Prostate Cancer Screening
It may surprise you that not all physicians and physicians groups such as xxxx are in agreement about prostate cancer screening.  The most commonly accepted screening regimen for prostate cancer includes a PSA and digital rectal exam yearly beginning at age 50. It should start at 40 if you have risk factors such as African-American race, or a close family member with prostate cancer.

Everyone agrees on the digital rectal exam (DRE) recommendations because in addition to giving information about the prostate, it is also a screen for colorectal cancer which is the third most common cancer. DRE alone detected 55% of prostate cancer. 50% of all palpated abnormalities of the prostate turn out to be prostate cancer.

Not everyone agrees on the PSA. It is irrefutable that the PSA allows us to diagnose prostate cancer earlier in the course of disease. It also has increased the number of men choosing curative intent treatment (surgery or radiation) and possibly cures. It has also increased the number of men experiencing side effects as a result of their chosen treatment (erectile dysfunction, incontinence, etc). To date, PSA testing has yet to be proven to change the ultimate survival from prostate cancer. Most urologists believe this will eventually be proven to be the case. PSA alone detects 82% of prostate cancer. Attempting to increase the specificity of PSA screening, there have been many modifications of the PSA test.

Likelihood of being diagnosed with Prostate Cancer: 

PSA < 4  is 2%     PSA 4-10 is 25%     PSA >10 is 50-67%
(Labrie, 1992; Catalona, 1994).

   PSA

1. What is the prostate-specific antigen (PSA)? protein produced by the cells of the prostate gland?

The prostate-specific antigen (PSA) test measures the level of PSA in the blood. A blood sample is drawn and the amount of PSA is measured in a laboratory. When the prostate gland enlarges, PSA levels in the blood tend to rise. PSA levels can rise due to cancer or benign (not cancerous) conditions. Because PSA is produced by the body and can be used to detect disease, it is sometimes called a biological marker or tumor marker.

As men age, both benign prostate conditions and prostate cancer become more frequent. The most common benign prostate conditions are prostatitis (inflammation of the prostate) and benign prostatic hyperplasia (BPH) (enlargement of the prostate). There is no evidence that prostatitis or BPH cause cancer, but it is possible for a man to have one or both of these conditions and to develop prostate cancer as well.

Although PSA levels alone do not always give doctors enough information to distinguish between benign prostate conditions and cancer, the doctor will take the result of this test into account in deciding whether to check further for signs of prostate cancer.

2. Why is the PSA test performed?

The U.S. Food and Drug Administration (FDA) has approved the PSA test for use in conjunction with a digital rectal exam (DRE) to help detect prostate cancer in men age 50 and older. During a DRE, a doctor inserts a gloved finger into the rectum and feels the prostate gland through the rectal wall to check for bumps or abnormal areas. Doctors often use the PSA test and DRE as prostate cancer screening tests in men who have no symptoms of the disease.

The FDA has also approved the PSA test to monitor patients with a history of prostate cancer to see if the cancer has come back (recurred). An elevated PSA level in a patient with a history of prostate cancer does not always mean the cancer has come back. A man should discuss an elevated PSA level with his doctor. The doctor may recommend repeating the PSA test or performing other tests to check for evidence of recurrence.

3. For whom might a PSA screening test be recommended? How often is testing done?

The benefits of screening for prostate cancer are still being studied. The National Cancer Instititute (NCI) is currently conducting the Prostate, Lung, colorectal, and ovarian Cancer Screening Trial, or PLCO trial, to determine if certain screening tests reduce the number of deaths from these cancers. The DRE and PSA are being studied to determine whether yearly screening to detect prostate cancer will decrease one's chance of dying from prostate cancer.

Doctors' recommendations for screening vary. Most encourage yearly screening for men over age 50; however men must be counseled about the risks and benefits on an individual basis and encourage patients to make personal decisions about screening.

Several risk factors increase a man's chances of developing prostate cancer. These factors may be taken into consideration when a doctor recommends screening. Age is the most common risk factor, with more than 96 percent of prostate cancer cases occurring in men age 55 and older.

Other risk factors for prostate cancer include family history and race. Men who have a father or brother with prostate cancer have a greater chance of developing prostate cancer. African American men have the highest rate of prostate cancer, while Native American men have the lowest.

4. How are PSA test results reported?

PSA test results report the level of PSA detected in the blood. The PSA level that is considered normal for an average man ranges from 0 to 4 nanograms per milliliter (ng/ml). A PSA level of 4 to 10 ng/ml is considered slightly elevated; levels between 10 and 20 ng/ml are considered moderately elevated; and anything above that is considered highly elevated. The higher a man's PSA level, the more likely it is that cancer is present. But because various factors can cause PSA levels to fluctuate, one abnormal PSA test does not necessarily indicate a need for other diagnostic tests. When PSA levels continue to rise over time, other tests may be indicated.

