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Prostate men need enlightening, not frightening


June 27 , 2012
Metastasized disease

In a recent mail I was asked what the difference was between various terms used to describe prostate cancer that had spread beyond the gland and capsule. After I had explained the position as I understood it, I thought this might be of value for a wider audience.

Broadly speaking there are four terms used more often than others: "systemic", "disseminated", "micrometastatic" and "metastatic." Just which of the last two terms is used will often depend on the probability of the dissemination having occurred or the evidence that this is the case. The bottom line being that a tumor is normally only defined as "metastatic" when it can be seen on an imaging test.

In trying to give a broad view of this subject, it is important to begin with a sense of history.

Before the widespread introduction of PSA testing or screening, metastatic prostate cancer was usually clearly evident on a bone scan, because men who were diagnosed at that time usually had advanced aggressive disease.

After the introduction of the PSA test, there was initially a general assumption that, even if they had a negative bone scan, most men with a diagnosis of prostate cancer on biopsy and a PSA greater than 50 ng/ml were at high risk for disseminated prostate cancer Because the metastasis could not be seen using available imaging tests it was termed "micrometastatic" disease.

It subsequently became clear that, because PSA is not prostate cancer specific, PSA alone is not a precise indicator of risk for metastatic or micrometastatic disease. Metastatic disease can in fact occur in men with very low PSA levels in those unusually aggressive variants which usually have a high Gleason Score of 8 or greater. It was assumed that micrometastatic disease could also occur even though it could not be seen. This led to a view that in some cases, the disease might be systemic by the time the cancer cells were big enough to be identified. The difference between "systemic" and "micrometastatic" being that in the former, inactive cancer cells might be lodged in remote parts of the body: in the latter cancer cells might be active even if they were unidentifiable.

These views led to the standard practice of bone scans being ordered for all diagnoses. There is a strong view that these bone scans create unnecessary expense. Studies that showed that most of the men diagnosed after the introduction of PSA testing were extremely unlikely to have metastasis detectable with a bone scan. As other scans were developed - CT scans, MRIs, PET scans, Color Doppler scans and even the ProstaScint test – these were used to try to identify prostate cancer in soft tissues. None of these is absolutely reliable producing both false positives (metastasis identified which does not exist) and false negatives (failing to identify metastasis which does exist).

A test named the Combidex was claimed to be the most accurate of tests in identifying metastasis to the lymph nodes, but the manufacturers failed to obtain FDA approval for the test. A research team (Bravo, Dattoli, Myers) have been developing and testing a scan similar to Combidex named provisionally as Feraheme USPIO (Ultrasmall Super Paramagnetic Iron Oxide). This is regarded as experimental although it is expected that some studies may be published soon.

In summary, "metastatic" prostate cancer can be identified reasonably accurately under carefully defined circumstances by a whole series of imaging techniques that include bone scans, but the bottom line is still the same - it is defined as "metastatic" when it can be seen on an imaging test. "Micrometastatic" prostate cancer can not be identified by definition - if it is identified it becomes "metastatic". In essence the term therefore refers to those cases where medical belief is that there is a probability of undiscovered metastasis.

One test that can identify a form of micrometastatic prostate cancer is a bone marrow biopsy. This might be a useful test for some of the men who have a significantly elevated PSA level, a high Gleason score, and negative bone and CT scans. There are also some newer tests in development that are potentially indicative of disseminated disease but have yet to be able to definitively and reliably demonstrate the presence of disseminated disease with accuracy (CTC scores and some new forms of monoclonal antibody are the most common of these).

Intermittent v Continuous ADT (Androgen Deprivation Therapy)
For some years now, a view has developed that Intermittent ADT (Androgen Deprivation Therapy) produces very similar results to Continuous ADT and is much more acceptable to those men – the majority – who have a significant change in their quality of life whilst they are on ADT. There have been many short term studies, some of which supported this belief. As is usually the case, other studies did not.

A presentation at the ASCO (American Society of Clinical Oncology) annual meeting earlier this month caused something of a stir. It was on an unusually long term study and the outcome challenged the belief that the intermittent approach was universally beneficial. The title of the study was Intermittent versus Continuous androgen deprivation in hormone sensitive metastatic prostate cancer patients.

There were two good pieces by Mike Scott on The "New" Prostate Cancer Infolink analyzing this dense abstract. The first was on JUNE 3 and the second on the next day JUNE 4 . These analyses are difficult to summarize. They, and the informed comments from other prostate cancer men, are worth reading by anyone trying to get their heads around this complex subject.

