Some thoughts about
over diagnosis and over treatment:
Over diagnosis normally results in over treatment. But are the computer models accurate? Are computer model results compatible with results obtained in real-life studies?
Let’s look at some of the over diagnosis definitions:
1. Definition of over diagnosis by MacGregor M et al:
The detection of a prostate cancer that, when left untreated, would not cause death.
Over diagnosis estimate: 84%
2. Definition of over diagnosis by Zappa M et al:
Over diagnosis (detection of latent prostate carcinomas) estimated by the proportional excess of cancers detected by screening with respect to that expected in its absence.
Over diagnosis estimate: 51% or 93% for age 60 or 65 at entry.
3. Definition of over diagnosis by Etzioni R et al:
Over diagnosis was defined, as the detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient’s lifetime.
Over diagnosis estimate: 15% in whites and 37% in blacks
As one can see these three definitions resulted in an incredible variance. In real life as more screening is applied at younger ages, the proportion of early disease with an insignificant character would tend to increase. Therefore an increase in diagnoses of insignificant PCa is possible and a current reality.
This would then be a real-life rate of insignificant disease detected by screening with PSA and DRE. What is that reported rate? Are these reported rates close to the computer-generated rates? Here are some studies:
1. Ohori M et al:
Of 306 clinically detected tumors 9% were unimportant and 29% were advanced.
2. Graif T et al:
A total of 2,126 men with clinical stage T1c prostate cancer were treated with radical prostatectomy. The proportion of men with an over diagnosed tumor was 1.3% to 7.1%.
3. Epstein JI et al:
Approximately 25% of radical prostatectomies performed for stage T1c disease show potentially insignificant prostate cancer.
4. Bartsch G et al:
In the Tyrol study, in which the mean age of screened men was <65 years, the estimate of over-diagnosis according to the criteria Epstein et al. was 8.7% .
It seems that from these real-life results, the degree of PCa over diagnosis is 1.3% to 25% as by the Epstein JI definition of disease insignificance. These results are based on cytoprostatectomy and radical prostatectomy actual cases. Given the variability of results by computer models as per the input data on age, incidence, definition, lead-time, population used and other variables it is more realistic to use actual surgical treatment (both TURP and RP) to identify insignificant prostate cancer to define over diagnosis.
One key factor in the whole discussion is to properly establish the real “indolent” nature of prostate cancer diagnosed these days. Those saying that over diagnosis is extreme need to demonstrate how they know that those individual patients would have never been affected by clinical stages in their lifetimes once diagnosed. More so when they are young and go untested. The calculation by computer models depend on so many variables that results can be questionable.
For example. Etzioni et al. reported:
The over diagnosis rates represent the proportion of screen-detected case patients whose death by causes other than prostate cancer would have preceded their date of clinical diagnosis and pertain to the modeled population, namely white men aged 60–84 in 1988, with prostate cancer detected through PSA screening between 1988 and 1998 inclusive:
Lead-time of 3 years: 17.38% over diagnosis
Lead-time of 5 years: 28.59% over diagnosis
Lead-time of 7 years: 39.24%
In other words, an estimated lead-time data point alone can have a 100%+ variance in a population when using a 3 or a 7 year lead-time in the calculation used by computer models. Of all computer models, Etzioni seems to have the results that more closely resemble results of surgical methods of identifying insignificant disease. Still, we are dealing with a 15% to 25% of over diagnosis at the present time. In such cases a more judicious treatment/no treatment option could reduce immediate treatment for these men. To reduce or even recommend against testing with PSA seems a bit radical until a better marker is discovered. Men continue to be confused about
the benefit of early detection given the opposing information provided to them.
The recent AUA recommendation is trying to solve an improperly defined amount of over diagnosis/over treatment and in doing so it will confuse more men. Such limitation of PSA testing can only result in more men diagnosed with more advanced disease and a higher risk of a prostate cancer death.
The views or opinions expressed here are my own and are not endorsed nor supported by any agency or institution. Ask your physician for medical advice.
DX at age 58 in 1992. RP; Orchiectomy; GS (4 + 2); bilateral seminal vesicle invasion; tumor attached to rectal wall; Stage T4; Last PSA Dec, 2012: <0.1 www.pcainaz.org