Prostate Biopsy & Grading of Tumours

Prostate biopsy is the only currently available test which

is able to definitively diagnose prostate cancer.

 

The Process of a Prostate Biopsy

 

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WHY?

A prostate biopsy is almost always necessary to diagnose prostate cancer. PSA and DRE alone are rarely sufficient to make the diagnosis. The goal is to detect cancer which would be significant to a patient (not all prostate cancers require treatment or pose a threat to a man's quality or quantity of life).

 

WHEN?

The process of scheduling a biopsy is as follows:

  1. We send the requisition. Please contact the hospital first if they have not called you within a few weeks of your office visit. Richmond Hospital: 604-278-9711 (ask for Diagnostic Imaging)
  2. Obtain your antibiotics and take as directed starting the night prior to biopsy. Read the pre-test instructions
  3. Call our office to schedule an appointment to review the results.

 

PREPARATION

Read the brochure before your test.

  1. Ensure that  you take your antibiotic as prescribed by your urologist starting the night prior to the day of your biopsy. Call our office if you loose the prescription.
  2. Use a Fleet enema prior to coming in for your test.
  3. Stop blood thinners prior to your biopsy.
    1. Coumadin (Warfarin). Stop 5 days before test. Obtain an INR the day before the test.
    2. Antiplatelet medications (ASA, Plavix), your Urologist will give you specific directions on if the medication needs to be stopped. Usually 5 days for ASA, 10 days for Plavix.

 

HOW?

Your prostate biopsy will be performed by a Radiologist. The biopsy takes 15-20 minutes.

 

  1. The radiologist will place a small ultrasound probe up the rectum to identify the prostate
  2. The nerves to the prostate are frozen with local anesthesic and a small needle. No sedation or general anesthetic are required.
  3. A small needle gun is then used to remove 8-12 very small core-shaped samples from the prostate. Each core measures about 10-20 mm (1/2 inch) in length and 2-3 mm wide. Most men describe the pain as a 2-3/10 where 10 is the worst pain they have had.

Ultrasound is used to take a representative sample from different parts of the gland. Ultrasound cannot diagnose prostate cancer by itself, but it can direct the Radiologist to take representative samples from the prostate.

 

WHAT TO EXPECT AFTER THE BIOPSY.

Most men do not have any serious problems following a prostate biopsy. Bleeding is usually transient and self-limited. Infection is the most concerning complication of a biopsy, but fortunately occurs in less than 4% of men with antibiotic prophylaxis.

 

Bleeding Infection

It is normal to have some bleeding after your prostate biopsy.

  1. Blood may appear in your urine, stool and ejaculate
  2. It usually lasts for a few days, but may last for a few weeks.
  3. It may be intermittent.
  4. It is rare that the bleeding is heavy enough to require any intervention. If you have brisk bleeding which does not settle quickly following the biopsy, please go to your nearest Emergency Room

The most serious complication following biopsy is infection. This usually occurs within the first couple of days after the biopsy. If you have a fever and feel unwell, please go immediately to your local emergency department and notify our office. Fortunately, infection is rare and occurs in only 1 in 50 men having biopsy. The antibiotics reduce the chance that you will get an infection.

 

Bacteria resistant to Ciprofloxacin are becoming more common (especially in people who have been on antibiotics or travelled to India or China). The general recommendation for a post-biopsy infection is MEROPENEM until the results of the cultures are back. 

 

FOLLOW-UP AFTER YOUR BIOPSY

Your urologist will ALWAYS want to have a face-to-face appointment to discuss the results of your biopsy, even if no cancer is found. It can take 2-3 weeks to receive a result and the hospital does not notify us of the date of your biopsy. Please call our office as soon as you have been given a date for your biopsy and our office will arrange an appointment.

