Prostate Cancer

  • Helena Luna Pais
  • João Ulrich
  • Leonor Ribeiro


Prostate cancer (PC a) is the second most common cancer worldwide in males. The incidence increases with age and positive family history. Most cancers are adenocarcinomas (>95%), multifocal and originated in the peripheral zone of prostate. Localized PCa is typically asymptomatic and is discovered through a rise in serum PSA or, less commonly, a suspicious digital rectum examination. Hesitance, urgency, poor urine stream, nocturia and incomplete bladder emptying are the most frequently reported symptoms. Their presence suggests advanced disease. On the other hand, bone pain raises the suspicion of metastatic disease. Transrectal ultrasound guided biopsy is the standard method of diagnosis. Treatment strategy is driven by tumor staging and can include a wide variety of approaches such as active surveillance, surgery, radiotherapy and/or medical therapy. Recently, there was the development of multiple new active treatment modalities, particularly in the setting of advanced disease.


Prostate cancer Diagnosis Treatment Prognosis Localized disease Metastatic castration-sensitive Metastatic castration resistant 


  1. 1.
    Josef Marx F, Karenberg A (2009) History of the term prostate. Prostate 69(2):208–213PubMedCrossRefGoogle Scholar
  2. 2.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA: Cancer J Clin 61(2):69–90Google Scholar
  3. 3.
    Bray F, Jemal A, Grey N, Ferlay J, Forman D (2012) Global cancer transitions according to the Human Development Index (2008–2030): a population-based study. Lancet Oncol 13(8):790–801PubMedCrossRefGoogle Scholar
  4. 4.
    Baade PD, Youlden DR, Cramb SM, Dunn J, Gardiner RA (2013) Epidemiology of prostate cancer in the Asia-Pacific region. Prostate Int 1(2):47–58PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Jacobsen SJ, Katusic SK, Bergstralh EJ et al (1995) INcidence of prostate cancer diagnosis in the eras before and after serum prostate-specific antigen testing. JAMA 274(18):1445–1449PubMedCrossRefGoogle Scholar
  6. 6.
    Konety BR, Bird VY, Deorah S, Dahmoush L (2005) Comparison of the incidence of latent prostate cancer detected at autopsy before and after the prostate specific antigen era. J Urol 174(5):1785–1788PubMedCrossRefGoogle Scholar
  7. 7.
    American Cancer Society (2003) Cancer facts & figures 2003. American Cancer Society, AtlantaGoogle Scholar
  8. 8.
    American Cancer Society (2011) Cancer facts & figures 2011. American Cancer Society, AtlantaGoogle Scholar
  9. 9.
    Hoffman RM, Gilliland FD, Eley JW, Harlan LC, Stephenson RA, Stanford JL, Albertson PC, Hamilton AS, Hunt WC, Potosky AL (2001) Racial and ethnic differences in advanced-stage prostate cancer: the prostate cancer outcomes study. J Natl Cancer Inst 93(5):388–395PubMedCrossRefGoogle Scholar
  10. 10.
    Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, Bray F (2012) International variation in prostate cancer incidence and mortality rates. Eur Urol 61(6):1079–1092PubMedCrossRefGoogle Scholar
  11. 11.
    Kiciński M, Vangronsveld J, Nawrot TS (2011) An epidemiological reappraisal of the familial aggregation of prostate cancer: a meta-analysis. PLoS One 6(10):e27130PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Castro E, Goh C, Olmos D, Saunders E, Leongamornlert D, Tymrakiewicz M, Mahmud N, Dadaev T, Govindasami K, Guy M et al (2013) Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J Clin Oncol Off J Am Soc Clin Oncol 31(14):1748–1757CrossRefGoogle Scholar
  13. 13.
    Ryan S, Jenkins MA, Win AK (2014) Risk of prostate cancer in Lynch syndrome: a systematic review and meta-analysis. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive OncologyGoogle Scholar
  14. 14.
    Masko EM, Allott EH, Freedland SJ (2013) The relationship between nutrition and prostate cancer: is more always better? Eur Urol 63(5):810–820PubMedCrossRefGoogle Scholar
  15. 15.
    Allott EH, Masko EM, Freedland SJ (2013) Obesity and prostate cancer: weighing the evidence. Eur Urol 63(5):800–809PubMedCrossRefGoogle Scholar
  16. 16.
    Leitzmann MF, Platz EA, Stampfer MJ, Willett WC, Giovannucci E (2004) EJaculation frequency and subsequent risk of prostate cancer. JAMA 291(13):1578–1586PubMedCrossRefGoogle Scholar
  17. 17.
    Dennis LK, Dawson DV (2002) Meta-analysis of measures of sexual activity and prostate cancer. Epidemiology 13(1):72–79PubMedCrossRefGoogle Scholar
  18. 18.
    DeMarzo AM, Nelson WG, Isaacs WB, Epstein JI (2003) Pathological and molecular aspects of prostate cancer. Lancet 361(9361):955–964PubMedCrossRefGoogle Scholar
  19. 19.
    Mazaris E, Tsiotras A (2013) Molecular pathways in prostate cancer. Nephro-Urol Monthly 5(3):792–800CrossRefGoogle Scholar
  20. 20.
