'Extreme' prostate biopsies: Too many or not enough?

Several institutions propose new sampling methods, pain-control protocols

Anne Scheck
UT CONTRIBUTING EDITOR

Anaheim, CA-Leading urologic researchers, including several speakers at the AUA annual meeting, have issued a needle-sharp advisory to urologists who perform prostate biopsies: more samples are warranted, and they need to be taken in a single setting. You could call it-as some physicians do-a case for one-stop "extreme biopsy."

The label may sound controversial, but many highly regarded members of the field support the concept.

"But the question is, 'What is the optimal number of cores, and where should the be directed?' That's up in the air right now," said William J. Catalona, MD, of Washington University if St. Louis, who co-moderated one of the impromptu-and heated-discussions of the issue during the annual meeting.

Some of those attending the AUA sessions contributed to the exchanges, lamenting the heavy dependence on repeat biopsies to make an accurate diagnosis, as well as the significant number of missed cancers that occur when a single sextant approach is used.

'Woefully inadequate'
The current biopsy procedures, at least as practiced at some institutions, are "woefully inadequate," affirmed Dr. Catalona, professor of urologic surgery at Washington University. Those shortcomings are being defeated at Washington University by including anterior and lateral sampling, along with the traditional sextant, he said.

But some leading institutions are going a step further. Angelo DeMarzo, MD, assistant professor of pathology, urology, and oncology, Johns Hopkins University, Baltimore, asserted that even the addition of anterior and lateral biopsies may not be sufficient in some cases.

"The ultimate goal is to employ a new imaging modality that can visualize prostate cancer and direct the needle biopsies to the lesion. This is currently not possible. Therefore, if you want to pick up all of the significant cancers, you probably need to do upwards of 50 biopsies," he said. "People laugh at this, but if it was me I'd say, 'Put me under and do about 50.' The other person I know who'd want to get much more extensively sampled is another pathologist."

Dr. DeMarzo said that he would not recommend such extensive biopsying at this time but added that further research is needed to determine the appropriate number.

"We need more studies in this area to determine the optimum number to better assess the presence, extent, and grade of cancer," he said.

Dr. DeMarzo voiced concern at the AUA meeting following a presentation of results from a study showing that standard biopsy procedures miss close to 25% of cancers. The study in question, by Dr. Catalona's group at Washington University, looked at 2,527 volunteers (age 40 years or older), 962 of whom were found to have prostate cancer. The researchers found that the vast majority of cancers-77%-were detected on the first biopsy session, and by the second, the number rose to 91%, with 97% at the third (as shown in the chart above). By the fourth biopsy, 99% of all cancers had been detected. In other words, the initial biopsy missed nearly one-fourth of cancers, pointed out Kimberly Roehl, PhD, a Washington University epidemiologist who presented the findings.

"There needs to be a better way," said Dr. DeMarzo.

Saturation biopsy
Better biopsy methods have been proposed, and results with newer strategies have recently been published in peer-reviewed journals. Not surprisingly, most of the new proposals are coming from large academic centers. But many community urologists still appear reluctant to adopt a strategy that involves taking more than six samples at once, according to those interviewed by Urology Times (see, "How many biopsies are needed for proper PCa detection?" page 32).

The Mayo Clinic in Rochester, MN, has begun an approach that is becoming known as the "saturation biopsy," in which certain carefully selected patients undergo a biopsy procedure that retrieves scores of specimens-all taken in one visit-under deep-conscious sedation. (Also see, "Clinicians address pain control with multiple biopsies," page 22.) The researchers published their first set of results on 224 men who had undergone negative sextant biopsies but who had elevated PSA levels, abnormal rectal exams, or previous high-grade prostatic intraepithelial neoplasia or atypia. Cancer was detected in 77 men-about one-third of these patients. Prostatectomy was performed in 52 of these patients, and the overwhelming majority of the tumors were found to be clinically significant (1 Urol 2001; 166:86-92).

"The patients seem happy. They don't care about whether it is 20 or 30 biopsies," said Michael Lieber, MD, professor of urology at the Mayo Medical School and senior author of the study.

The men seem to appreciate the procedure in two ways: the technique has been shown to turn up cancer otherwise missed, and if none is detected, it gives them a reassuring clean bill of health, he said.

