Cancer Grading System and Prostate Cancer Prognosis

6–8 minutes

A new 5-grade system overcomes many of the deficiencies of the existing Gleason system for grading prostate cancer, researchers say.

“I think it is inevitable that the new grading system will eventually replace the Gleason system,” Dr. Jonathan I. Epstein, from the Johns Hopkins Medical Institutions, Baltimore, Maryland, told Reuters Health by email.

“The system is: 1) simpler and more intuitive; 2) more accurate in predicting prognosis; and 3) has the potential to help reduce overtreatment of indolent prostate cancer.”

In a study of more than 20,000 men with prostate cancer treated with radical prostatectomy, the researchers found large differences in the five-year biochemical remission-free progression probabilities for Gleason scores 6 (96%), 3+4 (88%), 4+3 (63%), 8 (48%), and 9-10 (26%).

On univariate and multivariable analyses, the five-grade system performed better than any of the common groupings of Gleason grade categories, according to the July 10 European Urology online report.

“Using the new grading system makes it easier for clinicians to explain to patients how aggressive their cancer is and what is the best treatment depending on the grade,” Dr. Epstein said. “However, adopting new terminology and new grading systems takes place slowly and I anticipate that the new grading system and the Gleason will be used in parallel for several years before the Gleason system is eventually replaced.”

“There are no other proposed competing grading systems, although what is on the horizon is potentially combining the new grading system with other clinical measurements such as serum or molecular markers or radiographic findings to improve prognostication to an even greater extent,” Dr. Epstein said.

Dr. Damien M. Bolton, director of urology at the University of Melbourne, Australia, told Reuters Health by email that this grading system is unlikely to replace the Gleason grading system, “but hopefully it will make people more aware of the relative prognostic implications of these groups. Physicians and patients should know that 4+3=7 cancer is much more prognostically significant than 3+4=7 cancer. It doesn’t change the message that Gleason score 6 cancer should be considered for management by active surveillance.”

“The references in their article all demonstrate that similar views have been held for a long time,” Dr. Bolton said. “The key issue is to recognize that the distinction between the different Gleason scores is nonlinear.”

Dr. Joseph R. Wagner from Hartford Hospital, Hartford, Connecticut, told Reuters Health by email, “When I meet with patients, I tell them the Gleason score ranks their cancer’s aggressiveness on a scale 2-10 — 2 is good; 10 is bad. However, 2-5 essentially do not exist. We leave them on the scale in honor of Dr. Gleason. I mostly see 6-8 with some 9/10’s. I also tell patients there is a big difference between Gleason 3+4=7 and 4+3=7.”

“I feel there is a very good chance this will supplant the Gleason system,” Dr. Wagner said. “It would be much easier for patients to understand. Classifying Gleason 6 as Grade 1 would make some patients feel better about active surveillance, and Gleason 7 patients would be clearly subcategorized.”

Why Update the Gleason System?

Even with the 2014 revision, the Gleason score can be confusing for both patients and physicians. The main issue? A score of 7 can represent two very different risk profiles:

Gleason 3+4=7: mostly well-differentiated (less aggressive)
Gleason 4+3=7: mostly poorly differentiated (more aggressive)

This subtle difference can significantly impact treatment decisions. The new 5-grade system aims to clear up this ambiguity.

The New 5-Grade Prostate Cancer Groupings

Here’s how the new system breaks down:

Grade Group 1: Gleason score ≤ 6
Grade Group 2: Gleason score 3+4=7
Grade Group 3: Gleason score 4+3=7
Grade Group 4: Gleason score 8
Grade Group 5: Gleason score 9-10

Each group offers a clearer picture of cancer aggressiveness.

How Effective Is the New System?