    Benedettini E, Nguyen P, Loda M (2008) The pathogenesis of prostate cancer: from molecular to metabolic alterations. Diagn Histopathol 14(5):195–201CrossRefGoogle Scholar
  21. 21.
    Dickinson SI (2010) Premalignant and malignant prostate lesions: pathologic review. Cancer Control: J Moffitt Cancer Center 17(4):214–222CrossRefGoogle Scholar
  22. 22.
    Speakman MJ, Kirby RS, Joyce A, Abrams P, Pocock R (2004) Guideline for the primary care management of male lower urinary tract symptoms. BJU Int 93(7):985–990PubMedCrossRefGoogle Scholar
  23. 23.
    Frydenberg M, Stricker PD, Kaye KW (1997) Prostate cancer diagnosis and management. Lancet 349(9066):1681–1687PubMedCrossRefGoogle Scholar
  24. 24.
    Stenman U-H, Leinonen J, Zhang W-M, Finne P (1999) Prostate-specific antigen. Semin Cancer Biol 9(2):83–93PubMedCrossRefGoogle Scholar
  25. 25.
    Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, Mason M, Matveev V, Wiegel T, Zattoni F et al (2014) EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent—update 2013. Eur Urol 65(1):124–137PubMedCrossRefGoogle Scholar
  26. 26.
    Zappa M, Puliti D, Hugosson J, Schröder FH, van Leeuwen PJ, Kranse R, Auvinen A, Carlsson S, Kwiatkowski M, Nelen V et al (2014) A different method of evaluation of the erspc trial confirms that prostate-specific antigen testing has a significant impact on prostate cancer mortality. Eur Urol (0).
  27. 27.
    Loeb S, Bjurlin MA, Nicholson J, Tammela TL, Penson DF, Carter HB, Carroll P, Etzioni R (2014) Overdiagnosis and overtreatment of prostate cancer. Eur Urol 69(6):992–995Google Scholar
  28. 28.
    Lee R, Localio AR, Armstrong K, Malkowicz SB, Schwartz JS, Free PSASG (2006) A meta-analysis of the performance characteristics of the free prostate-specific antigen test. Urology 67(4):762–768PubMedCrossRefGoogle Scholar
  29. 29.
    Catalona WJ, Richie JP, deKernion JB, Ahmann FR, Ratliff TL, Dalkin BL, Kavoussi LR, MacFarlane MT, Southwick PC (1994) Comparison of prostate specific antigen concentration versus prostate specific antigen density in the early detection of prostate cancer: receiver operating characteristic curves. J Urol 152(6 Pt 1):2031–2036PubMedCrossRefGoogle Scholar
  30. 30.
    Vickers AJ, Savage C, O’Brien MF, Lilja H (2009) Systematic review of pretreatment prostate-specific antigen velocity and doubling time as predictors for prostate cancer. J Clin Oncol Off J Am Soc Clin Oncol 27(3):398–403CrossRefGoogle Scholar
  31. 31.
    Carter HB, Pearson JD, Metter EJ, Brant LJ, Chan DW, Andres R, Fozard JL, Walsh PC (1992) Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease. JAMA 267(16):2215–2220PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Nguyen K, Sabata B, Jain AK (2012) Prostate cancer grading: gland segmentation and structural features. Pattern Recogn Lett 33(7):951–961CrossRefGoogle Scholar
  33. 33.
    Epstein JI (2010) An update of the Gleason grading system. J Urol 183(2):433–440PubMedCrossRefGoogle Scholar
  34. 34.
    Shipley WU, Sacardino PT, Kaufman DS, Kattan MW (2006) Treatment of early stage prostate cancer. In: Vogelzang N (ed) Comprehensive textbook of genitourinary oncology, 3rd edn. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  35. 35.
    Rodrigues G, Warde P, Pickles T, Crook J, Brundage M, Souhami L, Lukka H (2012) Pre-treatment risk stratification of prostate cancer patients: a critical review. Can Urol Assoc J = Journal de l’Association des urologues du Canada 6(2):121–127PubMedCrossRefGoogle Scholar
  36. 36.
    Mohler JL, Kantoff PW, Armstrong AJ, Bahnson RR, Cohen M, D’Amico AV, Eastham JA, Enke CA, Farrington TA, Higano CS et al (2013) Prostate cancer, version 1.2014. J Natl Compr Cancer Netw : JNCCN 11(12):1471–1479CrossRefGoogle Scholar
  37. 37.
    Horwich A, Hugosson J, de Reijke T, Wiegel T, Fizazi K, Kataja V (2013) Prostate cancer: ESMO consensus conference guidelines 2012. Ann Oncol 24(5):1141–1162PubMedCrossRefGoogle Scholar
  38. 38.
    Madan RA, Shah AA, Dahut WL (2013) Is it time to reevaluate definitive therapy in prostate cancer? J Natl Cancer Inst 105(10):683–685PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Nepple KG, Stephenson AJ, Kallogjeri D, Michalski J, Grubb RL 3rd, Strope SA, Haslag-Minoff J, Piccirillo JF, Ciezki JP, Klein EA et al (2013) Mortality after prostate cancer treatment with radical prostatectomy, external-beam radiation therapy, or brachytherapy in men without comorbidity. Eur Urol 64(3):372–378PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Zumsteg ZS, Zelefsky MJ (2013) Improved survival with surgery in prostate cancer patients without medical comorbidity: a self-fulfilling prophecy? Eur Urol 64(3):381–383PubMedCrossRefGoogle Scholar
  41. 41.
