Gleason 6 and Misuse of the Term 'Cancer'

Lonely Man Commute
Death To Stock

Misuse of the term “cancer” has tragic implications. Real cancers require action, aggressive medical intervention with the goal of saving a life. But consider the potential havoc created by telling someone they have cancer when it is untrue. This ghastly calamity is occurring to 100,000 men every year in the United States in men who undergo a needle biopsy and are informed that they have prostate cancer with a grade of Gleason 6. But imagine the implications: What if the Gleason 6 variety of prostate cancer is not really cancer?

Is Gleason 6 Cancer?

The decision to categorize Gleason 6 as cancer was made back in the 1960s; doctors back then thought that the cells looked cancerous under the microscope. Now the dawning reality is that Grade 6 is not really cancer. However, changing the mindset about something that has been labeled cancer since the 1960s has been difficult. Many doctors in the prostate industry continue to recommend radical treatment for Gleason 6.

Grade 7 and Above Are Real Cancers

Part of the confusion is related to the obvious fact that other grades of prostate cancer (Gleason 7 and above) certainly exist and are occasionally fatal. The innocuous nature of Gleason 6 is constantly being confused with the higher-grade cancers, the ones that lead to mortality in about 30,000 men annually.

The problem has been a lack of careful scientific studies designed to precisely link the original Gleason score, determined at the time of diagnosis, to a cancer death that often occurs more than a decade later. Due to a lack of awareness that a problem even existed, there has been a long delay in performing the necessary studies.

This delay is also partly due to the slow-growing nature of prostate cancer. Even the subgroup of men who die from prostate cancer typically lives with it for ten to twenty years before they succumb. With such a long time-lag between diagnosis and death, researchers were not on the lookout for a subtype of prostate cancer that doesn’t cause death. Therefore, the results of such studies are only now becoming available.

What Does the Word “Cancer” Really Mean?

Since we are trying to make a precise distinction between Gleason 6 and higher types of prostate cancer lets clarify what the word “cancer” really means: Human cells with the capacity for metastases are cancerous. Cancer cells with the capacity to spread outside the prostate and into another organ are metastatic. Once the metastatic cells arrive in another organ, they start to proliferate and enlarge into tumors. When these tumors reach a certain size, they begin to cause malfunction of that organ. When organ malfunction is severe, the process becomes fatal.

Characterizations of Different Cancers

Cancers are classified by their site of origin, how big the tumor has grown, and their grade. For example, lung, brain, and prostate cancers all behave very differently simply because they originate from different organs. No matter which organ we are talking about, the larger the tumor, the more dangerous it is likely to behave.

Bigger tumors are more dangerous because they have a higher likelihood of harboring higher grade elements. Aggressive tumors have distinct characteristics that can be visually distinguished from low-grade tumor cells. This service is performed by a trained physician called a pathologist.

“Grade” is an expert visual analysis of the appearance of the cancer cells under the microscope. Grading can be used to predict the likelihood of future metastases. These days, the accuracy of grade determination is even further enhanced with the use of genetic tests that screen for specific genes known to associated with more aggressive behavior.

Evolution of Current Thinking About Prostate Cancer

Before PSA screening and needle biopsy became prevalent in the early 1990s, prostate cancer was often diagnosed after it had metastasized. Metastatic prostate cancer is indisputably dangerous and deadly. Through many years of caring for men with metastatic prostate cancer, doctors developed a defensive mindset: a prevalent, all-inclusive concern about the seriousness of prostate cancer. Naturally, this attitude of concern spilled-over on their attitude toward early-stage prostate cancer when it started to become common due to the increasing use of PSA screening and needle biopsies. So, for many years, doctors have been wrongly assuming that all early-stage prostate cancers will become metastatic if untreated.

How Can We Know the Gleason 6 Subtype of Prostate Cancer Will Not Spread?

Studies evaluating the long-term outcome of men with pure Gleason 6 have finally been completed. These studies had to be performed in surgical patients because surgical removal of the prostate enables thorough microscopic evaluation of the entire gland. Surgery is the only way to confirm that the original needle biopsy showing Grade 6 was accurate and that an area of higher-grade disease was not being missed.

Removing the whole prostate so it can be thoroughly examined by a pathologist is the only way to be sure that 100 percent of cancer in the prostate is truly Grade 6. Now, several large retrospective surgical studies involving thousands of men watched for more than 10 years’ post-operation, have been completed. The consistent finding is that Grade 6 does not metastasize.

Have Doctors Made a Big Mistake?

Prostate cancer is diagnosed with a strange and unique methodology. Twelve randomly-directed needle biopsies are stabbed through the rectal wall into the prostate without any attempt to target a specific abnormality. This odd process has worked reasonably well because the prostate is a relatively small gland, about the size of a walnut. The drawback is that because the stabs are random, they can miss higher-grade prostate cancer (Gleason 7 or above).

