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Management Strategies for Locally Advanced Prostate Cancer

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Abstract

Locally advanced prostate cancer represents a subpopulation of prostate cancer diagnosed in patients who are either untouched by screening efforts or whose disease has an unusually rapidly progressive natural history. The diagnostic work-up for the locally advanced patient is distinct from that of early stage disease in several respects in that it is related principally to ruling out metastases. The typical metastatic work-up consists of a serum alkaline phosphatase, bone scan, CT of the abdomen/pelvis, and chest x-ray. Once metastatic disease has been ruled out, individual components of the management of locally advanced prostate cancer patients may include surgery (palliative or curative), external beam radiation therapy (with photons or particles) or brachytherapy (with low-dose rate/permanent or high-dose rate/temporary radiation sources), and hormone therapy. Unlike in early stage disease, observation/watchful waiting is typically not a treatment option in locally advanced prostate cancer.

Of the curative local control modalities, the one most commonly used, and the one which has emerged as the clinical standard, is photon external beam radiotherapy (EBRT). Numerous randomised studies have shown that androgen ablation has an established role in conjunction with radiotherapy for locally advanced disease — the current standard of care is thus photon EBRT plus neoadjuvant and adjuvant androgen ablation. Long-term androgen ablation appears to be better than short-term ablation, even when hormone complications are considered. EBRT is typically delivered to the prostate, seminal vesicles and pelvic lymph nodes, although in some circumstances local fields to the prostate and seminal vesicles may be adequate. New treatment planning and delivery techniques, such as intensity-modulated radiotherapy and organ motion tracking, are being developed to reduce the morbidity of radiotherapy while permitting a higher delivered dose.

Further work is necessary to determine the precise sequencing and duration of hormone therapy in conjunction with radiotherapy and the optimum radiotherapy treatment volume. Additional work is also needed to determine the precise groups benefiting from other local control modalities such as surgery and brachytherapy. Finally, novel investigational strategies such as chemotherapy and gene therapy are being applied in an attempt to improve outcomes of locally advanced prostate cancer patients.

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References

  1. Jani AB, Hellman S. Early prostate cancer: clinical decision-making. Lancet 2003; 361(9362): 1048–53

    Article  Google Scholar 

  2. Gronberg H. Prostate cancer epidemiology. Lancet 2003; 361(9360): 859–64

    Article  PubMed  Google Scholar 

  3. Frankel S, Smith GD, Donovan J, et al. Screening for prostate cancer. Lancet 2003; 361(9363): 1122–8

    Article  PubMed  Google Scholar 

  4. Peschel RE, Colberg JW. Surgery, brachytherapy, and external-beam radiotherapy for early prostate cancer. Lancet Oncol 2003; 4(4): 233–41

    Article  PubMed  Google Scholar 

  5. Jemal A, Murray T, Ward W, et al. Cancer statistics, 2005. CA Cancer J Clin 2005; 55(1): 10–30

    Article  PubMed  Google Scholar 

  6. Merrill RM, Brawley OW. Prostate cancer incidence and mortality rates among white and black men. Epidemiology 1997; 8(2): 126–31

    Article  PubMed  CAS  Google Scholar 

  7. Murphy GP, Natarajan N, Pontes JE, et al. The national survey of prostate cancer in the United States by the American College of Surgeons. J Urol 1982; 127(5): 928–34

    PubMed  CAS  Google Scholar 

  8. AJCC (American Joint Committee on Cancer). Cancer staging manual. In: Greene FL, Page DL, Fleming ID, et al., editors. 6th ed. New York: Springer-Verlag, 2002: 310

  9. Bostwick DG, Grignon DJ, Hammond ME, et al. Prognostic factors in prostate cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 2000; 124(7): 995–1000

    PubMed  CAS  Google Scholar 

  10. Partin AW, Mangold LA, Lamm DM, et al. Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology 2001; 58(6): 843–8

    Article  PubMed  CAS  Google Scholar 

  11. Levran Z, Gonzalez JA, Diokno AC, et al. Are pelvic computed tomography, bone scan and pelvic lymphadenectomy necessary in the staging of prostatic cancer? Br J Urol 1995; 75(6): 778–81

    Article  PubMed  CAS  Google Scholar 

  12. Gleave ME, Coupland D, Drachenberg D, et al. Ability of serum prostate-specific antigen levels to predict normal bone scans in patients with newly diagnosed prostate cancer. Urology 1996; 47(5): 708–12

