 Home: PCU 1|2004:Peter R Carroll, MD
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| Edited comments by Peter R Carroll, MD |
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Recent trends in prostate cancer
A significant stage migration has occurred over the last five years. Urologists, radiation oncologists and others treating patients with prostate cancer should be mindful of this dramatic stage migration. According to data from Europe, 30 to 50 percent of the currently detected prostate cancers may be clinically insignificant. In other words, small and low-grade cancers that may not be a risk to the patient are being overdetected.
In addition, extended-pattern biopsies — even after controlling for PSA —result in an even greater number of lower-volume cancers being overdetected. PSA screening and the extended-pattern biopsies both contribute to the over-detection of prostate cancer. As clinicians, we must understand that some cancers currently being detected may not need immediate treatment. I’m hopeful that the use of watchful waiting will actually increase.
Watchful waiting in patients with low-risk features
Each year, our group treats about 750 new patients with prostate cancer —primarily with surgery and radiation. The most rapidly growing population for us right now is the patient treated with watchful waiting. Currently, we have about 160 men on watchful waiting, and that number is rapidly increasing. We have a number of clinical trials for these patients, because they’re an ideal population in which to evaluate at novel therapies.
In the younger man with low-risk features, we’re very cognizant of not compromising their ability to be cured, so their PSA and Gleason score must be low and they must have had an extended-pattern biopsy. At the present time, most patients will have between 10 and 18 biopsies, which results in less grade and stage miscalculations. Interestingly, the percent-free PSA tends to predict the likelihood of progression. Patients with a free PSA greater than 10 percent —usually between 15 and 20 percent — are candidates for watchful waiting.
According to our data in patients with low-risk disease on watchful waiting, between 30 and 50 percent will require treatment over the next three to five years. Patients most likely to require treatment are those who are younger or have a rising serum PSA. Patients with a low percent-free PSA generally will receive treatment.
For patients on watchful waiting, our ability to effectively treat them does not appear to be compromised; they tend to stay in the same risk category. I always advise patients that I cannot assure them 100 percent that watchful waiting will not compromise their ability to be effectively treated, but patients with low-risk disease tend to do well.
Management of patients with intermediate- or high-risk disease
The outcomes of treatment in men with intermediate-risk disease (PSA = 10-20 ng/mL, Gleason 7 and palpable cancer) are widely disparate. In patients with intermediate- and high-risk disease, well-validated nomograms should be used to identify their risk, because some patients with high-risk disease behave more like patients with intermediate-risk disease and vice versa. Patients with very high-risk disease (high grade, high T stage, high PSA) should be considered for clinical trials with hormonal therapy, chemotherapy, dendritic cell therapy, surgery, radiation, etcetera.
Randomized trial data suggest that hormonal therapy should be used along with radiation therapy in patients with intermediate- or high-risk disease. National trends from the last 10 years demonstrate an increased use of neoadjuvant and adjuvant hormonal therapy, but not all men are being appropriately treated. Some patients with high-risk disease who would benefit from combination therapy are not receiving it.
This may not be the case in patients with intermediate-risk disease because those randomized trial data are more recent. For example, the RTOG trial led by Mack Roach demonstrated a benefit from short-term hormonal therapy and radiation therapy to the prostate and pelvis in patients with intermediate-risk disease.
In a nonprotocol setting, patients with intermediate- or high-risk disease who are being treated with radiation therapy should also receive hormonal therapy. In patients with intermediate-risk disease, short-term hormonal therapy — four to six months — should be prescribed. Patients with high-risk disease may benefit from both neoadjuvant and adjuvant hormonal therapy for at least two years.
Early versus delayed hormonal therapy
The timing of hormonal therapy after a PSA relapse is now a matter of much debate. Many trials, such as Ed Messing’s trial published in the New England Journal of Medicine demonstrate a benefit from early hormonal therapy. In our data set, we found that hormonal therapy delivered early at PSA relapse after prostatectomy appears to be associated with a decreased risk of prostate cancer death. We are currently trying to determine in which patients the risk is reduced, because some of the patients with low-risk disease might not benefit. However, it’s becoming clear that the early use of hormonal therapy may be very important for patients with high-risk disease.
In the immediate postprostatectomy period in a patient with high-risk disease, we evaluate the postoperative hypersensitive PSA and the status of the margins, seminal vesicles and lymph nodes. Then, we treat these patients selectively. Patients with high-grade organ-confined tumors, negative margins and lymph nodes, and undetectable PSA will be watched. Patients with positive margins, depending on the extent and grade, may or may not receive radiation therapy. Patients with higher-risk features — seminal vesicle invasion, lymph node involvement — will be considered for a clinical trial of hormonal therapy with or without chemotherapy.
We are observing a relatively high use of hormonal therapy. According to the bulk of the data, hormonal therapy will impart a survival advantage in patients at very high risk. The questions are: How high a risk and when should it be instituted? In patients with a very long life expectancy, we have to be careful that we don’t expose them to treatment-associated side effects rather than benefit.
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| Dr Carroll is the Ken and Donna Derr-Chevron Chair and a Professor in the Department of Urology at the University of California in San Francisco. |
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