Prostate cancer is graded by examining tissue under a microscope and scoring how abnormal the cells look compared to healthy prostate tissue. The system uses a scale of patterns numbered 1 through 5, with higher numbers indicating more aggressive cancer. Two scores are combined into a Gleason score, which is then translated into a simpler 1-to-5 Grade Group that predicts how the cancer is likely to behave.
How the Gleason Score Works
When a pathologist examines your biopsy tissue, they identify the two most common growth patterns they see and assign each a grade from 1 to 5. Pattern 3 describes cancer cells that still form recognizable glands, just smaller and more irregular than normal. Pattern 4 includes cells that have started fusing together into sheets or forming complex structures called cribriform patterns, where multiple hollow spaces sit within a single mass of cancer cells. Pattern 5 describes cells with almost no gland structure at all.
The Gleason score is always written as a sum: the most common pattern plus the second most common pattern. A score of 3+4=7 means the pathologist saw mostly pattern 3 with some pattern 4. A score of 4+3=7 means pattern 4 dominated, with less pattern 3. Even though both add up to 7, the 4+3 combination is considered more aggressive because the dominant pattern carries more weight. If a third, higher-grade pattern is present, it replaces the secondary number in the equation. If only one pattern exists throughout the sample, that number is doubled (for example, 3+3=6).
Grade Groups 1 Through 5
In 2014, the International Society of Urological Pathology introduced Grade Groups to simplify how prostate cancer grades are communicated. The old Gleason system created confusion because a score of 6 sounded like it sat in the middle of a dangerous scale, when it actually represented the lowest grade of cancer diagnosed in practice. Grade Groups reframe this on a clearer 1-to-5 scale.
- Grade Group 1 (Gleason 3+3=6): The least aggressive form. Cancer cells still form distinct, separate glands.
- Grade Group 2 (Gleason 3+4=7): Mostly well-formed glands with a smaller component of fused or poorly formed glands.
- Grade Group 3 (Gleason 4+3=7): The more aggressive pattern dominates, with a smaller portion of well-formed glands.
- Grade Group 4 (Gleason 4+4=8, 3+5=8, or 5+3=8): Predominantly poorly formed, fused, or structureless cancer.
- Grade Group 5 (Gleason 9 or 10): The most aggressive, with little to no recognizable gland structure.
The National Comprehensive Cancer Network uses Grade Groups alongside tumor stage and PSA levels to place patients into risk categories that guide treatment decisions. Grade Group is one of the most important factors in determining whether a cancer can be monitored, needs localized treatment, or requires more intensive therapy.
Why the Grade Can Change After Surgery
A biopsy samples only a small fraction of the prostate, so the grade assigned from a biopsy does not always match what pathologists find when they examine the entire gland after surgery. In one study of 177 patients, roughly 55% had their Gleason score increase after prostatectomy, about 34% stayed the same, and around 11% had a decrease. The average score rose from 5.5 on biopsy to 6.2 on the surgical specimen. Across the broader research literature, upgrading happens in about 14% to 51% of cases, with an average around 36%.
This upgrading happens for practical reasons. A biopsy needle may miss a higher-grade area of the tumor. Cribriform pattern 4 can sometimes be difficult to distinguish from pattern 3 under the microscope, leading to initial underscoring. Some patients also see a shift within the same total score. Five patients in that study, for example, went from 3+4=7 to 4+3=7, meaning the dominant pattern changed even though the sum didn’t.
Cribriform Pattern and Its Significance
Not all pattern 4 cancer carries the same risk. Among the subtypes classified as pattern 4, cribriform architecture stands out as particularly aggressive. Cribriform pattern is defined as a solid sheet of cancer cells containing multiple visible hollow spaces, with no normal tissue separating individual glands. Its presence is linked to higher rates of cancer spreading beyond the prostate, involvement of seminal vesicles, and positive surgical margins.
In one study, lymph node spread was found in 50% of patients whose biopsies contained cribriform pattern, compared to 10% of those without it. Both the European Association of Urology and the American Urological Association now consider the presence of cribriform pattern a reason not to pursue active surveillance, even in otherwise low-risk cancers. European guidelines require pathologists to specifically report whether cribriform pattern is present in biopsy specimens.
How Imaging Scores Differ From Grades
If you had an MRI before your biopsy, your report may include a PI-RADS score from 1 to 5. This is not a cancer grade. PI-RADS scores reflect how suspicious a lesion looks on imaging: a score of 1 means clinically significant cancer is highly unlikely, while 5 means it is highly likely. The score helps your doctor decide whether a biopsy is needed and where to target it. The actual cancer grade can only be determined after a pathologist examines tissue under a microscope.
How Variant Types Are Graded
Most prostate cancers are standard (acinar) adenocarcinoma, but variant forms exist and follow specific grading rules. The general principle is that variants are graded the same way as typical prostate cancer, based on the architectural pattern of the cells, with one exception: small cell carcinoma, which is not assigned a Gleason score at all because it behaves fundamentally differently.
Ductal adenocarcinoma, which forms papillary fronds or cribriform structures, is graded as Gleason pattern 4+4=8 (Grade Group 4). It behaves comparably to high-grade acinar cancer. The diagnosis is written to preserve both pieces of information, such as “prostatic ductal adenocarcinoma (Gleason score 4+4=8).” When ductal cancer is mixed with standard acinar cancer, the ductal portions are assigned pattern 4 and factored into the overall score.
Foamy gland carcinoma, a variant where cells have a distinctive bubbly appearance, is graded purely on its structural pattern while ignoring the unusual-looking cell contents. Most foamy gland cancers end up as Gleason 3+3=6, though higher-grade versions exist. The key point across all variants is that the architecture, meaning how the cells organize themselves into structures, matters more than how individual cells look.