WHAT IS A FALSE POSITIVE?

That is a very important question for prostate cancer activists. Deconstructing the term false positive is the key to understanding the best way to approach prostate cancer awareness and early detection in the midst of the current controversy swirling around the PSA test.

Disagreement about the PSA test is nothing new. For a number of years advocates for early detection have felt undermined by statements that the PSA test is “unreliable” or “not a very good test.” The anti- PSA side of the argument got a major boost last September, when Dr. Thomas Stamey, the urologist who published the original research in 1987 which led to the widespread use of the PSA test, recanted his previous pro-PSA views after publishing new research. The PSA test, in his view, is very good at predicting the size of a man’s prostate, but not at predicting the amount or severity of his cancer. “The PSA era is over,” he said. A statement like that hits a prostate cancer activist right in the gut.

The value of early detection via the PSA test is self-evident to men with metastasized prostate cancer who wish their tumors had been detected at earlier stage and also to those who believe their cancer could not have been cured without the early warning provided by a PSA test.

Early detection has long been the mantra in cancer treatment. Indeed, one of the goals of Canada’s Strategy for Cancer Control is to “improve cancer care through better screening…” Is prostate cancer somehow an exception?

Yes, according to some. Cancer of the prostate is generally regarded as a less serious disease than most cancers. And, in fact, as cancers go, prostate cancer has a relatively low ratio of new cases to deaths.

As our table shows, the ratio of new cases to deaths is much lower for prostate cancer than for most cancers. Mind you, it is quite similar to ratios for breast cancer in the same year: 21,200 new cases and 5200 deaths in 2004. We know – and this is not in dispute – that prostate cancer is the second leading cause of cancer death among men. Eighty-one Canadian men die of it every week. So in essence, this public argument boils down to, do the lives of these matter and, if they do, what’s the best way to identify them and treat them? Another important question is: Who decides what information a man can get about his own prostate health? This brings us to another layer of this controversy: the public health mindset. An individual thinks in terms of his own health – the information and professional advice he wishes to have about his health and the decisions he makes based on that information. Those who make health policy or decide how public dollars will be spent think differently. They think less about individuals and more about measurable health outcomes in the general population. They also must determine the best way to get the biggest bang for the taxpayer’s buck when it comes to public expenditure on health care. With respect to diseases like cancer, some of the best evidence of money well spent on early screening is lives saved. Unfortunately, the prevailing view is that existing data does not show that detecting prostate cancer early is saving lives. Death rates from prostate cancer have gone down, although some observers attribute that to improved treatment more than early detection. A recent study prepared by analysts from Statistics Canada concluded: “While evidence suggests that PSA testing contributed to an increase in the diagnosis of prostate cancer in its early stages, no data indicates that this resulted in decreased mortality.”

That doesn’t necessarily mean that PSA screening does not save lives. It may simply mean we don’t have the data to prove it yet. Although detecting cancer early makes it easier to treat, thus increasing survival rates, it’s a tricky thing to prove the early detection/survival connection with statistics. That challenge is magnified with prostate cancer. Because most prostate tumors develop slowly, many men for whom the disease could be potentially fatal can live long enough to die of other causes. Others for whom it will ultimately be lethal can also live for a long time. Therefore, using information from the general population, which is from what many studies have done up to now, it takes a longer term study to establish whether or not early screening for prostate cancer leads to longer life for a significant number of men. Large-scale studies currently underway in Europe should provide a better indication as to whether or not PSA screening helps men live longer. One, the ERSPC (European Randomized Study of Screening for Prostate Cancer) trial is a controlled study involving about 200,000 men. However, results will not be available for a few more years.
In the meantime, what are we left with? Some facts are not in dispute.

• Prostate Cancer is the most common malignancy in men.
• Prostate Cancer is still the second leading cancer killer of North American men.
• Clinically significant prostate cancer is easier to treat if it is caught early.

That seems to add up to a compelling argument in favour of early detection. If we don’t make use of the PSA test, what is the alternative? Research evidence shows that, on it’s own, a digital rectal exam is not a reliable method for finding clinically significant prostate cancer at an early stage.

What are we left with? The PSA test.

Now, about false positives. Those who question the public benefit of widespread PSA screening are concerned that it will lead to over-treatment, by identifying minor cancers that don’t need treatment. Cancer of the prostate does not always require immediate or aggressive treatment, and recent research suggests that current methods of evaluating the severity of tumors are not as precise than experts once believed.

In a Globe and Mail article last September, Toronto surgeon, Dr. Laurence Klotz, acknowledged that until recently it was thought PSA scores became elevated as a result of the development of the larger volume of cancer. He pointed out that Dr. Stamey’s research showed that this was not true with respect to mildly elevated (4-10) PSA scores.