    Loblaw A, Zhang L, Lam A, Nam R, Mamedov A, Vesprini D, Klotz L (2010) Comparing prostate specific antigen triggers for intervention in men with stable prostate cancer on active surveillance. J Urol 184(5):1942–1946PubMedCrossRefGoogle Scholar
  42. 42.
    Ross AE, Loeb S, Landis P, Partin AW, Epstein JI, Kettermann A, Feng Z, Carter HB, Walsh PC (2010) Prostate-specific antigen kinetics during follow-up are an unreliable trigger for intervention in a prostate cancer surveillance program. J Clin Oncol Off J Am Soc Clin Oncol 28(17):2810–2816CrossRefGoogle Scholar
  43. 43.
    Trinh QD, Bjartell A, Freedland SJ, Hollenbeck BK, Hu JC, Shariat SF, Sun M, Vickers AJ (2013) A systematic review of the volume-outcome relationship for radical prostatectomy. Eur Urol 64(5):786–798PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Trinh QD, Sammon J, Sun M, Ravi P, Ghani KR, Bianchi M, Jeong W, Shariat SF, Hansen J, Schmitges J et al (2012) Perioperative outcomes of robot-assisted radical prostatectomy compared with open radical prostatectomy: results from the nationwide inpatient sample. Eur Urol 61(4):679–685PubMedCrossRefGoogle Scholar
  45. 45.
    Cathcart P, Murphy DG, Moon D, Costello AJ, Frydenberg M (2011) Perioperative, functional and oncological outcomes after open and minimally invasive prostate cancer surgery: experience from Australasia. BJU Int 107(Suppl 3):11–19PubMedCrossRefGoogle Scholar
  46. 46.
    Montorsi F, Wilson TG, Rosen RC, Ahlering TE, Artibani W, Carroll PR, Costello A, Eastham JA, Ficarra V, Guazzoni G et al (2012) Best practices in robot-assisted radical prostatectomy: recommendations of the Pasadena Consensus Panel. Eur Urol 62(3):368–381PubMedCrossRefGoogle Scholar
  47. 47.
    Cagiannos I, Karakiewicz P, Eastham JA, Ohori M, Rabbani F, Gerigk C, Reuter V, Graefen M, Hammerer PG, Erbersdobler A et al (2003) A preoperative nomogram identifying decreased risk of positive pelvic lymph nodes in patients with prostate cancer. J Urol 170(5):1798–1803PubMedCrossRefGoogle Scholar
  48. 48.
    Ischia J, Gleave M (2013) Radical prostatectomy in high-risk prostate cancer. Int J Urol 20(3):290–300PubMedCrossRefGoogle Scholar
  49. 49.
    Kumar S, Shelley M, Harrison C, Coles B, Wilt TJ, Mason MD (2006) Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. Cochrane Database Syst Rev 4:Cd006019Google Scholar
  50. 50.
    Morris DE, Emami B, Mauch PM, Konski AA, Tao ML, Ng AK, Klein EA, Mohideen N, Hurwitz MD, Fraas BA et al (2005) Evidence-based review of three-dimensional conformal radiotherapy for localized prostate cancer: an ASTRO outcomes initiative. Int J Radiat Oncol Biol Phys 62(1):3–19PubMedCrossRefGoogle Scholar
  51. 51.
    Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, Lee AK, Pollack A (2008) Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys 70(1):67–74PubMedCrossRefGoogle Scholar
  52. 52.
    Wang L, Hoban P, Paskalev K, Yang J, Li J, Chen L, Xiong W, Ma CC (2005) Dosimetric advantage and clinical implication of a micro-multileaf collimator in the treatment of prostate with intensity-modulated radiotherapy. Med Dosim 30(2):97–103PubMedCrossRefGoogle Scholar
  53. 53.
    Michalski JM, Yan Y, Watkins-Bruner D, Bosch WR, Winter K, Galvin JM, Bahary JP, Morton GC, Parliament MB, Sandler HM (2013) Preliminary toxicity analysis of 3-dimensional conformal radiation therapy versus intensity modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group 0126 prostate cancer trial. Int J Radiat Oncol Biol Phys 87(5):932–938PubMedCrossRefGoogle Scholar
  54. 54.
    Zelefsky MJ, Levin EJ, Hunt M, Yamada Y, Shippy AM, Jackson A, Amols HI (2008) Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 70(4):1124–1129PubMedCrossRefGoogle Scholar
  55. 55.
    Xu N, Rossi PJ, Jani AB (2011) Toxicity analysis of dose escalation from 75.6 gy to 81.0 gy in prostate cancer. Am J Clin Oncol 34(1):11–15PubMedCrossRefGoogle Scholar
  56. 56.
    Dasu A (2007) Is the alpha/beta value for prostate tumours low enough to be safely used in clinical trials? Clin Oncol (R Coll Radiol) 19(5):289–301CrossRefGoogle Scholar
  57. 57.