From my point of view, I think it is very important to know that this study was on men who had late stage disease that had metastasized and who were still hormone-sensitive. So the outcomes would not necessarily apply to men who commenced ADT because of a bio-chemical failure evidenced by a rising or detectable PSA after their primary therapy. Incidentally, you will see a reference to "SWOG performance status of 0-2". It is not clear to me what this is, apart from a measure established by Southwest Oncology Group, but I have been unable to find a definition.

As mentioned in the December Yana E-Letter last December, there is an unfortunate belief that once a man is on ADT his days are numbered and I have seen many references to ADT being effective for 18 to 24 months when the disease will become hormone resistant, metastasize and lead to an early death. Whilst it is the sad truth that men who are unfortunate enough to be diagnosed with metastasized disease with one of the very aggressive forms of the disease may have a shortened life, as this study shows that is not always the case. Like most scientific studies the report uses median survival times in interpretation and discussion. Ever since I read The Median Is Not The Message, I always try to have a look at the fate of those to the right of the median. Doing this, we see from this study between 23 and 29 per cent of the men survived to live at least 10 years, despite their metastasized disease. As a 'glass half full' man, I find that encouraging.
Ultra-sensitive PSA
I have been intrigued for almost two years by some curious changes in the levels reported in ultra-sensitive PSA (usPSA) tests from men who chose surgery. I am in an unusual position in seeing so many update reports from so many men across the world. I started noticing that an unexpectedly large number of these men were reporting upward movement in their usPSA levels, sometimes after many years of stable results. There have always been some men whose usPSA levels had changed - the so-called biochemical failure. One long term Swedish report showed such failures occurring as long as 20 years after surgery.

But those failures are usually much more likely to occur in the early years after surgery, not nine or ten years later. Although unusual changes in PSA can often be because a laboratory has changed the assay being used, with reports coming in from different countries, this seemed to be an unlikely cause. It seemed probable to me that one, or more, of the manufacturers of usPSA assays may have changed the way the assays operated - perhaps using a different medium.

This thought gained some ground when I started to read media pieces about the shortage of certain drugs such as this one Drug Shortages Force Change in Cancer Treatment and remembered reading another - Worldwide Shortage of Isotopes for Medical Imaging Could Threaten Quality of Patient Care We had in fact experienced this when one of Anthea's medications was suddenly "not available". She was given a generic for several months before we learned, by way of a substantial media campaign that supplies of the original medications would become available again.

So, could the changes in usPSA level be as a result of a shortage such as those reported? Or a supplier going out of business in these difficult economic times? I don't know the answer to that. One laboratory admitted that their results would be "about 15%" higher following changes they had made, but I haven't been able to ascertain anything more definite than that. It is interesting to see however that two Yana Members - Mike C in Canada and Eric Taylor in Australia have both reported that their doctors have changed the way in which usPSA results are reported.

I think it is important that anyone who has an unexpected rise in their usPSA results should discuss this thoroughly with their medical advisors to establish if there has been any change in laboratory conditions before they make any decision.
Yana men - updates
There was some sad news this month when Val mailed me about her sad loss. Bernard Power passed on in April.

I think there is a valuable lesson for some of us to learn from Val's poignant message. She regrets that Bernard and his friends kept his deterioration in health from her. I have always kept some aspects of my health issues from Anthea so as not to worry her. I will not do that in the future.

On a happier note John Farrow reported in an update that although he had been on a placebo in the Zytiga study he was signed up for, his PSA seemed to have stabilised.

Roy White has sent in another update. His PSA was over 10,000 ng/ml but is now down to 7,300 ng/ml - still not low enough to start his next trial.
I doubt that anyone can have missed the widely debated draft recommendation of the the U.S. Preventive Services Task Force

For men of any age, the USPSTF recommends that doctors and patients do not screen for prostate cancer because the potential benefits do not outweigh the harms. However, the USPSTF realizes that some men may continue requesting the PSA test and some physicians may continue offering it. The decision to start or continue screening should be an informed one that reflects an understanding of the possible benefits and harms and should respect an individual man's preferences.

This piece The Danger Of Fearing Cancer is more balanced.
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Go along toA Richer Life by Seeing the Glass Half Fullfor a nice piece on positivity.