Biopsy

If the PSA test or the DRE indicate that cancer may be present, then the doctor may recommend biopsy. In a biopsy, tissue samples are taken from the prostate gland and examined by a pathologist under a microscope, who will look for abnormalities in the tissue architecture and cell structure. Well-differentiated cells are more normal in appearance, while poorly differentiated cells are more abnormal in appearance. Generally speaking, the more abnormal the cells appear, the more aggressive the cancer.

Biopsy of the prostate is problematic because prostate tumors are usually quite small. If the biopsy reveals no cancerous cells, it may be that there is no cancer present. Up to 80 cores may be taken if there is a strong probability of cancer. Even with multiple samples, however, it is possible for the biopsy to miss a tiny tumor. If there is a high likelihood that an individual has cancer (for instance there is a family history of prostate cancer, or the individual's PSA level is high or is rising quickly), but the biopsy tissue samples don't contain any cancerous cells, then the doctor may do a follow-up biopsy in 6 months.

There are three types of prostate biopsy:

• Transrectal. The transrectal systematic (typically 12-core) biopsy is the most common method of prostate biopsy. A transrectal biopsy is guided by transrectal ultrasound (TRUS), in which an ultrasound probe is inserted into the rectum. The TRUS creates an image of the prostate on a monitor and helps to guide the doctor in collecting samples. For biopsy purposes, the prostate is divided into six (or more) zones, and samples are taken from each zone. The biopsy gun uses spring-loaded hollow needles to collect tissue samples from the prostate through the rectum (for larger prostate glands, many more tissue samples may be taken). This is normally a quick procedure under local anesthesia and only minimally painful. Side effects of a transrectal biopsy may include a small amount of bleeding from the rectum as well as blood and urine in the semen afterwards.
  The transrectal systematic biopsy is limited in its effectiveness. It is blind in that the standard (also known as gray-scale) ultrasound is generally unable to discriminate between normal and abnormal tissue. Transrectal systematic biopsies can have false-negative rates of 10-20%.
  
• Transperineal. In a transperineal biopsy, a small incision is made in the perineum (the area between the anus and the scrotum). As in a transrectal biopsy, tissue is collected using a biopsy gun, and 6-12 cores are usually taken. Some doctors feel the transperineal 12-core biopsy is a more sensitive cancer detection method than the transrectal method. The patient may be put under general anesthesia. Side effects of a transperineal biopsy may include some tenderness, as well as blood in the semen, for 1-2 months following the procedure.
  
• Transurethral. In a transurethral biopsy, a lighted cytoscope is inserted up into the urethra so that the physician can look directly at the prostate gland, after the area has been numbed with a local anesthetic. A cutting loop is inserted through the cytoscope. The doctor turns the loop and extracts a small amount of tissue with each turn.
  

Lesion-Guided Biopsy

Standard ultrasound-guided biopsies frequently miss prostate cancers because conventional ultrasound can't reliably detect cancerous tissue. There are new methods, such as MRI and contrast ultrasound, that are better at telling the difference between normal tissue and cancer, but they are not broadly established at this time. MRI scans are expensive, and, as yet, there is no agreed-upon standard. Contrast ultrasound is approved in Europe but not in the US.

MRI-Guided Biopsy

An MRI-guided biopsy is a two-step process. First, MRI scans are taken to identify suspicious lesions. Then, the lesions are biopsied using MR-compatible instruments under direct MRI guidance.

MRI-Ultrasound Fusion Biopsy

A new type of biopsy technique that is currently being developed is the MRI-ultrasound fusion biopsy. In it, previously obtained MRI data is registered to standard real-time ultrasound data using computer software. In this way, needles can be targeted during the ultrasound-guided biopsy to suspicious areas that were identified by MRI.

Contrast Ultrasound-Guided Biopsy

In contrast ultrasound-guided prostate biopsy, contrast ultrasound imaging is used to identify and target suspicious lesions. (Note: Contrast ultrasound is approved in Europe but not in the US.)

Cancer Grading

Biopsy samples are sent to the lab, where a pathologist will look at thin slices of the tissue under a microscope to determine if cancerous cells are present. If they are present, the abnormal cells will be graded on the basis of how much they resemble normal prostate cells. The most abnormal-appearing cells are likely to be the most aggressive. Different systems may be used for grading, but the one most often used in the US is the Gleason system, developed by Dr. Donald Gleason in 1966.

In the Gleason system, cancer cells are graded both on how normal the individual cells appear and on their architectural pattern, that is, the way the individual cells are organized in the patterns of a normal gland. Cells are ranked on a scale of 1-5.

• Cells given a grade of 1 or 2 will look very much like a normal prostate cell and are termed well differentiated. They will probably not be very aggressively malignant.
  
• Cells of grade of 3 are the most common malignant type found. The cells are still considered well differentiated, but there is infiltration into the muscle cells of the prostate.
  
• Cells of grade 4 start to lose their architectural form and are almost entirely unable to form individual gland units.
  
• Cells ranked as grade 5 look highly abnormal under a microscope and termed poorly differentiated or undifferentiated. This type of cell is likely to be very aggressive.
  

The Combined Gleason Score

In examining cancer cells under a microscope, pathologists try to identify the two most prevalent cell patterns. They assign a Gleason grade to each pattern. There may be both a primary (most common) and a secondary (less common) pattern, or there may be just one pattern throughout. This is done because Dr. Gleason discovered that by combining the grades of two patterns, he was better able to determine the patient's prognosis (whether he would do well or badly).

So a Gleason score is actually the sum of two numbers:

• The lowest possible score is 2, where both the primary and secondary patterns have a grade of 1. Prostate cancer cases with a Gleason score below 4 are very rare.
  
• A typical Gleason score might be 7 (4 + 3), when the primary pattern has a grade of 4 and the secondary pattern has a grade of 3.
  
• The highest possible Gleason score is 10 (5 + 5), where the primary and secondary patterns both have grades of 5.
  

Why Is the Gleason Score Important?

The Gleason score helps doctors to better understand the course the cancer will probably take and how best to treat it. By combining the patient's Gleason score with his PSA level and the clinical stage estimated by the physician, it is possible for the doctor to estimate the probability that the patient has localized or locally advanced prostate cancer of different types. The lower the Gleason score, the better the patient's prognosis (outlook), and the longer he is likely to survive. But this rule is not set in stone. Men with low Gleason scores sometimes fare badly, and men with high scores have been known to do well.