If you are taking Proscar (Finasteride) the PSA levels are dropped by about 50%. As far as we know right now, this does not change your chance of getting prostate cancer. Commonly doctors multiple the PSA by 2 and apply the same normal ranges as above for counseling patients.

5. What if the test results show an elevated PSA level?

A man should discuss elevated PSA test results with his doctor. There are many possible reasons for an elevated PSA level, including prostate cancer, benign prostate enlargement, inflammation, and infection to name a few. If there are no other indicators that suggest cancer, the doctor may recommend repeating DRE and PSA tests regularly to monitor any changes.

If a man's PSA levels have been increasing or if a suspicious lump is detected in the DRE, the doctor may recommend other diagnostic tests to determine if there is cancer or another problem in the prostate. A urine test may be used to detect a urinary tract infection or blood in the urine. The doctor may recommend imaging tests, such as ultrasound (a test in which high-frequency sound waves are used to obtain images of the kidneys and bladder, xrays or cystoscopy (a procedure in which a doctor looks into the urethra and bladder through a thin, lighted tube). Medicine or surgery may be recommended if the problem is BPH or an infection.

If cancer is suspected, the only way to tell for sure is to perform a biopsy. For a biopsy, samples of prostate tissue are removed and viewed under a microscope to determine if cancer cells are present. The doctor may use ultrasound to view the prostate during the biopsy, but ultrasound cannot be used alone to tell if cancer is present.

6. Why is the PSA test controversial?

Using the PSA test to screen men for prostate cancer is controversial because it is not yet known if the process actually saves lives. Moreover, it is not clear if the benefits of PSA screening outweigh the risks of followup diagnostic tests and cancer treatments.

The procedures used to diagnose prostate cancer may cause significant side effects, including bleeding and infection. Prostate cancer treatment can cause incontinence and impotence. For these reasons, it is important that the benefits and risks of diagnostic procedures and treatment be taken into account when considering whether to undertake prostate cancer screening.

7. What research is being done to improve the PSA test?

Scientists are researching ways to distinguish between cancerous and benign conditions, and between slow-growing cancers and fast-growing, potentially lethal cancers. Some of the methods being studied are:

• PSA velocity: PSA velocity is based on changes in PSA levels over time. A sharp rise in the PSA level raises the suspicion of cancer.
• Age-adjusted PSA: Age is an important factor in increasing PSA levels. For this reason, some doctors use age-adjusted PSA levels to determine when diagnostic tests are needed. When age-adjusted PSA levels are used, a different PSA level is defined as normal for each 10-year age group. Doctors who use this method suggest that men younger than age 50 should have a PSA level below 2.5 ng/ml, while a PSA level up to 6.5 ng/ml would be considered normal for men in their 70s. Doctors do not agree about the accuracy and usefulness of age-adjusted PSA levels.
• PSA density: PSA density considers the relationship of the PSA level to the size and weight of the prostate. In other words, an elevated PSA might not arouse suspicion in a man with a very enlarged prostate. The use of PSA density to interpret PSA results is controversial because cancer might be overlooked in a man with an enlarged prostate.
• Free versus attached PSA: PSA circulates in the blood in two forms: free or attached to a protein molecule. With benign prostate conditions, there is more free PSA, while cancer produces more of the attached form. Researchers are exploring different ways to measure PSA and to compare these measurements to determine if cancer is present.
• Other screening tests: Scientists are also developing screening tests for other biological markers, which are not yet commercially available. These markers may be present in higher levels in the blood of men with prostate cancer.

  Prostate Biopsy
There are two main indications for prostate biopsies: an abnormal rectal examination (for example are hard area felt on the prostate), and/or an elevation of the PSA blood test. In the majority of prostate cancers, one or both of these screening tests are abnormal. Should you be diagnosed with prostate cancer, the results of the biopsy a key piece of information that will allow you and your doctor to discuss your treatment of choice. To avoid any unnecessary bleeding you should discontinue and aspirin, arthritis medications, and blood thinners prior to the biopsy as these medications can increase bleeding after the procedure.

  On the day of your prostate biopsy:
An enema will be given to clear and fecal material from the area of the prostate.
A urine sample will be examined to rule out any infection
Antibiotics will be given to lessen the chances for infection as a result of the procedure

You may need special antibiotic coverage if you have any foreign material implanted in your body (for example heart valves, artificial hips/knees, vascular grafts) and you should alert your doctor to their presence.

