Latest Developments in Prostate Cancer Treatment
by William J. Catalona, M.D.
Taking the Information Plunge...
Each year, Dr. Catalona presents a course at the American Urological Association Meeting in which he reviews selected articles from the medical literature to update urologists on the latest developments in prostate cancer treatment. We thought the QUEST readers would be interested in highlights from this year's course.
The American Cancer Society strengthened its guidelines for prostate cancer screening, stating that it is not appropriate for doctors to recommend against prostate cancer screening. Screening is also recommended for high-risk men in their forties.
Cancer statistics from the American Cancer Society show that prostate cancer death rates continue to fall at nearly 5% per year in the era of PSA testing, suggesting that early detection and effective treatment improve outcomes.
Lower PSA thresholds for recommending biopsy are debated. A new study shows that 24% of men with PSA between 2.5 and 4 have prostate cancer.
Free PSA and PSA density measurements are the best methods for increasing the accuracy of PSA testing.
PSA density refers to the PSA divided by the prostate volume. PSA density is the notion that a man with an enlarged prostate is entitled to have a higher PSA than a man with a small prostate. If a man with a small prostate has a high PSA, one has to worry more about cancer being present.
More than 6 biopsies should be obtained initially to avoid missing cancers and having to repeat biopsy sessions. Local anesthesia allows more biopppsy cores to be taken with less discomfort.
Eighty percent of tumor recurrences after radical prostatectomy occur during the first five years. The percentage of tumors that recur depends upon the types of patients that are accepted for treatment.
In my series, 17% of patients had recurrences 15 years after the series began. In some series, nearly 10% of patients have recurrences within the first year.
The important point is to know its a myth that if the tumor has not recurred within five years, it wont recur. Actually, 20% of recurrences take place more than five years after treatment.
Thus, men should be monitored for 10-15 years after treatment.
The chance of prostate cancer progressing within 5 years in men who are managed with watchful waiting is 50%.
Age-adjusted PSA ranges risk delaying the diagnosis of cancer in men in their 60s and 70s.
Age-specific reference ranges refer to an older man being entitled to a higher PSA than a younger man. This is a misconception but one that has stuck with many doctors and patients.
The idea of this misconception is that a man in his 40s should have a PSA less than 2.5, a man in his 50s should have a PSA less than 3.5, a man in his 60s should have a PSA less than 4.5, and a man in his 70s should have a PSA less than 6.5.
Using this false premise, men in there 60s and 70s are disadvantaged because their PSA is allowed to rise higher before an alarm is sounded.
External beam radiotherapy with higher doses using 3-dimensional conformal treatment protocols provides better cancer control and fewer side effects.
In times past, radiotherapy was given by passing the beam front-to-back and right-to-left. The field treated was box shaped.
Three-dimensional conformal therapy is a new form of radiotherapy where the software creates a sculpted, curved treatment field that conforms to the prostate or other target tissue area and is curved to avoid radiation to surrounding normal structures.
More radiation is delivered to the tumor and less to the surrounding tissues; therefore, better cancer control with fewer side effects.
Laparoscopic radical prostatectomy is feasible, but treatment outcomes are still uncertain.
Catheter removal is feasible one week after radical prostatectomy in selected patients with a low risk for complications.
The Chinese herbal preparation, PC Spes, lowers PSA levels in the majority of men with hormone-refractory prostate cancer, but it is uncertain whether PC Spes has unique activity that is different from those of all estrogens.
Hormone-refractory prostate cancer is a stage of the tumor that appears no longer to be responsive to conventional hormonal therapy (methods that lower the plasma testosterone level). PC Spes is temporarily effective in such patients.
Favorable results are reported with radioactive seed implantation techniques, but questions remain about how the results are measured.
Results of surgery are simply measured. If the tumor has been completely excised, the PSA should be undetectable. If the PSA is measurable, then the treatment has failed to remove all the cancer.
With radiotherapy, its more complicated. Usually the PSA goes down and then gradually goes back up if radiation is unsuccessful. Radiation oncologists dont call treatment a failure until they have three successive PSA rises measured 6 months apart and then they call the time of failure half way between the lowest PSA level and the first PSA rise.
This interpretation affects survival curves in a way that often makes them look 10-20% better than they really are.
PSA levels rise (bounce) in about one-third of patients treated with radioactive seeds approximately 18 months after treatment. This increase is believed to occur because of inflammation in the prostate and not tumor recurrence.
Hormonal therapy before prostatectomy reduces the incidence of positive margins but does not decrease the cancer recurrence rate.
A positive surgical margin is a cancerous surgical margin. The tumor extends to the edge of what was removed. Thus, there is a high likelihood that some cancer may be left behind.
Postoperative radiation therapy can salvage many patients who have recurrence after radical prostatectomy. Treatment results are better when treatment is begun before the PSA level rises above 1.
Postoperative radiation therapy reduces tumor recurrence rates in men who have adverse findings (extra-prostatic extension of cancer or positive surgical margins) on the pathology report after radical prostatectomy.
The preferred use of hormonal therapy (early versus late and intermittent versus continuous) is controversial. It is possible that results may be better with early, continuous hormonal therapy, but side effects, such as hot flashes, weight gain, and osteoporosis are greater with early, continuous treatment, and quality of life is better with late, intermittent hormonal therapy.
Some forms of secondary hormonal therapy such as antiandrogens, estrogens, and glucocorticoids may actually stimulate prostate cancer growth. If the PSA is rising, these agents should be discontinued.
Docetaxel (Taxotere) is an effective chemotherapeutic agent for prostate cancer that no longer responds to hormonal therapy.