RATIONALE: Radiation therapy uses high energy x-rays to damage tumor cells. Hormone therapy combined with radiation therapy may be a more effective treatment for prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of four different combinations of radiation and hormone therapy in treating patients with prostate cancer.

OBJECTIVES: I. Examine whether total androgen suppression (TAS) with flutamide/goserelin and whole-pelvic irradiation followed by a cone-down boost to the prostate improves progression-free survival at 5 years by at least 10% compared to TAS and prostate-only irradiation in patients with adenocarcinoma of the prostate at significant risk of nodal involvement. II. Examine whether induction and concurrent (neoadjuvant) TAS and radiotherapy improves the progression-free survival at 5 years by at least 10% compared to adjuvant TAS and radiotherapy. III. Compare treatments with regard to local control, time to distant failure, and overall survival.

OUTLINE: Randomized study. Arm I: Neoadjuvant Antiandrogen Therapy with Radiotherapy. Flutamide, FLUT, NSC-147834; Goserelin, Zoladex, ZDX, NSC-606864; with irradiation of the whole pelvis followed by a boost to the prostate using photons of at least 6 MV. Arm II: Neoadjuvant Antiandrogen Therapy with Radiotherapy; FLUT; ZDX; with irradiation of the prostate using equipment as in Arm I. Arm III: Radiotherapy followed by Adjuvant Antiandrogen Therapy. Irradiation as in Arm I; followed by FLUT; ZDX. Arm IV: Radiotherapy followed by Adjuvant Antiandrogen Therapy. Irradiation as in Arm II; followed by FLUT; ZDX.

PROJECTED ACCRUAL: 1,200 patients will be accrued over 2.5 years.

• Drug: flutamide
• Drug: goserelin
• Radiation: low-LET photon therapy

• Taussky D, Bae K, Bahary JP, Roach M 3rd, Lawton CA, Shipley WU, Sandler HM. Does Timing of Androgen Deprivation Influence Radiation-Induced Toxicity? A Secondary Analysis of Radiation Therapy Oncology Group Protocol 9413. Urology. 2008 Feb 29; [Epub ahead of print]
• Lawton CA, DeSilvio M, Roach M 3rd, Uhl V, Kirsch R, Seider M, Rotman M, Jones C, Asbell S, Valicenti R, Hahn S, Thomas CR Jr. 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. 2007 Nov 1;69(3):646-55. Epub 2007 May 24.
• Roach M 3rd, DeSilvio M, Valicenti R, Grignon D, Asbell SO, Lawton C, Thomas CR Jr, Shipley WU. Whole-pelvis, "mini-pelvis," or prostate-only external beam radiotherapy after neoadjuvant and concurrent hormonal therapy in patients treated in the Radiation Therapy Oncology Group 9413 trial. Int J Radiat Oncol Biol Phys. 2006 Nov 1;66(3):647-53.
• Roach M 3rd, DeSilvio M, Lawton C, Uhl V, Machtay M, Seider MJ, Rotman M, Jones C, Asbell SO, Valicenti RK, Han S, Thomas CR Jr, Shipley WS; Radiation Therapy Oncology Group 9413. 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 May 15;21(10):1904-11.
• Millar J, Boyd R, Sutherland J. 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: in regard to Lawton et al. (Int J Radiat Oncol Biol Phys 2007;69:646-655.). Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):316; author reply 316. No abstract available.
• Williams S, Wiltshire K. Updated analysis of RTOG 94-13: in regard to Lawton et al. (Int J Radiat Oncol Biol Phys 2007;69:646-655). Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):315; author reply 315-6. No abstract available.
• Ganswindt U, Paulsen F, Corvin S, Eichhorn K, Glocker S, Hundt I, Birkner M, Alber M, Anastasiadis A, Stenzl A, Bares R, Budach W, Bamberg M, Belka C. Intensity modulated radiotherapy for high risk prostate cancer based on sentinel node SPECT imaging for target volume definition. BMC Cancer. 2005 Jul 28;5:91.
• Johnke RM, Edwards JM, Evans MJ, Nangami GN, Bakken NT, Kilburn JM, Lee TK, Allison RR, Karlsson UL, Arastu HH. Circulating cytokine levels in prostate cancer patients undergoing radiation therapy: influence of neoadjuvant total androgen suppression. In Vivo. 2009 Sep-Oct;23(5):827-33.
• Roach M 3rd. The role of PSA in the radiotherapy of prostate cancer. Oncology (Williston Park). 1996 Aug;10(8):1143-53; discussion 1154-61. Review.

DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Any stage with an estimated risk of node involvement at least 15% (and therefore at significant risk for local and/or systemic failure) based on pretreatment PSA and Gleason score (GS), e.g.: GS of 7 and PSA greater than 7.5 ng/mL GS of 6 and PSA greater than 22.5 ng/mL GS of 5 and PSA greater than 37.5 ng/mL PSA greater than 4 and less than 100 ng/mL Highest pretreatment value determined by a monoclonal assay that has a normal range of 0-4 ng/mL PSA measured by polyclonal assay (e.g., Yang) that has a normal range of 0-2.5 ng/mL may need to be divided by a conversion factor of approximately 1.5 GS determination required prior to entry No distant metastases No biopsy proven lymph node involvement Ineligible for protocol RTOG-9408 (clinical stages T2c-T4 with GS of 6 or higher are eligible for this study)

PATIENT CHARACTERISTICS: Age: Any age Performance status: Karnofsky 70-100% Hematopoietic: Not specified Hepatic: Liver function tests no greater than 1.2 times normal Renal: Not specified Other: No major medical or psychiatric illness that would prevent completion of treatment or interfere with follow-up No second malignancy within 5 years except superficial nonmelanomatous skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: At least 90 days since testosterone At least 60 days since finasteride Radiotherapy: No prior radiotherapy Surgery: No more than 60 days since surgical staging No radical surgery or cryosurgery