Your doctor will use an ultrasound probe that is inserted in the rectum to visualize the prostate. This is usually painless, and likened to the feeling of a rectal examination. The prostate is visualized in total in 2 planes, and an estimate of the volume/size is made. Larger prostates produce more PSA, therefore this can be one of the non-cancerous reason to have an elevated PSA.

  The Gleason Grading System
The Gleason Grading System is used to evaluate or "grade" prostate cancer cells obtained by needle biopsy. A pathologist will look at the biopsied prostate tissue under a microscope. The pathologist will examine the way that the cancerous cells look compared to normal prostate cells. If the cancerous cells appear to resemble the normal prostate tissue very closely, they are said to be very well differentiated and are considered to be Gleason grade 1.

This means that the tumor is not expected to be fast growing. On the other hand, if the cells in question look fairly irregular and very different from the normal prostate cells, then they are very poorly differentiated and are assigned a Gleason grade 5.

Grades 2-4 are used for tumors that fall between grades 1 and 5 with higher numbers corresponding to a faster growing tumor. Because prostate cancer tissue is often made up of areas that have different grades, the pathologist will closely examine the areas that make up the largest portion of the tissue.

Gleason grades are then given to the two most commonly occurring patterns of cells. Once the two grades have been assigned, a Gleason score can be determined. This is done by adding together the sum of the two Gleason grades.  Gleason scores range from 2 to 10. The higher the score, the more aggressive the cancer.

The most commonly diagnosed score is 3+3=6. You should thoroughly discuss your results with your physician. Your doctor can explain what your Gleason score, along with your other risk criteria for your individual situation.

<< Less Aggressive     More Aggressive >>

  Prostate Cancer - Watchful Waiting
Watchful waiting is a treatment option for men who have been diagnosed with prostate cancer, or are likely to have it based on screening criteria such as elevated PSA or abnormal digital rectal exam. In the short term, watchful waiting has no major side effect which is why it is desirable to many patients.

In general prostate cancer is a slow growing as compared to other types of cancers. However, every case is different. The Gleason score is the pathologist's interpretation of the aggressiveness of the cancer. The score can range from 2 (almost normal) to 10 (very aggressive).

There are a large study of men diagnosed with prostate cancer, who chose watchful waiting. The study shows the chance of death due to prostate cancer as well as all other causes at 5, 10, and 15 years after diagnosis. There are different categories depending on the Gleason Score, and the patients' age at diagnosis. It is useful to review this study when considering watchful waiting.

Competing Risk Analysis of Men Aged 55 to 74 Years at Diagnosis
 Managed Conservatively for Clinically Localized Prostate Cancer

When excluding low grade cancers (Gleason 2-4) which are diagnosed infrequently, the study confirms a few things. Younger men (<60) who have longer life expectancies also have high chance for their cancer becoming significant (ie causing death, metastasizing (spreading), causing bone pain, bleeding, obstructing urine flow.) Therefore, watchful waiting is a poor choice in their case. Alternatively, older patient (>75) especially with significant other illnesses may be better candidates for watchful waiting because they have a higher chance of dieing of alternative illnesses.

  Brachytherapy (Radiation Prostate Seed Implant)
Short-term complications include: blood in urine (hematuria), blood in semen (hematospermia), minor discomfort under scrotum, and worsened urinary symptoms (urgency, frequency), and urinary retention.

Long-term complications include radiation damage to surrounding organs (bladder, rectum) which can present with unprovoked bleeding. Incontinence is not a problem unless the patient requires a surgical treatment to remove obstructing prostate tissue (TURP, etc). Erectile Dysfunction affects 50% of men within 5 yrs of treatment.

  Cryotherapy
Cryotherapy involves freezing the prostate gland. It is one of the newer treatments for prostate cancer. Although some urologist are using it a primary therapy for prostate cancer, most reserve this for patients who are believe to have local recurrence of the cancer after failed external beam radiation (XRT), or seeds (brachytherapy). At present, it cannot be performed for failure after prostatectomy.

It is performed similar to a seed implant (brachytherapy). Transrectal ultrasound guidance it used. A warming catheter is placed into the sensitive urethra to keep it from being frozen and damaged. Sensors are placed in areas which should not be frozen such as the rectum, urinary sphincter, etc. Freezing needles are place precisely into the prostate, and an ice ball forms. Several freeze and thaw cycles are performed with the result of killing prostate cancer cells. Repeat treatments can be performed if there is evidence of remaining, or recurrent cancer in the prostate.

