Prostate cancer is one of the most commonly diagnosed cancers. In 2016 there were more than 1.6 million men diagnosed with prostate cancer globally, and in 2019 more than 174,000 new cases in the United States. The American Cancer Society has estimated that in 2019 there will be about 175000 new cases diagnosed in the U.S., with 31,620 deaths from the disease, which is an increase of about 6% to 7% from 2018.  The condition is often clinically indolent, and many times no intervention is required. However, the disease can be very devastating. One of the most lethal progressions of the disease involves osteoblastic bony metastasis. The diagnosis of prostate cancer is suspected when individuals have a hard enlarged prostate or nodule on physical exam as well as an elevated prostate-specific antigen (PSA) level on laboratory analysis. The diagnosis is confirmed with a biopsy and on histologic assessment. The Gleason score is the primary histologic assessment tool that is used to grade prostate malignancies and has proven to have significant prognostic value.[1][2][3][4]

The basis of the Gleason grade is primarily on the architecture or arrangement of the malignant cells within the tumor as well as other factors such as degree of differentiation. Since the prostate is a gland, the less glandular the microscopic appearance, the higher the Gleason grade, which ranges from 1 to a maximum of 5. The Gleason score is always a sum of two numbers. These two numbers represent the Gleason grade of the predominant pattern added to the grade of the next most common pattern. If only one Gleason grade is present, then this is doubled.  It is usually written as an equation such as 3+4=7. In this example, the predominant grade is pattern 3, the secondary grade would be pattern 4, and the Gleason score would, therefore, be 7. If the predominant pattern was grade 4, it would be written as 4+3=7 and would represent a higher overall Gleason score and a higher grade malignancy even though the total was still the same at 7. If there were a third pattern of higher grade, this number would replace the secondary grade pattern number.  A Gleason score of less than 6 usually indicates indolent cancer that is less likely to be clinically significant. Scores of 8 or greater are generally associated with poorly differentiated tumors with a worse prognosis.[5][6]

In 2014, the International Society of Urological Pathology consensus conference recommended some changes to the Gleason scoring system.  They recommended adding the percentage of Gleason pattern 4 as well as 5 new grades of prostate cancer based on the Gleason score.  These grades would include all Gleason scores of 6 or less in grade I, Gleason 3+4=7 in grade II, Gleason 4+3=7 in grade III, Gleason 4+4=8 in grade IV.  and all Gleason 9 and 10 in grade V.[7]

However, despite these advances and guidelines, there remains a considerable difference in Gleason grading even between experienced pathologists.[8] 

Another issue involves the development of subpatterns of Gleason grade 4.  In many cases, it can be challenging to differentiate ill-formed and/or fused glands from the less aggressive grade 3 pattern. This differentiation can be critical in determining which patients might be eligible for active surveillance or deferred therapy from those who should proceed directly with definitive, curative treatment.[9] There is also concern that the Gleason grade 4 cribriform subpattern may have a more significant negative prognostic impact than other patterns of the same Gleason grade.[10]

Immunohistochemistry is another promising area of research that could suggest which Gleason grade 3 patients are more likely to progress or upgrade to more aggressive histology, which could be very helpful clinically in patients who are potential candidates for active surveillance. Early indications are that overexpression of Ki67 could indicate a higher risk of Gleason grade progression.[11]

The Gleason score is essential in determining the prognosis of prostatic malignancies; however, it is not absolute. The Gleason score is subject to interpretation; pathologists might vary in their interpretations and assessments. Other factors are also important in the prognosis of prostate cancer. An increasing PSA is indicative of a poor prognosis. Physical exam findings may also indicate a poor prognosis. Tumor staging is based on radiographic assessment (evidence of nodal or metastatic disease) and can also be used to assess the prognosis.[5][6]