On May 18, 2025 former President Joseph R. Biden announced he had prostate cancer with a Gleason* score of 9.** But how is a Gleason score calculated and what does each score means regarding the risk of metastasizing prostate cancer? And how do clinicians use the grading system to guide treatment for patients with prostate cancer? And while the Gleason score is important, which other factors determine risk and guide treatment for prostate cancer?
A diagnosis of prostate cancer
Each year, a subset of the approximately 313,780 men diagnosed with prostate cancer in the United States will be diagnosed with what is considered an aggressive form of the disease. In simple terms, this means that the tumor is likely to grow quickly and spread to other parts of the body. [1]
Understanding how aggressive a patient’s prostate cancer is helps clinicians to identify patients who might benefit from extensive treatment, or identify patients who may qualify for a more conservative approach. The Gleason score is a methodology used by clinicians to help determine the aggressiveness of a prostate tumor and help plan treatment and determine prognosis.
Calculating the Gleason Score
For most cancer types, tumors are assigned a grade, with grade 1 tumors looking the most normal and grade 5 tumors the most abnormal. The Gleason grading system, which is used to classify prostate cancer, using samples from a prostate biopsy.
The higher the score, the more aggressive the cancer. The Gleason score usually ranges from 6 to 10. The lower the Gleason score, the more the cancer cells look like normal cells and are likely to slowly grow and spread. However, most prostate cancers have scores of 6 or higher.
While less aggressive than cancer cells may look like normal, healthy or non-cancerous cells, other cancer cells may look very different from normal cells may be more aggressive.
In comparison to other forms of cancer, prostate cancer is more likely to be multifocal—meaning the prostate can have several tumors, each of which could have a distinct grade. [2] Prostate cancer is also highly heterogeneous, and one part of a prostate tumor may look very different than another part of that same tumor. This heterogeneity is a major contributor to lethal outcomes, drug resistance, and therapeutic failures, and presents a key challenge to precision medicine goals [2]
The Gleason grading system is designed to accounts for these differences by combining grades from different regions of the prostate cancer. To calculate the score, pathologists analyze prostate tissue collected from a biopsy, identify the two most representative cellular patterns, and finally, assign each of these a grade.
The sum of these grades is the Gleason score.
Pathologists typically include the grade of each pattern when reporting the score with the grade of most representative pattern listed first, which generally makes up the largest areas of the biopsied tissue sample.
For example, if a cancer’s most common pattern were grade 4 and the second most common were grade 3, then the pathologists report may state ‘Gleason score 7 (4 + 3)’ or ‘Gleason score 4 + 3 = 7.’ Because each cellular pattern can have a grade between 1 and 5, Gleason scores can theoretically range from 2 (1 + 1) to 10 (5 + 5).
Interpreting the Gleason Score – What does it mean?
- Gleason score of 6 means that the cancer has a low risk of growing and spreading.
- Gleason score of 7 means that the cancer has an intermediate risk. Based, in part, on the grade of the most common cellular pattern, this risk can be further classified as favorable (Gleason score 7 (3 + 4)) or unfavorable (Gleason Score 7 (4 + 3))
- Gleason scores of 8, 9, or 10 mean that the cancer has a high risk of growing and spreading. These cancers are considered aggressive.
Gleason Score and Treatment?
Based on recommendation from the American Urological Association (AUA) [3][4][5] a majority of patients with low-risk cancers is active surveillance, This approach involves closely monitoring the patient’s disease in lieu of starting treatment. Active surveillance might also be an option to be considered for patients with favorable intermediate-risk cancers, while other patients with favorable intermediate-risk cancers might choose radiation or surgery.
In contrast, patients with aggressive cancers, including unfavorable intermediate-risk and high-risk tumors, are typically recommended to undergo surgery or radiation combined with hormone therapy, as long as they are expected to live at least 10 more years.
Overall, the Gleason score is just one of many factors that determine risk and guide treatment decisions for prostate cancer. Other factors associated with a prostate cancer’s risk of growing and spreading include its stage, molecular features, and levels of the prostate-specific antigen (PSA) in the patient’s blood. And finally, treatment decisions are also influenced by the patient’s age, overall health, and preferences.
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Note:* The Gleason scoring system was devised in the 1960s and 1970s by Donald F Gleason, MD, Ph.D.,(1920–2008) a pathologist at the Minneapolis Veterans Affairs Hospital and members of the Veterans Administration Cooperative Urological Research Group.
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This article is based on an article first published in Cancer Research Catalyst, the official blog of the American Association for Cancer Research (AACR).
Reference
[1] Cancer Stat Facts: Prostate Cancer. National Cancer Institute (NCI) Online Last accessed on May 22, 2025.
[2] Ge R, Wang Z, Cheng L. Tumor microenvironment heterogeneity an important mediator of prostate cancer progression and therapeutic resistance. NPJ Precis Oncol. 2022 May 4;6(1):31. doi: 10.1038/s41698-022-00272-w. PMID: 35508696; PMCID: PMC9068628.
[3] Eastham JA, Auffenberg GB, Barocas DA, et al. Clinically localized prostate cancer: AUA/ASTRO guideline, part I: introduction, risk assessment, staging, and risk-based management. J Urol. 2022;208(1):10-18.
[4] Eastham JA, Auffenberg GB, Barocas DA, et al. Clinically localized prostate cancer: AUA/ASTRO guideline, part II: principles of active surveillance, principles of surgery, and follow-up. J Urol. 2022;208(1):19-25.
[5] Eastham JA, Auffenberg GB, Barocas DA, et al. Clinically localized prostate cancer: AUA/ASTRO guideline. Part III: principles of radiation and future directions. J Urol. 2022;208(1):26-33.
Featured image: Doctor talking a with patient in hospital exam room. Photo courtesy: © 2019 – 2025 Fotolia/Adbobe. Used with permission.
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