[from www.boston.com]- Regular screening for prostate cancer may prevent the deaths of a small number of men but exposes many more to potentially needless treatments accompanied by serious complications, according to two landmark studies that fail to settle a long-running debate about the value of screening.

The reports, published online yesterday by The New England Journal of Medicine, are the first to explore whether the widely used prostate-specific antigen test, known as the PSA, actually leads to a reduction in deaths from prostate cancer, the second-leading cause of cancer mortality among men.

If there is any benefit to testing – and the preliminary findings, which emerge from research projects in the United States and Europe, could not agree on that point – it is likely to be small.

The studies appear destined to incite further soul searching about the risks and benefits of screening more broadly, challenging long-held assumptions that it is always better for patients to know if cancer is lurking.

Prostate cancer tends to be slow-growing, and doctors lack molecular markers that could easily distinguish the relatively small number of killer tumors from those likely to remain harmless – what one specialist called “toothless tigers.” As a result, the calculus of screening has remained murky even as it has proliferated, with an estimated 25 million PSA tests performed annually.

“The intent of screening is to reduce the pain and suffering and mortality from prostate cancer,” said Dr. Philip Kantoff, a prostate cancer specialist at Dana-Farber Cancer Institute who was not involved in the research. “It is possible, and even probable, in my opinion that it does do that, but the cost is high particularly in the first 10 years. The side effects from the whole process are felt immediately, and the benefits don’t get experienced for at least 10 years.”

The US study concluded that after following men for a decade, those screened annually with the PSA or a rectal exam were no more likely to avoid death from prostate cancer than those tested less frequently or not at all.

The European researchers found that men undergoing screening once every four years were 20 percent less likely to succumb to prostate cancer than those not tested regularly. But the most telling data from that study may be these: More than 1,400 men had to be tested to prevent one death from prostate cancer, and nearly 50 patients faced treatment, including surgery, to result in one fewer death.

“I’m 50 times more likely to receive unnecessary treatment than I am to be the one who avoided the prostate cancer death,” said Dr. H. Gilbert Welch, a Department of Veterans Affairs researcher in White River Junction, Vt., who studies the consequences of cancer screening. “From my perspective, that’s not a very good gamble.”

Specialists said the findings, which carry significant caveats, suggest that doctors and patients alike should embrace a more nuanced approach toward prostate screening and the treatment of incipient tumors. For some patients, especially the elderly and even younger men with no family history or other risk factors, deciding to forgo screening should not be viewed as a reckless decision.

“These studies make it difficult to have a one-size-fits-all recommendation,” said Dr. Michael Barry, of Massachusetts General Hospital, who has extensively studied prostate cancer screening. “If a man has his eyes open and knows the risks and knows what the trade-offs are, he may either want or not want the PSA.”

Since its adoption in the late 1980s, PSA testing has been bolstered by studies showing that prostate deaths overall were declining. Testing was sometimes given credit, but at the same time that screening was becoming more widespread, treatments for the disease were improving.

But those treatments can leave a man impotent or incontinent without any guarantee that a tiny tumor lodged in the prostate would ever have threatened his life.

The lead author of the US study, Dr. Gerald Andriole, said he hoped the studies will “temper those sort of knee-jerk responses” that have led to men with positive PSA tests being rushed into the operating room.

“PSA and the fear of prostate cancer are absolutely ingrained in Western societies,” said Andriole, chief of urologic surgery at Washington University in St. Louis. “If we could have a very candid conversation with patients who have very tiny tumors, maybe we could spare them the side effects of aggressive treatment of prostate cancer.”

But the researcher who oversaw the European study, Dr. Fritz Schröder, said that it’s important for patients to know that his study found that screening may save lives. Until now, when doctors discussed the risks and benefits of prostate cancer screening with patients, it “was more or less a Russian roulette,” said Schröder, a urology specialist at Erasmus Medical Center in the Netherlands.

The studies, which are continuing, both have significant shortcomings that might shed light on why they reached different conclusions.

The US study, which includes more than 76,000 men, divided them into two groups: One that was screened regularly and a second that received standard care, which resulted in about half of those men still being tested for prostate cancer at least once.

The study identified relatively few deaths caused by prostate cancer: 50 among the men screened regularly, and 44 in the other group.

Schröder criticized the US findings as “a study that was not conducted in the right way.”

All the research centers participating in the US study followed a standard set of rules governing patient testing. But the European study involved researchers in different countries following different protocols, a process that US scientists said might render those findings less significant.

Dr. Christopher Logothetis, a prostate cancer specialist at MD Anderson Cancer Center in Houston, said that armed with the new studies, men’s own risk perceptions may dictate whether they’re tested.

A patient with a significant fear of prostate cancer – perhaps his father died from the disease – may decide he is willing to accept the risks of treatment. Conversely, another man may decide that the potential of being left impotent or incontinent after treatment outweighs a long-term fear of cancer.