The team analyzed data from over 20,000 men who had undergone prostate surgery. The five-year progression-free survival rates varied widely by group:

Grade Group 1 (Gleason 6): 96%
Grade Group 2 (3+4): 88%
Grade Group 3 (4+3): 63%
Grade Group 4 (8): 48%
Grade Group 5 (9-10): 26%

In both univariate and multivariable analyses, the new system outperformed the traditional Gleason-based groupings in predicting outcomes.

What This Means for Patients

The new grading model may help:

Simplify conversations between doctors and patients
Reduce overtreatment of less aggressive cancers
Improve acceptance of active surveillance, especially for men with Grade Group 1 (Gleason 6)

“I tell patients there is a big difference between 3+4 and 4+3,” said Dr. Joseph R. Wagner of Hartford Hospital. “This system makes that much clearer.”

Will It Replace Gleason?

While many experts are optimistic, change in the medical field tends to be gradual. For now, both systems will likely be reported together:
Example: Gleason score 3+4=7 (Grade Group 2)

“Classifying Gleason 6 as Grade 1 would make some patients feel better about active surveillance,” Dr. Wagner added.

Dr. Damien M. Bolton from the University of Melbourne agrees the system enhances understanding but believes the Gleason scale will remain a part of medical culture for the foreseeable future.

What’s Next?

While no competing grading systems are on the horizon, researchers are interested in pairing the 5-grade system with molecular markers, imaging, and blood tests to further improve accuracy.

Even with its most recent revision in 2014, the Gleason grading system can assign the same score to significantly different risk groups. For example, a Gleason score of 7 can represent mostly well-differentiated cancer with a lesser component of more poorly differentiated cancer (Gleason 3+4=7) or mostly poorly differentiated cancer with a smaller component of well-differentiated cancer (4+3=7).

Patient Q&A: Understanding the New Prostate Cancer Grading System

Q: What is the difference between the Gleason score and the new grade group system?
A: The Gleason score ranges from 6 to 10, but it combines two patterns of tumor cells, which can confuse patients. For example, a Gleason 3+4=7 is very different from 4+3=7 — but both are just called “7.” The new 5-grade group system separates these into Grade Group 2 and Grade Group 3, making the prognosis much clearer and easier to understand.

Q: Why does 4+3=7 mean a worse prognosis than 3+4=7?
A: Because the first number represents the dominant cancer pattern. A 4+3=7 means more of the tumor is made up of the more aggressive “pattern 4” cells, while 3+4=7 is mostly the less aggressive “pattern 3.” So even though the total score is the same, the cancer behaves differently.

Q: What does Grade Group 1 mean? Should I still be worried?
A: Grade Group 1 corresponds to a Gleason score of 6. This is considered the least aggressive form of prostate cancer and is often eligible for active surveillance instead of immediate treatment. It’s still important to monitor closely with your doctor.

Q: Will doctors stop using the Gleason score altogether?
A: Not yet. Most medical reports now include both systems. Example: Gleason 3+4=7 (Grade Group 2). The goal is to eventually switch fully to the simpler 5-grade system, but that transition takes time across hospitals and labs.

Q: Can this new system help me decide on treatment?
A: Yes. Because it gives a more accurate picture of how aggressive the cancer is, it helps doctors and patients make better decisions — like whether to choose surgery, radiation, or simply watch and wait.

Was the System Updated After 2014?

The 5-grade group system was formally proposed in 2013–2014 by Dr. Jonathan Epstein and colleagues and has not been revised since in terms of structure. However, it was officially adopted by the World Health Organization (WHO) in 2016 as the new standard for prostate cancer grading. Since then:

It has gained wide acceptance in pathology and urology communities globally.
Many medical institutions now report both Gleason and Grade Group systems side-by-side.
Researchers have continued studying how to combine it with MRI findings, PSA density, and genomic biomarkers for even better risk stratification.

As of mid-2025, no new grading system has replaced or modified the 5-grade group framework, and it remains the recommended classification standard used in guidelines by the WHO, American Urological Association, and NCCN (National Comprehensive Cancer Network).