RISING PSA AFTER RADICAL PROSTATE SURGERY

PSA stands for Prostate Specific Antigen and is a blood test that is used to screen for the presence of prostate cancer and, in those men known to have prostate cancer, PSA becomes a tool to measure the effectiveness of the treatments that have been used.

WHAT IS PSA, AND HOW DO WE MEASURE IT?
An antigen is a medical or biological term for a substance or protein that stimulates the body to make antibodies.

Prostate Specific Antigen is a protein found in the serum that is unique or specific for the prostate, both normal prostate and prostate cancer cells. In the case of prostate cancer, the PSA will reflect the presence of the tumor, wherever the cancer cells are present in the body. No other tissues or body parts can make Prostate Specific Antigen. Therefore, the PSA levels can be measured in an individual's serum and with this information we are able to follow prostate cancer. PSA is not harmful and a rising PSA in the blood by itself is only a laboratory test or assay of a small amount of this unique protein in your blood. It is the prostate cancer itself which must be treated, not the PSA.

Prostate cancer manufactures PSA and as the prostate cancer grows, more PSA is released into the blood stream and the PSA values rise. Conversely, if the cancer is diminishing the PSA values fall. This fact allows us to track treatment effectiveness using PSA levels.

WHAT IS THE SIGNIFICANCE OF THE PSA IF I HAVE PROSTATE CANCER?
When a man has had a radical prostatectomy, the entire prostate is removed. Therefore, the PSA should be unmeasurable. Simply, when there is no prostate, there should be no PSA. The normal PSA values for men after radical prostatectomy is less than the lowest value that laboratories can accurately measure today (this may vary from lab to lab from 0.02 ot 0.3). The normal values printed on laboratory sheets that say ‘less than 4.0’ are screening values for men who still have their prostate.

If a man has measurable PSA after radical prostatectomy, he has residual or recurrent prostate cancer or, in rare cases, has a small remnant of benign prostate tissue left behind. The PSA presence does not tell where the prostate cancer is, only that it is somewhere. Prostate cancer may return close to the area where the prostate was removed (local recurrence) or it may return in any body tissue away from the prostate (distant spread), most commonly in bone, or lymph nodes not removed at the time of surgery. In men who have measurable and rising PSA after radical prostatectomy, the PSA will continue to rise suggesting that prostate cancer is present and growing. In most cases the rate of rise of the PSA reflects the growth rate of the residual cancer. If a small remnant of benign prostate tissue is left behind, the PSA will remain at very low levels, usually less than 0.1, and will not rise.

WHEN SHOULD THE FIRST PSA BE DRAWN AFTER RADICAL PROSTATECTOMY?
While there is no set standard, we normally wait six weeks after surgery to check the first PSA. PSA is cleared out of the blood relatively slowly and we wait this long to make sure that we are not measuring residual PSA from the original disease and the manipulation of the prostate and prostate cancer during the operation. We then measure the PSA every three months for the first year, every six months the second year, and then yearly for ten years. Each year that the PSA is unmeasurable gives a higher chance that the next years blood draw will also be favorable. After 5-6 years of negative PSAs, it is unlikely that the cancer will return or the PSA will ever be measurable.

What type of PSA test do I need?
Free PSA, Complex PSA (PSA-ACT), hK2 and other new PSA screening tests have no benefit over the current used PSA tests in patients who already have a diagnosis of prostate cancer. They are helpful only in screeing situations in helping us determine who needs or does not need a biopsy.

WHAT TO DO WHEN THE PSA LEVEL IS FOUND TO BE MEASURABLE?
Again, whether the first PSA at six weeks, or any later PSA is MEASURABLE and RISING makes no difference. The presence of persistant and rising PSA signals the fact that cancer cells are present. In addition, some prostate cancers do not make PSA. These are rare, perhaps a few percent of all prostate cancers. Recurrence of this rare situation will be detected like other cancers, by X-ray or symptoms.

Whenever cancer is present, we try to determine the stage of the cancer. That is, where is it? If we can localize the cancer, we have a better chance of treating it and following its course. The tests that will be done might include a rectal examination and ultrasound and biopsy of the area where the prostate was removed. Many prostate cancers will return close to the prostate, in the tissues around the bladder, rectum and urethra (tube connected to the bladder that runs through the penis). Other cancers will recur at distant sites, particularly bone, and more particularly, the bones of the pelvis and spine. To complete the evaluation, a bone scan, chest X-ray, CAT scan or MRI might be done depending on how recently those tests might have been done.

WHERE MIGHT THE CANCER BE?
Historically, about 50% of cancers will return close to the prostate, the rest will be found at distant sites. Factors that suggest distant spread rather than local recurrence includes a higher grade cancer (Gleason score of 8-10), or involvement of lymph nodes or the seminal vesicles. Factors that might suggest local recurrence would be clear cut evidence that cancer had been cut across on the specimen removed. The most difficult task is to localize the remaining cancer.

Before most radical surgeries, tests are usually done to show that no spread of the cancer has occurred outside the prostate. Most commonly done are the bone scan and chest X-ray. These tests are unlikely to change over the six months to a year, so that repeating them too early may give little information.

