Very long-term response to antiandrogen withdrawal in metastatic prostate cancer

Confirming just how strange prostate cancer can actually be sometimes, here is a very unusual case history associated with antiandrogen withdrawal from a group of Japanese researchers.

Sano et al. had been treating a 72-year-old man with metastatic prostate cancer by using complete androgen blockade with an LHRH agonist and bicalutamide (Casodex). The patient had also received external beam radiotherapy (at 70 Gy) to the prostate for local control of the primary tumor. Prior to his initial treatment in 2004, the patient had had a PSA of nearly 600 ng/ml and clear evidence of metastasis to his hip and femoral head. Initially, post-treatment, the man’s PSA level was well controlled (effectively undetectable) for 4 years.

After 4 years, the patient’s PSA started to rise again (to 0.34 ng/ml in early 2009), suggesting the first step in initiation of castration-resistant prostate cancer and, as is usual under such circumstances, his physicians stopped the bicalutamide in order to initiate antiandrogen withdrawal. The patient’s PSA level went back down again to an undetectable level (0.00 ng/ml), but, rather than starting to rise again after a few months, which is what normally happens, this patient’s PSA has continued to be undetectable for the past 6 years. There has also been no evidence of bone or other soft tissue metastases on bone or CT scans since the initiation of complete androgen blockade.

This is certainly the longest response to antiandrogen withdrawal that your sitemaster has ever heard of in the past 25+ years. However, as Sano et al. point out, it confirms that, for men who have been being treated with combined androgen blockade, the potential of antiandrogen withdrawal could always be a significant opportunity when the patient’s PSA starts to rise again.

Quite why this particular patient should have responded so well to antiandrogen withdrawal raises interesting questions for the prostate cancer research community. As indicated above, the impact of antiandrogen withdrawal in men on combined androgen blockade was recognized back in the early 1990s, but when it has a positive effect, that effect has usually been limited to something like 6 months.

The full text of the paper does not tell us, but we are currently assuming that the patient has remained on LHRH agonist therapy since the antiandrogen withdrawal. One wonders what might happen if the LHRH agonist was stopped in a case like this.

4 Responses

  1. If I can play doctor here, I would like to know how low the patient’s T and DHT levels were while he had been on Lupron. If they were very very low, then adding the bicalutamide would arguably not make much difference in its intended effect of blocking the androgen receptors. In fact, as you well know, the bicalutamide has the effect of increasing T. Perhaps the increase in T caused by the bicalutamide while the patient was on CAB also allowed more androgen to enter the cell (perhaps because the bicalutamide was not very effective in blocking the androgen receptor for this patient, at least after 4 years on the drug). When the bicalutamide was withdrawn, T dropped, causing PSA to fall. And the Lupron has been very effective for this patient. I suppose it all depends, as you have said many times, upon the individual patient’s response to the Lupron and bicalutamide.. OK, Sitemaster, now please set me straight! : – )

  2. Richard:

    (1) Since the patient’s serum T and serum DHT lavels aren’t given in the full text of the paper, I can’t help you with that question.

    (2) If your hypothesis was correct, then surely by now — after 25+ years — we would have come across a lot more patients who had had this sort of outcome after antiandrogen withdrawal? Yes? No?

    (3) If I knew how to “set you [and everyone else] straight” on this issue I think I’d be in line for a follow-up to Dr. Huggins Nobel Prize by now! (But I don’t think I’m even in the same Universe, let alone the same ballpark).

    (4) I suspect that this all has something to do with this particular patient’s immuno-endocrine response to the androgen deprivation therapy … and we know that can vary wildly from patient to patient.

  3. Sitemaster: I’m not sure we can draw any conclusions from this case study since this patient is clearly an “exceptional responder” to ADT in every way. How often do we hear of someone with an initial PSA of 600 with bone mets whose PSA becomes undetectable on ADT alone? He seems fortunate to have a variety of PCa that is nearly 100% responsive to ADT — extremely rare and possibly unheard of until now.

  4. Dear Len:

    Actually it used to be very common for men diagnosed with this type of PSA level to respond extremely well to hormone therapy … but until the late 1980s we had no test to demonstrate this. I don’t think it is that unusual to see this level of response to combined ADT. However, the number of men in America who get diagnosed with a PSA level this high is now very small compared to what it was in the late 1980s and early 1990s.

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