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Advantages and Limitations of Prostate Biopsy

 

Biopsy is necessary to diagnose cancer. There is no currently available blood test, imaging test or other test which can establish the diagnosis of prostate cancer. In very rare cases, the weight of evidence from ciinical evaluation may make a biopsy redundant  - but in such cases advanced, incurable disease is always present. In men with potentially curable disease, a biopsy is always necessary.

 

False-negative biopsies are a limitation. A prostate biopsy is a sample of from the prostate. The sample is evaluated by a specially trained physician (Pathologist) with a microscope, sometimes using special techniques to define the different structures in the sample. The pathologist reports their findings based on the tissue that was taken and evaluated. Note that only a very small part of the prostate is taken, but with ultrasound guidance the goal is to take representative samples from the prostate gland. The entire tissue in the prostate cannot be completely evaluated with currently available tests. With today's technology, evaluating the entire gland with 100% certainty would require removing the entire gland - an unattractive prospect for any man.

 

Therefore, the 'pathology report' which results from the process of a prostate biopsy specifically comments only on the samples taken from the prostate. It is reasonable to extend these findings to the rest of the prostate because the samples which are obtained by ultrasound guided biopsy are representative of what is happening in the entire gland. As a result, the one caveat of a prostate biopsy is that it cannot exclude the presence of prostate cancer with 100% certainty.

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Value of Prostate Biopsy & Grading of Prostate Cancer

 

The purpose of the prostate biopsy is not simply to determine if cancer is present. Many men are aware that prostate cancer is increasingly common as men age - it is felt that over half of all men above the age of 80 harbour cancer and is surprisingly common in younger men (up to 1 in 5 men in their 60's have prostate cancer). In addition, biopsy is an imperfect test - some men who have cancer will not have it detected on a biopsy because the inherent nature of a biopsy is one of 'sampling' and therefore sampling error can occur (cancer present but the needle doesn't hit the tumour).

 

What then is the value of biopsy? The value is RISK ASSESSMENT. Risk of suffering ('morbidity') or dying ('mortality') from the prostate cancer. Everything in decision making for prostate cancer comes down to assessment of tyhe risks (and benefits) of different courses of action. The biopsy is quite frequently (thought not always) the most important part of the risk assessment.

 

A negative biopsy ('no cancer') can, in most situations, provide very good reassurance that there is little to worry about (note that this is subtly but importantly different than nothing to worry about). A positive biopsy tells you that cancer is present, but without additional information has very, very limited value. Remember that the vast majority of men will die of causes other than prostate cancer - a very significant 3-4% of the male population does die of prostate cancer and a larger number are ravaged by it; the flip side is that 96-97% of men do NOT die of prostate cancer. In addition, the majority of men with a diagnosis of prostate cancer do NOT succumb to the disease. The question real question is:

 

What is the risk of suffering or dying from prostate cancer IF it is present?

 

This is a much more complicated question to answer but the details present from a positive biopsy actually provide a great deal of insight. The information from a biopsy can be divided into the following categories - remember that not all information should be equally weighted - some information may be much more important that other and everything must be taken in the context of the entire clinical picture.

 

  1. Cancer: present or not.
    1. No cancer: value dependent on the quality of biopsy and the context - these influence the chances that the biopsy is a 'false negative'. Things such as the size of prostate, number of cores, image guided or not, pre-test likelihood (was a palpable nodule present and was it sampled, what was the PSA, etc.)
  2. Grade of tumor: see below
  3. Volume of tumor: more is generally worse. It can be measured in several ways.
    1. Number of cores which have cancer
    2. Percent of cores having cancer
    3. Amount of tumor present within each core: either a percent or absolute length
  4. Other: there are a few other features. Sometimes they go hand in hand with the other features and don't really add much information. Other times they help refine the risk and should rarely should be used in determining how to manage the tumor. 
    1. Perineural invasion (PNI): cancer is seen around the small nerves within the prostate. Cancer may uses these conduits as a path to spread outside of the prostate capsule. PNI can increase the chances that extraprostatic extension (EPE) will be found at the time of surgery. It can guide the surgical approach but does not exclude surgery or radiation as treatment options.
    2. Lymphovascular invasion (LVI): this is almost exclusively seen in the highest grade/risk tumors. Usually goes hand in hand with Gleason 8 or higher tumors (Grade Group 4/5 and 5/5). This is a poor prognostic factor and associated with a higher risk of disease spread to the lymph nodes and outside the capsule. Rarely affects management choice, but the risk of relapse is always higher - as it is for patients with high-grade tumors.


