Patient information: Prostate cancer diagnosis and staging

PROSTATE CANCER OVERVIEW

Prostate cancer is a malignancy of the prostate gland, an organ that forms a ring around the urethra, near its connection to the bladder (figure 1). The urethra is the tube that carries urine from the bladder to the outside of the body.

Prostate cancer is the most common cancer affecting men. Every year, more than 200,000 American men are diagnosed with prostate cancer, and nearly 30,000 die from this disease. Over the last 15 years, the increasing use of prostate cancer screening with blood tests of prostate-specific antigen (PSA) has led to more men being diagnosed at an early stage, when the cancer is still limited to the prostate gland and is highly curable. A separate topic review discusses screening tests for prostate cancer. (See "Patient information: Prostate cancer screening".)

This topic discusses the evaluation of men with early prostate cancer. A topic review that discusses treatment options, outcomes from therapy, and treatment-related side effects for early stage prostate cancer is available separately. (See "Patient information: Prostate cancer treatment; early stage cancer".) A topic review that discusses treatments for advanced prostate cancer is available separately. (See "Patient information: Prostate cancer treatment; advanced cancer".)

PROSTATE CANCER DIAGNOSIS

Most men are diagnosed with prostate cancer as a result of an elevated prostate specific antigen blood test. Less commonly, cancer is diagnosed based upon an abnormal rectal examination.

Prostate specific antigen — PSA is a protein produced by the prostate. The PSA test measures the amount of PSA in a sample of blood. Most men with prostate cancer have an elevated PSA concentration, although an elevated PSA level does not necessarily mean there is a cancer. In addition, there is no PSA level at which the risk of having prostate cancer is zero. However, the most common cause for an elevated PSA is benign prostatic hyperplasia (BPH), a noncancerous enlargement of the prostate. (See "Patient information: Benign prostatic hyperplasia (BPH)".)

Generally speaking, the higher the PSA, the greater the chance that a cancer is present. However, only 30 percent of men with an elevated PSA will have prostate cancer. (See "Patient information: Prostate cancer screening".)

Prostate biopsy — A prostate biopsy is generally recommended if a man's rectal examination is abnormal (the prostate feels enlarged or is irregularly shaped), or if the risk of cancer is increased based upon the following factors:

• The man's race
• Family history
• If the PSA level is elevated or has increased since the previous year

The biopsy is usually performed in a physician's office. Prior to the procedure, most men are given a course of antibiotics to reduce the risk of infection from the procedure. It is not usually necessary to stop eating or drinking before the biopsy. The man is positioned in the fetal position, lying on the side with the knees held against the chest. A urologist or a radiologist will perform the procedure.

Before the biopsy, the physician usually applies an anesthetic gel to the rectum and/or injects the patient with a local anesthetic to numb the lining of the rectum [1]. An ultrasound probe (a thin wand) is inserted into the rectum to locate the prostate and guide the biopsies. A spring-loaded device is used to rapidly remove a 1/16 inch (2.5 mm) by 1/2 inch (20 mm) long cylinder of tissue from the prostate; this is usually repeated 12 times to ensure that tissues from the entire prostate are sampled. Most men report mild to moderate discomfort during the procedure; the use of anesthesia generally reduces this discomfort. The entire procedure usually takes about 15 minutes.

The biopsy samples are then examined with a microscope by a pathologist. The results are usually available within one week. After the procedure, most men feel soreness in the rectum or perineum. Blood may be seen from the rectum or in the urine (for several days) or semen (for up to several months). In rare cases, excessive bleeding occurs and a treatment to stop bleeding (called cauterization) from a blood vessel in the rectum or prostate is needed. Other rare complications can include persistent fever or prostate infection, which is usually treated with antibiotics given into a vein.

Biopsy grade — If cancer is present, the amount of cancer and aggressiveness of the tumor (called the Gleason grade) are determined. The pathologist typically reports a primary grade (between 1 to 5) and a secondary grade, also between 1 and 5. The grade is determined by the appearance of the cancerous glands in the sample; if the tissue appears similar to normal prostate tissue, a grade of 1 is assigned. If the tissue has none of the normal features and cancer cells are seen throughout the sample, a grade of 5 is assigned (picture 1). Grades 2 through 4 are assigned to tissues whose appearance is between 1 and 5.

