There is only one way to make a diagnosis of prostate cancer: through a prostate biopsy. A prostate biopsy is the removal of samples of tissue from your prostate. The samples are sent to a pathology laboratory for analysis.
A prostate biopsy collects samples (known as “cores”) by inserting thin, hollow needles through your rectum and into your prostate. This procedure can be painful and so, although most men don’t need actually need anesthesia, it is now customary to provide a mild local anesthetic.
Needles are directed to the proper parts of your prostate using an ultrasound probe inserted in your rectum. So called “transrectal ultrasound” or TRUS can help your doctor to decide which areas of the prostate look suspicious for cancer, but it cannot establish diagnosis. Ultrasound can also measure the size (volume) of your prostate. This can be helpful later in choosing a treatment. There is no absolutel definition of the “right” number of biopsy cores that need to be taken.
Under normal circumstances the cores are taken from the bottom (“base”), the middle, and the top (“apex”) of each side (“lobe”) of your prostate. The bigger the prostate (i.e., the bigger the “haystack”) the harder it may be to find the cancer. If you have a very large prostate, adequate sampling may require a so-called “saturation” approach that removes 40 or 50 cores — and sometimes even more.
Even if a first biopsy shows no cancer, there may still be cancer: 10 percent of repeat prostate biopsies show cancer. However, there are no rules about whether to repeat a negative first biopsy. Only you and your doctor together can decide on the need for a repeat biopsy if the first biopsy is negative. Your decision will depend on clinical suspicion as established by your DRE, PSA, age, family history, and unusual aspects of your prostate tissue from the first biopsy, as well as the technical adequacy of that biopsy.
The Pathology Report
Prostate biopsy cores are sent to the pathology laboratory in a preservative such as formaldehyde.
The pathologist places the cores onto a grid (see Figure 2) and fixes them in place with paraffin wax, which enables thin slicing. The slices are stained so as to show up the microscopic cellular features upon which diagnosis is based (see Figure 3 and section on “Understanding Gleason grading“).
Figure 2 (left). Biopsy core on grid. and Figure 3 (right). Healthy prostate tissue.
Photomicrograph of normal, healthy prostate tissue, showing an organized structure with prostate epithelial cells (stained blue) which surround and line prostate glands (white areas) courtesy of Mark A. Rubin, MD, Brigham and Women’s Hospital and Harvard Medical School.
The pathologist examines the biopsy cores under the microscope to identify physical characteristics of cancer, other features that may suggest cancer, or associated signs suggestive of cancer or cancer precursors. In particular, the pathologist will look for the following:
- Actual cancer cells and their pathological charcteristics
- Where in the cores these cancer cells occur (which then correlate to their original position in the prostate)
- Groups of cells showing “prostatic intra-epithelial neoplasia” or “PIN,” which may be a precursor to prostate cancer
- Groups of other unusual types of cell called “atypical small acinar proliferation” (ASAP), also known as “atypia”
- Cells that are inflamed or atrophied (partial or complete cell wasting).
Even in the absence of cancer cells, certain findings could justify a repeat biopsy. For example, if you have prostatic intra-epithelial neoplasia (PIN) on a first biopsy, the chance of prostate cancer on a repeat biopsy is up to 60 percent.
Your biopsy reports should identify the patient (you), the doctor, the date of biopsy, the locations from which samples were taken, and the number and lengths of the cores, which helps determine sampling adequacy.
If cancer is detected, the pathologist counts up the number of cores involved, the part(s) of the prostate involved, and the proportion of each core showing cancer. This method of assessing cancer involvement helps to determine your cancer “stage” – how big the cancer is and what parts of your prostate are cancerous. This information can affect treatment decisions.
The pathology report should also note whether your cancer involves microscopic nerves inside the prostate (“intraprostatic” nerves). If the cancer affects the intraprostatic nerves, the condition is called “perineural invasion.” Perineural invasion can affect cancer stage because it signals a greater likelihood of spread of the cancer outside the prostate itself to the nearby lymph nodes.
Second Pathological Opinions
The pathological diagnosis of prostate cancer is a subtle and subjective art. Pathologists often do not agree with each other’s characterization of specific samples. In the best centers, pathologists commonly review slides with each other and/or send them to reference laboratories.
Many treating physicians insist on a very careful review (a second pathological opinion) of biopsy samples by a pathologist of their choice before making decisions about treatment. Given the critical importance of biopsy data in treatment decisions, it often makes sense to have the biopsy samples and results reviewed before treatment.
If you have a positive biospy, you should talk to your doctors about having a second pathological opinion on your biopsy samples before you make any treatment decision, especially if the information provided by the biopsy results is open to interpretation.