UROLOGICAL ONCOLOGY

Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma – long-term results of phase III RTOG 85-31
Pilepich MV, Winter K, Lawton CA, Krisch RE, Wolkov HB, Movsas B, Hug EB, Asbell SO, Grignon D
University of California, Los Angeles, School of Medicine, Los Angeles, CA, USA
Int J Radiat Oncol Biol Phys. 2005; 61: 1285-90

• Purpose: Radiation Therapy Oncology Group protocol 85-31 was designed to evaluate the effectiveness of adjuvant androgen suppression, using goserelin, in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy (RT).
• Methods and Materials: Eligible patients were those with palpable primary tumor extending beyond the prostate (clinical Stage T3) or those with regional lymphatic involvement. Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and/or seminal vesicle involvement was documented histologically. Stratification was based on histologic differentiation, nodal status, acid phosphatase status, and prior prostatectomy. The patients were randomized to either RT and adjuvant goserelin (Arm I) or RT alone followed by observation and application of goserelin at relapse (Arm II). In Arm I, the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression.
• Results: Between 1987 and 1992, when the study was closed, 977 patients were entered: 488 to Arm I and 489 to Arm II. As of July 2003, the median follow-up for all patients was 7.6 years and for living patients was 11 years. At 10 years, the absolute survival rate was significantly greater for the adjuvant arm than for the control arm: 49% vs. 39%, respectively (p = 0.002). The 10-year local failure rate for the adjuvant arm was 23% vs. 38% for the control arm (p < 0.0001). The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24% vs. 39% (p < 0.001) and 16% vs. 22% (p = 0.0052), respectively, both in favor of the adjuvant arm.
• Conclusion: In a population of patients with unfavorable prognosis carcinoma of the prostate, androgen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival. The improvement in survival appeared preferentially in patients with a Gleason score of 7-10.
  
  
• Editorial Comment
  Androgen suppression adjuvant to radiotherapy is often performed, for better or worse. The long-term sequelae of this therapy e.g. bone demineralization and loss of muscle, are slowly recognized and will be in the focus of a later comment. The advantage of adjuvant therapy especially with regard to survival, however, was disputable. The long-term outcome data of this RTOG trial supports the efficacy of adjuvant hormone therapy.
  Briefly, both progression measured as local and distant failure, and survival with or without evidence of disease were statistically significant better in the treatment arm. With regard to Gleason score, the subset of patients with Gleason 8-10 benefited most.

Dr. Andreas Bohle
Professor of Urology
HELIOS Agnes Karll Hospital
Bad Schwartau, Germany