It is imperative to have a well-defined and candid system that can be used as a comprehensive tool by physicians to determine the prognosis of any cancer patient. For prostate cancer, Gleason score is the yardstick used for such prognostic determination. Gleason score is a scientific and significant biologic manifestation of prostate cancer aggressiveness determined through biopsy. It is a fundamental tool used by urologists to determine the treatment regimen and prognosis of a prostate cancer patient.
The Gleason scoring system, originally developed and described by Dr. Donald Gleason in 1974, is based on microscopic tumor patterns in the biopsy sample. Essentially the pathologist determines the extent of prevalence or loss of normal glandular architecture of the prostate gland, inclusive of the shape, size and differentiation of the glands. Thus, the biopsy sampling strategy goes a long way in determining correct Gleason score prediction, and is also the most prominent reason for the assignment of a faulty Gleason score. Standard, transrectal biopsy samples, in comparison to needle biopsies, are recommended for correct Gleason score prediction.
Gleason Scoring for Prostate Cancer
There are 5 basic prostate tumor grades or tissue patterns. The lowest number assigned on the Gleason scale is 1 and the maximum is 5. Two Gleason grade numbers are assigned for the most prominent (primary grade) and the second-most prominent site (secondary grade) of the tumor within the prostate gland; the sum of the two Gleason grade numbers is called the Gleason Score or Gleason Sum. The primary grade has to be greater than 50% of the total pattern observed in the tumor, whereas the secondary grade has to be less than 50% but greater than 5% of all the patterns observed in the tumor.Hence, the Gleason score can range from 2 (1+1) to 10 (5+5). The following are the basis of the assignment of the Gleason grade numbers at the primary and secondary site:
- Grade 1: Tumor cells closely mimic the normal cells; well differentiated glandular structure, closely packed.
- Grade 2: Moderately differentiated glandular structure; but, are visibly larger and have more interspaced tissues between the glandular structures.
- Grade 3: Cells are significantly smaller, darker and less discernible; only partially differentiated glandular structures are visible; some cells might be observed in adjacent vascular lumen.
- Grade 4: Hardly any glandular structure visible; lot of cells observed in adjacent vascular lumen.
- Grade 5: No recognizable glandular structures; laminar covering of cells in the adjacent tissue regions.
What does the Gleason score signify?
Gleason score is directly correlative to the aggressiveness of the prostate tumor and inversely proportional to the patient’s prognosis.
Shortcomings of the Gleason scoring system
This system is clearly subjective by nature. In other words, it is all in eye of the beholder. This is not the sole limitation of this system; there are also others. For instance, not every pathologist has the similar ability or knowledge in judging the Gleason grade and therefore, the outcomes for the similar biopsy read by two dissimilar pathologists can be diverse. Also, the minor needle biopsies occasionally do not give a precise account of the tumour itself.
As the grade increases, the diagnosis becomes poorer.
1) SUBJECTIVE: The whole grading system is based on the pathologist’s observation of the tumor biopsy. Extensive, multi-center and multi-year study has shown that most patients are given a Gleason score of 6 to 8. Gleason scores of 9 and 10 are hardly reported, as patients mostly do not survive to that stage or the differential assignment of grading becomes too difficult at the most advanced stage. Similarly, transrectal prostate biopsies do not give enough clarification to assign a tumor Gleason score of 2 to 4.
2) DIFFERENT EXPERTISE: Since the most critical part of the scoring system is the pathologist’s assertion, the pathologist expertise level is a vital cog in the correct assignment of the Gleason score. Hence, pathologist training is as important, if not more, as the quality of the biopsy sample.
3) GLEASON SCORE IS NOT THE ONLY ABSOLUTE FOR CLASSIFYING PROSTATE TUMOR: Research has shown that patients with Gleason score of 7 exhibits largely a heterogeneous group of tumors that can be sub-classified based on the amount of Gleason grade score of 4 or 5 tumors present. Such sub-stratification, in turn, gives a more definitive idea of the prognosis rather than using the overall Gleason score.
4) UNDERGRADING: When radical prostatectomy is performed the exact Gleason score can be ascertained from the surgical specimen. Historically, the predicted Gleason score is always less than the actual Gleason score as observed in the surgical specimen. What this does is adaption of a treatment strategy that is not appropriate to tackle the disease and thus the treatment regimen does not produce the expected results. Undergrading can also be fatal for patients adapting the ‘watchful waiting’ strategy, where the patients wait to see how the tumor progresses and/or responds to initial treatment before deciding on surgery.
What should be done to substantiate the importance of Gleason score?
Transrectal biopsies and quantitative interpretation by the pathologist should be combined with the following:
(i) Zonal origin (peripheral vs. transition zone) of the biopsy specimen;
(ii) Percentage of positive biopsy samples;
(iii) Invasive rate of tumor cells in the pericapsular fat of the prostate gland; and
(iv) Perineural invasion to the adjacent nerves by the prostate tumor cells.
Thus Gleason score is a very important tool, and combining with the aforementioned determinants can form a complete, comprehensive and accurate indicator of prognosis of a prostate cancer patient. And like any other system, continuous critical assessment and improvement based on research findings will help objective use of the Gleason score.