ATLANTA -- The long-running debate about treatment choices for early localized prostate cancer remained the focus of much research into the disease during 2006, a year in which malignancy of the gland was the second leading cause of cancer deaths in American men.
ATLANTA, Dec. 26 -- The long-running debate about treatment choices for early localized prostate cancer remained the focus of much research into the disease during 2006, a year in which malignancy of the gland was the second leading cause of cancer deaths in American men.
The American Cancer Society estimated that there were 234,460 prostate cancers diagnosed in 2006.On the other hand, death rates were down, with 27,350 men projected to die of prostate cancer in 2006, going from 10% of all cancer deaths in 2005 to 9% in 2006.
Both PSA (prostate specific antigen) testing and improvement in treatment are given credit for the decline in mortality, although even that is in dispute. Although PSA testing appeared helpful in monitoring treatment, studies of watchful waiting in localized disease versus active intervention in containing overall mortality have been conflicting, adding to the long-running debate about the risks and benefits of screening.
The American Cancer Society and the American Urological Association have recommended screening for prostate cancer in men over 50, whereas the American College of Physicians has suggested discussing its benefits and risks, and the U.S. Preventive Services Task Force has found insufficient evidence to recommend screening.
The following summary reviews some of the highlights of the year in prostate cancer research. For fuller accounts, links to the individual articles published in MedPage Today have been provided.
In response to the guidelines of the various groups, Yale's John Concato, M.D., put it simply, saying that screening almost always increases detection of disease. However, his team's retrospective case-control study of 71,661 veterans at 10 VA hospitals in Connecticut found that screening did not appear to decrease mortality. Of the men who died of prostate cancer, 14% were screened with PSA, compared with 13% of the men in the control group. Furthermore, PSA screening did not affect all-cause mortality.
In a somewhat stark but realistic report, researchers at the University of California San Francisco found that older men with limited life expectancy are being screened much too often, given the potential harm that may follow a positive test versus the likelihood of benefit in the next 10 years.
In a cohort study of 59,642 U.S. veterans, 70 and older, many non-clinical factors, such as marital status and region of the country, had a greater effect on PSA screening than health.
Some physicians may be uncomfortable incorporating life expectancy into screening, a discomfort partly driven by fear of malpractice liability. However screening elderly men in poor health is not considered a standard of care, UCSF's Louise Walter, M.D., said.
Not unexpectedly, obesity turned out to distort PSA results, and to be an obstruction in biopsy with an increased likelihood of yielding a false negative. Regardless of race, obese men had lower PSAs than normal-weight men. As a result, an obese man with a slightly elevated PSA might be at greater risk for prostate cancer than a man with a similar PSA and a normal BMI, Jay Fowke, Ph.D., of Vanderbilt found in a study.
Furthermore, when it comes to biopsy, because obese men tend to have larger prostates, biopsy may be more likely to miss a tumor, Duke researchers reported.
Taking a closer look at PSA levels themselves, Johns Hopkins researchers advised that the velocity, or the rate of PSA change, not the absolute level, is the key to determining who has a life-threatening malignancy. Typically, a PSA level of 4.0 ng/mL determines who needs treatment and who doesn't. But the rate at which the hormone level changes is a better guide and can be evaluated years before a cancer is diagnosed, they reported.
Data from the National Cancer Institute's SEER registries (Surveillance, Epidemiology, and End Results) showed that more than half of 24,405 men with low-risk prostate cancer who were candidates for "watchful waiting" received aggressive treatment instead, according to University of Michigan researchers. Of the men identified as low risk, 55% had initial curative treatment, 10% had a prostatectomy, and 45% had radiation therapy.
Furthermore, a Johns Hopkins study found that men who postpone surgery for treatment of localized low-grade prostate tumors do not reduce their chance for curative therapy.