    Botrel TE, Clark O, Pompeo AC, Bretas FF, Sadi MV, Ferreira U, Dos Reis RB (2013) Hypofractionated external-beam radiation therapy (HEBRT) versus conventional external-beam radiation (CEBRT) in patients with localized prostate cancer: a systematic review and meta-analysis. Core Evidence 8:1–13PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Roach M 3rd, DeSilvio M, Lawton C, Uhl V, Machtay M, Seider MJ, Rotman M, Jones C, Asbell SO, Valicenti RK et al (2003) Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: radiation Therapy Oncology Group 9413. J Clin Oncol Off J Am Soc Clin Oncol 21(10):1904–1911CrossRefGoogle Scholar
  59. 59.
    Roach M 3rd, Marquez C, Yuo HS, Narayan P, Coleman L, Nseyo UO, Navvab Z, Carroll PR (1994) Predicting the risk of lymph node involvement using the pre-treatment prostate specific antigen and Gleason score in men with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 28(1):33–37PubMedCrossRefGoogle Scholar
  60. 60.
    Lawton CA, DeSilvio M, Roach M 3rd, Uhl V, Kirsch R, Seider M, Rotman M, Jones C, Asbell S, Valicenti R et al (2007) An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys 69(3):646–655PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Lawton CA, Michalski J, El-Naqa I, Buyyounouski MK, Lee WR, Menard C, O’Meara E, Rosenthal SA, Ritter M, Seider M (2009) RTOG GU radiation oncology specialists reach consensus on pelvic lymph node volumes for high-risk prostate cancer. Int J Radiat Oncol Biol Phys 74(2):383–387PubMedCrossRefGoogle Scholar
  62. 62.
    Polkinghorn WR, Zelefsky MJ (2013) Improving outcomes in high-risk prostate cancer with radiotherapy. Rep Prac Oncol Radiother J Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology 18(6):333–337Google Scholar
  63. 63.
    Zietman AL, Prince EA, Nakfoor BM, Park JJ (1997) Androgen deprivation and radiation therapy: sequencing studies using the Shionogi in vivo tumor system. Int J Radiat Oncol Biol Phys 38(5):1067–1070PubMedCrossRefGoogle Scholar
  64. 64.
    Sanguineti G, Marcenaro M, Franzone P, Foppiano F, Vitale V (2003) Neoadjuvant androgen deprivation and prostate gland shrinkage during conformal radiotherapy. Radiother Oncol J Eur Soc Therap Radiol Oncol 66(2):151–157CrossRefGoogle Scholar
  65. 65.
    Bria E, Cuppone F, Giannarelli D, Milella M, Ruggeri EM, Sperduti I, Pinnaro P, Terzoli E, Cognetti F, Carlini P (2009) Does hormone treatment added to radiotherapy improve outcome in locally advanced prostate cancer?: meta-analysis of randomized trials. Cancer 115(15):3446–3456PubMedCrossRefGoogle Scholar
  66. 66.
    Nguyen PL, Je Y, Schutz FA, Hoffman KE, Hu JC, Parekh A, Beckman JA, Choueiri TK (2011) Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. JAMA: J Am Med Assoc 306(21):2359–2366CrossRefGoogle Scholar
  67. 67.
    Bolla M, Van Tienhoven G, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Billiet I et al (2010) External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol 11(11):1066–1073PubMedCrossRefGoogle Scholar
  68. 68.
    Pilepich MV, Winter K, Lawton CA, Krisch RE, Wolkov HB, Movsas B, Hug EB, Asbell SO, Grignon D (2005) Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma--long-term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys 61(5):1285–1290PubMedCrossRefGoogle Scholar
  69. 69.
    Roach M 3rd, Bae K, Speight J, Wolkov HB, Rubin P, Lee RJ, Lawton C, Valicenti R, Grignon D, Pilepich MV (2008) Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol 26(4):585–591PubMedCrossRefGoogle Scholar
  70. 70.
    Denham JW, Steigler A, Lamb DS, Joseph D, Turner S, Matthews J, Atkinson C, North J, Christie D, Spry NA et al (2011) Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol 12(5):451–459PubMedCrossRefGoogle Scholar
  71. 71.
    Cosset JM, Hannoun-Levi JM, Peiffert D, Delannes M, Pommier P, Pierrat N, Nickers P, Thomas L, Chauveinc L (2013) Permanent implant prostate cancer brachytherapy: 2013 state-of-the art. Cancer radiother : journal de la Societe francaise de radiotherapie oncologique 17(2):111–117CrossRefGoogle Scholar
  72. 72.
    Ghadjar P, Keller T, Rentsch CA, Isaak B, Behrensmeier F, Stroux A, Thalmann GN, Aebersold DM (2009) Toxicity and early treatment outcomes in low- and intermediate-risk prostate cancer managed by high-dose-rate brachytherapy as a monotherapy. Brachytherapy 8(1):45–51PubMedCrossRefGoogle Scholar
  73. 73.
    Corner C, Rojas AM, Bryant L, Ostler P, Hoskin P (2008) A Phase II study of high-dose-rate afterloading brachytherapy as monotherapy for the treatment of localized prostate cancer. Int J Radiat Oncol Biol Phys 72(2):441–446PubMedCrossRefGoogle Scholar
  74. 74.