The primary and secondary grade numbers are then combined together to form the Gleason score. The higher the Gleason grade, the more aggressive (fast-growing) the tumor appears. If the cancerous tissue shows primarily grade 3 and secondarily grade 4 areas of tumor involvement, the combined Gleason score is "3 plus 4" or 7. Currently, about 90 percent of men with newly diagnosed prostate cancer have a Gleason score of 6 or 7.

• Gleason scores between less than 6 are typically referred to as low grade (also called well-differentiated).
• Gleason scores between 6 and 7 are referred to as intermediate grade.
• Gleason scores between 8 and 10 tumors are high grade (or poorly differentiated).

The number of biopsy cores that contain cancer and the percentage of the core that contains cancer provide important information about the volume of cancer that is likely to be found at surgery. Simply stated, a man whose tumor involves most of the biopsy cores has more advanced disease than a man whose tumor involves only a small portion of one core.

PROSTATE CANCER STAGING

Prior to selecting the best treatment option, it is critically important to determine the stage of the disease. The most accurate way to determine this is by surgically removing the prostate. However, several factors can be measured before surgery to predict whether a prostate cancer is likely to be confined to the prostate gland (termed organ-confined disease) or spread beyond the prostate gland, and therefore, more advanced.

The most important pretreatment factors include the clinical stage, the blood level of the PSA, the tumor volume (as determined by the number of positive biopsy samples, and the extent of cancer involvement within each biopsy sample) and the degree of aggressiveness of the tumor, referred to as the Gleason grade.

Prostate cancer stage — Physicians use a system to describe the extent, or stage of a cancer. The tumor-node-metastasis (TNM) system is the most common method used to stage prostate cancer (table 1).

In this system,

• T1 tumors are microscopic and cannot be felt during rectal examination (figure 2)

• T2 tumors can be felt with a rectal examination, but appear to be confined to the prostate gland
• T3 tumors have grown beyond the prostate into the capsule of connective tissue that surrounds the gland, or into the seminal vesicles (glands near the prostate that secrete fluid into the reproductive tract) (figure 1)

• T4 tumors have grown locally beyond the prostate, and involve nearby tissues

The finding of a T3 or T4 tumor suggests a more advanced tumor that is not likely to be cured, even with aggressive surgery. The stage assigned by a rectal examination is termed a clinical or "c" stage, while a man who has undergone surgical removal of the prostate with microscopic evaluation will be assigned a pathologic, or "p" stage.

PSA level — The vast majority of men with prostate cancer have elevated levels of PSA in the blood. The PSA level at the time of diagnosis can help to determine the likelihood that prostate cancer has spread beyond the prostate.

As PSA levels increase, the likelihood of disease spread to tissues beyond the prostate gland rises. Men with a PSA concentration less than 10 ng/mL have a 70 to 80 percent chance of having organ-confined disease, compared to 50 percent for those with PSA levels 10 to 50 ng/L, and only 25 percent with higher PSA levels [2].

The pretreatment PSA level can also predict the likelihood of a cancer recurrence after treatment. Men with a lower PSA concentration are more likely to be cancer-free five years after treatment than those with a higher pretreatment PSA level. However, the highest grade cancers (eg, Gleason score 8 and above) often do not cause PSA levels to become elevated.

Bone scan — Bone scans are imaging tests that may be recommended for men with high-grade cancer to determine if the cancer has spread (metastasized) to the bones. To perform a bone scan, a small amount of a radioactive substance is injected into a vein; any areas of bone that contain cancer are highlighted during the scan because they absorb more of the radioactive material than normal bone. A bone scan is not usually necessary in men with low-grade (T1 or T2) cancer on physical examination, a Gleason score of less than or equal to 6, and a PSA value less than 10 ng/mL.

CT scan — A CT (computed tomography) scan of the abdomen and pelvis may be recommended to determine if the cancer has spread beyond the prostate and to plan treatment. In some cases, CT scans are done in conjunction with a needle biopsy of lymph nodes that appear enlarged.

To perform a needle biopsy, the pelvis and abdomen are first scanned with the CT. Abnormal appearing lymph nodes are then located with a thin needle, which is inserted through the skin. The placement of the needle is confirmed with a CT scan. A sample of tissue is then removed and examined with a microscope to determine if there is evidence of cancer within the lymph node.

A CT scan is not usually necessary in men with low-grade (T1 or T2) cancer on physical examination, a Gleason score of less than or equal to 6, and a PSA value less than 10 ng/mL.

