Researchers at Johns Hopkins have attempted to correlate data on PSA doubling time (PSADT) with data on prostate cancer progression in men being treated with intermittent androgen deprivation therapy (IADT) after biochemical recurrence of prostate cancer.
This paper by Keizman et al. is based on a retrospective analysis of data from 96 patients with progressive prostate cancer treated with IADT at Johns Hopkins since 1995.
There patients were treated with IADT using either an LHRH agonist alone or a combination of an LHRH agonist with an antiandrogen. Treatment was usually initiated when the patient reached a threshold PSA level of 10-20 ng/ml, and the initial drug treatment lasted for either 6 or 9 months. Cycles were repeated until the development of castration resistance.
Analysis of the available data revealed the following:
- Patients received an average (mean) of 2.8 treatment cycles over a mean follow-up time of 71 months.
- 57/96 patients (59 percent) remain on treatment.
- 39/96 patients (41 percent) became hormone refractory, with a rising PSA (n = 8) or developed positive bone or soft tissue scans with clear evidence of metastatic disease (n = 31).
- The PSADT (median 2.3 months) during the first off-treatment period was significantly shorter than the baseline pre-treatment PSADT (median 7.3 months) but remained stable in subsequent cycles.
- When adjusted for testosterone recovery, the PSADT during off-treatment periods (median 3.7 months) was significantly longer than that based on all PSA determinations (median 2 months).
- Several factors could clearly be associated with disease progression, including
- Pre-treatment PSADT (≥ 6 vs. < 6 months)
- PSADT during the first off-treatment period (≥ 3 vs. < 3 months)
- PSA nadir during the first treatment period (< 0.1 vs. ≥ 0.1 ng/ml)
The authors conclude that, during IADT for progressive disease, the PSADT becomes shorter, and that this shortening of the PSADT is associated with testosterone recovery. They also conclude that the PSADT prior to initiation of IADT and during the first off-treatment interval is associated with disease progression.
They go on to suggest that if these data can be validated in a prospective clinical study, it may be possible to use PSADT to guide treatment with IADT and in future clinical trial design.