    Rodrigues G, Yao X, Loblaw DA, Brundage M, Chin JL (2013) Low-dose rate brachytherapy for patients with low- or intermediate-risk prostate cancer: a systematic review. Can Urol Assoc J = Journal de l’Association des urologues du Canada 7(11–12):463–470PubMedCrossRefGoogle Scholar
  75. 75.
    Ghilezan M (2012) Role of high dose rate brachytherapy in the treatment of prostate cancer. Cancer Radiother 16(5–6):418–422PubMedCrossRefGoogle Scholar
  76. 76.
    Sanda MG, Dunn RL, Michalski J, Sandler HM, Northouse L, Hembroff L, Lin X, Greenfield TK, Litwin MS, Saigal CS et al (2008) Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med 358(12):1250–1261PubMedCrossRefGoogle Scholar
  77. 77.
    Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC, Partin AW (2005) Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA: J Am Med Assoc 294(4):433–439CrossRefGoogle Scholar
  78. 78.
    Swanson GP, Lerner SP (2013) Positive margins after radical prostatectomy: implications for failure and role of adjuvant treatment. Urol Oncol 31(5):531–541PubMedCrossRefGoogle Scholar
  79. 79.
    Thompson IM Jr, Tangen CM, Paradelo J, Lucia MS, Miller G, Troyer D, Messing E, Forman J, Chin J, Swanson G et al (2006) Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA: J Am Med Assoc 296(19):2329–2335CrossRefGoogle Scholar
  80. 80.
    Van der Kwast TH, Bolla M, Van Poppel H, Van Cangh P, Vekemans K, Da Pozzo L, Bosset JF, Kurth KH, Schroder FH, Collette L (2007) Identification of patients with prostate cancer who benefit from immediate postoperative radiotherapy: EORTC 22911. J Clin Oncol 25(27):4178–4186PubMedCrossRefGoogle Scholar
  81. 81.
    Wiegel T, Bottke D, Steiner U, Siegmann A, Golz R, Storkel S, Willich N, Semjonow A, Souchon R, Stockle M et al (2009) Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. J Clin Oncol Off J Am Soc Clin Oncol 27(18):2924–2930CrossRefGoogle Scholar
  82. 82.
    Stephenson AJ, Scardino PT, Kattan MW, Pisansky TM, Slawin KM, Klein EA, Anscher MS, Michalski JM, Sandler HM, Lin DW et al (2007) Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol 25(15):2035–2041PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Allen GW, Howard AR, Jarrard DF, Ritter MA (2007) Management of prostate cancer recurrences after radiation therapy-brachytherapy as a salvage option. Cancer 110(7):1405–1416PubMedCrossRefGoogle Scholar
  84. 84.
    Nguyen PL, D’Amico AV, Lee AK, Suh WW (2007) Patient selection, cancer control, and complications after salvage local therapy for postradiation prostate-specific antigen failure: a systematic review of the literature. Cancer 110(7):1417–1428PubMedCrossRefGoogle Scholar
  85. 85.
    Chade DC, Eastham J, Graefen M, Hu JC, Karnes RJ, Klotz L, Montorsi F, van Poppel H, Scardino PT, Shariat SF (2012) Cancer control and functional outcomes of salvage radical prostatectomy for radiation-recurrent prostate cancer: a systematic review of the literature. Eur Urol 61(5):961–971PubMedCrossRefGoogle Scholar
  86. 86.
    Bubendorf L, Schopfer A, Wagner U, Sauter G, Moch H, Willi N, Gasser TC, Mihatsch MJ (2000) Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol 31(5):578–583PubMedCrossRefGoogle Scholar
  87. 87.
    Loblaw DA, Mendelson DS, Talcott JA, Virgo KS, Somerfield MR, Ben-Josef E, Middleton R, Porterfield H, Sharp SA, Smith TJ et al (2004) American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer. J Clin Oncol Off J Am Soc Clin Oncol 22(14):2927–2941CrossRefGoogle Scholar
  88. 88.
    Byar DP (1973) Proceedings: The Veterans Administration Cooperative Urological Research Group’s studies of cancer of the prostate. Cancer 32(5):1126–1130PubMedCrossRefGoogle Scholar
  89. 89.
    Oefelein MG, Feng A, Scolieri MJ, Ricchiutti D, Resnick MI (2000) Reassessment of the definition of castrate levels of testosterone: implications for clinical decision making. Urology 56(6):1021–1024PubMedCrossRefGoogle Scholar
  90. 90.
    Seidenfeld J, Samson DJ, Hasselblad V, Aronson N, Albertsen PC, Bennett CL, Wilt TJ (2000) Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Ann Intern Med 132(7):566–577PubMedCrossRefGoogle Scholar
  91. 91.
    Prostate Cancer Trialists’ Collaborative Group (2000) Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet 355(9214):1491–1498CrossRefGoogle Scholar
  92. 92.
    Schmitt B, Wilt TJ, Schellhammer PF, DeMasi V, Sartor O, Crawford ED, Bennett CL (2001) Combined androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer: a systematic review. Urology 57(4):727–732PubMedCrossRefGoogle Scholar
  93. 93.