The Gleason Grading System and the Grade Group Systems

 

Virtually all prostate cancers are adenocarcinoma. When the term 'prostate cancer' is used, this is what is referring to. There are rare types of prostate cancer (different histologies), but these asccount for much less than 5% of cancers (for example, small cell carcinoma). Adenocarcinoma originates from the cells responsible for the creation of fluid in the prostate ejaculate - the epithelial cells within the acini of the gland. There are hundreds of thousands of prostate acini in the prostate - they are like the leaves on a tree - and they create small amounts of fluid rich in PSA. The secreted fluid is then collected in the small ducts until they empty into the urethra during ejaculation. When the cells start behaving in an unregulated manner, they may 'jump the fence' and spread through the prostate and elsewhere in the body.

 

The appearance of the prostate cancer under a microscope which correlates (follows/trends) with the behavior of the cancer over time. The microscopic appearance also correlates with the underlying genetic changes.

 

Hence, the appearance of the cancer can help predict the future behavior of the cancer. 

 

The original Gleason grading system is a way to correlate the appearance with risk. The interpretation and application have changed over time - this is very, very important and why some background is important. The formula looked something like this:

 

Primary Gleason GRADE + Secondary Gleason GRADE = Gleason SCORE

 

Primary Grade is always the 'most common pattern in the specimen'. This is determined 'geographically'. As an anology, earth has 2 common surface features - water and land. The most 'common' feature is water. Similarly, the most common pattern, regardless of it's grade, is assignied the 'Primary Grade'. 

 

Secondary Grade in a biopsy is currenty the highest grade. This was not always the case - it used to be the second most common geographic pattern. It has been recognized that the highest grade predicts tumor behavior better than the second most common pattern.

 

Lastly, THE LOWEST GRADE WHICH CAN CURRENTLY BE ASSIGNED IS A 3/5 (THREE OUT OF FIVE). In the past, the lower grade was a 1/5 (one out of five). It has since been appreciated that Gleason 1/5 and 2/5 do NOT behave in any sort of cancerous manner despite the fact that the appearance is different from normal prostate tissue. As a results, the lowest grade and score combination is the following:

 

Primary Grade 3/5 + Secondary Grade 3/5 = Gleason Score 6/10

 

It is not currently possible to have a lower-risk grade then a 6/10 - a Gleason Score 6/10 tumor is the lowest category of grade for a prostate cancer. In the past, Gleason 1/5 tumors were still read  by the Pathologist as cancer and therefore Gleason Score 2/10-5/10 tumors were possible. This is no longer the case - and no patient is every assigned a Gleason Score of less than 6/10 in the current era. For obvious reasons, this has created a great amount of confusion amongst patients and non-urologists. Intuition tells us that the closer the number is to the maximum of 10, the worst the tumor must be. This is, in fact, the opposite. Low grade tumors rarely cause problems as the overall picture is usually one of low risk (though there are always exceptions) and these are often managed with an Active Surveillance approach. Here is a sampling the current Gleason Grades and possible Gleason Scores

 

Gleason Score Gleason Grade Combinations
6/10

3+3

Comment: this is the only way to get a 6/10. LOWEST score and lowest risk

7/10

3+4

4+3

Comment: There is a very large difference in behavior between these 2 grades. Primary Gleason Grade 4/5 tumors (4+3) are much higher risk than Primary Gleason Grade 3/5 (3+4) tumors. Big difference in risk is wiped out by communicating risk using the overall Gleason Score  Doctors sometimes described 3+4 as "low tier intermediate risk' pathology.

