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32 percent of CRPC men sent to non-metastatic trial were actually metastatic


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Jim Marshall (not a doctor) said ...

This study was trialling a new agent for men with castrate resistant prostate cancer, but with no metastases.

The researchers tested the men that doctors had enrolled in the study, to be sure they really were not metastatic.

However, they found that 32% of the men were actually metastatic.

They checked to see that the problem was not with one type of specialist, or in one part of the world. But the mis-identified men were evenly spread.

So they call for doctors to regularly check castrate resistant men for metastases, because the best treatment for non-metastatic men may differ from the best treatment for metastatic men.

So, if you:

  • are castrate resistant (PSA tests rising while testosterone tests stay very low);
  • not yet metastatic;

they advise your doctor to arrange regular scans (perhaps bone scan, or a special PET scan or MRI scan) to check you have not advanced to metastatic.

... end Jim

J Urol. 2012 Jul;188(1):103-9. Epub 2012 May 12.

Detection of Previously Unidentified Metastatic Disease as a Leading Cause of Screening Failure in a Phase III Trial of Zibotentan Versus Placebo in Patients with Nonmetastatic, Castration Resistant Prostate Cancer.

Yu EY, Miller K, Nelson J, Gleave M, Fizazi K, Moul JW, Nathan FE, Higano CS.


University of Washington School of Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington.



Understanding the extent of disease in asymptomatic patients with castration resistant prostate cancer is important when making treatment decisions and designing clinical trials. The ENTHUSE M0 (ENdoTHelin A USE) trial (NCT00626548) was a large phase III study comparing the endothelin A receptor antagonist zibotentan with placebo in patients with nonmetastatic, castration resistant prostate cancer. The study was stopped prematurely after early efficacy review indicated that it was unlikely to meet its co-primary objectives of improved overall and progression-free survival vs placebo. Screening failed in an unexpectedly high number of patients. We investigated this screening failure rate to promote better classification of patients thought to have nonmetastatic castration resistant prostate cancer and inform the design of future clinical trials in this setting.


The number of patients enrolled in and subsequently excluded from study was analyzed by geographic region and by the specialty of the investigating clinician (oncology or urology) who enrolled the study patients.


Of 2,577 patients enrolled in a total of 350 hospital based centers in 39 countries screening failed in 1,155 (45%). The most common reason for screening failure was the detection of metastatic disease in 32% of all screened patients and in 71% of those in whom screening failed. The leading reasons for failed screening did not differ between investigator specialties overall or by geographic region.


The high frequency of asymptomatic metastasis in men thought to have nonmetastatic, castration resistant prostate cancer highlights the importance of periodic staging assessments for the condition. Optimal treatment modalities may differ for metastatic and nonmetastatic disease.

Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

PMID: 22583636

This extract can be found on http://PubMed.com, and is in the public domain.

On PubMed.com there will be a link to the full paper (often $30, sometimes free).

Any highlighting (except the title) is not by the author, but by Jim Marshall.

Jim is not a doctor.

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It seems to me that there may be another metastatic case. As I understand it, during a radical prostatectomy, the prostate and the associated lymph nodes are surgically removed. In my case, there was no subsequent rise in the PSA for nearly two years. My urologist concluded that one or more cancer cells had escaped into my blood circulation system, so my disease was now metastatic. I was then started on hormone treatment (Zoladex) when the PSA had just passed 0.8. My cancer had now clearly colonised some other area of my body, but where? I was advised that there would be no point in doing a bone scan at that stage, as nothing would show at such a low PSA level.

If there is an official staging label for this situation, I have not heard of it. On the other hand, I am not prepared to allow my PSA to climb to a level usually associated with positive bone scans – even if that would provide the experts with the means of assigning my cancer a handy staging label.

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Unique you may be in many ways, but not in terms of prostate cancer staging.

If there is clinical evidence of metastases you are M1.

If there is no clinical evidence of metastases you are M0.

If the doctor surmises, because of rising PSA after primary treatment (unfortunately a very common thing amongst in our group of advanced men), that you may have metastases, you are still M0 until there is clinical evidence.

Some of our members who are in the same situation as you would be entitled to enter clinical trials (and wish to) if they were M1, but despite their rising PSA, no scan has yet shown evidence of metastases, so they must wait.


You may have seen a summary of the TNM staging system in this post a few days ago:


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So, our doctors may recognise that we have metastatic cancer but, because we have been fortunate enough (so far) to have contained our disease to a low level, they will just label us M0, pretend there is nothing wrong with us, and do no research aimed at ridding us of our disease. Only when our current therapy fails, and a bone scan signals that our disease has progressed significantly, will they consider helping us.

Don’t get me wrong; more-advanced cases are clearly more urgent, and more deserving of public dollars. But isn’t prevention supposed to be better than cure? Isn’t that a bit like refusing to spend money on getting rid of a Helicobacter.pylori infection on the grounds that stomach ulcers or pernicious anaemia have not yet been detected?

The PCa staging system is clearly inadequate. A more accurate staging method would recognise that our true staging value is greater than zero, but less than 1. If this index could be measured, we may find that we have an index of, say, M0.4. In mathematics, a value that lies between two dimensions is called a fractional index, and an object that exists in such a dimension is known as a “fractal”. Well, fellow fractals, we at least have a label. All we need now is a bit of research funding – and somebody who cares enough about us to try to help .

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