Prostate Cancer: After Biopsy; what does it mean?

When a man has an elevated PSA level, his doctor is likely to recommend one of two approaches: Do nothing and see what happens (called “watchful waiting”), or have a biopsy. Doing the actual biopsy, however, is often something of a challenge, given that the organ is pretty small and is located in a rather difficult-to-reach spot. As a result, doctors do what they call “blind biopsies,” meaning they snip out several pieces of prostate tissue and hope that at least one of them comes from the tumor so they’ll be able to assess just how serious the cancer is. Unfortunately, this method often picks up only healthy tissue, missing the tumor entirely, and produces a false negative. More biopsies may be ordered, which may or may not identify anything. Biopsies are painful and can take as long as a month to heal.

A new high-tech technique that uses MRI and ultrasound to guide the biopsy needle straight to the tumor is currently being tested by Dr. Leonard Marks, a professor of urology at the University of California Los Angeles, and colleagues. A small study using this experimental technique found tumors in 53 percent of the 171 men who participated. The results, while preliminary, were reported in the Journal of Urology.

A biopsy is a sample of tissue taken from the body in order to examine it more closely. The pathologist sends your doctor a report that gives a diagnosis for each sample taken. Information in this report will be used to help manage your cancer. The questions and answers that follow are meant to help you understand medical language you might find in the pathology report from your prostate biopsy.

At least initially, the pathology report is one of the most important factors in the management of your prostate health, especially if you have been diagnosed with cancer. For example, it can provide valuable information about the location and extent of the cancer, thus helping your physician decide whether to recommend active surveillance, hormone treatment, radiation therapy, or surgery.

With that in mind, you might think that preparing and reading a pathology report would be straightforward — but unfortunately the opposite is true. Pathology reports are not prepared uniformly. In fact, they can vary considerably even within a single institution. They may not be labeled thoroughly or contain enough specifics for you and your doctor to make a good treatment decision. At the same time, the information that is included in the report may be difficult to interpret. You may also get conflicting interpretations depending on how the report was prepared and who is reading it. It is entirely possible for two pathologists to look at the same biopsy slides and yet disagree about whether you have cancer!

What is adenocarcinoma?
You may find in the report Adenocarcinoma. It is the type of cancer that develops in gland cells. It is the most common type of cancer found in the prostate gland.

Gleason Score/Grade

You may also see on your report Gleason grade or score and might be wondering; what is the Gleason grade or Gleason score? What do the numbers in the Gleason score mean, for example 3+4=7 or 3+3=6? The Gleason score is named after Dr. Donald Gleason, the pathologist who first studied and devised a scoring system to describe the aggressiveness of prostate cancers. This system helps to separate the less aggressive prostate cancers from those that are more aggressive; the rabbits and birds from the turtle!

In more technical terms, it represents the "grade" of the tumor, which is a measure of the degree of differentiation of prostate cancer cells. Differentiation refers to how "normal" a cancer cell appears under a microscope when compared to a normal prostate cell. If the cancer is poorly differentiated or undifferentiated, then it looks very abnormal. If the cancer is well differentiated, then it looks similar to normal cells. The more aggressive cancers are poorly differentiated, and these tumors have little or no regulation of their growth, allowing them to multiply in an uncontrolled manner (thus making it an aggressive cancer).

Be aware that when a prostate is biopsied for diagnosis and then subsequently removed with a radical prostatectomy, Gleason scores are the same between the biopsy and surgery specimens only 75% of the time. In about 20% of the cases, the surgery specimen actually ends up having a higher Gleason score (and thus a more aggressive cancer) than what was previously found on the initial biopsy. The reverse (lower Gleason score at surgery than at biopsy) happens less than 5% of the time. These discrepancies can be due to an incomplete biopsy or the expertise of the pathologist. Because the pathologist’s interpretation is subjective, it is important to have your tumor reviewed by an expert pathologist. Many experts recommend having a second pathologist review the specimen to be sure the Gleason grading is correct. The Gleason score is actually a sum of two Gleason grades

Pathologists assigned numbers from 1 to 5 based on the intensity of the cells in the cancerous tissue look like normal prostate tissue under the microscope. Grades 1 and 2 are not often used for biopsies − most biopsy samples are grade 3 or higher.

If the cancerous tissue looks much like normal prostate tissue, a grade of 1 is assigned. If the cancer cells and their growth patterns look very abnormal, a grade of 5 is assigned.

Grades 2 through 4 have features in between these extremes. Since prostate cancers often have areas with different grades, a grade is assigned to the 2 areas that make up most of the cancer. These 2 grades are added to yield the Gleason score (also called the Gleason sum). The highest a Gleason score can be is 10. The first number assigned is the grade that is most common in the tumor. For example, if the Gleason score is written as 3+4=7, it means most of the tumor is grade 3 and less is grade 4, and they are added for a Gleason score of 7. Other ways that this Gleason score may be listed in your report are Gleason 7/10, Gleason 7 (3+4), or combined Gleason grade of 7. If a tumor is on found all the same grade (for example, grade 3), then the Gleason score is reported as 3+3=6.

Although most often the Gleason score is based on the 2 areas that make up most of the cancer, there are some exceptions when a core sample has either a lot of high-grade cancer or there are 3 grades including high-grade cancer. In these cases, the way the Gleason score is determined is modified to reflect the aggressive nature of the cancer.

