When men over age 50 have their annual check-ups, the doctor often checks blood levels of prostate-specific antigen (PSA) to screen for prostate cancer. A new study suggests that PSA levels may also predict prostate growth in men with benign prostatic hyperplasia (BPH), or benign prostatic hypertrophy.

The Proscar Long-Term Efficacy and Safety Study enrolled more than 3,000 men over age 50 with a diagnosis of BPH and randomized them to receive either finasteride (Proscar) or placebo for four years. Participants came from 95 centers; at 13 of these centers, 10 percent of the men had MRIs to measure their prostate volume when the study began and each year after. In the current report, the researchers looked at information from the men who’d taken placebo to see what baseline measurements predict growth of the prostate.

The size of a man’s prostate is a good indicator of problems to come. For example, the larger a man’s prostate, the more likely it is that he will have an acute urinary retention problem. Men with large prostates also are less likely to respond to drug treatment and more likely to need prostate surgery.

Based on data from 164 patients, the researchers found that the prostate continued to grow steadily over the four years of the study, and the older a man, the more his prostate grew each year. Prostate-specific antigen levels also tended to rise with age.

What predicted prostate growth the best, however, was the amount of PSA in the blood when the study began. Almost one-third of the men with PSA levels less than 2.0 ng/ml had a decrease in their prostate size over the four years, compared to just one of those with a PSA level of more than 2.0 ng/ml.

Since men with large prostates are more likely to have problems, having a way to predict prostate growth would help doctors. And since many doctors use prostate-specific antigen tests to screen for prostate cancer anyway, they should be able to use the results to help manage prostate growth too.

Writing in the January issue of The Journal of Urology, the researchers explain that this simple idea may be harder to get across than you’d think. In the past, prostate size was considered unimportant, and doctors focused on treating urinary symptoms. Now that research has shown that PSA and prostate size do predict adverse outcomes, doctors will need to change their approach to thinking about management and future risk rather than just symptoms.

A recent analysis of the control arm of the Prostate Cancer Prevention Trial (PCPT) has revealed that 15.2% of men with a Prostate Specific Antigen (PSA) value less than 4 ng/mL had prostate cancer detected via prostate biopsy. Current recommendations suggest PSA levels lower than 4 ng/mL do not indicate clinically significant prostate cancer; thus, the study results are groundbreaking news because no prevalence data for this group of men was previously available.

The PCPT trial enrolled men older than 55 with a prostate specific antigen (PSA) value less than 3 ng/mL and an American Urologic Society (AUS) score below 20. The men in this trial were randomly assigned to receive finasteride 5 mg or a matching placebo daily and followed for seven years with annual PSA and digital rectal exam (DRE) screening, with 9,459 men assigned to the placebo arm. After seven years of PSA and DRE screening, the men who never had a PSA higher than 4 ng/mL, an abnormal DRE, prostate surgery of any type, and had a prostate biopsy (minimum of six samples) at the end of the study were evaluated for cancer prevalence. There were 2,950 men, ages 62 to 91, who met these criteria, and in 449 (15.2%) of those men, prostate cancer was detected. Always controversial, the use of the Analysis of the patient demographics revealed that age and race did not predict those who would have prostate cancer, but a positive family history (affected brother, father, or son) did correlate with an increased risk of prostate cancer (p = 0.004). The mean prostate specific antigen (PSA) score of men with cancer was 1.78 + 0.92 ng/mL, significantly different from those without cancer at 1.34 + 0.86 ng/mL (p = 0.001). The mean annual rise in PSA (0.32 to 0.46 ng/mL) was also significantly higher in men with prostate cancer (p = 0.001).

Since prostate specific antigen (PSA) was first described in 1979, the ability of the test to predict clinically significant prostate cancer has been hotly debated. What is a normal versus an abnormal PSA value; was the test sensitive and able to reliably detect it; and what would the costs be from false-positive results in patient harm and to society in unnecessary procedures performed? — all have been questioned over the past two decades. A prostate specific antigen (PSA) level higher than 4 ng/mL is the standard indicator for a man likely to have clinically significant prostate cancer. For men with a PSA level between 4 and 10, approximately 25% will have prostate cancer. For PSAs higher than 10, this number rises to nearly 50% of patients having prostate cancer detectable by biopsy.

Even with new data on the prevalence of prostate cancer in men with a prostate specific antigen (PSA) below 4, this information does not provide any additional direction on whom to treat. The finding that 15% of men with normal PSA values have early-stage prostate cancer requires the review of prostate screening practices, more importantly because the incidence of cancer likely to be aggressive (Gleason score greater than 7), although low at 2.3%, was sprinkled throughout the PSA distribution. Not all of these patients would undergo invasive therapy, because depending on the patient’s age and life expectancy, treatment may range from watchful waiting to prostatectomy for this stage of cancer.

What to do now? It was already known, based on autopsy studies, that 15% to 60% of men ages 62 to 91 had unrecognized prostate cancer.However, none of these men diagnosed at autopsy actually died of their cancer. Thus, what patients really need to know is what the best screening method is to ensure that men who undergo biopsies and other therapies are at risk for cancer-driven effects that will affect the length and quality of their life. While a small number of the cancers found in this study were aggressive based on their Gleason score, the low prostate specific antigen (PSA) values indicate a small volume of disease that is unlikely to imminently impact a patient’s quality of life. Further limitations of this study are that its results apply only to Caucasian men older than 62. The minimum age of these patients was 62, and minorities were poorly represented in the final sample. In the otherwise asymptomatic male with a PSA of 0 to 4 ng/mL, current recommendations still continue with close follow-up of AUS score, digital rectal exam (DRE), and prostate specific antigen (PSA) to guide definitive therapy if indicated in that specific individual. The information from this study further emphasizes the critical need for patients’ annual follow-up with their oncologist or urologist to facilitate medical interventions if and when they are needed. Meanwhile, new biomarkers and stratification schema are being pursued as oncologists work to further define better diagnostics and care algorithms in the treatment of those with this challenging disease.

