Dec 7, 1999 -- New York / PSA Rising. If patients with large tumors confined to the prostate decide to take radiation therapy, they may improve the longterm odds of avoiding PSA progression and metastasis by taking hormone treatment before, during and after radiation treatments, a new study suggests.

The data presented show that radiation therapy without hormones has a high failure rate as measured by PSA relapse within five years and a poor rate as measured by development of distant metastasis within eight years. If hormones are added, these failure rates improve.

The study of 1,000 patients treated in facilities nationwide found that the overall rate of PSA relapse (a rising PSA level) and distant metastases were significantly decreased with the use of hormones combined with radiation compared to radiation alone, says Eric Horwitz, M.D., associate member at Fox Chase Cancer Center in Philadelphia, PA. Dr. Horwitz presented the study November 3 at the American Society for Therapeutic Radiology and Oncology annual meeting in San Antonio, TX.

Almost Thirty Per Cent Improvement in PSA Relapse, But Failure Rate Remains High
PSA relapse (failure) for patients who received hormones was 59 percent at five years compared to 86 percent for those who were treated with radiation alone. For patients who received hormones,distant metastases relapse was 28 percent at eight years compared with 39 percent for those treated with radiation therapy alone, he says. Patients were also less likely to have distant metastases if they had long-term hormones, he adds.

Another recent study finds that "Conventional radiation alone has little curative potential for Stage III disease. Doses The Fox Chase study indicates that the greatest benefit of adding hormones to radiation is for patients who receive the hormones for an extended period. Among patients with Gleason score 7 - 10 tumors receiving radiation and hormones, those who took the hormones before, during and after treatment fared the best, notes Dr. Horwitz. But still only 52 percent of these patients were without a PSA relapse at five years. This compares to a dismal 27 percent for patients who only received hormones before and during radiation therapy and even worse 14 percent of those who had radiation therapy alone, he says. Patients were also less likely to have distant metastases if they had long-term hormones, he adds.

Patients with Gleason score 7 tumors do not usually receive hormones, notes Dr. Horwitz. He says these findings indicate they may benefit.

Abstracts of Related Studies [abstracts will open in a separate browser window. This window will minimize at the bottom of your screen for opening if you wish to come back to this site]:

Int J Radiat Oncol Biol Phys 1999 Jul 1;44(4):809-19 Conventional external-beam radiation therapy alone or with androgen ablation for clinical stage III (T3, NX/N0, M0) adenocarcinoma of the prostate. Zagars GK, Pollack A, Smith LG Department of Radiation Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA. "Conventional radiation alone has little curative potential for Stage III disease. Doses

Adding Hormone Therapy to Radiation Helps Survival of High Risk Patients October 1998 story on results of study by Mac Roach, III, MD, associate professor of radiation oncology and medicine at University of California, San Francisco.

Radiat Oncol Investig 1999;7(4):249-59 Is there a role for short-term hormone use in the treatment of nonmetastatic prostate cancer? Horwitz EM, Hanlon AL, Pinover WH, Hanks GE Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. [email protected]

J Urol 1999 Dec;162(6):2024-8 Neoadjuvant hormonal therapy before radical prostatectomy and risk of prostate specific antigen failure. Meyer F, Moore L, Bairati I, Lacombe L, Tetu B, Fradet Y Laval University Cancer Research Center, and the Department of Social and Preventive Medicine, Laval University, Quebec, Canada. "Treatments with antiandrogen alone for any duration, and those combining antiandrogen and luteinizing hormone-releasing hormone analogue for 3 months or less were not associated with improved survival. However, patients receiving combined therapy for more than 3 months had a significantly lower risk of PSA failure than those treated with radical prostatectomy alone (hazards ratio 0.52, 95% confidence interval 0.29 to 0.93). CONCLUSIONS: Prolonged neoadjuvant hormonal therapy combining antiandrogen and luteinizing hormone-releasing hormone analogue may improve disease-free survival after radical prostatectomy."