Prostate cancer is often multifocal; this means that tumors can be located in more than one section of the prostate gland. These different tumors can be of different grades. One area may be Gleason 6 and another area may show Gleason 8. Therefore, when needles are randomly jabbed into the gland, it is possible for the biopsy to detect only Gleason 6 when actually Gleason 8 is also present. Studies performed to date indicate that about one out of three men who undergo a well-performed 12-core random needle biopsy showing Gleason 6 actually have undetected higher-grade disease somewhere else in the prostate.

Relying only on this random biopsy technique, doctors could potentially be fooled into believing a patient has only Gleason 6 when in some cases the grade is actually higher. This is the original source of the false belief that Gleason 6 can metastasize. Men diagnosed with “Gleason 6,” who underwent treatment, and later had a cancer relapse, led the doctors to believe that Gleason 6 cancer cells themselves had metastasized. We now know that the recurrences, the ones that were thought to be coming from Gleason 6, were actually only occurring in men who had Gleason 7 or higher prostate cancer that was hidden in another area of the prostate and was undetected by the original prostate biopsy.

Traditional Ways to Compensate for the Biopsy’s Inaccuracy

To make sure prostate cancer mortality is minimized, the standard approach has been to recommend radical surgery or radiation to everyone, “just to be safe.” Treating everyone completely covers the possibility of undiagnosed higher-grade disease and eliminates the doctor’s medical liability if a relapse occurs in the future. Unfortunately, over the last 20 years, this aggressive policy has led to unnecessary treatment in more than two million men and the treatment can cause impotence and incontinence.

Now that doctors are realizing the drawbacks of recommending treatment for everyone, another option called active surveillance has been gaining acceptance. Over the last 10 years, active surveillance has become more and more accepted as a viable way to manage selected men with Gleason 6 prostate cancer. Active surveillance is accepted by the National Comprehensive Care Network (NCCN), The American Society of Clinical Oncology (ASCO) and the American Urological Association (AUA) as a standard way to treat Gleason 6.

Men who are initially diagnosed with Grade 6 are closely monitored with frequent checking of their PSA. They also undergo periodic 12-core needle biopsies every few years in an attempt to detect any high-grade disease that may have been missed on the initial biopsy. The policy of PSA testing and periodic biopsies is certainly unattractive, but radical treatment with surgery or radiation has even worse effects. However, just recently, new scanning techniques are becoming available that provide an alternative to random biopsy.

MRI Imaging and the Biopsy

Biopsies are unpleasant and sometimes they cause life-threatening infections or bleeding. Though random biopsy has been considered the gold standard for prostate cancer diagnosis, how does it compare to modern imaging with multi-parametric MRI?

This question was thoroughly tested in a large study involving 600 men with high PSA levels who volunteered to undergo a multi-parametric MRI, a random biopsy and a saturation biopsy to test which approach was the most accurate (a saturation biopsy involves 30+ needles into the prostate under anesthesia and is the most accurate way to diagnose prostate cancer). Compared to the saturation biopsy, random biopsy detected 75 percent of the men who had a higher-grade disease. The multi-parametric MRI detected 90 percent of the men who had clinically significant prostate cancer.

This study clearly proved that well-performed, multi-parametric MRI is substantially more accurate than random biopsy. Unfortunately, most urologists, the type of doctors who are charged with the responsibility for supervising active surveillance candidates, are still only trained in the random biopsy method for staging and monitoring prostate cancer.


Men with Gleason 6 don’t have cancer in the true sense of the word. There is no risk of it metastasizing. Until recently, a major drawback of active surveillance has been the need to repeat the random biopsy periodically. The advent of multi-parametric MRI appears to be a much superior alternative. These days, a man diagnosed with Gleason 6 has the option of embarking on a surveillance program without the need for periodic 12-core needle biopsies.

Was this page helpful?
Article Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Kulac I, Haffner MC, Yegnasubramanian S, Epstein JI, De Marzo AM. Should Gleason 6 be labeled as cancer?Curr Opin Urol. 2015;25(3):238–245. doi:10.1097/MOU.0000000000000165

  2. Epstein JI, Zelefsky MJ, Sjoberg DD, et al. A Contemporary Prostate Cancer Grading System: A Validated Alternative to the Gleason ScoreEur Urol. 2016;69(3):428–435. doi:10.1016/j.eururo.2015.06.046

  3. Cleveland Clinic. Prostate cancer. Updated July 24, 2015

  4. National Foundation for Cancer Research. The hallmarks of metastasis. Updated August 22, 2019.

  5. Prostate Cancer Research Institute. The prostate cancer staging guide.

  6. Yang R, Cao K, Han T, et al. Perineural invasion status, Gleason score and number of positive cores in biopsy pathology are predictors of positive surgical margin following laparoscopic radical prostatectomyAsian J Androl. 2017;19(4):468–472. doi:10.4103/1008-682X.173444

  7. Willis SR, Ahmed HU, Moore CM, et al. Multiparametric MRI followed by targeted prostate biopsy for men with suspected prostate cancer: a clinical decision analysisBMJ Open. 2014;4(6):e004895. doi:10.1136/bmjopen-2014-004895