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Low testosterone predicts improved outcomes with continuous ADT in prostate cancer
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Patients with prostate cancer who achieved low nadir serum testosterone within the first year of continuous androgen-deprivation therapy demonstrated improved cause-specific survival and duration of response, according to results of a post-hoc analysis.
Lawrence Klotz, MD, of the department of urology at the University of Toronto Sunnybrook Health Sciences Centre, and colleagues evaluated data from patients with non-metastatic biochemical prostate cancer recurrence after radiation alone or with surgery who were enrolled on the PR-7 study. Researchers had assigned patients intermittent ADT (n = 690) or continuous ADT (n = 696).
In the current analysis, researchers sought to evaluate the association between nadir testosterone level and disease progression in 626 evaluable patients in the continuous ADT arm.
Of these patients, 226 developed castration-resistant prostate cancer (CRPC). The median time to CRPC was 10 years, and the 5-year event-free rate was 69% (95% CI, 65-72).
Patients underwent serum testosterone measurements every 2 months for 1 year. A majority of patients (78%) achieved nadir testosterone at or below 0.7 nmol/L, whereas 21% achieved nadir testosterone between 0.7 nmol/L and 1.7 nmol/L, and 1% had nadir levels of 1.7 nmol/L or greater.
Patients with the lowest nadir testosterone levels were significantly older than those with the highest levels (mean age, 74.3 years vs. 69.6 years; P ˂ .001).
The risk for developing CRPC was greater in patients with 0.7 nmol/L to 1.7 nmol/L nadir testosterone levels (HR = 1.62; 95% CI, 1.2-2.18) and in patients with nadir levels of 1.7 nmol/L or greater (HR = 1.9; 95% CI, 0.77-4.7) compared with patients with the lowest levels.
The risk for death from disease was significantly greater in patients with intermediate nadir levels (HR = 2.08; 95% CI, 1.28-3.38) and the highest nadir levels (HR = 2.93; 95% CI, 0.7-12.3) compared with those with levels below 0.7 nmol/L.
“Our study demonstrates that serum testosterone ≤0.7 nmol/L during the first year of ADT predicts for an improved duration of response in men undergoing continuous ADT for biochemical failure,” Klotz and colleagues concluded.
In an accompanying editorial, Daniel L. Suzman, MD, and Emmanuel S. Antonarakis, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, questioned whether achieving a serum testosterone level below 0.7 nmol/L should be the goal of treatment.
“We believe there are some reasons to be cautious,” Suzman and Antonarakis wrote. “For one, periods of testosterone normalization are the goal of intermittent hormone therapy. Because the primary analysis of the PR-7 study showed that intermittent hormone therapy was non-inferior to continuous therapy with respect to OS, the importance of further testosterone manipulation following ADT is unclear. Moreover, the need for ADT in the setting of non-metastatic biochemically recurrent prostate cancer remains controversial, regardless of whether it is delivered in continuous or intermittent fashion.” – by Cameron Kelsall
Disclosure: Klotz reports research funding from Ferring Pharmaceuticals and honoraria from Abbvie, Amgen, Astellas Pharma, Aventis and Janssen Pharmaceuticals. Antonarakis reports honoraria and research funding from and consultant/advisory roles with Aragon, Dendreon, Exelixis, Genentech, Janssen, Johnson & Jonson, Medivation, Millennium, Novartis and Sanofi. Please see the study for a full list of all other researchers’ relevant financial disclosures.
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