Nadir testosterone within first year of androgen-deprivation therapy (ADT) predicts for time to castration-resistant progression: a secondary analysis of the PR-7 trial of intermittent versus continuous ADT

Abstract

Purpose: Three small retrospective studies have suggested that patients undergoing continuous androgen deprivation (CAD) have superior survival and time to progression if lower castrate levels of testosterone (< 0.7 nmol/L) are achieved. Evidence from prospective large studies has been lacking.

Patients and methods: The PR-7 study randomly assigned patients experiencing biochemical failure after radiation therapy or surgery plus radiation therapy to CAD or intermittent androgen deprivation. The relationship between testosterone levels in the first year and cause-specific survival (CSS) and time to androgen-independent progression in men in the CAD arm was evaluated using Cox regression.

Results: There was a significant difference in CSS (P = .015) and time to hormone resistance (P = .02) among those who had first-year minimum nadir testosterone ≤ 0.7, > 0.7 to ≤ 1.7, and ≥ 1.7 nmol/L. Patients with first-year nadir testosterone consistently > 0.7 nmol/L had significantly higher risks of dying as a result of disease (0.7 to 1.7 nmol/L: hazard ratio [HR], 2.08; 95% CI, 1.28 to 3.38; > 1.7 nmol/L: HR, 2.93; 95% CI, 0.70 to 12.30) and developing hormone resistance (0.7 to 1.7 nmol/L: HR, 1.62; 95% CI, 1.20 to 2.18; ≥ 1.7 nmol/L: HR, 1.90; 95% CI, 0.77 to 4.70). Maximum testosterone ≥ 1.7 nmol/L predicted for a higher risk of dying as a result of disease (P = .02).

Conclusion: Low nadir serum testosterone (ie, < 0.7 mmol/L) within the first year of androgen-deprivation therapy correlates with improved CSS and duration of response to androgen deprivation in men being treated for biochemical failure undergoing CAD.

Trial registration: ClinicalTrials.gov NCT00003653.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

© 2015 by American Society of Clinical Oncology.

Figures

Fig 1.

PR-7 CONSORT diagram. ADT, androgen-deprivation therapy; CAD, continuous androgen deprivation; CRPC, castration-resistant prostate cancer; PSA, prostate-specific antigen.

Fig 2.

Time to castration-resistant prostate cancer according to (A) median, (B) nadir, and (C) maximum first-year testosterone (testo) levels. HR, hazard ratio.

Fig 3.

Cause-specific survival according to (A) median, (B) nadir, and (C) maximum first-year testosterone (testo) levels. HR, hazard ratio.