Thursday, March 4, 2010

Congress and Prostate Cancer

The House Oversight Committee held hearings today on prostate cancer and testing. The American Cancer Society issued new guidelines for screening. NIH recounts them as follows:

In new guidelines released Wednesday, the society says that men who choose to be tested should get an annual screening if their level of prostate-specific antigen, or PSA, is 2.5 nanograms per milliliter (ng/mL) or higher. But men whose PSA is under that threshold can be safely screened every two years. Men with a PSA level of 4.0 ng/mL or higher should consider getting further evaluation, such as a biopsy. Previous guidelines had suggested that men with a PSA of less than 4.0 ng/mL should be screened annually.

While the cancer society does not recommend screening for anyone -- even men at risk -- it does offer suggested intervals for screening if men choose to be tested.

The ACS states:

Studies are being done to try to figure out if early detection tests for prostate cancer in large groups of men will lower the prostate cancer death rate. The most recent results from 2 large studies were conflicting, and didn't offer clear answers.

Early results from a study done in the United States found that annual screening with PSA and DRE did detect more prostate cancers, but this screening did not lower the death rate from prostate cancer. A European study did find a lower risk of death from prostate cancer with PSA screening (done about once every 4 years), but the researchers estimated that about 1,400 men would need to be screened (and 48 treated) in order to prevent one death from prostate cancer. Neither of these studies has shown that PSA screening helps men live longer (lowered the overall death rate).

The statement is just wrong about the two studies released in 2009. We have detailed the errors in prior postings. To summarize they two studies used the 4.0 level and the testing was sporadic at best. The answer is that mortality was not changed if you wait until a 4.0 is reached. The set point was reduced to 2.0 as data was obtained but the trial never tested the lower level thus by leaving it at 4.0 they allowed the cancers to grow to a terminal stage.

They continue:

Prostate cancer tends to be a slow growing cancer, so the effects of screening in these studies may become clearer in the coming years. Both of these studies are being continued to see if longer follow-up will give clearer results.

This is also in error. Prostate cancer falls in two categories; slow growing or indolent and this represents about 90% of all such cancers and fast growing deadly type which kills in 4 years or less. The recommendation of the ACS is a death verdict for the men in the latter category. The problem is that we do not know genetically how to determine this category.

For example, we now know that two factors, percent free PSA and PSA velocity are major factors and not just PSA. Percent free is a measure of the percent of cells which are functioning normally, albeit they may be PIN cells, prostatic intraepithelial neoplasia, high grade, HGPIN, which may be a precursor to prostate cancer. HG PIN must be monitored by biopsy on a schedule of three to four times a year! Not ignored. Velocity is critical since it is a reasonable measure for the growth of cells. Also a measure for both PIN and prostate cancer.

We know that even a biopsy can at best be 10-25% in error. A 20 core biopsy can still miss cancer with a 10% probability. In addition a second biopsy using 14 or more cores may find cancer 25% of the time or more on a second testing!

The aggressive prostate cancer can kill a man in less than 4 years! Do we want that risk? If you are in that group I would think not. What further helps, family history. If you have had a first degree relative who died in a short period then it is highly likely that you have inherited the genetic errors that allow rapid growth, namely the elimination of the PTEN gene and thus metastasis.

The ACS also states:

Because of these complex issues, the American Cancer Society recommends that doctors more heavily involve patients in the decision of whether to get screened for prostate cancer. To that end, ACS's revised guidelines recommend that men use decision-making tools to help them make an informed choice about testing. The guidelines also identify the type of information that should be given to men to help them make this decision.

The problem is how do you involve a man if the physician has no understanding and in fact is confused given the literature. Biopsy is not a gold standard, it may be a silver or bronze. If the biopsy yields a Gleason 6, rarely less since most pathologists will grade 3+3 yielding Gleason 6, and almost never grade a 1 nor even a 2, then one still does not know the genetic makeup, the true determinant. In fact most physicians do not understand the genetic factors, including many urologists. Thus in many ways it is the blind leading the blind, and the ACS has done nothing more than put stumbling blocks in the way. Further by testifying before Congress they have done men a disservice. Yet it does reduce Medicare costs, we just let those old folks die, and yes many young ones two. Why men do not revolt like women is a mystery!