A team from Ohio State University, Columbus, has published evidence for what it calls "the extended sector biopsy," in which an additional six samples-beyond that of the typical sextant-are taken. The researchers, led by Robert Bahnson, MD, professor of surgery and director of urology at Ohio State, found that, by expanding the traditional biopsy, they detected a substanital number of cancers that otherwise would be missed. This finding caused them to speculate that one in seven such cases (13.5%) might otherwise escape dis-

"That's a substantial portion of cancers that would have been missed if we hadn't done a more extensive set of biopsies," Dr. Bahnson said.

He also pointed out that performing the extended sector biopsy offers advantages to the patient in terms of time and cost for treatment.

"One of the reasons for doing a more extensive biopsy is that there is a certain percentage of patients who we bring back for a second biopsy and do find cancer," he said. "If we can eliminate the need for a second biopsy, all the better for the patient."

In addition, urologic researchers from Stanford, who based their conclusions on a 390-patient study, have called for sextant plus transition-zone biopsies in men who have prior negative biopsies with an elevated or a rising PSA (Urology 2001; 57: 1117-20).

At the same time, investigators from Johns Hopkins assert that maximum cancer-detection rates are potentially highest by using a method that combines routine sextant and posterolateral needle biopsies (Urology 2001; 57: 1112-6).

Does the current round of research mean that additional biopsies need to be taken all at once? Not necessarily, according to a few other recent reports. This past year, under a grant from the National Cancer Institute, physicians from the departments of radiology and urology at the University of Michigan, Ann Arbor, published resuits of an investigation into the use of ultra- sound Doppler for selecting biopsy sites. The Michigan team found that ultrasound I provided a way to discriminate-at least to some extent-the cancer-positive locations from other tissue, a finding they postulate could improve the yield of current prostate biopsy methods (Urology 2:001; 57: 1128-32.).

Conflicting findings
Complicating the push for more biopsies .is the conflictual tone of some recent research. While much of the current datal suggest that current biopsy methods are over-looking a deplorable number of cancers, other studies have concluded that current approaches are adequate.

For example, a group of researchers from Vanderbilt University, Nashville, TN, found that, among 135 prostate cancer patients who had undergone radical prostatectomy, there was no advantage to increasing the number of prostate-needle biopsy cores. They divided the number of patients according to core samples taken, and found no difference in the amount of prognostic information obtained when compairing those patients in which fewer than six cores were removed and those in which more than six were taken. Their conclusion: Increasing the number of prostate needle biopsies may enhance detection, but it does not improve prognostic yield.

Dr. Catalona pointed out that there is a strong, vocal camp in medicine that considers such measures insupportable by recent evidence, such as data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Some physicians have begun citing the finding as evidence that the risk of dying from prostate cancer is considerably less than previously assumed. As a result, critics say, any increase in screening efforts, including enhanced biopsy regimens, are viewed as unnecessary.

"I can just hear some say that the use of more intensive biopsy regimens by urologists may lead to the detection of more clinical methods to follow or predict prostate cancer, aside from further refinement of the PSA test. The search has included attempts to more clearly define specific characteristics of the p53 gene in order to stratify patients (Mod Pathol2001: 14:428- 36) as well as documenting and analyzing the expression of cadherins and catenins in mRNA as a possible indicator of disease progression (UrolRes 2000; 28:308-15).

New imaging techniques and tissue-pressure measurement devices also have been getting some attention. So far, however, the PSA test remains among the most highly proven screens for detecting cancer, along with neurone-specific enolase, a marker for neuroblastomas; and CA 125, a compound associated with ovarian cancer.

Adding somc kindling to the debate, Stanford's Thomas Stamey, MD, the pioneering PSA advocate who demonstrated that the serologic marker was proportional to prostate cancer volume, now doubts its predictability, at least in a substantial number of cases. He now supports a serum marker based on Gleason 415 cancers (Urology nmes 2001; 29: 1, 30).

Meanwhile, the prostate cancer research group at Johns Hopkins has demonstrated a fairly straightforward nomogram-one that does not rest solely on PSA and its constituents. The nomogram combines PSA screening, digital rectal examination, and consideration of age (in years). Its use has been shown to increase the probability of cancer detection, compared with a single PSA cut-off ( Urology 2001 ; 57:1100-4).UT