Continuous vs. intermittent androgen deprivation therapy for metastatic prostate cancer

To analyze the predictive value of PSA for progression and the role of testosterone for quality of life (QOL) in patients with androgen deprivation therapy (ADT) for metastatic prostate cancer.

PSA and testosterone data were used from a phase III trial randomizing patients without progression and PSA < 4 ng/ml (n = 193), after 6 months induction course, between continuous (CAD) (n = 96) and intermittent (IAD) (n = 97) ADT. The 2-year risk of progression was calculated for baseline PSA, 'fast' and 'slow' PSA decline to < 4 ng/ml (60 days cut-off), PSA nadir, performance status and pain. Testosterone kinetics and QOL were also evaluated. Univariate Kaplan Meier survival analysis and log rank tests were used to compare the risk of progression.

For progression analysis, 173 patients' data were available. The 2-year risk of progression for baseline PSA < 50 ng/ml, 50 to <500 ng/ml, and ≥ 500 ng/ml was 25%, 55%, and 76% (P = 0.03) in CAD, and 38%, 64%, and 85% (P = 0.006) in IAD, respectively. The 2-year risk of progression for PSA nadir ≤ 0.2 ng/ml, and > 0.2 to 4 ng/ml in CAD was 31% and 70% (P < 0.001), respectively. In the IAD group, a similar trend was seen. Patients with PSA nadir ≤ 0.2 ng/ml, though had significantly higher 2-year risk of progression compared to CAD (53% vs. 31% (P = 0.03), respectively. PSA decline showed no predictive value. Patients without pain had a significantly lower 2-year risk of progression in both groups. Without ADT testosterone remained at castrate level for 4 months. After the first and second IAD cycle 92% and 46%, respectively, had a normalized testosterone. No QOL difference was found, although more side effects occurred in CAD.

Metastatic prostate cancer patients with high baseline PSA, pain, and high PSA nadir have a poor prognosis with ADT. Patients with low PSA nadir do significantly worse with IAD compared with CAD. Low testosterone after ADT and incomplete testosterone recovery may explain similar QOL. Therefore, IAD is not a good treatment option for many metastatic prostate cancer patients.