    Article  PubMed  CAS  Google Scholar 

  13. Tsuda K, Yu KK, Coakley FV, et al. Detection of extracapsular extension of prostate cancer: role of fat suppression endorectal MRI. J Comput Assist Tomogr 1999; 23(1): 74–8

    Article  PubMed  CAS  Google Scholar 

  14. Manyak MJ, Hinkle GH, Olsen JO, et al. Immunoscintigraphy with indium-111-capromab pendetide: evaluation before definitive therapy in patients with prostate cancer. Urology 1999; 54(6): 1058–63

    Article  PubMed  CAS  Google Scholar 

  15. Sanz G, Rioja J, Zudaire JJ, et al. PET and prostate cancer. World J Urol 2004; 22(5): 351–2

    Article  PubMed  CAS  Google Scholar 

  16. Harisinghani MG, Barentsz J, Hahn PF, et al. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 2003; 348(25): 2491–9

    Article  PubMed  Google Scholar 

  17. Prostate Cancer Trialists’ Collaborative Group. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet 2000; 355(9214): 1491–8

    Article  Google Scholar 

  18. Fusi A, Procopio G, Della Torre S, et al. Treatment options in hormone-refractory metastatic prostate carcinoma. Tumori 2004; 90(6): 535–46

    PubMed  CAS  Google Scholar 

  19. Crain DS, Amling CL, Kane CJ. Palliative transurethral prostate resection for bladder outlet obstruction in patients with locally advanced prostate cancer. J Urol 2004; 171 (2 Pt 1): 668–71

    Article  PubMed  Google Scholar 

  20. Ward JF, Slezak JM, Blute ML, et al. Radical prostatectomy for clinically advanced (cT3) prostate cancer since the advent of prostate-specific antigen testing: 15-year outcome. BJU Int 2005; 95(6): 751–6

    Article  PubMed  Google Scholar 

  21. van den Ouden D, Schroder FH. Management of locally advanced prostate cancer. 1: staging, natural history, and results of radical surgery. World J Urol 2000; 18(3): 194–203

    Article  PubMed  Google Scholar 

  22. Schulam PG, Link RE. Laparoscopic radical prostatectomy. World J Urol 2000; 18(4): 278–82

    Article  PubMed  CAS  Google Scholar 

  23. Akakura K, Isaka S, Akimoto S, et al. Long-term results of a randomized trial for the treatment of stages B2 and C prostate cancer: radical prostatectomy versus external beam radiation therapy with a common endocrine therapy in both modalities. Urology 1999; 54(2): 313–8

    Article  PubMed  CAS  Google Scholar 

  24. Blasko JC, Ragde H, Grimm PD, et al. Prostate brachytherapy: importance of technique. J Clin Oncol 1996; 14(6): 1965–7

    PubMed  CAS  Google Scholar 

  25. Martinez AA, Pataki I, Edmundson G, et al. Phase II prospective study of the use of conformal high-dose-rate brachytherapy as monotherapy for the treatment of favorable stage prostate cancer: a feasibility report. Int J Radiat Oncol Biol Phys 2001; 49(1): 61–9

    Article  PubMed  CAS  Google Scholar 

  26. Hanks GE, Krall JM, Hanlon AL, et al. Patterns of care and RTOG studies in prostate cancer: long-term survival, hazard rate observations, and possibilities of cure. Int J Radiat Oncol Biol Phys 1994; 28(1): 39–45

    Article  PubMed  CAS  Google Scholar 

  27. Krengli M, Liebsch NJ, Hug EB, et al. Review of current protocols for proton therapy in USA. Tumori 1998; 84(2): 209–16

    PubMed  CAS  Google Scholar 

  28. Forman JD, Yudelev M, Bolton S, et al. Fast neutron irradiation for prostate cancer. Cancer Metastasis Rev 2002; 21(2): 131–5

    Article  PubMed  CAS  Google Scholar 

  29. Bagshaw MA, Kaplan ID, Cox RC. Prostate cancer. Radiation therapy for localized disease. Cancer 1993; 71 (3 Suppl.): 939–52

    Article  PubMed  CAS  Google Scholar 

  30. Zietman AL, Coen JJ, Dallow KC, et al. The treatment of prostate cancer by conventional radiation therapy: an analysis of long-term outcome. Int J Radiat Oncol Biol Phys 1995; 32(2): 287–92

    Article  PubMed  CAS  Google Scholar 

  31. Huggins C. Endocrine-induced regression of cancers. Science 1967; 156(778): 1050–4

    Article  PubMed  CAS  Google Scholar 

  32. Jani AB. The effectiveness of combining hormone therapy and radiotherapy in the treatment of prostate cancer. Expert Opin Pharmacother 2004; 5(12): 2469–77