Endorectal coil MRI — Endorectal coil MRI uses magnetic resonance imaging to assess the prostate and the surrounding tissues. To perform the test, a thin wire covered with a balloon is inserted into the rectum. The balloon is inflated before the test to hold the coil in place. The patient lies on an examination table, which moves inside a large cylinder-shaped tube during the test. The test usually takes about 45 minutes.

Although this technique is not yet widely available, it is particularly helpful in evaluating the possibility that the cancer has extended outside of the prostate capsule or into the seminal vesicles in men who are considering surgery. This procedure may also help to determine if a nerve-sparing prostate operation is appropriate.

PREDICTING THE PROSTATE CANCER STAGE

Determining the correct stage of prostate cancer is critical in selecting the most appropriate treatment. All of the potentially curative therapies are have potentially serious complications; these risks can be justified only if the treatment has a reasonable chance of achieving a cure.

In general, a tumor that is confined to the prostate gland should be curable; the odds of cure diminish considerably when the cancer has extended to the outer surface of the prostate and penetrated the capsule (extraprostatic extension), invaded the seminal vesicles, or metastasized to the lymph nodes.

Using combinations of clinical and pathologic factors such as pretreatment PSA, biopsy Gleason score, and T stage provide a more reliable estimate of the following:

• The likelihood that cancer is confined to the prostate and is potentially curable
• The risk of cancer recurrence after surgery or radiation therapy.

Predicting organ-confined cancer — The Partin model combines the clinical tumor (T) stage, the Gleason score from the tumor biopsy, and the blood PSA level to estimate the likelihood that a man will have organ-confined, and thus, potentially curable disease at the time of surgery (table 2).

Other tools, called nomograms, can estimate the risk of cancer recurrence in men with newly diagnosed prostate cancer or following initial treatment. A number of validated nomograms developed by the Memorial Sloan-Kettering group are accessible on line (www.mskcc.org/mskcc/html/10088.cfm). We suggest that you review the information from these nomograms with your healthcare provider.

Risk of recurrence — Models that use the PSA, biopsy Gleason score, and clinical stage (eg, T2) can be used to predict the chance of being cancer-free after undergoing surgery or radiation. In general, these models stratify patients into one of three defined risk groups [3]:

• Low-risk — Clinical stage T1c or T2a, PSA level <10 ng/mL, and biopsy Gleason score of 6 or less. Men with low-risk disease have a greater than 85 percent chance of being cancer-free five years after treatment with either surgery or radiation therapy.
• Intermediate-risk — Clinical stage T2b, PSA 10 to 20 ng/mL, and a biopsy Gleason score of 7. Men with intermediate-risk disease have approximately a 50 to 70 percent chance of being cancer-free at five years after treatment.
• High-risk — Clinical stage T2c disease, PSA >20 ng/mL, and a biopsy Gleason score of 8 or higher. Men with high-risk prostate cancer have an approximately 33 percent chance of being cancer-free five years after treatment.

PROSTATE CANCER TREATMENT

A discussion of the treatment options, outcomes from therapy, and treatment-related side effects for early stage prostate cancer is available separately. (See "Patient information: Prostate cancer treatment; early stage cancer".) A topic review that discusses treatments for advanced prostate cancer is also available. (See "Patient information: Prostate cancer treatment; advanced cancer".)

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Prostate cancer screening
Patient information: Prostate cancer treatment; early stage cancer
Patient information: Prostate cancer treatment; advanced cancer
Patient information: Benign prostatic hyperplasia (BPH)

Professional Level Information:
Active surveillance for men with early prostate cancer
Early stage prostate cancer: Predicting the pathologic extent of disease and clinical outcome
Follow-up surveillance after treatment for prostate cancer
Interpretation of prostate biopsy
Overview of the clinical presentation, diagnosis, and staging of prostate cancer
Rising serum PSA following local therapy for prostate cancer: Definition and risk stratification
Rising serum PSA following local therapy for prostate cancer: Diagnostic evaluation

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Cancer Institute

       1-800-4-CANCER
       (www.cancer.gov)

• American Society of Clinical Oncology

      (www.cancer.net/portal/site/patient)

• National Comprehensive Cancer Network

      (www.nccn.com)

• American Cancer Society

       1-800-ACS-2345
      (www.cancer.org)

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• US TOO! International, Inc

      (www.ustoo.org)

Patient Support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Cancer Forum

      (http://cancer.about.com/forum)

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