The best chance of finding a definite site of recurrence are random biopsies of the area around the prostate’s prior location. These biopsies are positive in about 20% of patients when no nodules are present on rectal examination. If an area of suspicion can be felt on rectal examination, the percentage rises. The area of recurrence may still be nearby, but missed by the random biopsy needle. If these biopsies show no cancer, then the actual site will be difficult, if not impossible to localize for some time, perhaps 1 to 3 years or longer. Repeat biopsies of the area may be indicated at a later time if there is strong suspicion that the cancer was nearby the prostate and was not found in the first biopsies. The length of time may depend on the growth rate of the cancer which relates to the rate of rise of the PSA. Factors which suggest distant spread (rather than local spread) would be: Gleason grade of 8 or greater, seminal vesicle or lymph node cancer at surgery, and a measurable PSA within one year of surgery.

WHAT TO DO?? - THE THREE SCENARIOS

CANCER IS FOUND NEARBY THE PROSTATE AND NOWHERE ELSE
If the cancer is truly localized to the area around the prostate, then radiation therapy can be considered to treat the remaining disease. Technically, if the radiation treatments are successful, the cancer can still be cured. Normally this requires 5-7 weeks of treatments, 15 minutes a day, 5 days a week. The risks include radiation damage to the bladder and rectum and sphincter mechanism with bleeding, frequency, urgency and incontinence of urine, stool or both. Usually these symptoms reside after treatment but a small percentage of men will have symptoms indefinitely. On a more serious note, despite treatment of local disease, not all cancers will be cured with post surgery radiation. Most of the PSAs will fall, sometimes to unmeasurable levels, but a significant number will recur despite treatment. The reasons for failure include cancers that are not sensitive to radiation and cancers that were spread to distant sites before treatment but could not be recognized. Is it worthwhile to treat?? We don’t know for sure, but if the cancer is felt to be localized to the area around the previous prostate location, I feel that the benefits of possibly curing the cancer outweighs the risks of the radiation and the chances that more distant disease is present. The chances of obtaining a good response is related to the level of PSA at the time of treatment. Patients with a PSA less than 2 when radiation treatments were given had longer survival than those with PSAs greater than 2. Patients with Gleason scores more than 7, lymph node or seminal vesicle involvment and fast rising PSAs have only a small chance of being cured by radiation treatments.

CANCER IS FOUND AT DISTANT SITES OR BOTH DISTANT AND NEARBY
If the cancer is found elsewhere, even at only one spot, it is very likely that more areas exist that cannot be seen. Radiation or surgery in these situations cannot be used for cure. Sometimes a specific area will cause symptoms, or in the case of a bone, have the risk of fracture. In these circumstances, we recommend radiation to the specific area. If a weight bearing bone is not involved and no symptoms are present, the best options are the use of hormone treatments or observation until symptoms or danger are imminent.

There is no solid proof that treating early with hormones extends life expectancy, but some evidence exists that treating early will prevent recurrence for a longer period of time. If the side effects of hormone deprivation are unacceptable (impotency, no libido, hot flashes), then delay in treatment may improve quality of life without shortening life expectancy.

Another approach may be the rate of rise of the PSA. Experience suggests that the faster rising PSAs will cause trouble sooner. A recent study from UCLA suggested that if the PSA doubles within a year that a high probability for bone spread exists. If the ‘doubling time of PSA’ is more than one year, many patients remained without cancer problems for 6 or 7 years. Another approach would be to look at the grade of the original cancer. Higher grades (8,9,10) would be more likely to spread earlier and more aggressively and therefore might benefit from early treatment with hormones.

THE AREA OF RECURRENCE CANNOT BE FOUND
This is a dilemma, particularly in men with suspicious margins suggesting that the cancer is nearby the prostate bed. A significant proportion of these men (perhaps ~50%) treated blindly by radiation will have a reduction or disappearance of PSA for a period of time. The response seems not to be permanent in a large percentage of men, but still it does represent that only chance of cure if the disease is, in fact, only near the prostate surgery and radiation sensitive. In many cases we are reluctant to recommend radiation if the biopsies show no cancer for fear of treating an area where no cancer may exist. Treating without a positive biopsy would create a risk for radiation complications without any benefit. Repeat biopsies of the area may be indicated at a later time if there is strong suspicion that the cancer was nearby the prostate and was not found in the first biopsies. The chances of obtaining a good response is related to the level of PSA at the time of treatment. Patients with a PSA less than 2 when radiation treatments were given had longer survival than those with PSAs greater than 2.

As mentioned above, hormone treatment for PSA elevation without other findings is controversial. There is some proof that treating early with hormones extends life expectancy, and much evidence exists that treating early will prevent recurrence for a longer period of time. If the side effects of hormone deprivation are unacceptable (impotency, no libido, hot flashes), then delay in treatment may improve quality of life without shortening life expectancy too much. As mentioned above, the PSA rate of rise (or the time it takes the PSA to double in value) and the grade of the cancer should be taken into consideration when making a decision whether or not to start treatment. Many patients elect to delay treatment until actual evidence of spread of the cancer can be found. The most common area of spread is to the bones and bone spread occurs rarely with the PSA below 10. If the bone scan is positive, we usually recommend therapy with hormone treatments or if the bone disease is limited we might suggest radiation treatment to the areas of involvment only.

Hormone therapy should be instituted quickly for any patient with known spread of cancer to an area which might cause a life threatening situation. Involvment of weight bearing bones, particularly hips or spine, blockage of urinary flow or kidneys, brain or bone marrow involvment are examples of life threatening situations.

SUMMARY
Some the these issues have not been completely described here, including the various forms and side effects of hormone deprivation therapy. Your urologist will be happy to go over this with you in more detail or provide further reading.