Sunday, March 26, 2017

To Test or Not To Test?

Prostate cancer mortality had dropped more than 50% with the introduction of PSA testing as shown above. The along came the previous Administration and its Medical advisors and they recommended the elimination of PSA testing. The result appears above, albeit the SEER data stopped reporting because of alleged massive irregularities in the data gathered. I guess if the facts don't measure up to the "theory" one then changes the facts. Welcome to Washington.

As just reported in UroToday:

In the last update of the ERSPC with follow-up truncated at 13 years, a significant 21% relative reduction in prostate cancer was demonstrated in intention to screen analyses, and 27% in men who actually attended screening. The absolute risk reduction of death from prostate cancer at 13 years was 1.28 fewer prostate cancer deaths per 1,000 men randomized. A total of 781 men needed to be invited to screening and 27 to be diagnosed with prostate cancer to avert one death from the disease. These numbers are predicted to go lower in the next update of the study incorporating 16 years of follow-up. The main disadvantage of screening is the increased risk of over-diagnosis of prostate cancer due to screening, meaning detection of non-significant low risk cancers. Despite showing a clear prostate cancer mortality reduction, the findings were not sufficient to justify population-based screening. The harms of screening will need to be further assessed and strategies to overcome over-diagnosis and overtreatment will need to be implemented. In the interim, well-informed men suitable for screening should be able to undergo PSA testing if they wish, after careful consideration of the pros and cons. Dr. Hugosson emphasized on the incidence of prostate cancer after termination of screening which has doubled. He also noted that there is a difference in the intensity of screening in different European countries. This translates into differences in mortality reduction. Additionally, the number of PSA tests is also correlated to mortality. Results show that the better patients are screened and the more PSA blood test are done, less death occurs.

Even the above has problems:

1. Fundamentally and simplistically, PCa falls into two distinct types; indolent (Type I) and aggressive (Type II).  Frankly we really do not know which is which other than Type II can go from nothing to death in four to five years. Type I just seems to go no where fast. Many genetic studies have examined those with less than sterling results. We have estimated that 10% are Type II and 90% are Type I.

2. Thus measuring for PCa with PSA annually really only affects Type II, in general. Thus is the incidence if say 100,000 pa and there are 10,000 Type II, and we do not test them then they will all die. In fact. the PCa is so aggressive that no matter what they will almost surely die.

3. In addition is there are some of the Type I who will die, a small percent, say 5%.

4. Then the total mortality is say 15%. This is just a back of the envelope calculation to make the point.

5. Now we also have a strange set of data. Namely the incidence of PCa is dropping. Namely the denominator is dropping for reasons we do not seem to fully understand. The results below are difficult to reason with since there is a massive peak and then a precipitous drop. The real world does not work this way unless we understand why. Bad data, however, does.

6. Now what does this all say? Well simply that PSA seems to help, and perhaps even helps in reducing the incidence, if we believe that data. The other problem of course is the diagnosis of HGPIN initially as carcinoma in situ. This may or may not be swept into the total. Since HGPIN may disappear then how does one readjust the data? There does not seem to be an answer to this.

7. Now a second result from UroToday on the use of MRI is also telling.

8. The use of Multi Parametric MRI has been suggested as essential. They state:

...utilizing multiparametric MRI (mpMRI) for all patients when clinically indicated for prostate cancer. He highlighted that mpMRI truly encompasses three different entities: prostate (i) anatomy (T2-weighted imaging (T2W)), (ii) biology (diffusion-weighted imaging (DWI)), and (iii) vascularity (dynamic contrast enhancement (DCE)). T2W imaging allows for an excellent assessment of the transitional and peripheral zones of the prostate, as well as the neurovascular bundles. DCE..

 We have argued that based upon some tests that MRI often picks up previous biopsy scar tissues which may get vasculated as suspect then actually requiring a subsequent biopsy.

9. A second study indicating that MRIs can be performed is a simpler environment (ie mpMRI) where they state:

that mpMRI has improved biopsy decision making and the yield of clinically significant prostate cancer, albeit with the caveat of significant cost and time. On the other hand, bMRI (T2W and diffusion-weighted imaging (DWI)) can give a “quick, 15 minute, no frills MRI of the prostate” .... described how when he started in the prostate imaging arena nearly 20 years ago, he wanted “everything” that an MRI had to offer, namely T2, DWI, diffusion contrast enhancement (DCE), and spectroscopy. Over time it became evident to... that MR-spectroscopy was costly and added very little to the clinical picture. Since then he has also advocated for only utilization of DCE (ie mpMRI) for challenging cases.

The same argument as above also applies. MRIs are expensive and the use of gadolinium has significant adverse effects in some, especially the use of cumulative gadolinium.

10. Overall we still see significant uncertainties with PCa and the fact that a Government entity removes from the toolbox the only tool we may have to save money under the guise of preventing "harms", namely discomfort after an exam, pales in contrast to the horrible death from this disease.

Thus despite the Government's clawing hold on health care, perhaps a walk down a cancer ward, if any still exist, could enlighten some of the folks i Washington! Yet I doubt it.