A prostate cancer specialist breaks down prostate cancer staging and grading and identifies several shortcomings of established risk stratification methods for patients with clinically localized disease.
Mark Emberton, BSc, MBBS, FRSC (Urol), MD, FMedSci: Yes. So the reason for doing the biopsy is to find out the grade of the cancer. So is it a pussy cat that can be left alone, is it a tiger that needs immediate intervention, or is it something in between. Typically there were five numbers associated with prostate cancer grading, and this is Dr. Gleason's score. So 1, 2, 3, 4, and 5. There are lots of five point scales in prostate cancer. It's interesting that the Gleason score had got rid of 1, then it got rid of 2. There's debate about whether 3 has any clinical significance. 5 is rare, and so we're kind of left with a very compressed score that is largely about the proportion of pattern 4. And I think that's where we are today in terms of the utility of Gleason score and the biopsy, it's to determine the proportion of pattern 4. If there's a small amount of pattern 4, it's grade group two, if there's a larger amount of pattern 4, it's grade group three. So in other words, if it's over 50%, if it's all pattern four, it goes to grade group four. And if there's a present of pattern 5, it goes to grade group five. So it's really about the amount of pattern 4. And the way that Gleason plays out is the compression of the scale means that we're really left with a binary system of low proportion pattern 4, Gleason 3 + 4, versus higher proportion pattern 4. And if you biopsy lesions and you don't biopsy randomly, Gleason 3 + 3 disappears, and you are largely left with a pattern 4 issue. And the targeted biopsies, because they provide such a high yield of tissue, in other words we get centimeters of cancer rather than millimeters of cancer, which was associated with the historical biopsies. The pathologist is allow- is- can make a very precise determination on proportion of pattern 4.
So using historical risk stratifications in today's system, I think is problematic. And there are lots of categorizations of risk that are based and were formulated using transrectal biopsy, based on sextant biopsies, which we know to be very imprecise. So I was talking about this just the other day in a lecture. I think the notion of risk at present is very, very hard to determine because the- all the existing models had all the errors of the overdiagnosis and the underdiagnosis errors associated with our verification test, which was sextant transrectal biopsy. I think risk in the future is going to have to incorporate some measure of prostate cancer volume. It is very, very strange that our TNM classification of prostate cancer risk does not include volume. It's the only solid organ cancer that doesn't. And I think there's also going to be some feature extraction that we can get from imaging. So in other words, MRI derivatives are getting better and better at giving us some inclination of the type of Gleason score that is within the prostate. And also whether there are histological variants of the Gleason pattern, such as the cribriform pattern, which many people think makes the cancer more aggressive. So I think we're at a point that we need to abandon historical risk classification systems and think about new ones that incorporate all the new information that we're currently eliciting. And that includes information on volume, possibly location within the prostate, possibly multiplicity, and in future will include molecular inputs both from the blood, from the urine and from the tissue.