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Old 08-31-2010, 08:07 PM   #4
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Re: PSA Relapse Following Salvage Radiotherapy, can you help?

Hi Baptista,

I'm glad you were able to get the NCCN guidelines, and I'll insert some comments in blue, for contrast with your text and quotation.

[QUOTE=Baptista;4318573]Hi Jim,

I appreciate your post above. I did my investigation at NCCN as you advised and got an insight of their recommendations for cases like mine. Surely the guidelines confirm HT as my next treatment. However, there is no recommendation on a “trigger” for starting the treatment in asymptomatic cases, neither on a decisive methodology (continuous vz intermittent).

The experts in blockade whom I follow closely all believe that intermittent blockade is clearly superior to continuous blockade. There is a mound of clinical experience that indicates that, but there is not an abundance of studies.

It seems that individual cases will require different decisions. That may be the reason for Dr. Choo’s report in insufficiency of trials and data to best treat cases of relapse after major treatments..

In regards to the timing, I quote here a summary of the text, for any one that might be interested in knowing its contents;
(NCCN Guidelines "Prostate Cancer" V.3.2010)
Timing of ADT for Advanced Disease (PSA recurrence or metastatic disease)
1) The timing of ADT for patients whose only evidence of cancer is rising PSA is influenced by PSA velocity, patient anxiety, and the short and long-term side effects of ADT.
2) A significant proportion of these patients will ultimately die of their disease; their prognosis is best approximated by the absolute level of PSA, the rate of change in the PSA level(PSA "doubling time"), and the initial stage, grade, and PSA level at the time of definitive therapy.
3) Earlier ADT may be better than delayed ADT, although the definitions of early and late (what level of PSA) are controversial. Since the benefit of earlier ADT is not clear, treatment should be individualized until definite studies are done. Patients with an elevated PSA (>50 ng/ml)

I am really surprised the NCCN would mention such a high PSA as a trigger point. While there are debates about trigger point considerations, I'm thinking that the experts would want hormonal therapy started at least at a PSA of 10 or lower.

and/or a shorter PSA doubling time (or a rapid PSA velocity) and an otherwise long life expectancy should be encouraged to consider ADT earlier.
4) Treatment should begin immediately in the presence of tumors-related symptoms or overt metastases (category 1). Earlier ADT will delay the appearance of symptoms and of metastases, but it is not clear whether earlier ADT will prolong survival.

The experts I follow are all convinced that it does, and I'm convinced they are right. The problem here is that NCCN is dedicated to "evidence based medicine," and they prefer evidence from randomized "well-designed" trials, or ideally from double-blind, large, long-term, placebo controlled clinical trials. That kind of evidence is extremely hard to get due to ethical constraints, practicalities of trial design, and logistics. However, the evidence-based-medicine establishment has great difficulty appreciating this, probably because prostate cancer has such long survival, unlike almost all other cancers.

The complications of long-term ADT have not been adequately documented.

The experts know a great deal about these side effects and how to avoid or mitigate them. They have published a lot about this. Dr. Mark Scholz, one of the foremost experts in side effects of hormonal blockade, has a new book out - "Invasion of the Prostate Snatchers." I suspect he spends a lot of time on side effects and avoiding them. Conversely, the vast majority of non-expert doctors seem to me to be surprisingly ignorant about not only the side effects but how to deal with them.

In regards to Optimal ADT, it says;
5) No clinical data supports the use of triple androgen blockade (finasteride or dutasteride with combined androgen blockade).

That is actually a false statement, very likely based on ignorance rather than bad intent. Clinical data has been collected that supports triple blockade in several practices. Some of it has even been published in prestigious medical journals. However, while the statement is false, there have only been a few formal publications in peer reviewed journals on triple blockade, so the basis for the NCCN's impression is understandable.

6) Intermittent ADT may reduce side effects without altering survival compared to continuous ADT but the long term efficacy of intermittent ADT remains unproven.

(Your case proves that intermittent ADT works very well)

Again, proof is difficult to come by as mentioned above. However, a number of studies have been done that strongly suggest intermittent ADT works at least as well as continuous ADT.

Accordingly, in a setting of low PSA velocity<0.75, PSADT>8 moths and asymptomatic, the only trigger would be to soften patients’ anxiety and/or to accept ADT’s side effects. This leads to the consideration of a “long life expectancy”.
I am 61 so I would like to try the earlier ADT, triple blockade.

I have also searched other forums on prostate cancer to get answers for similar third-line treatment cases, but couldn’t find posts related to experienced cases. I got the impression that I should keep posting about my experience so that it may help others on the same boat.

There are some areas that you would find interesting. Also, several of the experts in triple blockade will be presenting in September at the National Conference on Prostate Cancer in Los Angeles, as they have in prior years.

Thanks for the help and interest.

I'm glad to help. Take care,