segunda-feira, outubro 15, 2007

Detection comes earlier

And So Do Tough Questions
Without fanfare, treatment of prostate cancer has reached a watershed moment. In 2007, for the first time, deaths from the disease will account for less than 10 percent of all cancer deaths in men, continuing a downward trend that began in the 1980s. This success stems largely from earlier detection of these tumors, which many experts credit to wider — and much debated — use of the controversial prostate-specific antigen blood test.
“The treatment options for prostate cancer have not changed a lot over the past 20 years,” said Dr. Alan W. Partin, director of the Johns Hopkins Brady Urological Institute in Baltimore. “What is making the biggest difference is that we are picking up the cancer earlier than ever before and curing it.”
But the news is not all good. Prostate cancer remains the second leading cancer killer among men; an estimated 27,000 patients will die of it this year, and one in six men will develop the disease at some point in his life. While the antigen test, known as P.S.A., has been a blessing in many ways, experts say, its limitations are more apparent each year. New diagnostic and treatment strategies are desperately needed if progress is to be sustained.
The P.S.A. test measures levels of a protein produced by the prostate. A reading of 4 ng/ml — nanograms per milliliter of blood — or higher is generally considered a warning of prostate cancer. Ideally, experts say, men should get a baseline reading at age 40. If the P.S.A. is lower than 0.6 ng/ml, the patient should be tested again at age 45. If the reading is greater than 0.6 ng/ml, screening should take place every two years.
If a digital rectal exam reveals a suspicious lump, men generally are advised to get an immediate biopsy even if P.S.A. levels are low. Men ages 40 to 49 are also referred for biopsies if their P.S.A. readings are greater than 2.5 ng/ml. For men ages 50 to 59, that threshold is 30 ng/ml; for men over 60, it is 4.0 or higher. Positive test results must be confirmed by biopsy, and high P.S.A. levels do not always mean cancer is present.
In part because of its complexity, the P.S.A. test has long been controversial. Prostate cancer deaths are decreasing in the United States, where routine testing occurs, and they are increasing in countries like Sweden, where it does not. Still, critics note, while routine P.S.A. testing and detection may have improved cancer survival rates, evidence that it reduces death rates over all in large groups of men has been mixed.
Particularly in older men, the benefits of P.S.A. screening may not outweigh the risks, because a high reading can lead to expensive and perhaps unnecessary follow-up tests, not to mention surgical treatments with serious consequences, like incontinence and impotence. Prostate cancer is a slow-moving disease, researchers note, and a diagnosis at age 75 means a man is more likely to die with prostate cancer than of it. For many patients, “watchful waiting” is the reasonable — but underused — therapeutic option.
Still, older men are receiving P.S.A. tests in startling numbers. After examining the medical records of 600,000 men 70 and older over a two-year period, researchers at the University of California, San Francisco, reported in 2006 that more than half were given P.S.A. tests. More than 36 percent of the men 85 and older received P.S.A. tests, including a sizeable number with a life expectancy of less than a year.
“At what age to stop screening with P.S.A. is not clear-cut,” said Dr. Peter Scardino, chairman of the department of surgery and urologic oncology at Memorial Sloan-Kettering Cancer Center. “Medical organizations have generally recommended it only for men with a life expectancy of at least 10 more years.”
Some experts believe that screening can be discontinued by age 70 if a man has been regularly tested and has maintained low P.S.A. levels. Even when P.S.A. testing is appropriate, many doctors have begun relying more heavily on the rate at which P.S.A. increases over time, called P.S.A. velocity, rather than the absolute reading at any given time. These days many men are referred for a biopsy if P.S.A. readings increase by more than 0.2 ng/ml per year for two years, or if the reading is greater than 4.0 but has increased by more than 0.75 ng/ml per year.
Better diagnostics are needed, researchers know, particularly new biomarkers that more accurately measure disease progression. One of the most promising is early prostate cancer antigen marker-2, which may more reliably identify early prostate cancers than the P.S.A. test, thereby reducing the number of unnecessary biopsies. If successful in current trials, the test could be available in mid-2009.
There is no one-size-fits-all treatment for prostate cancer, and a lack of definitive clinical evidence continues to make it difficult for patients and their doctors to make informed decisions. Radical prostatectomy surgery, which now can be performed robotically or laparoscopically, is still the gold standard for treatment because of its high cure rate. But side effects like incontinence and erectile dysfunction remain significant considerations for men facing a decision about how to treat their cancer.
For smaller, less aggressive tumors, radiation therapies like brachytherapy — the insertion of radioactive “seeds” into the prostate — and high-dose external beam radiation therapy also yield high cure rates. But these procedures, too, raise significant concerns: though incontinence rates are lower, about half of patients undergoing radiation therapy experience erectile dysfunction within five years.
Just a few years ago, chemotherapy was the therapeutic strategy of last resort for killing circulating prostate cancer cells, but now regimens using the cancer drug docetaxel have been shown to provide a survival benefit of months, even years.
Even better treatments may come from biological therapies, stem cell injections or radiation oncology, three areas of intense research. New chemotherapeutic agents, monoclonal antibodies and vaccines are being tested, and more than 200 experimental drugs are being studied. Still, it may take years of research to move them through testing to the local pharmacy, if they make it there at all.
Until then, men facing prostate cancer must continue to reckon with a bewildering array of options regarding testing and treatment. The arrival of the P.S.A. test 20 years ago was a wonderful start. But it was only a start.
NYTimes 30.08.07