medwireNews: Pre-salvage radiotherapy (SRT) prostate-specific antigen (PSA) levels may help identify patients with biochemical recurrence after radical prostatectomy who are most likely to benefit from long-term antiandrogen treatment, research shows.
The secondary analysis of the phase 3 RTOG 9601 trial found that patients with pre-SRT PSA levels above 1.50 ng/mL derive significant overall survival (OS) benefit from 2 years of treatment with bicalutamide 1.50 mg/day following SRT.
By contrast, those with a PSA level of 0.6 ng/mL or lower were at increased risk for non-prostate cancer death, and cardiac and neurologic toxicity.
The primary analysis of the trial showed that men with a positive surgical margin or pathologic T3 disease after radical prostatectomy with pre-SRT PSA of 0.2–4.0 ng/mL had significantly better OS when randomly assigned to receive bicalutamide than placebo.
But Daniel Spratt (University of Michigan School of Medicine, Ann Arbor, USA) and co-investigators note that “hormone therapy has associated morbidity, and there are no validated predictive biomarkers to identify which patients derive most benefit from treatment.”
To address this, they analyzed the trial’s data according to pre-SRT PSA levels.
The researchers report that, among the 118 men with PSA level above 1.50 ng/mL, those treated with bicalutamide had a significant 55% lower risk for death from any cause during a median 13 years of follow-up than those treated with placebo. At 12 years, this was equivalent to an absolute survival benefit of 25 percentage points.
By contrast, there was no significant difference in OS between the two treatment groups among the 642 men with a PSA level of 1.50 ng/mL or lower.
Moreover, the researchers found that there was significant interaction between pre-SRT PSA and bicalutamide treatment effect after adjustment for age, Gleason score, T-stage, surgical margin, and nadir PSA.
Indeed, additional subanalysis by PSA level showed that the 253 men with a level of 0.61–1.50 ng/mL had a significant 39% lower risk for death associated with bicalutamide use, whereas the 389 participants with a level at or below 0.60 ng/mL derived no OS benefit from the antiandrogen treatment.
Furthermore, among the 389 men who received early SRT (PSA ≤0.60 ng/mL), those given bicalutamide had a significant 1.94-fold increased risk for death from causes other than prostate cancer relative to those who received placebo.
Bicalutamide was associated with a 2.48-fold significantly increased risk for late grade 3–5 cardiac and neurologic toxicity compared with placebo regardless of PSA level, but individuals receiving early SRT had the highest odds ratio (OR) for these events at 3.57. By comparison, the OR among patients with a PSA of 1.50 ng/mL or higher was 2.96.
Spratt and co-authors comment in JAMA Oncology: “Pre-SRT PSA is not only a predictive biomarker to identify benefit from antiandrogen therapy, but it also is useful in a discussion of potential harm.”
They conclude that this measure “can serve as both a prognostic and predictive serum biomarker to guide hormone therapy use with SRT” and note ongoing clinical trials may “further help personalize hormone therapy use in men receiving early SRT.”
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