    Shahinian VB, Kuo YF, Freeman JL, Goodwin JS (2005) Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med 352(2):154–164PubMedCrossRefGoogle Scholar
  94. 94.
    Smith MR, Lee H, Nathan DM (2006) Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab 91(4):1305–1308PubMedCrossRefGoogle Scholar
  95. 95.
    Braga-Basaria M, Muller DC, Carducci MA, Dobs AS, Basaria S (2006) Lipoprotein profile in men with prostate cancer undergoing androgen deprivation therapy. Int J Impot Res 18(5):494–498PubMedCrossRefGoogle Scholar
  96. 96.
    Hussain M, Tangen CM, Berry DL, Higano CS, Crawford ED, Liu G, Wilding G, Prescott S, Kanaga Sundaram S, Small EJ et al (2013) Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med 368(14):1314–1325PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Choueiri TK, Xie W, D’Amico AV, Ross RW, Hu JC, Pomerantz M, Regan MM, Taplin ME, Kantoff PW, Sartor O et al (2009) Time to prostate-specific antigen nadir independently predicts overall survival in patients who have metastatic hormone-sensitive prostate cancer treated with androgen-deprivation therapy. Cancer 115(5):981–987PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Hussain M, Tangen CM, Higano C, Schelhammer PF, Faulkner J, Crawford ED, Wilding G, Akdas A, Small EJ, Donnelly B et al (2006) Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol Off J Am Soc Clin Oncol 24(24):3984–3990CrossRefGoogle Scholar
  99. 99.
    Yuan X, Balk SP (2009) Mechanisms mediating androgen receptor reactivation after castration. Urol Oncol 27(1):36–41PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Lam JS, Leppert JT, Vemulapalli SN, Shvarts O, Belldegrun AS (2006) Secondary hormonal therapy for advanced prostate cancer. J Urol 175(1):27–34PubMedCrossRefGoogle Scholar
  101. 101.
    Landstrom M, Damber JE, Bergh A (1994) Estrogen treatment postpones the castration-induced dedifferentiation of Dunning R3327-PAP prostatic adenocarcinoma. Prostate 25(1):10–18PubMedCrossRefGoogle Scholar
  102. 102.
    Pont A, Williams PL, Azhar S, Reitz RE, Bochra C, Smith ER, Stevens DA (1982) Ketoconazole blocks testosterone synthesis. Arch Intern Med 142(12):2137–2140PubMedCrossRefGoogle Scholar
  103. 103.
    FDA Drug Safety Communication: FDA limits usage of Nizoral (ketoconazole) oral tablets due to potentially fatal liver injury and risk of drug interactions and adrenal gland problems.
  104. 104.
  105. 105.
    Potter GA, Barrie SE, Jarman M, Rowlands MG (1995) 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 38(13):2463–2471PubMedCrossRefGoogle Scholar
  106. 106.
    Attard G, Belldegrun AS, de Bono JS (2005) Selective blockade of androgenic steroid synthesis by novel lyase inhibitors as a therapeutic strategy for treating metastatic prostate cancer. BJU Int 96(9):1241–1246PubMedCrossRefGoogle Scholar
  107. 107.
    de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F et al (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364(21):1995–2005PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S et al (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368(2):138–148PubMedCrossRefGoogle Scholar
  109. 109.
    Rathkopf DE, Smith R, Bono J (2013) Updated interim analysis (IA) of COU-AA-302, a randomized phase III study of abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy [abstract 5]. J Clin Oncol 31(Suppl 6)Google Scholar
  110. 110.
    Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A et al (2009) Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science (New York, NY) 324(5928):787–790CrossRefGoogle Scholar
  111. 111.
    Scher H, Fizazi K, Saad F (2012) Effect of MDV3100, an androgen receptor signaling inhibitor (ARSI), on overall survival in patients with prostate cancer postdocetaxel: results from the phase III AFFIRM study. In: 2012 Genitourinary Cancers Symposium: J Clin Oncol 30, 2012 (suppl 5; abstr LBA1)Google Scholar
  112. 112.
    Beer TM, Armstrong AJ, Sternberg CN, Higano CS, Iversen P, Loriot Y, Rathkopf DE, Bhattacharya S, Carles J, Bono JSD et al (2014) Enzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC): results of phase III PREVAIL study. J Clin Oncol 32(suppl 4; abstr LBA1^)Google Scholar
  113. 113.
    Loriot Y, Bianchini D, Ileana E, Sandhu S, Patrikidou A, Pezaro C, Albiges L, Attard G, Fizazi K, De Bono JS et al (2013) Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). Ann Oncol 24(7):1807–1812PubMedCrossRefGoogle Scholar
  114. 114.
    Bianchini D, Lorente D, Rodriguez-Vida A, Omlin A, Pezaro C, Ferraldeschi R, Zivi A, Attard G, Chowdhury S, de Bono JS (2014) Antitumour activity of enzalutamide (MDV3100) in patients with metastatic castration-resistant prostate cancer (CRPC) pre-treated with docetaxel and abiraterone. Eur J Cancer (Oxford, England: 1990) 50(1):78–84CrossRefGoogle Scholar
  115. 115.
