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E-LETTER #17 - GO TO INDEX FOR EARLIER LETTERS

 

Prostate men need enlightening, not frightening May 2013
Guidelines Aplenty

 

The American Urology Association (AUA) and the American Society for Radiation Oncology (ASTRO) issued a number of revised guidelines earlier this month. One dealt with PSA testing, supporting the recent changes and seems to have been accepted with less of the clamour that the original amendment received.

Two other sets of recommendations/guidelines will probably be of more interest to readers of this E-Letter. One deals with what is termed ART (Additional/Adjuvant Radiation Therapy) to be applied after surgery. This is often termed SRT (Salvage Radiation Therapy) in discussions on the Internet. The guidelines and relevant information are available here Adjuvant and Salvage Radiotherapy after Prostatectomy: ASTRO/AUA Guideline

The second deals with the management of patients with non-metastatic and metastatic castration-resistant prostate cancer (CRPC). This condition is known by many different acronyms but refers to disease that is no longer responding to ADT (Androgen Deprivation Therapy) known popularly as hormone therapy. The relevant information can be downloaded here Castration-Resistant Prostate Cancer: AUA Guideline

Links to both sets of recommendation will be incorporated in the Yana site.

I thought it might be worth commenting on the SRT (Salvage Radiation Therapy) issue in particular because too often (for my liking) men report that they have biochemical recurrence after a miniscule apparent rise in ultra-sensitive PSA and as a consequence they are undergoing SRT or this has been strongly recommended by their doctors. The new guidelines are not so adamant and seem not to support this position. The relevant ones are:

Guideline Statement 5. Clinicians should define biochemical recurrence as a detectable or rising PSA value after surgery that is less than or equal to 0.2 ng/ml with a second confirmatory level less than or equal 0.2 ng/ml. (Recommendation; Evidence Strength: Grade C)

Guideline Statement 7. Physicians should offer salvage radiotherapy to patients with PSA or local recurrence after radical prostatectomy in whom there is no evidence of distant metastatic disease. (Recommendation; Evidence Strength: Grade C)


It may be worth noting the reference to the Grade C Evidence Strength. Needless to say there are many definitions of this, or similar, terms. One reference uses the term "Low Quality". The U.S. Preventive Services Task Force refers to: At least fair scientific evidence suggests that there are benefits provided by the clinical service, but the balance between benefits and risks are too close for making general recommendations. Clinicians need not offer it unless there are individual considerations. Other recommendations are based on what is termed "Clinical Principle" Defined in the AUA site as a statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature [The emphasis is mine] I personally term these clinical principles "medical beliefs". They may or may not be correct - in some c ases they are outdated.

As Mike Scott says in his commentary:

There may be some considerable controversy about the interpretation of this new guideline. It is certainly the case that numerous men with "adverse pathologic findings including seminal vesicle invasion, positive surgical margins, and extraprostatic extension" at the time of surgery, and whose PSA level drops to an undetectable level post-surgery, have no rise in their PSA level after their surgery and appear to have been clinically cured of the original cancer. The question is therefore going to be exactly how individual surgeons apply some over the above guidance - i.e., by duly informing the patient but by adding "However, in your case I think we can afford to wait and monitor your PSA rather than applying radiation therapy immediately."

The other issue that does not seem to be addressed in this guidance at all is the patient's PSA doubling time. The situation of a man with a rising PSA post-surgery that goes from 0.1 to 0.4 over a period of 6 years (i.e., a PSA doubling time of 2 years) would seem be very different to that of a man who's PSA is doubling every 6 months or so and therefore goes from 0.1 to 0.4 in just 12 months. The former may never show signs of significant metastatic disease; the latter, on the other hand, probably will.


What Mike is saying, and I agree with him, is that these recommendations should be treated as suggestions to be considered against the background information applying to individual cases. They should not be taken as clear "orders to proceed".

Dr Charles "Snuffy" Myers on Testosterone

 

Dr Myers is well known to most prostate cancer men who have been on the Internet for some time. He recently re-published a piece he wrote in 2012 about Xtandi (formerly known as MDV3100). You can read the piece here Ask Dr Myers

Dr Myers in dealing with Xtandi and other options also has some information on the current theories about how and when Testosterone does and doesn't fuel prostate cancer growth. Here is an extract to whet your appetite:

When drugs like Lupron and Casodex have failed, the cancer is not in fact hormone resistant. In fact, the cancer has adapted by becoming even more sensitive to testosterone. This cancer can change to grow at testosterone levels 1/100 to 1/1,000 of that found in a normal adult male.