Both Dr. Klotz, and Dr. Michael Jewett, a urologist/oncologist/ surgeon at Toronto’s Princess Margaret Hospital have both stated publicly that recent research may prompt doctors to be more selective about which men are treated. However, that does not mean that the PSA test results provide no useful information. Dr. Klotz also noted: “A rapid rise in PSA has been clearly demonstrated to be associated with aggressive prostate cancer.

Furthermore, by the time someone develops advanced prostate cancer, the PSA is almost always very high.” Moreover, Dr. Stamey himself points out that monitoring PSA levels is very useful indicator of how much residual cancer remains in a patient after prostatectomy.

This does not sound like a useless test.

In fact, an analysis of data by Canadian urologists Francois Meyer and Yves Fradet found that the accuracy of screening for Prostate Cancer using PSA plus DRE was about the same as using mammography plus physical exam to screen for breast cancer in women.

The real issue that has been identified recently is not problems with the PSA test itself, but what happens after the PSA test. If a single PSA result of 4 or above leads automatically to a biopsy, many men will be found to have cancer. The real problem – and experts agree on this – is that it’s not easy to tell the cancer that needs treatment from the cancer that does not need treatment.

Treating a cancer that doesn’t really need to be treated would be true false positive. However, you can’t know that a tumor does not need treatment if you don’t even know it is there.

Let’s imagine a case where a man’s PSA score is elevated or is rising. He and his doctor decide to opt for a biopsy which reveals cancer. And let’s say, for the sake of argument, meticulous medical assessment suggests that this particular cancer does not need treatment. First of all, can the man know that for sure? In one study, 200 men who would have been considered false positives since their initial biopsies had found no cancer, underwent a repeat biopsy within a year. In 24 of them, the second biopsy revealed cancer.

Second, even if a man could be told with absolute certainty that his cancer did not need treatment, is it better for him to not know about that cancer than to know about it? And who decides whether or not a man has a chance to know: the man himself or someone sorting through statistics in an office?

To say that men should not have access to a test that can detect prostate cancer in its earliest stages is strikingly paternalistic.

Men do have the right to information about their health. They also need to know the facts about prostate cancer including the fact that, by itself, a PSA test result is not a clear indicator of whether or not a man has clinically significant cancer. In other words a moderately high PSA score is not something to panic about. Men need to know that a diagnosis of prostate cancer does not necessarily mean you have to undergo invasive treatment. They also need to know that a low PSA score does not guarantee that you are cancer-free.

In recent study which, among other things, monitored men’s PSA levels for a number of years, it was found that 15 percent of subjects (all men were biopsied at the end of the study) whose PSA levels had been low were found to have cancer. Dr. Stephen Strum, a prostate cancer specialist, from Ashland, Oregon, who gave the keynote address at the CPCN National Conference last August, is still bullish on the PSA test. He calls it “the single most important biomarker in the history of cancer medicine.” For Dr. Strum, the key is how you use the information. One PSA test, provides baseline information about a man’s prostate health.

That information needs to be combined with other information:

• Information about a man’s age and general health.
• Risk factors related to ethnicity, lifestyle and family health history.
• Other means of gathering information about his prostate health, including DREs, future PSA test results, other kinds of tests, and in some cases biopsy results.
• Reliable knowledge about prostate cancer and how it usually develops.

Collecting this data puts a man in a position to be able to make informed decisions about his health. Dr. Strum notes that prostate health is often correlated with a man’s cardiovascular and bone health. He predicts that bone health will been shown to be a very important factor as to whether a man’s cancer remains confined to his prostate or spreads to other parts of his body.

Dr. Klotz contends that effective use of early detection tools can result in a situation where cancer development is detected at an early enough stage than for many men, the cancer will be manageable simply through lifestyle and diet changes. If continued PSA monitoring shows that it is reaching clinical significance, then more aggressive treatment can commence.

But none of these decisions are possible if we return to a standard where the only screening for prostate cancer is a digital rectal exam. In that case, we’re asking men to play a lottery. It’s a lottery with pretty good odds for most people, but for the losers the costs are very high.

It all comes down to information. We can hope for the development of new and better (and simple and cheap) screening tests for prostate cancer. Dr. Fradet and his colleagues are working on a urine test which detects a gene associated with prostate cancer. But, as it stands the simple, inexpensive PSA test provides one of the only ways for a man to get information about the health of his prostate, the gland that is the source of the cancer that kills more men than any other cancer but lung cancer.

When it comes to a man’s prostate health, clearly it is better to know something than to know nothing. And when it comes to cancer, the earlier you know about it, the better the chance of successful treatment. Aman has two ways of finding out about his prostate cancer at an early stage. One is some sort of blind luck. The other is the PSA test. Which one should we ask our brother, sons and friends to rely on?