Radiation Therapy With or Without Antiandrogen Therapy in Treating Patients With Stage I or Stage II Prostate Cancer

RATIONALE: Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. Androgens can stimulate the growth of prostate cancer cells. Hormone therapy using flutamide, goserelin, and leuprolide may fight prostate cancer by reducing the production of androgens. It is not yet known which regimen of antiandrogen therapy is most effective for prostate cancer. PURPOSE: Randomized phase III trial to study the effectiveness of radiation therapy with or without antiandrogen therapy in treating patients who have stage I or stage II prostate cancer.

Sex

Male

Minimum age

18 Years

Inclusion criteria:

* Histologically confirmed locally confined adenocarcinoma of the prostate with primary tumors confined to the prostate, clinical stage T1b,1c, 2a or 2b.
* Negative nodes evaluated by imaging methods (classified in the study as NX) or by surgical sampling (classified in the study as N0).
* Karnofsky performance status ≥ 70.
* PSA is mandatory, must be ≤ 20)
* No prior hormonal therapy, radiation or chemotherapy.
* Prior finasteride for prostate hypertrophy allowed if discontinued at least 60 days prior to randomization.
* Prior testosterone administration allowed if at least 90 days elapsed since last administration.
* No evidence of distant metastasis or other synchronous primary. Patients with prior invasive malignancy who were disease free for at least 5 years could be eligible with pre-randomization approval by the study chairman.
* Treatment begins within 21 days after randomization.
* Patients signs a study-specific informed consent form.
* Alanine Aminotransferase (ALT) within 2x upper normal limits.

Exclusion criteria:

* Stage T1a or ≥ T2c disease.
* Lymph node involvement (N1 - N3).
* Evidence of distant metastasis. (M1)
* PSA \> 20.
* Radical surgery or cryosurgery for carcinoma of the prostate, previous irradiation, antiandrogen therapy or chemotherapy.
* Previous or concurrent cancers other than basal cell or squamous cell skin carcinoma.

Patients with squamous cell carcinomas required to be NED (no evidence of disease) for a minimum of two years prior to study entry.

* Major medical or psychiatric illness which, in the investigator's opinion, would prevent completion of treatment and would interfere with follow-up.
* Karnofsky performance status of \< 70.

• BACKGROUNDBruner D, Scott C, McGowan D, et al.: Factors influencing sexual outcomes in prostate cancer patients enrolled on radiation therapy oncology group studies 90-20 and 94-08. [Abstract] Proceedings of the International Society for Quality of Life Research 7: 575, 1998.
• BACKGROUNDBruner DW, Scott CB, McGowan D, et al.: Validation of the sexual adjustment questionnaire (SAQ) in prostate cancer patients enrolled on Radiation Therapy Oncology Group studies 90-20 and 94-08. [Abstract] Int J Radiat Oncol Biol Phys 42 (suppl 1): A-156, 202, 1998.
• BACKGROUNDJohnke 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. PMID 19779119
• RESULTJones CU, Hunt D, McGowan DG, Amin MB, Chetner MP, Bruner DW, Leibenhaut MH, Husain SM, Rotman M, Souhami L, Sandler HM, Shipley WU. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011 Jul 14;365(2):107-18. doi: 10.1056/NEJMoa1012348. PMID 21751904
• RESULTMcGowan D, Hunt D, Jones C, et al.: Effect of short-term endocrine therapy prior to and during radiation therapy on overall survival in patients with T1b-T2b adenocarcinoma of the prostate and PSA equal to or less than 20: initial results of RTOG 94-08. [Abstract] 2010 Genitourinary Cancers Symposium, March 5-7, 2010, San Francisco, California. A-6, 2010.
• DERIVEDSpratt DE, Tang S, Sun Y, Huang HC, Chen E, Mohamad O, Armstrong AJ, Tward JD, Nguyen PL, Lang JM, Zhang J, Mitani A, Simko JP, DeVries S, van der Wal D, Pinckaers H, Monson JM, Campbell HA, Wallace J, Ferguson MJ, Bahary JP, Schaeffer EM, Sandler HM, Tran PT, Rodgers JP, Esteva A, Yamashita R, Feng FY. Artificial Intelligence Predictive Model for Hormone Therapy Use in Prostate Cancer. NEJM Evid. 2023 Aug;2(8):EVIDoa2300023. doi: 10.1056/EVIDoa2300023. Epub 2023 Jun 29. PMID 38320143
• Jones CU, Pugh SL, Sandler HM, Chetner MP, Amin MB, Bruner DW, Zietman AL, Den RB, Leibenhaut MH, Longo JM, Bahary JP, Rosenthal SA, Souhami L, Michalski JM, Hartford AC, Amin PP, Roach M 3rd, Yee D, Efstathiou JA, Rodgers JP, Feng FY, Shipley WU. Adding Short-Term Androgen Deprivation Therapy to Radiation Therapy in Men With Localized Prostate Cancer: Long-Term Update of the NRG/RTOG 9408 Randomized Clinical Trial. Int J Radiat Oncol Biol Phys. 2022 Feb 1;112(2):294-303. doi: 10.1016/j.ijrobp.2021.08.031. Epub 2021 Sep 1.