EXPECTANT MANAGEMENT OF LOCALIZED PROSTATE CANCER


Over the past 30 years, we have become quite expert in surgery and various forms of radiation to treat prostate cancer. However, not every man will benefit from treatment since some cancers will never progress to a harmful state. Research suggests that there are men who can safely forego treatment -instead undergoing careful follow up for any evidence of progression. This type of therapy is called 'expectant management'

Prostate cancer is the most prevalent male cancer, but the majority of men with the disease do not die of prostate cancer. A recent study evaluated the cause of death in men over age 70 years who were diagnosed with prostate cancer in the PSA era -more than twice the number of men died of other causes than died of prostate cancer. This does not mean that prostate cancer does not kill men, but rather that some older males have a slowly progressive form of the disease that will not threaten them during the remaining years of their life. The key is to be able to identify those older men who can safely forego treatment for now.

Which patients are the best candidates for no immediate treatment or expectant management?

Those men who have a limited life expectancy because of older age or other health problems, who have cancers that are too far advanced to cure with any treatment, or older men who have small volume prostate cancers that are not poorly differentiated should consider no immediate treatment as an option.

Even without treatment, prostate cancer that is not poorly differentiated (Gleason pattern score 7 or above) and still localized to the prostate, takes more than 10 years to spread and cause harm. Therefore, men who do not have a 10-year life expectancy because of older age at diagnosis or because of other serious health problems maybe best managed without any treatment.

Men who have disease that is too far advanced to cure with radiotherapy or surgery -yet there is no evidence of distant disease on scans and no symptoms- may choose expectant management. For these men, initiation of early hormonal therapy may prolong life but not significantly enough to justify the side effects from the treatment and a choice of no treatment will maintain quality of life.

In addition, it is known that about 10 to 20 percent of prostate cancers detected with PSA testing (and normal digital rectal examination) are very small cancers that are not poorly differentiated. These tumors may not cause harm -especially in older men who have less time for the tumor to progress.

Thus, expectant management is very appropriate for those men who:

    are too old or too ill to benefit from cancer treatment
    have cancer that is too far advanced to cure
    have cancer that is thought to be small and less likely to progress during the remaining years of life.


Expectant management may be appropriate for those men who have all of the following findings:

older age -usually over 65 years
cancer can not be felt on digital rectal examination
PSA appropriate for prostate size meaning that the PSA density (PSA divided by ultrasound determined prostate volume) is 0.15 or less
combined Gleason grade or score is 6 or less and no more than 2 biopsy cores contain cancer and
cores containing cancer should not have more than 50 percent involvement with cancer


What does expectant management mean?

In the past, expectant management meant no treatment until the development of metastatic disease, at which time androgen ablation (hormonal) therapy was initiated. However, for those men who are thought to have small PSA-detected prostate cancers, and who choose expectant management, it makes sense to monitor the situation closely and intervene -if necessary- at a time when cure is still possible. We refer to this as expectant management with curative intent. This means that men undergo periodic evaluations including PSA tests, digital rectal examinations, and prostate biopsies. If there is evidence that the cancer is progressing, treatment is recommended.

Is it possible to accurately identify those men who have small PSA detected cancers that are less likely to progress without treatment?

The answer depends upon your definition of accurate. Studies have shown that cancers less than 0.5 cc (smaller than an eraser tip) can be identified correctly about 75 percent of the time using PSA and information from the prostate biopsy.

* If the PSA density (PSA divided by prostate volume on ultrasound) is lower than 0.1 and there are no adverse findings on needle biopsy (Gleason score 7 or greater, or more than two needle biopsies containing prostate cancer, or more than 50 percent involvement of any core with cancer), then there is a 70 to 80 percent chance that the prostate cancer is small volume (less than 0.5 cc).

* If the PSA density is 0.1 or more, or if there are any adverse findings on needle biopsy, then there is a 70 to 80 percent chance that the tumor is larger than 0.5 cc.

Are there any other tests that are useful for predicting which prostate cancers need to be treated?

It is possible that free PSA percentage is predictive of the aggressiveness of prostate cancers. Three separate studies with very different designs have concluded that percent free PSA is predictive of the biology of the tumor, and all three studies came to the conclusion that a percent free PSA of 15 was the cutoff value that was most predictive. Based on these data, we are less enthusiastic about expectant management in men who have a percentage of free PSA that is consistently less than 15.