Lupron and Casodex fail because they are not powerful enough.Prostate cancer accomplishes this by several different mechanisms. Prostate cancer cells can make their own testosterone, making them independent of outside sources. The cells can increase the amount of androgen receptor so that it traps enough testosterone to continue to grow, like using a larger sail in a light wind. The cancer cells can also change the androgen receptor so that it treats Casodex or Eulexin as if it were testosterone, so that drugs that are used to block testosterone now act as if they were testosterone! This is why some patients respond when Casodex is stopped.

Finally, the androgen receptor can be altered so that it is activated with little or no testosterone. The end result of all of this research is that we now know that it is quite uncommon for prostate cancer to become androgen independent. This led to a blossoming in research to find drugs able to restore hormone-responsiveness in men with advanced prostate cancer.


I am not sure whether this will help you to a greater understanding or not. it surely got my head a spinning!!

Different strokes?

 

No doubt some of you would have seen the recent media releases about what the New York Times called - Prostate Test Could Cut Need For Surgery. You can read the a sample of them here New York Times or here Wall Street Journal if you haven't seen the release previously.

One of the thoughts that struck me as I read the various reports was how the standards used in bringing conventional tests and "cures" to market differ have changed. And how they differ from the standards applied to "alternative" medicine. I asked myself how the launch for this test would meet the three criteria I apply to claims made for any alternative therapy. I referred to these in E-Mail #7 under the header "Will This Work?"

1. Is there any independent evidence to support the claims being made?
2. Will the person providing the information benefit directly or indirectly from what they are claiming?
3. How long is it since the evidence supporting the claim was collected or completed?

The answers, for this test are:

1. There is no independent evidence. The test has not been approved by the FDA.
2. Yes, indeed they will at almost $4,000 per test, and possibly from an increase in share price, if the can convince the medical world that their test is better than others that are being pushed at present
3. Although the primary evidence has been collected fairly recently, there is none about the long term value of the test. As Mike Scott said in his commentary on The "New" Prostate Cancer Infolink:

The problem with the test is that all of the available data so far are based on analyses of data from patients who went on to have radical prostatectomies, i.e., the comparison is of the effectiveness of the test carried out on biopsy samples to predict the pathological results post-surgery. What we don't have at this time are any data that tell us, based on a prospective clinical trial, what the outcomes of men have been at 5 and 10 years after decisions about treatment (or active monitoring) were made based on the results of the Oncotype DX test at the time of initial biopsy.

A number of specialist doctors are quoted as having some doubts, but in the end, the use of the test will not depend on their views, but on the efficacy of the salesmen selling the test to doctors who may or may not benefit from that process. How does that differ from the "quack" selling a miracle cure? And how will it help newly diagnosed men when faced with so many differing, and expensive, test options?

There are still too many "medical beliefs" used to make vital decisions that are not based on sound data. It is always best for anyone to try to gather their own information and seek answers to puzzling apparent contradictions from their doctor before making any life changing decisions.

Yana update
Boxer Joe had a bad diagnosis back in 2006, but like the true fighter he was he declined to accept the two year survival prediction. Jessie has told the story of how he fought on bravely until he was finally overwhelmed last month. Our thoughts go out to Jessie and all Joe's family.

Our apologies again to anyone who was affected by the disruption in service last month. We are not happy about how and why it happened and our service provider's reaction to our requests for help. We intend to move to a new service provider who will be able to cope more effectively with the increase in traffic.

One good thing that came out of the circular e-mail that we sent out was that there was a flood of updates - 164 in the last month and all handled by the system that Mark set up. If you haven't updated lately do so now - it really helps the newly diagnosed to know you're still with us.
Two useful studies - HG-PIN and AS
A finding of HG-PIN (High Grade Prostatic Intraepithelial Neoplasia) in a biopsy has, for a considerable time, been seen as a precursor to diagnosis of prostate cancer despite the lack of any clear evidence. This study concludes that HG-PIN does not have a higher predictive value for subsequent cancer than PSA alone and a previous diagnosis of HG-PIN does not predict for higher-grade cancer.

One of the objections to a choice of AS (Active Surveilance) is the risks connected to repeat biopsy procedures.This study provides some insight into the possible risks, particularly for men who choose Active Surveilance.
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