    Article  PubMed  CAS  Google Scholar 

  33. Jani A, Vogelzang NJ. Re: Neoadjuvant hormonal ablative therapy before radical prostatectomy: a review. Is it indicated? J Urol 2001; 166(2): 631–2

    Article  PubMed  CAS  Google Scholar 

  34. Pilepich MV, Winter K, John MJ, et al. Phase III radiation therapy oncology group (RTOG) trial 86–10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate. Int J Radiat Oncol Biol Phys 2001; 50(5): 1243–52

    Article  PubMed  CAS  Google Scholar 

  35. Laverdiere J, Gomez JL, Cusan L, et al. Beneficial effect of combination hormonal therapy administered prior and following external beam radiation therapy in localized prostate cancer. Int J Radiat Oncol Biol Phys 1997; 37(2): 247–52

    Article  PubMed  CAS  Google Scholar 

  36. Lawton CA, Winter K, Murray K, et al. Updated results of the phase III Radiation Therapy Oncology Group (RTOG) trial 85-31 evaluating the potential benefit of androgen suppression following standard radiation therapy for unfavorable prognosis carcinoma of the prostate. Int J Radiat Oncol Biol Phys 2001; 49(4): 937–46

    Article  PubMed  CAS  Google Scholar 

  37. 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): 103–6

    Article  PubMed  CAS  Google Scholar 

  38. Hanks GE, Pajak TF, Porter A, et al. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02. J Clin Oncol 2003; 21(21): 3972–8

    Article  PubMed  CAS  Google Scholar 

  39. Roach 3rd M, DeSilvio M, Lawton C, et al. 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 2003; 21(10): 1904–11

    Article  PubMed  Google Scholar 

  40. Jani AB, Kao J, Hellman S. Hormone therapy adjuvant to external beam radiotherapy for locally advanced prostate carcinoma: a complication-adjusted number-needed-to-treat analysis. Cancer 2003; 98(11): 2351–61

    Article  PubMed  CAS  Google Scholar 

  41. Jani AB, Su A, Milano MT. Intensity modulated versus conventional pelvic radiotherapy for prostate cancer: analysis of acute toxicity. Urology 2006; 67(1): 147–51

    Article  PubMed  Google Scholar 

  42. Jani AB, Roeske JC, Rash C. Intensity-modulated radiation therapy for prostate cancer. Clin Prostate Cancer 2003; 2(2): 98–105

    Article  PubMed  Google Scholar 

  43. Radiation Therapy Oncology Group. A phase III trial to evaluate the duration of neoadjuvant total androgen suppression (TAS) and radiation therapy (RT) in intermediate-risk prostate cancer (RTOG 99-10) [online]. Available from URL: http://www.rtog.org [Accessed 2006 Feb 6]

  44. Jani AB, Gratzle J, Muresan E, et al. Analysis of acute toxicity with use of transabdominal ultrasonography for prostate positioning during intensity-modulated radiotherapy. Urology 2005; 65(3): 504–8

    Article  PubMed  Google Scholar 

  45. Jani AB, Gratzle J, Muresan E, et al. Impact on late toxicity of using transabdominal ultrasound for prostate cancer patients treated with intensity modulated radiotherapy. Technol Cancer Res Treat 2005; 4(1): 115–20

    PubMed  Google Scholar 

  46. Jani AB. Organ motion and IMRT in prostate cancer therapy. Cancer J 2003; 9(4): 244–6

    Article  PubMed  Google Scholar 

  47. Vicini FA, Vargas C, Edmundson G, et al. The role of high-dose rate brachytherapy in locally advanced prostate cancer. Semin Radiat Oncol 2003; 13(2): 98–108

    Article  PubMed  Google Scholar 

  48. Klein EA, Kupelian PA, Dreicer R, et al. Locally advanced prostate cancer. Curr Treat Options Oncol 2001; 2(5): 403–11

    Article  PubMed  CAS  Google Scholar 

  49. Pettaway CA, Pisters LL, Troncoso P, et al. Neoadjuvant chemotherapy and hormonal therapy followed by radical prostatectomy: feasibility and preliminary results. J Clin Oncol March 2000; 18(5): 1050–7

    CAS  Google Scholar 

  50. Konety BR, Eastham JA, Reuter VE, et al. Feasibility of radical prostatectomy after neoadjuvant chemohormonal therapy for patients with high risk or locally advanced prostate cancer: results of a phase I/II study. J Urol 2004; 171 (2 Pt 1): 709–13