PSA test doesn’t detect tumor’s severity, Stanford University study says

The leading test to detect prostate cancer is “clinically useless” at determining the size or severity of a man’s tumor, and is only of “limited” value at predicting cure rates from surgery to remove the diseased gland, a new study says.

The test, which measures a blood enzyme called prostate-specific antigen (PSA), is likelier to find benignly enlarged prostates and prompt overly aggressive treatment, according to the scientists who conducted the study.

The study, which appears in the January issue of the Journal of Urology, “is quite a disappointment,” says Dr. John McNeal, a Stanford University pathologist and a co-author of the paper.

“We used to think [PSA testing] was good. But what we would like it to tell us is whether a PSA that is not much elevated is elevated because of [normal prostate growth] or whether it’s elevated because of prostate cancer.” And the protein, at least at moderate levels, can’t do that, McNeal says.

Dr. Peter Albertsen, chief of urology at the University of Connecticut in Farmington, says the study “is not going to knock prostate-specific antigen (PSA) screening off the map by any means.”

However, Albertsen adds, PSA testing is undergoing a crisis of confidence similar to that of screening mammography, another exam whose value has come under questioning.

“I think there’s enough tantalizing evidence to think” that routine prostate-specific antigen (PSA) screening saves lives, Albertsen adds. But there’s not enough evidence to be sure.

Almost 190,000 American men are diagnosed annually with prostate cancer, and 30,000 will die from it, according to the American Cancer Society. Prostate-specific antigen (PSA) testing is widespread in men over age 50, but no study has proved that it saves lives by helping doctors identify prostate tumors when they’re still curable.

One reason: prostate cancer grows glacially. So while most men will die with cancer of the gland, relatively few will die of it. Aggressive treatment of slowly growing tumors may therefore cause more harm than good, some experts argue.

In the latest study, Dr. Thomas Stamey, a Stanford University urologist, and his colleagues studied the relationship between PSA scores in 875 men who underwent radical prostate surgery, in which the gland was completely removed, between 1984 and 1997.

Stamey’s group analyzed prostate-specific antigen (PSA) readings taken from many of the men both before and after their operation.

The largest tumors did produce extremely elevated PSA levels, topping 22 nanograms per milliliter of blood. Scores of more than 9 ng/ml were somewhat associated with aggressive disease, as measured by standard gauges of malignancy.

But for prostate-specific antigen (PSA) values between 2 and 9 ng/ml, the culprit was often not cancer but benign prostatic hypertrophy (BPH), or normal swelling of the gland.

Nor did PSA testing predict cure rates: Surgery success was the same for men whose pre-operation PSA was lower than 4 ng/ml as it was for those with a score of 10 ng/ml.

The prostate-specific antigen (PSA) enzyme is secreted by cells in the prostate, and mildly elevated values often reflect a larger than normal gland. BPH is as common as cancer, a fact many men don’t realize.

Scientists have been trying to tweak the prostate-specific antigen (PSA) test to make it more reliable, but whether these new techniques will be more sensitive to cancers remains a mystery. In fact, PSA is a misnomer, since the enzyme is secreted not only in the prostate but in the breast as well.

What To Do

Every man has a prostate-specific antigen (PSA) level, and any score between one and four could be totally normal, McNeal says. The tricky part comes in deciding what to do if the test comes back between 7 and 8. Despite his group’s findings, McNeal says he would probably undergo a biopsy if his own PSA test were in that range.

It is well accepted by urologists that the higher a man’s blood level of prostate specific antigen (PSA) prior to treatment for prostate cancer, the worse the prognosis for cure. But new data presented at the annual meeting of the American Urological Association in Atlanta early this month challenges this common wisdom.

“Serum PSA drawn preoperatively does not reflect a change in cure rate until the level reaches nine ng/ml. The cure rates by radical prostatectomy are all the same between two and nine ng/ml,” stated Dr. Thomas A. Stanley of Stanford University in Palo Alto, California. He presented his data and conclusions to fellow urologists in a special lecture at the meetings.

Dr. Stanley looked at long-term data from 695 men with prostate cancer. As expected, among men with preoperative prostate specific antigen levels above 10 ng/ml, higher PSA levels predicted lower cure rates. But he looked specifically at those men whose PSA levels were between two and nine ng/ml. His surprising findings: the cure rate was about 80 percent across the whole range.

“PSA is a very good marker above nine ng/ml,” stated Dr. Stanley. “But something else is driving prostate specific antigen other than the cancer between two and nine”. And that something else, he reasons, is benign prostate enlargement.

“I believe our diagnosis of prostate cancer in men with a prostate specific antigen between two and nine ng/ml is pure serendipity, unrelated to morphologic variables of the cancer or to its cure rate,” says Dr. Stanley. It is well known that benign prostatic hyperplasia (BPH), a non-cancerous condition, also elevates prostate specific antigen. The researcher noted that among men with prostate cancer, PSA levels did not reflect either cancer stage or size of the tumor.

“The bottom line is that we urgently need a far better marker for prostate cancer than prostate specific antigen,” Dr. Stanley concluded.

If the findings are supported by more research, the clinical approach to treating men with prostate cancer could change: men with lower prostate specific antigen levels might be told to delay surgery “because the chance of cure should be about 80 percent until prostate specific antigen crosses the nine ng/ml threshold,” he stated.