February 6, 2009

Interpreting a Rising PSA After Failed Local Therapy


By E. David Crawford, M.D., Professor of Surgery and Radiation Oncology, Urologic Oncology, University of Colorado

Prostate Specific Antigen (PSA) has been called the most important tumor marker in oncology. Certainly in prostate cancer, it has revolutionized our ability to detect the disease early, as well as follow the course of the disease in patients after being treated with different therapies. Following a successful radical prostatectomy, all prostate tissue should be removed and the PSA should be undetectable. Some assays report a level of 0, while others report less than .2 ng/ml. If the PSA level begins to elevate after a radical prostatectomy, this usually signals failure of treatment. However, it does not mean the patient is going to succumb to prostate cancer.

Radiation therapy is commonly employed to treat localized prostate cancer. Since the prostate remains and can be a source of PSA, there exists a great deal of debate in describing what constitutes failure. Several recent publications suggest that following successful external beam radiation or seed implants, patients who remain free of disease have an almost undetectable PSA level. There seems to be little argument that once the PSA begins to rise from a baseline level (called nadir level) that this constitutes failure. There are many things to consider when faced with a patient who exhibits a rising PSA after failed local therapy.

When faced with a patient with a rising PSA after local therapy, there are a number of questions that need to be asked. First, why did this patient fail? Second, is this patient still potentially curable with local radiation (if the patient had a prior radical prostatectomy), or with complete removal of the prostate (if the patient has failed radiation)? The third point to consider is what effect the treatment will have both on the quality and quantity of life. In evaluating the patient who has failed, it is important to ascertain whether he was curable at the time of the original treatment.

Once it is established that the PSA is rising, it is usually advisable to search for disease beyond the prostate. This may include a bone scan and, under some circumstances, a Prostacint scan. A Prostacint scan is performed after injecting a monoclonal antibody that detects prostate specific membrane antigen linked to a radioactive substance. A positive Prostacint scan suggests the presence of a local recurrence of prostate cancer. With these tests, the physician is trying to determine whether the cancer represents a local recurrence, a distant event (usually in bone or lymph nodes), or a combination of both. In some cases, a biopsy of the prostate or the prostatic bed is performed following either radiation or radical prostatectomy. Unfortunately, none of these tests provide 100% assurance that we are only dealing with a local recurrence. For example, a patient may have a PSA that has gone from 0 to .5 ng/ml to 1.0 ng/ml, years after a radical prostatectomy. A bone scan and Prostacint scan may be negative, but unrecognized disease could still exist in distant places. Nevertheless, if a bone scan is positive for disease that is usually strong evidence that disease is beyond the prostate.

Even though prostate cancer is detected early and the prostatectomy specimen shows a cancer confined to the prostate, failure can still occur. Not everyone who has a cancer that falls within the above criteria is cured. Somewhere between 5-20% of these patients will eventually fail. It is not always known why that happens, but some possibilities include a local recurrence possibly from prostate tissue left behind, implantation of cancer into the area of removal which occurred at the time of surgery, or possibly unrecognized early spread of the disease even when it was confined to the prostate.

Salvage prostatectomy offers a chance to cure some patients who fail radiation therapy. The keys to selecting these patients are by evaluating the stage and grade of the cancer, their longevity, their quality of life concerns, and overall health. We have performed a number of these procedures and actually do it from a perineal approach beneath the scrotum. The procedure is well tolerated, and most patients are only hospitalized 24 hours. Unfortunately, the majority of patients who undergo this procedure who were potent before, are impotent afterwards. This is due to the fact that there is an extensive amount of reaction around the prostate and it is difficult to do a nerve-sparing procedure after radiation therapy. There is also a risk of incontinence and even in patients who are ultimately not incontinent, it takes months before control of the urine returns.

There is no strong evidence that hormonal therapy of any type will improve survival in patients with a rising PSA. Even though there are no studies that suggest hormonal therapy will improve survival, there are some suggestions that early hormonal therapy is better than later.

One question patients often ask is: “If I watch my PSA, how long will it be before the cancer spreads?” In fact, the cancer may have already spread but we can’t find it! Recent studies suggest that the time from when a patient exhibits a biochemical failure following radical prostatectomy until they have documented metastatic disease is anywhere from 5-8 years. There are many novel therapies such as finasteride and flutamide (antiandrogen agents) available to treat this condition. Gene therapy is also being used. Additionally, differentiation agents (which slow the growth of the cancer), anti-angiogenesis (which affects blood vessels), and other compounds are being investigated for effectiveness in this setting. One strategy to consider is if the doubling time of these cancers can be extended by even small amounts, chances are the patient will die of something other than prostate cancer. In fact, stabilization of PSA by some of these novel methods is an important finding. It may not be necessary for the PSA to plummet to 0 for the patient to be considered “cured.” In fact, stable disease is very important.

Rising PSA after a local therapy such as radical prostatectomy, radiation therapy, or radioactive seed implants signals a failure. In the past, the only way we would know that a man failed therapy would be the symptoms that appeared from spread of the disease. Now, we have a simple blood test that can give us a lead time of many years before there is a problem. Before the advent of PSA, many of these men would have lived a normal life and died of something other than prostate cancer. Nevertheless, a rise in PSA after local therapy gives us the opportunity to choose a number of different approaches, including just watching the PSA level.

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Tags: Prostate Cancer, Uncategorized