By: Dan Sperling, MD
A quick Gleason score refresher
The Gleason grade is the method used to evaluate the aggressiveness of prostate cancer. It is determined by visual analysis of tissue samples taken from the prostate gland by means of a needle biopsy. Aggressiveness is scored on a range of 1-5. A low score indicates a majority presence of cells that appear normal (well-differentiated). Higher scores are assigned to poorly differentiated cells based on the degree of abnormality. Gleason grades are reported as a sum of two separate scores, based on the two needle specimens with the greatest percentage of cancer cells, with the higher percentage reported first (primary). Thus, a Gleason score of (4+3 = 7) is considered more aggressive than (3+4 = 7), despite the fact that they both total 7, because the primary number of 4 indicates a higher presence of more aggressive cells.
High Gleason scores predict RP failure
Radical prostatectomy (RP) is still considered the gold standard of prostate cancer treatment. Patients with low risk, early stage disease, and a Gleason grade of 6 (3+3) who undergo surgical removal have very high rates of cancer control. However, Gleason grades equal to or higher than a total of 7 (4+3) are predictive of biochemical failure, meaning the eventual occurrence of measurable and/or rising PSA. In other words, the surgery did not remove all the cancer, or the cancer had already penetrated the margins of the prostate capsule.
The problem with determining Gleason grade accurately has to do with the conventional 12-core TRUS-guided biopsy. Rates of underdiagnosing prostate cancer have been reported as high as 25-30%[i] (one author suggests 40-50%[ii]) based on a comparison between the pre-surgery biopsy results and the post-surgery examination of the actual specimen that was found to have higher grade or more extensive disease than originally thought.
MRI reveals aggressive prostate cancer
With improved imaging, specifically 3T multiparametric MRI (3T mpMRI), the ability now exists to correlate biopsy results with a visual analysis of tumor activity. In fact, in some studies of 3T mpMRI, the results suggest that this advanced imaging may be more reliable at identifying higher grade tumors rather than small, low-grade tumors. This means that without undergoing more biopsies, patients can be informed of a more accurate risk profile before deciding to go through with surgery and its attendant risks.
According to a 2013 article in the British Journal of Urology[iii], at least two of the three functional parameters (diffusion weighted imaging or DWI, dynamic contrast-enhancement or DCE, and spectroscopy or MRI-S) are necessary to characterize aggression. The authors concluded that mpMRI’s high specificity (>95%) in identifying aggression may be useful in determining if their disease is of an extent to make surgery, or at least nerve-sparing surgery, worth reconsidering.
Other authors point to the high accuracy of mpMRI, especially the functional parameter of DWI, in determining higher grades of prostate cancer before surgery.[iv],[v] Keep in mind that MRI is a noninvasive means of gathering information that may or may not confirm biopsy results. Before committing to the surgery itself with its risks of lifestyle impact, and the economic factors for the healthcare system as well as patients, would it not make sense to add a pre-surgery 3T mpMRI as a standard of diagnostic care? Determining which men would be at increased risk for surgical failure would do them a great service, not only in sparing them the involved procedure and longer recovery, but also in determining an alternative treatment plan that will not lessen longevity and perhaps assure the preservation of their urinary and sexual quality of life.
[i] T. Graif, S. Loeb, K.A. Roehl, et al. Under diagnosis and over diagnosis of prostate cancer. J Urol. 2007;178:88-92
[ii] Taneja, S. MRI in men at suspicion of prostate cancer. Presented May 17 2014, Annual American Urological Association (Orlando, FL).
[iv] Hambrock T, Somford DM, Huisman HJ et a. Relationship between apparent diffusion coefficients at 3.0-T MR imaging and Gleason grade in peripheral zone prostate cancer. Radiology 2011;259(2):453-61.
[v] Chamie K, Sonn GA, Finley DS et al. The role of magnetic resonance imaging in delineating clinically significant prostate cancer. Urology 2014;83(2):369-75.