Prostate Cancer Prostatic Dis. 2013;16(1):50–5. doi:10.1038/pcan.2012.20. First placebo controlled randomized double blinde study of pomegranate extract.

    Article  CAS  PubMed  Google Scholar 

  57. Kessler ER Su L-J, Yang X, Lu X, Morales D, Anduha M, Chronister Nicole, Wacker Michael, Thomas W. Flaig, Michael Glode L and Elaine Tat Lam. Phase II trial of acai juice product in biochemically recurrent prostate cancer. Genitourinary Cancers Symposium; February 20. J Clin Oncol. 2013. p. 230.

  58. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995–2005. doi:10.1056/NEJMoa1014618.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. The Lancet Oncology. 2012;13(10):983–92. doi:10.1016/s1470-2045(12)70379-0.

    Article  CAS  PubMed  Google Scholar 

  60. Logothetis CJ, Basch E, Molina A, Fizazi K, North SA, Chi KN, 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. The Lancet Oncology. 2012;13(12):1210–7. doi:10.1016/s1470-2045(12)70473-4.

    Article  CAS  PubMed  Google Scholar 

  61. Rathkopf DE, Smith MR, de Bono JS, Logothetis CJ, Shore ND, de Souza P, et al. Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302). Eur Urol. 2014;66(5):815–25. doi:10.1016/j.eururo.2014.02.056.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, et al. 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. The Lancet Oncology. 2015;16(2):152–60. doi:10.1016/s1470-2045(14)71205-7.

    Article  CAS  PubMed  Google Scholar 

  63. Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371(5):424–33. doi:10.1056/NEJMoa1405095.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Loriot Y, Miller K, Sternberg CN, Fizazi K, De Bono JS, Chowdhury S, et al. Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial. The Lancet Oncology. 2015;16(5):509–21. doi:10.1016/s1470-2045(15)70113-0.

    Article  CAS  PubMed  Google Scholar 

  65. Evans CP, Higano CS, Keane T, Andriole G, Saad F, Iversen P, et al. The PREVAIL study: primary outcomes by site and extent of baseline disease for enzalutamide-treated men with chemotherapy-naive metastatic castration-resistant prostate cancer. Eur Urol. 2016; doi:10.1016/j.eururo.2016.03.017.

    Google Scholar 

  66. Bianchini D, Lorente D, Rodriguez-Vida A, Omlin A, Pezaro C, Ferraldeschi R, et al. Antitumour activity of enzalutamide (MDV3100) in patients with metastatic castration-resistant prostate cancer (CRPC) pre-treated with docetaxel and abiraterone. European journal of cancer (Oxford, England: 1990). 2014;50(1):78–84. doi:10.1016/j.ejca.2013.08.020.

    Article  CAS  Google Scholar 

  67. Azad AA, Eigl BJ, Murray RN, Kollmannsberger C, Chi KN. Efficacy of enzalutamide following abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer patients. Eur Urol. 2015;67(1):23–9. doi:10.1016/j.eururo.2014.06.045.

    Article  CAS  PubMed  Google Scholar 

  68. Carver BS, Chapinski C, Wongvipat J, Hieronymus H, Chen Y, Chandarlapaty S, et al. Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell. 2011;19(5):575–86. doi:10.1016/j.ccr.2011.04.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 2009;69(19):7507–11. doi:10.1158/0008-5472.can-09-2994.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Song CW, Lee H, Dings RP, Williams B, Powers J, Santos TD, et al. Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells. Scientific reports. 2012;2:362. doi:10.1038/srep00362.

    PubMed  PubMed Central  Google Scholar 

  71. Nangia-Makker P, Yu Y, Vasudevan A, Farhana L, Rajendra SG, Levi E, et al. Metformin: a potential therapeutic agent for recurrent colon cancer. PLoS One. 2014;9(1):e84369. doi:10.1371/journal.pone.0084369.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Zhang Y, Guan M, Zheng Z, Zhang Q, Gao F, Xue Y. Effects of metformin on CD133+ colorectal cancer cells in diabetic patients. PLoS One. 2013;8(11):e81264. doi:10.1371/journal.pone.0081264.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Smith MR, Manola J, Kaufman DS, Oh WK, Bubley GJ, Kantoff PW. Celecoxib versus placebo for men with prostate cancer and a rising serum prostate-specific antigen after radical prostatectomy and/or radiation therapy. J Clin Oncol Off J Am Soc Clin Oncol. 2006;24(18):2723–8. doi:10.1200/jco.2005.03.7804.

    Article  CAS  Google Scholar 

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Fakhrejahani, F., Madan, R.A. & Dahut, W.L. Management Options for Biochemically Recurrent Prostate Cancer. Curr. Treat. Options in Oncol. 18, 26 (2017). https://doi.org/10.1007/s11864-017-0462-4

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