    Efstathiou E, Titus M, Tsavachidou D, Hoang A, Karlou M, Wen S (2011) MDV3100 effects on androgen receptor (AR) signaling and bone marrow testosterone concentration modulation: a preliminary report. In: 2011 ASCO Meeting. J Clin Oncol (Meeting Abstracts) 29:4501Google Scholar
  116. 116.
    Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, Armitage GR, Wilson JJ, Venner PM, Coppin CM 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 Off J Am Soc Clin Oncol 14(6):1756–1764CrossRefGoogle Scholar
  117. 117.
    Kantoff PW, Halabi S, Conaway M, Picus J, Kirshner J, Hars V, Trump D, Winer EP, Vogelzang NJ (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 Off J Am Soc Clin Oncol 17(8):2506–2513CrossRefGoogle Scholar
  118. 118.
    Berry W, Dakhil S, Modiano M, Gregurich M, Asmar L (2002) Phase III study of mitoxantrone plus low dose prednisone versus low dose prednisone alone in patients with asymptomatic hormone refractory prostate cancer. J Urol 168(6):2439–2443PubMedCrossRefGoogle Scholar
  119. 119.
    Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I et al (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351(15):1502–1512PubMedCrossRefGoogle Scholar
  120. 120.
    Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF (2008) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol 26(2):242–245PubMedCrossRefGoogle Scholar
  121. 121.
    Kellokumpu-Lehtinen PL, Harmenberg U, Joensuu T, McDermott R, Hervonen P, Ginman C, Luukkaa M, Nyandoto P, Hemminki A, Nilsson S et al (2013) 2-weekly versus 3-weekly docetaxel to treat castration-resistant advanced prostate cancer: a randomised, phase 3 trial. Lancet Oncol 14(2):117–124PubMedCrossRefGoogle Scholar
  122. 122.
    Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, Mason M, Matveev V, Wiegel T, Zattoni F et al (2014) EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 65(2):467–479PubMedCrossRefGoogle Scholar
  123. 123.
    de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels J-P, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L 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(9747):1147–1154PubMedCrossRefGoogle Scholar
  124. 124.
    Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB et al (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363(5):411–422PubMedCrossRefGoogle Scholar
  125. 125.
    Scher HI, Morris MJ, Basch E, Heller G (2011) End points and outcomes in castration-resistant prostate cancer: from clinical trials to clinical practice. J Clin Oncol Off J Am Soc Clin Oncol 29(27):3695–3704CrossRefGoogle Scholar
  126. 126.
    Papandreou CN, Daliani DD, Thall PF, Tu SM, Wang X, Reyes A, Troncoso P, Logothetis CJ (2002) Results of a phase II study with doxorubicin, etoposide, and cisplatin in patients with fully characterized small-cell carcinoma of the prostate. J Clin Oncol Off J Am Soc Clin Oncol 20(14):3072–3080CrossRefGoogle Scholar
  127. 127.
    Flechon A, Pouessel D, Ferlay C, Perol D, Beuzeboc P, Gravis G, Joly F, Oudard S, Deplanque G, Zanetta S et al (2011) Phase II study of carboplatin and etoposide in patients with anaplastic progressive metastatic castration-resistant prostate cancer (mCRPC) with or without neuroendocrine differentiation: results of the French Genito-urinary tumor group (GETUG) P01 trial. Ann Oncol 22(11):2476–2481PubMedCrossRefGoogle Scholar
  128. 128.
    Zhang TY, Agarwal N, Sonpavde G, DiLorenzo G, Bellmunt J, Vogelzang NJ (2013) Management of castrate resistant prostate cancer—recent advances and optimal sequence of treatments. Curr Urol Rep 14(3):174–183PubMedCrossRefGoogle Scholar
  129. 129.
    Epstein JI, Zelefsky MJ, Sjoberg DD, Nelson JB, Egevad L, Magi-Galluzzi C, Vickers AJ, Parwani AV, Reuter VE, Fine SW, Eastham JA, Wiklund P, Han M, Reddy CA, Ciezki JP, Nyberg T, Klein EA (2016) A contemporary prostate Cancer grading system: a validated alternative to the Gleason score. Eur Urol 69(3):428–435Google Scholar
  130. 130.
    Epstein JI (2016) New prostate cancer grade group system correlates with prostate cancer death in addition to biochemical recurrence. Br J Cancer 114(10):1069–1070Google Scholar
  131. 131.
    Hahn AW, Higano CS, Taplin M-E, Ryan CJ, Agarwal N (2018) Metastatic castration-sensitive prostate Cancer: optimizing patient selection and treatment. Am Soc Clin Oncol Educ Book (38):363–371Google Scholar
  132. 132.
    Sweeney CJ, Chen Y-H, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong Y-N, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS (2015) Chemohormonal therapy in metastatic hormone-sensitive prostate Cancer. N Engl J Med 373(8):737–746Google Scholar
  133. 133.