Do you have Gleason score of 6, 7, 8, or 9-10 on your Report?

So your report is likely to have one of these numbers. Take not that because grades 1 and 2 are not often used for biopsies, the lowest Gleason score of a cancer found on a prostate biopsy is 6. These cancers may be called well differentiated or low-grade and are likely to be less aggressive; that is, they tend to grow and spread slowly. Cancers with Gleason scores of 8 to 10 may be called poorly differentiated or high-grade. These cancers are likely to grow and spread more quickly, although a cancer with a Gleason score of 9-10 is twice as likely to grow and spread quickly as a cancer with a Gleason score of 8. Cancers with a Gleason score of 7 can either be Gleason score 3+4=7 or Gleason score 4+3=7...but there is a little difference between these two patients with the same scores.

i. Gleason score 3+4=7 tumors still have a good prognosis (outlook), although not as good as a Gleason score 6 tumors.

ii. A Gleason score 4+3=7 tumor is more likely to grow and spread than a 3+4=7 tumor, yet not as likely as a Gleason score 8 tumor.

The Gleason score is very important in predicting the behavior of a prostate cancer and determining the best treatment options. Still, other factors are also important, such as: The blood PSA level, imaging tests et al.

Grade Groups?
The International Society for Urologic Pathology's (ISUP) and World Health Organization, in 2014, adopted a simplified patient-centric grading system composed of 5 prognostic Grade Groups (Am J Surg Pathol 2016;40:244, Prostate 2016;76:427) as proposed in 2013 based on data from Johns Hopkins (BJU Int 2013;111:753) and subsequently validated by biochemical recurrence hazard ratios on cases from 5 large academic centers (Eur Urol 2016;69:428)

Grade Groups are a new way to grade prostate cancer to address some of the issues with the Gleason grading system.

As noted above, currently in practice the lowest Gleason score that is given is a 6, despite the Gleason grades ranging in theory from 2 to 10. This understandably leads some patients to think that their cancer on biopsy is in the middle of the grade scale. This can compound their worry about their diagnosis and make them more likely to feel that they need to be treated right away.

Another problem with the Gleason grading system is that the Gleason scores are often divided into only 3 groups (6, 7, and 8-10). This is not accurate, since Gleason score 7 is made up of two grades (3+4=7 and 4+3=7), with the latter having a much worse prognosis. Similarly, Gleason scores of 9 or 10 have a worse prognosis than Gleason score 8. To account for these differences, the Grade Groups range from 1 (most favorable) to 5 (least favorable):

Grade Group 1 = Gleason 6 (or less)
Grade Group 2 = Gleason 3+4=7
Grade Group 3 = Gleason 4+3=7
Grade Group 4 = Gleason 8
Grade Group 5 = Gleason 9-10
Although eventually the Grade Group system may replace the Gleason system, the two systems are currently reported side-by-side.

There can also be perineural invasion meaning that the cancer cells were seen surrounding or tracking along a nerve fiber within the prostate. When this is found on a biopsy, it means that there is a higher chance that the cancer has spread outside the prostate. Still, perineural invasion doesn’t mean that the cancer has spread, and other factors, such as the Gleason score and amount of cancer in the cores, are more important. In some cases, finding perineural invasion may affect treatment, so if your report mentions perineural invasion, you should discuss it with your doctor.

High-grade prostatic intraepithelial neoplasia or high-grade PIN

High-grade prostatic intraepithelial neoplasia (high-grade PIN) is a pre-cancer of the prostate. It is not important in someone who already has prostate cancer. In this case, the term 'high-grade' refers to the PIN and not the cancer, so it has nothing to do with the Gleason score or how aggressive your cancer is. The biopsy report also can mentions acute inflammation (acute prostatitis) or chronic inflammation (chronic prostatitis)?

Most cases of prostatitis reported on biopsy are not caused by infection and do not need to be treated. In some cases, inflammation may increase your PSA level, but it is not linked to prostate cancer. The finding of prostatitis on a biopsy of someone with prostate cancer does not affect their prognosis or the way the cancer is treated.

Atrophy, adenosis, or atypical adenomatous hyperplasia

These are terms for things the pathologist might see under the microscope that are benign (not cancer), but that sometimes can look like cancer. Atrophy is a term used to describe shrinkage of prostate tissue (when it is seen under the microscope). When it affects the entire prostate gland it is called diffuse atrophy. This is most often caused by hormones or radiation therapy to the prostate. When atrophy only affects certain areas of the prostate, it is called focal atrophy. Focal atrophy can sometimes look like prostate cancer under the microscope. Finding any of these is not important if prostate cancer is also present.

Seminal vesicle involvement during Biopsy.
The seminal vesicles are glands that lie just behind the prostate. Sometimes part of a seminal vesicle is sampled during a biopsy. This is not a cause for concern.

Atypical glands, atypical small acinar proliferation (ASAP), glandular atypia, or atypical glandular proliferation

It means the pathologist saw something under the microscope that is worrisome for cancer, but he or she is not 100% sure that cancer is present. Finding any of these is not important if prostate cancer is also present. My final advice to you is to always ask your doctor the meaning of the pathology report before deciding to start treatment. Thank you for reading. For further information concerning your pathology report call on 0541234556.

Next Week: Why pathologists may disagree on your report

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