Prospective evaluation of testosterone (T) recovery and PSA relapse following 18 months of androgen deprivation (ADT) after prostatectomy (RP): Results from the TAX-3501 trial.

Abstract

5023 Background: Surgical adjuvant trials in men with prostate cancer (PCa) employing progression free (PFS) and overall survival (OS) endpoints require large sample sizes and long-term follow-up, challenging planned study completion. Recent adjuvant trials are designed to evaluate PSA progression as the primary study endpoint. Since PSA is T-responsive, a thorough understanding of T recovery kinetics after ADT is needed. Methods: TAX-3501 was a randomized phase III adjuvant study post-RP in men with high-risk PCa (n=228) comparing 18 months of hormonal therapy with (CHT) or without (HT) docetaxel either immediately (I) or deferred (D). We analyzed the T recovery data in 108 patients treated with HT who had at least one post-treatment T value. Results: After a median post-treatment follow-up of 676 days (d) (interquartile range 478-847 d) 90 (83%) and 64 (59%) of men had T recovery to >150 ng/dL and to baseline respectively. No significant differences in T recovery between groups were observed (Table). The median time to T recovery from the last day of treatment to >150 ng/dL was 306 d (95% CI, 294-345 d) and to baseline was 487 d (95% CI, 457-546 d). The baseline T recovery in the combined docetaxel [i.e. I(CHT)+D(CHT)] and HT arms [i.e. I(HT)+D(HT)] was not significantly different at 458 d (95% CI, 336-529 d) and 535 d (95% CI, 457-749 d) respectively (HR 1.4, P=0.18). After a median total follow-up of 3.4 years(IQR 2.3–3.8 years) 39/228 (17%) patients had PSA progression, metastatic progression occurred in 1 patient. Conclusions: Prospective analyses of T kinetics in TAX-3501 indicate that recovery is prolonged after 18 months of HT and PSA relapses occur late. Given that PSA is androgen responsive, concomitant post-HT T monitoring is critical for understanding PSA relapse rates after HT. Further, since the correlation of PSA relapse with PFS and OS in the adjuvant setting remains poorly defined, metastasis-free survival may be a more reliable and meaningful clinical endpoint. Clinical trial information: NCT00283062. [Table: see text]