    James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, Ritchie AWS, Parker CC, Martin Russell J, Attard G, de Bono J, Cross W, Jones RJ, Thalmann G, Amos C, Matheson D, Millman R, Alzouebi M, Beesley S, Birtle AJ, Brock S, Cathomas R, Chakraborti P, Chowdhury S, Cook A, Elliott T, Gale J, Gibbs S, Graham JD, Hetherington J, Hughes R, Laing R, McKinna F, McLaren DB, O’Sullivan JM, Parikh O, Peedell C, Protheroe A, Robinson AJ, Srihari N, Srinivasan R, Staffurth J, Sundar S, Tolan S, Tsang D, Wagstaff J, Parmar MKB (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(10024):1163–1177Google Scholar
  134. 134.
    Fizazi K, Tran NP, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Özgüroğlu M, Ye D, Feyerabend S, Protheroe A, De Porre P, Kheoh T, Park YC, Todd MB, Chi KN (2017) Abiraterone plus prednisone in metastatic, castration-sensitive prostate Cancer. N Engl J Med 377(4):352–360Google Scholar
  135. 135.
    James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, Ritchie AWS, Amos CL, Gilson C, Jones RJ, Matheson D, Millman R, Attard G, Chowdhury S, Cross WR, Gillessen S, Parker CC, Russell JM, Berthold DR, Brawley C, Adab F, Aung S, Birtle AJ, Bowen J, Brock S, Chakraborti P, Ferguson C, Gale J, Gray E, Hingorani M, Hoskin PJ, Lester JF, Malik ZI, McKinna F, McPhail N, Money-Kyrle J, O’Sullivan J, Parikh O, Protheroe A, Robinson A, Srihari NN, Thomas C, Wagstaff J, Wylie J, Zarkar A, Parmar MKB, Sydes MR (2017) Abiraterone for prostate Cancer not previously treated with hormone therapy. N Engl J Med 377(4):338–351Google Scholar
  136. 136.
    Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A et al (2018) Articles radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet [Internet] 392(10162):2353–2366Google Scholar
  137. 137.
    Boeri L, Sharma V, Karnes RJ (2018) Radiotherapy for newly diagnosed oligometastatic prostate cancer. Lancet 392(10162):2327–2328Google Scholar
  138. 138.
    Burdett S, Boevé LM, Ingleby FC, Fisher DJ, Rydzewska LH, Vale CL, van Andel G, Clarke NW, Hulshof MC, James ND, Parker CC, Parmar MK, Sweeney CJ, Sydes MR, Tombal B, Verhagen PC, Tierney JF (2019) Prostate radiotherapy for metastatic hormone-sensitive prostate Cancer: a STOPCAP systematic review and meta-analysis. In: European urologyGoogle Scholar
  139. 139.
    Longo DL, Sartor O, de Bono JS (2018) Metastatic Prostate Cancer. N Engl J Med 378(7):645–657Google Scholar
  140. 140.
    Eisenberger M, Kim CS, Lajos G, Ford D, Bono J De. 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. 2017;35(28)Google Scholar
  141. 141.
    Oudard S, Fizazi K, Sengeløv L, Daugaard G, Saad F, Hansen S et al (2017) Cabazitaxel versus Docetaxel as first-line therapy for patients with metastatic castration-resistant prostate Cancer : a randomized phase III trial — FIRSTANA. 35(28)Google Scholar
  142. 142.
    Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA The 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol:1Google Scholar
  143. 143.
    Parker C, Gillessen S, Heidenreich A, Horwich A (2015) Cancer of the prostate: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 26(suppl 5):v69–v77Google Scholar
  144. 144.
    Lee WR, Dignam JJ, Amin MB, Bruner DW, Low D, Swanson GP, Shah AB, D’Souza DP, Michalski JM, Dayes IS, Seaward SA, Hall WA, Nguyen PL, Pisansky TM, Faria SL, Chen Y, Koontz BF, Paulus R, Sandler HM (2016) Randomized phase III noninferiority study comparing two radiotherapy fractionation schedules in patients with Low-risk prostate Cancer. J Clin Oncol 34(20):2325–2332Google Scholar
  145. 145.
    Catton CN, Lukka H, Gu C-S, Martin JM, Supiot S, Chung PWM, Bauman GS, Bahary J-P, Ahmed S, Cheung P, Tai KH, Wu JS, Parliament MB, Tsakiridis T, Corbett TB, Tang C, Dayes IS, Warde P, Craig TK, Julian JA, Levine MN (2017) Randomized trial of a Hypofractionated radiation regimen for the treatment of localized prostate Cancer. J Clin Oncol 35(17):1884–1890Google Scholar
  146. 146.
    Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield D, Graham J, Kirkbride P, Logue J, Malik Z, Money-Kyrle J, O’Sullivan JM, Panades M, Parker C, Patterson H, Scrase C, Staffurth J, Stockdale A, Tremlett J, Bidmead M, Mayles H, Naismith O, South C, Gao A, Cruickshank C, Hassan S, Pugh J, Griffin C, Hall E (2016) Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol 17(8):1047–1060Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Helena Luna Pais
    • 1
  • João Ulrich
    • 2
  • Leonor Ribeiro
    • 1
  1. 1.Medical Oncology DepartmentHospital de Santa Maria, Centro Hospitalar de Lisboa NorteLisbonPortugal
  2. 2.Radiation Oncology DepartmentHospital de Santa Maria, Centro Hospitalar de Lisboa NorteLisbonPortugal

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