    Article  PubMed  Google Scholar 

  51. Hussain M, Smith DC, El-Rayes BF, et al. Neoadjuvant docetaxel and estramustine chemotherapy in high-risk/locally advanced prostate cancer. Urology 2003; 61(4): 774–80

    Article  PubMed  Google Scholar 

  52. Zelefsky MJ, Kelly WK, Scher HI, et al. Results of a phase II study using estramustine phosphate and vinblastine in combination with high-dose three-dimensional conformal radiotherapy for patients with locally advanced prostate cancer. J Clin Oncol 2000; 18(9): 1936–41

    PubMed  CAS  Google Scholar 

  53. Cancer and Leukemia Group B. Phase II study of neoadjuvant paclitaxel, estramustine, carboplatin, and androgen ablation followed by radiotherapy in patients with poor-prognosis locally advanced prostate cancer (CALGB 99811) [online]. Available from URL: http://www.calgb.org [Accessed 2006 Feb 6]

  54. Radiation Therapy Oncology Group. A phase III protocol of androgen suppression (AS) and radiation therapy (RT) vs AS and RT followed by chemotherapy with paclitaxel, estramustine, and exisuland (TEE) for localized, high-risk, prostate cancer (RTOG P-0014) [online]. Available from URL: http://www.rtog.org [Accessed 2006 Feb 6]

  55. Radiation Therapy Oncology Group. A phase III randomized study of patients with high-risk, hormone-naive prostate cancer: androgen blockade with 4 cycles of immediate chemotherapy versus androgen blockade with delayed chemotherapy (RTOG P-0014) [online]. Available from URL: http://www.r-tog.org [Accessed 2006 Feb 6]

  56. Chhikara M, Huang H, Vlachaki MT, et al. Enhanced therapeutic effect of HSV-tk+GCV gene therapy and ionizing radiation for prostate cancer. Mol Ther 2001; 3(4): 536–42

    Article  PubMed  CAS  Google Scholar 

  57. Chen Y, DeWeese T, Dilley J, et al. CV706, a prostate cancer-specific adenovirus variant, in combination with radiotherapy produces synergistic antitumor efficacy without increasing toxicity. Cancer Res 2001; 61(14): 5453–60

    PubMed  CAS  Google Scholar 

  58. Freytag SO, Rogulski KR, Paielli DL, et al. A novel three-pronged approach to kill cancer cells selectively: concomitant viral, double suicide gene, and radiotherapy. Hum Gene Ther 1998; 9(9): 1323–33

    Article  PubMed  CAS  Google Scholar 

  59. Colletier PJ, Ashoori F, Cowen D, et al. Adenoviral-mediated p53 transgene expression sensitizes both wild-type and null p53 prostate cancer cells in vitro to radiation. Int J Radiat Oncol Biol Phys 2000; 48(5): 1507–12

    Article  PubMed  CAS  Google Scholar 

  60. Herman JR, Adler HL, Aguilar-Cordova E, et al. In situ gene therapy for adenocarcinoma of the prostate: a phase I clinical trial. Hum Gene Ther 1999; 10(7): 1239–49

    Article  PubMed  CAS  Google Scholar 

  61. DeWeese TL, van der Poel H, Li S, et al. A phase I trial of CV706, a replication-competent, PSA selective oncolytic adenovirus, for the treatment of locally recurrent prostate cancer following radiation therapy. Cancer Res 2001; 61(20): 7464–72

    PubMed  CAS  Google Scholar 

  62. Freytag SO, Khil M, Strieker H, et al. Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer. Cancer Res 2002; 62(17): 4968–76

    PubMed  CAS  Google Scholar 

  63. Teh BS, Aguilar-Cordova E, Kernen K, et al. Phase I/II trial evaluating combined radiotherapy and in situ gene therapy with or without hormonal therapy in the treatment of prostate cancer: a preliminary report. Int J Radiat Oncol Biol Phys 2001; 51(3): 605–13

    Article  PubMed  CAS  Google Scholar 

  64. Freytag SO, Stricker H, Pegg J, et al. Phase I study of replication-competent adenovirus-mediated double-suicide gene therapy in combination with conventional-dose three-dimensional conformal radiation therapy for the treatment of newly diagnosed, intermediate- to high-risk prostate cancer. Cancer Res 2003; 63(21): 7497–506

    PubMed  CAS  Google Scholar 

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Jani, A.B. Management Strategies for Locally Advanced Prostate Cancer. Drugs Aging 23, 119–129 (2006). https://doi.org/10.2165/00002512-200623020-00003

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