How does a man with a PSA-detected prostate cancer that is thought to be small volume make a choice between expectant management and treatment?

We do not encourage healthy men under age 65 to strongly consider expectant management because of their longer life expectancy, and the uncertainty of whether a tumor will progress during the remaining years of life. For older men with PSA-detected prostate cancers that are thought to be small volume, expectant management is one of the options that can be considered. A man should weigh the potential loss of quality of life with treatment (radiation or surgery) against the possibility that the window of opportunity for cure will disappear without treatment. In the era before PSA testing became widespread, men over age 65 with localized prostate cancer that was not poorly differentiated, had a probability of death from prostate cancer in the range of 25 percent over 15 years without treatment. Now, with PSA testing, prostate cancers are detected on average 5-7 years earlier than in the pre-PSA era. Since tumors are being detected earlier than ever before, one would anticipate that the probability of death from prostate cancer for men over age 65 years with a PSA detected cancer (not poorly differentiated) would be lower than 25 percent over 15 years with expectant management. This, however, currently remains unproven.

What does a man have to loose with expectant management of a PSA-detected cancer?

The major concern is that while expectant management is taking place, the tumor will progress beyond the prostate to the point where cure is no longer possible. We are following many men with PSA-detected prostate cancers who have chosen expectant management because their cancer is small volume disease.
Although we do not have long follow-up to make definitive statements, but about 30 percent of men with follow-up have had adverse findings on a repeat prostate biopsy one year or more after the initial prostate biopsy diagnosed the cancer. At this point, treatment was recommended. Of these men, a subset have undergone radical prostatectomy, and 90 percent have been found to have curable prostate cancer after removal of the prostate.

Thus, we can say at this point that if a man is thought to have small volume disease, there is a 30 percent chance that he will be found to have more extensive disease on follow-up biopsy, and if so, about a 90 percent chance that the cancer will be curable at that point with surgery.

If a man decides on expectant management, what recommendations are made for follow-up of the cancer?

Because of the uncertainty associated with prostate biopsy in missing larger volume cancers, we recommend that any man interested in expectant management undergo a repeat prostate biopsy (12 to 14 cores) with wide area sampling to minimize the chance that more extensive -or higher grade- disease was missed on the initial biopsy. This may be suggested initially or a year or two later depending on the adequacy of the original biopsies.

If the repeat biopsy does not turn up more extensive disease, and the individual is comfortable with expectant management, we recommend a PSA and digital rectal examination at three to six month intervals and a prostate biopsy to monitor the progress of the disease depending on the PSA and DRE findings.

Is a regular or yearly prostate biopsy necessary?

Some centers have found in following men with PSA-detected prostate cancers, that changes in PSA are not reflective of who will and will not be found to have more extensive disease on follow-up biopsies. They conclude that one should not depend on PSA to sound the alarm that treatment is now necessary when following men who have chosen expectant management. This has not been the findings in some others clinics and much will depend of other factors such as grade, extent, age, other diseases.

If a man chooses expectant management, what dietary changes should he make?

Most men ask what they should be doing in terms of dietary changes to help prevent progression of the disease. This is an area of intense interest now but it's one that is clouded by the fact that dietary supplements are a billion dollar industry in the U.S. This often makes it hard for consumers to distinguish between science and marketing. There is a very nice review on the topic of nutrition and cancer in CA, A Cancer Journal for Clinicians, published for the American Cancer Society. The review can be found on their web site http://www.ca-journal.org

The bottom line is that there is an association between intake of animal fat and the incidence of prostate cancer, and that fruits and vegetables can reduce the risk of many cancers. Thus, a diet that is mostly made up of food from plant sources (fruits, vegetables, soy), and that limits the intake of high fat foods makes sense for now.

As for vitamin supplementation, there is now some preliminary evidence that vitamin E and selenium may be protective with regard to prostate cancer. However, the trials that suggest this were not designed to address a relationship between prostate cancer, vitamin E, and selenium, so strong recommendations for supplementation of vitamin E and selenium cannot be made based on the available data. The same is true for lycopene intake. There is not yet any definitive evidence on which to base a recommendation.

If you have more questions---feel free to ask.