PCa Commentary
 

Six-Months Androgen Suppression Plus Radiotherapy - Strong Support For An Overall Survival Benefit In Men With Clinically Localized Intermediate And High Risk Prostate Cancer. (October 2004)

D’Amico et al reported (JAMA, August 2004) a randomized controlled trial that compared androgen suppression therapy (AST) with an LHRH agonist plus Flutamide 250 mg TID given for 2 months prior to, during, and after 70.35 Gy 3D-CRT (102 men) to RT alone (104 men). The RT covered the prostate plus a 1.5 cm. margin and included the seminal vesicles. Patients were stratified into four groups: 1), PSA 20 - 40 ng/mL; 2), biopsy Gleason score of at least 7; 3), PSA 10 - 20 and a biopsy Gleason score of 6 or less; and 4), low risk patients in whom an MRI showed seminal vesicle invasion or extra capsular extension. Bone scans were negative and lymph nodes were assessed as normal by MRI or CT. PSA failure was defined as a “PSA > 1.0 ng/mL, and increasing by more than .2 ng/mL on 2 consecutive measurements”. Upon PSA failure, AST “salvage” was either restarted or initiated at an unstandardized point but “at a PSA level of approximately 10 ng/mL”. The median follow-up was 4.52 years.

Results: “Estimates of overall survival were significantly longer for patients who were treated with 3D-CRT plus AST compared to patients receiving only 3D-CRT”: estimated 5 year survival was 88% vs 78%. In the RT only group there were 6 prostate cancer deaths and none in the combined treatment group. Survival at five years without AST salvage (ie survival without progression) was significantly longer in the combined therapy groups, 82% vs 57%.

[Editor’s note: The generalization claiming accrued benefit in this small study is supported by the essential similarity of the characteristics of the subjects in the two study arms. There was a slight difference in number of men in the cT1b, cT1c, and cT2b categories: 3D-CRT 41, 25, and 33 vs 3D-CRT+AST 54, 20, and 27. However, practical clinical application of the findings of this study would have been better facilitated (if there had been sufficient cases) by separate outcome comparisons within the 4 categories of enrollees, particularly since there was not a clear-cut “intermediate-risk group” as conventionally defined. As reference, Kupelian has reported (Radiation and Oncology, 2004, pp. 29-33) an approximate 80% five year freedom from biochemical recurrence for cT1-T2 staged men treated with EBRT (n = 340) and permanent seed brachytherapy (n = 733) and an overall 7-year estimated survival of approximately 95% for both treatment modalities.]

In an accompanying editorial DeWeese noted that the D’Amico study was the first to find an overall survival benefit in men with clinically localized disease. He pointed to the Bolla trial (RT vs RT + 3 year AS) which also had shown a cause specific and overall survival, but the Bolla study focused on locally advanced, high-risk, cancer (5 year overall survival: RT - 62%, RT+AS - 78%; cause specific survival, 79% vs 94%). DeWeese concluded that these two trials “strongly argue that patients with locally advanced and high risk prostate cancer are appropriately treated with a combination of AST and RT and the benefits of such combination therapy are real and quantifiable. However, he felt that some outstanding issues have to be addressed before calling these regimens “standard”.

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