Urology 1999 Nov;54(5):884-90 Biochemical failure does not predict overall survival after radical prostatectomy for localized prostate cancer: 10-year results. Jhaveri FM, Zippe CD, Klein EA, Kupelian PA Department of Urology, Cleveland Clinic Foundation, Ohio 44195, USA. OBJECTIVES: To compare rates of overall survival in men with biochemical failure (bF) to those with no bF after radical prostatectomy for localized prostate cancer. METHODS: Radical prostatectomy was performed in 1132 consecutive patients between June 1986 and September 1998, and bF (prostate-specific antigen [PSA] 0.2 ng/mL or greater) was documented in 213 patients (19%), with a mean follow-up of 56 months (range 1 to 125). Ninety-nine patients were treated with androgen ablation and/or radiation therapy at the time of bF. Kaplan-Meier estimates of bF, metastasis-free survival, and overall survival were generated and compared using the log-rank test. RESULTS: The 10-year overall survival rates for patients with bF (88%) versus no bF (93%) were similar (P = 0.94). The survival rates of patients with bF were not statistically different than those of patients without bF when compared by age older than 65 years, preoperative PSA greater than 10 ng/mL, biopsy or specimen Gleason score 7 or greater, clinical Stage T2b-3, presence of extracapsular extension, positive surgical margins, and seminal vesicle invasion. Patients who received second-line treatment also had a similar 10-year overall survival rate (86%, P = 0.97). For the 213 patients with bF, the metastasis-free survival rate at 10 years was 74%. The overall survival rate for patients with distant metastasis (56%) was markedly lower (P

Urology 1999 Sep;54(3):495-502 Does androgen suppression enhance the efficacy of postoperative irradiation? A secondary analysis of RTOG 85-31. Radiation Therapy Oncology Group Corn BW, Winter K, Pilepich MV Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA "With a median follow-up of 5 years, the estimated progression-free survival rate (failure defined as prostate-specific antigen [PSA] greater than 0.5 ng/mL) was 65% for the men who received combination therapy and 42% for those treated by RT alone with hormones reserved for relapse (P = 0.002). Differences in the rates of freedom from biochemical relapse were observed when failure was defined as PSA of 1.0 to 3.9 ng/mL (71% versus 46%; P = 0.008) and PSA greater than 4.0 ng/mL (76% versus 55%; P = 0.05), respectively. No differences were observed between the groups with respect to the end points of local control, distant failure, and overall survival. The use of immediate androgen suppression (ie, LHRH agonists) and the absence of pathologic nodal involvement were independently associated with prolongation of freedom from biochemical relapse ...."

J Clin Oncol 1999 Nov;17(11):3664-3675 Treatment of Locally Advanced Prostate Cancer: Is Chemotherapy the Next Step? Oh WK, Kantoff PW Lank Center for Genitourinary Oncology, Department of Adult Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA. "The use of adjuvant hormonal ablation therapy in combination with external-beam radiotherapy has shown improvement in progression-free and overall survival ....Optimal management of locally advanced prostate cancer remains undefined. Standard treatment options include RP, external-beam radiotherapy, or hormonal ablation therapy, alone or in combination. New approaches being tested include improved methods for delivering radiation or combining hormonal ablation with surgery or radiation. It is possible that other forms of systemic therapy, including chemotherapy, may become important components of multimodality treatment. Clinical trials designed to test this hypothesis are ongoing."

Ann Oncol 1999 Aug;10(8):891-8 Recent advances in the treatment of prostate cancer. Kuyu H, Lee WR, Bare R, Hall MC, Torti FM Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC, USA. "Although neoadjuvant hormonal therapy prior to radical prostatectomy decreases positive surgical margin rates, longer follow-up is needed to support survival improvement of this combined modality therapy. Androgen deprivation combined with radiation therapy appears to improve disease-free survival (and survival in one series) in patients with locally advanced cancer. Another approach to locally advanced prostate cancer using three-dimensional conformal radiation therapy may improve long term outcome. The data are currently insufficient to conclude that interstitial low dose rate brachytherapy is equivalent to conventional treatments: patients with small tumor volumes and low Gleason grade seem to obtain more benefit, whereas for large tumors with higher gleason grades this approach seems inferior to conventional treatments. In advanced prostate cancer recent data suggest that immediate hormonal therapy improves survival. In this group of patients the use of maximum androgen blockade remains controversial but may adversely affect quality of life compared to orchiectomy alone. Intermittent hormonal therapy may improve quality of life, although effect upon survival is unknown. Chemotherapy in combination with androgen deprivation is currently being studied as front-line therapy in advanced prostate cancer."

Hematol Oncol Clin North Am 1999 Jun;13(3):489-501 Permanent radioactive seed implantation in the treatment of prostate cancer. Stock RG, Stone NN Department of Radiation Oncology, Mount Sinai Medical Center, New York, New York, USA. "Prostate brachytherapy has come a long way in the last 15 years, from an open free-hand technique with which seed placement was often inaccurate to the highly technical and accurate procedure of today. It has become a viable treatment option for low-risk patients along with EBRT and prostatectomy. Its most promising use may be in combination with hormonal therapy and EBRT in moderate- to high-risk patients, for whom it may offer improved outcomes over standard single-modality therapies."