8/10

4+4

3+5

5+3

Comment: all of these are high risk tumors - as are all grades similar or higher.

9/10

4+5

5+4

10/10

5+5

Comment: only a single combination will result in a 10/10. Frequently accompanied by lymphovascular invasion and perineural invasion, but these are secondary features. The mere presence of a 10/10 is the dominant risk factor and will over shadow all other risk features (e.g. PSA, Palpability of tumor, etc.)

 

Many 'Risk Stratification' Systems will try and simplify these groups to Low, Intermediate and High risk groups. This approach simplifies for communication but throws away a whole lot of valuable information in decision making and should be avoided.

 

In order to overcome the issues inherent in communiation of risk resulting from historical issues with the Gleason Grading system, a new Grade Group system has been adopted. The Grade Group system has kept the best parts of the Gleason Scoring system (which is well entrenched and understood by doctors) and removed much of the confusion in how the risk groups  It has the smallest number of categories that differentiate outcomes The new grading system:

  1. Provides more accurate grade stratification (the meaningful differences between groups is highlighted better).
  2. There are fewer groups than before.
  3. The lowest risk group is now 1/5 - which has the potential to reduce over-treatment of low-risk patients.

 

The Grade Group provides a score out of 5 (five) with the lowest risk group being 1/5 and the highest 5/5.

GRADE GROUP Gleason Grade Combination and Score
1/5

LOWEST RISK GROUP

3+3=6/10

2/5 3+4=7/10
3/5 4+3=7/10
4/5 4+4=7/10
5/5

HIGHEST RISK GROUP

4+5=9/10

5+4=9/10

5+5=10/10

 

IF YOU CAN UNDERSTAND THAT THE RESULTS OF THE BIOPSY HELP PREDICT THE LIKELHOOD THE TUMOR WILL SPREAD OVER TIME AND THAT THIS RISK IS COMMUNICATED BY THE GRADE THEN YOU UNDERSTAND THE UTILITY OF THE BIOPSY.

 

Prostate Biopsy: Frequently Asked Questions

 

Question: Does a biopsy spread cancer?

Answer: No. There is no risk that a prostate biopsy will seed cancer along the biopsy site or cause it to spread through the body. Some types of non-prostate cancer can be seeded with a biopsy, but multiple studies have demonstrated that prostate cancer does not behave like that.

 

Question: How accurate is prostate prostate biopsy?

Answer: See the discussion above. If cancer is found in the sample, then the prostate definitely contains cancer. If no cancer is found in the sample, then the prostate is unlikely to contain cancer. Sometimes the results of a biopsy are indeterminant and additional testing is required.

 

Question: Are there any 'non-invasive' alternatives to prostate biopsy to diagnose cancer

Answer: No. Obtaining a sample of prostate tissue, either by biopsy or transurethral resection, is the only definitive way to diagnose prostate cancer. There are rare circumstances where a presumptive diagnosis of prostate cancer is made based on clinical evaluation and where the risks of a biopsy are not justified given the clinical picture.

 

Question: Why has my urologist has recommended a transurethral resection of the prostate (TURP) to diagnose cancer.

Answer: If a prostate biopsy has not demonstrated cancer, in select circumstances a diagnostic TURP may be recommended when the risks of harboring cancer are greater than the risks of a TURP. While prostate biopsy is good for diagnosing cancers in the peripheral zone, is not as accurate for diagnosing cancers located centrally in the 'transitional zone'. Therefore, sampling the tissue from the transitional zone is sometimes recommended, especially in men with larger glands. A diagnostic TURP is less invasive than a therapeutic TURP, but does require a visit to the operating room with general or spinal anesthesia and can be associated with blood in the urine for 3-6 weeks post-operatively. Fortunately, most prostate cancers occur in the peripheral zone and therefore prostate biopsy is the right test for most men.

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