PSADT and the progression of prostate cancer in men on IADT

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.

One Response

  1. When I read such studies of IADT, I am struck by the vast chasm that separates IADT that does not include finasteride or Avodart and that which does. I am not surprised that Johns Hopkins experts, including Dr. Eisenberger, do not include finasteride or Avodart. With some difficulty I was able to find an oncologist back in 2000 who was willing to add finasteride to the Lupron and Casodex I was then on, but he thought I should see an expert for a second opinion. The expert was Dr. Eisenberger, the senior author of the study, and he advised me to throw away the rest of the finasteride tablets as they were useless. Fortunately, my oncologist and I thought I should at least finish the bottle, and my PSA soon began plunging downward from about 0.6 where it was leveling off, dropping all the way to < 0.01. I still admire the work that Johns Hopkins and Dr. Eisenberger do, but that admiration does not extend to hormonal therapy.

    Most of the patients I know on IADT3 have done better than I have, but that's understandable as I have had neither radiation nor surgery, as many of them have had, and my case was much more challenging at the outset (baseline PSA 113.6, GS 4 + 3 = 7 per Dr. Epstein at JHU, all cores positive, most 100%, prostate "rock hard", stage 3, with perineural invasion. Yet even I have done far better than the average man in this study.

    The mean follow-up time in this study is 71 months, just short of 6 years. My first cycle took me through 65 months (31 months on, 34 months off therapy), and I am now in my third off-therapy period, maintaining with just finasteride, at 11 years and 4 months since the initial diagnosis. My second and third on-therapy phases were deliberately shorter, at 19 months, as the objective was to achieve a nadir of < 0.01 and then go off therapy, rather than staying below 0.05 for a year, the objective for my first cycle. I achieved < 0.01 for the second cycle, and got to 0.02 for the third.

    Regarding nadir, the JHU team believes that getting to a PSA below 0.1 is a favorable indicator. The doctors I follow have documented that a patient needs to get to at least < 0.05 or the therapy should be altered as his case is too aggressive for first line IADT3. (Strum SB, Scholz MC, McDermed JE. Oncologist. 2000;5:45-52.)

    A Journal of Urology paper from the same practice documents success with finasteride in the off-therapy period for 101 men, comparing men on IADT3 (with finasteride) vs. IADT2 (without finasteride). The on-therapy period for men in the study averaged 15.8 months, considerably longer than the 6 to 9 months for men in the JHU study. However, the time off therapy, which averaged just 3.7 months — about 41% to 62% of the 6 to 9 months on therapy at JHU — averaged 15 months for the IADT2 group (about a month off for each month on), and a striking 31 months — double — for IADT3. Moreover, while the JHU group restarted therapy when the PSA rose to the 10 to 20 ng/ml range, the Scholz team restarted at a PSA of just 5.0 ng/ml for IADT2 and just 2.5 ng/ml for IADT3, far lower than the JHU trigger points. Therefore, if the Scholz team had used the much higher JHU threshold range, their time off therapy periods would have been even longer! (Scholz MC, Jennrich RI, Strum SB, et al. Urol. 2006;175:1673-8.)

    As I noted, with my challenging case I have not done as well with my own IADT3, with figures closer to a month off for a month on, but I am delighted.

    Regarding the overall length of success on first-line blockade (I'm not sure second line is even envisioned at JHU), JHU apparently is achieving about 6 years of success, based on their mean follow-up time of 71 months, with their version of IADT before what they consider castrate-resistant prostate cancer has developed. In sharp contrast, Dr. Scholz has stated that there are two typical outcome patterns for the IADT3 patients in his practice: either success of first-line IADT3 therapy through about 10 or 11 years, or indefinitely long success. Moreover, after first-line IADT3 has failed to control the cancer, instead of considering the patients castrate resistant, second-line IADT is used, adding a number of additional years of success to the hormonal therapy approach.

    Anyone care to speculate on the chances that these researcher/physicians at JHU will even try adding finasteride or Avodart?

    I sure know which approach I want, and which I recommend.

    Yes, the difference between the approaches is a vast chasm!

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