  Hormone Therapy
Prostate cancer requires the male hormone testosterone in order to continue to progress. By removing the source or blocking the hormone effects, the prostate cancer and PSA regress. This form of therapy is usually instituted when other treatment options are not advisable, or there has been spread (metastasis) or high likelihood of spread based on a significantly elevated PSA. It sometimes used in combination with radiation therapy and has been proven to give better results when the cancer is locally advanced. It is also used on occasion to shrink the prostate "downsize" prior to seed therapy (brachytherapy) when the prostate cannot be adequately seeded due to pelvic bone interference.

Hormone therapy is not curative. The prostate and prostate cancer regress and go into a state of suspended animation as a result of the hormones. Eventually the prostate cancer mutates enough where is no longer needs the testosterone in order to progress. How long it remains effective is gauged by the PSA. Response length varies but overall mean duration is 18-24 months. Once the PSA begins to rise, doctors call the cancer "hormone refractory" and the cancer is beginning to grow again. Once the PSA reaches 4.0, the average time to disease progression is 6-8 months and the median time to death is 12-18 months. Once the patients exhibit any symptoms referable to the cancer, the median survival for hormone refractory disease is less than 1 year. Treatment options for hormone refractory disease are few. Chemotherapy regimens are under investigation, but primarily only improve the quality of life not the survival.

The most commonly used regimen of hormone therapy is what is called continuous androgen blockade. This means that the hormones are given on a continuous basis. As doctors have search for ways to prolong the effectiveness of hormones on prostate cancer they have begun to experiment with intermittent androgen blockade. Injections are given, and the PSA first goes down and then begins to rise slowly as the medication wears off. At some predetermined PSA level another injection is given. It has not been proven to show better or worse cancer control rates than continuous therapy. It does lessen some of the common side effects to be discussed below. Complete androgen blockade refers to blocking both testosterone from the testicles, as well as similar chemicals produced by the adrenal glands. This can be useful when LH-RH agonists are no longer effective by themselves.

The most widely used class of medicine to block testosterone is call LH-RH agonists (Lupron, Zoladex). They overstimulate the pituitary gland to eventually lower the production of testosterone. It is common during the first few weeks to have a "flare" before the testosterone levels fall. This can sometime cause worsened symptoms of hot flashes, or bone pain. The shots are given in 1,3, or 4 month intervals. There is also an implant (Viadur) which can deliver the medication for a full year. They all should result in castration-like levels of testosterone and the PSA should become undetectable (<0.1). Common side effects include loss of hot flashes or sweating (57%), sweating (10%) loss of sexual interest (libido) and erectile dysfunction (impotence) in 90%, weakness, weight gain, muscle and bone loss. Vitamin D and Calcium supplements are usually recommend.

The second form of medical therapy is non-steroidal antiandrogens. Instead of lowering testosterone production, these medication (casodex, flutamide, etc) prevent testosterone from binding the its receptor on prostate cancer cells. Because testosterone levels are preserved there isn't the problems with loss of sexual interest, and erectile dysfunction. Many times these medications are given in conjunction with LH-RH agonist to prevent the flare symptoms after an injection. The problems with these medications include the high cost, toxicities, and that they have not been approved for use alone (monotherapy) thus they are not covered by most insurances. Anti-androgens can cause breast growth/tenderness (gynecomastia) in 47%, transient liver damage (hepatitis), diarrhea, and hot flashes.

The last option is the most economical of the treatments. The testicles are the source of male testosterone. Surgical castration with bilateral orchiectomy can be performed. This is a rapid way of getting regression of the prostate cancer which is sometime done emergently to prevent paralysis when the cancer has spread (metastasized) to the spine and in compressing the spinal cord.

  Zometa
Osteoporosis is a disease predominately found in women. Cancers, especially prostate cancer, can spread (metastasize) to the bones. These cancer deposits can be painful and  predisose the cancer patient to pathologic fractures. Also, LH-RH agonist hormone therapy is commonly used to treat metastatic prostate cancer. Unfortunately, this medication is known to contribute to further osteoporosis. As you can see the prostate cancer patient has several risk factors for skeletal related events.

Fortunately, with a a regimen of calcium and vitamin D supplementation along with monthly Zometa infusions, we are now preventing continued bone loss. As a result, our patients stay symptom free from their bone disease.

ZOMETA® (zoledronic acid for injection) belongs to a class of drugs called bisphosphonates (biss-foss-fon-ates) that slows the bone-destroying activity that occurs with bone metastases. Fosamax is a commonly known medication in this class of drugs. They directly work against the abnormal cells that cause the "wearing away" (resorption) of bone and help slow down the abnormal build-up of unstable bone. Bisphosphonates are used to help improve bone strength in many diseases associated with bone resorption, including cancer.