After adjusting for age and PSA density at the time of diagnosis, men who delayed surgery for more than two years did not increase their risk of noncurable prostate cancer compared with men who had surgery three to four months after diagnosis
The Hopkins study came shortly after researchers from Fox Chase Cancer Center in Philadelphia reported at the ASCO prostate meeting that among 48,606 men, active intervention for localized prostate cancer led to better outcomes than classic watchful waiting, as defined by delaying treatment until the start of symptoms.
In a December follow-up of their ASCO report, the Fox Chase investigators said that among Medicare-age men with low- and intermediate-risk prostate cancer, those treated with radical prostatectomy or radiation therapy had a 31% lower risk of death during the next 12 years than men followed by watchful waiting.
A variety of factors beyond PSAs entered into treatment decisions. For example, studies found that decisions for localized disease tended to be driven more by patients' fears and misconceptions and by whether the urologist preferred androgen deprivation, rather than by the nature of the tumor or the patient's age.
In still another study, an analysis of peer-reviewed articles focusing on the decision-making process for localized prostate cancer found that urologists nearly always indicated that surgery is the optimal treatment, while radiation oncologists chose their own specialty.
Turning to actual treatment news, trying to compare some of the reports is like dealing with apples and oranges.
A large meta-analysis of 4,373 patients found that progression-free survival was prolonged by 10% in men with locally advanced prostate cancer who received both radiation and hormone therapy, according to Italian researchers at the Elena Cancer Institute in Rome.
For early prostate cancer, however, a single-institution study found that brachytherapy was as effective as external-beam radiation. Researchers at Massachusetts General Hospital in Boston compared 132 men treated with high-dose brachytherapy with 132 controls given high-dose external-beam radiation and found no difference in the rate of biochemical failure, as determined by a reproducible rise in PSA level.
Two years of androgen deprivation therapy reduced the risk of progression for patients with locally advanced prostate cancer, according to researchers at the Fox Chase Cancer Center.
Men given hormone therapy for two years after radiation and hormone therapy had a disease-specific survival (the good news), but there was no statistically significant difference between the groups for overall survival (the bad news). However, a study at the Cleveland Clinic suggested possible untoward results from hormone therapy longer than six months, including a two-fold increased risk of death and an increased risk of diabetes and cardiovascular disease.
Health Food and Vitamins
Finally, in the never-ending annals of cancer and nutrition, pomegranate juice, which may help stabilize PSA levels, had its day in the headlines, a finding not unnoticed by supermarkets, health-food stores, and upscale chefs.
According to a study a the University of California Los Angeles, drinking a glass of the anti-oxidant-rich juice each day increased PSA doubling time from 15 months to 54 months, certainly a boon to older patients.
In other good news (at least for smokers), vitamin E supplements cut the prostate cancer risk for smokers by 71% and beta-carotene supplements reduced the risk for men with low baseline plasma levels of the antioxidant. The disappointing finding, however, was that neither antioxidant showed a benefit in the general population.
Finally, translating positive findings from heart disease to cancer remained frustrating. For example, Rand Health researchers found that eating fish rich in omega-3 fatty acids turned out to be ineffectual for cancer in general, despite the benefits it seems to have in warding off heart disease.
More contradictory results included the finding that men who self-reported high levels of cholesterol had about a 50% increased risk for prostate cancer, and if they were older than 65, the risk climbed to 80%, according to researchers in Italy. This finding, if borne out by additional research, might please statin makers.
However, a meta-analysis of 26 trials by University of Connecticut investigators concluded that statins do not prevent cancer.
Several highly publicized retrospective studies found that statins had a dramatic effect on several malignancies, including prostate cancer, but according to the researchers, these studies could not demonstrate causality. Analysis, found that the overall incidence of cancer was not reduced among participants using statins compared with control groups.
Finally, Texas researchers reported that Proscar (finasteride) increased PSA sensitivity for both overall and high-grade prostate cancer but did not cause any extra aggressive malignancies, according to an analysis of more than 9,000 men.