SEATTLE-Current screening techniques allow the early detection of prostate cancer in large numbers of men every year. The problem is that prostate cancer appears to be an almost ubiquitous malignancy in men over the age of 50. The question, then, is which patients require intervention to prevent their cancer from becoming life threatening?

Three commonly used parameters are somewhat helpful in this regard: Gleason grade, tumor volume, and extent of tumor infiltration, said Michael Brawer, MD, of the University of Washington, Seattle.

In his presentation at the Pacific Northwest Cancer Foundation Meeting on Transperineal Brachytherapy for Early Stage Prostate Cancer, Dr. Brawer noted that a number of new markers such as oncogenes and tumor microvasculariza-tion are currently being evaluated.

Histologic (Gleason) grading does work, he said, in predicting the probability of metastasis. The problem is, the majority of cancers that are detected by early screening fall into a middle ground where the picture is not so clear.

He said that tumor volume is also helpful in predicting metastatic disease and seminal vesicle invasion. But it is difficult to assess the shape and volume of a tumor by remote methods. Although transurethral ultrasound (TRUS) is helpful in visualizing the extent of the tumor outside of the capsule, it is not otherwise useful in staging the cancer. "Pathologic stage and echogenicity may indicate higher grade cancer," Dr. Brawer said, "but so far we haven't seen any difference."

Biopsy is used to determine the extent of the tumor, ie, whether the cancer is found on one side of the prostate (B1), both sides (B2), or shows extracapsular extension. The more biopsy sites that contain cancer cells, the larger the tumor volume, which worsens the prognosis.

The best combination at present for determining prostate cancer prognosis is biopsy, histological staging, and PSA values, he said.

The position of the tumor may have some predictive value, but not a great deal. "Prostate cancer likes to escape the gland along the neurovascular bundle," Dr. Brawer said. "Cancer in the apex has a preferred position for exiting, so this may be a slightly worse area to find the tumor, but this hasn't been highly predictive." He noted that DNA heterogeneity (ploidy) also has not proved to be useful.

Newer Techniques

An area that needs further study is that of neuroendocrine differentiation of the tumor, Dr. Brawer said. Apparently an increase in the subset of prostate cancer cells that express neuroendocrine markers has been correlated with an increased rate of tumor progression in some studies, but others have shown no such correlation. Expression of the oncogenes bcl-2 and p53 may also indicate greater tumor progression, but again results have been mixed.

A parameter that seems especially promising, Dr. Brawer said, is the extent of microvascularization of a particular tumor. "Tumor angiogenesis is extremely important," he said. "Once a neoplasm is greater than 1 mm in diameter, it has to induce a blood supply from the surrounding tissue."

Dr. Brawer and his colleagues have quantitated microvessel density via computer and correlated this with pathologic stage. They found that this technique yielded a significant increase in their ability to detect which cancers had progressed beyond the prostate, particularly when microvessel density was more than 120 vessels/mm.

Another technique for detecting ex-traprostatic disease that has shown good preliminary results uses reverse transcriptase PCR (polymerase chain reaction), Dr. Brawer said. The researchers used primers against PSA and prostate membrane antigen to probe for small numbers of circulating cancer cells.

"There's nothing new here," he said. "We've known cancer cells circulate. The question is, are these circulating cells able to give rise to metastases and predict a negative outcome?"

Dr. Brawer noted that the PCR technique thus far is about 72% to 88% as sensitive as PSA levels in predicting extraprostatic metastases. These are encouraging results, but he noted that further markers need to be developed to prove that those cancer cells that can be detected actually have the potential to cause metastatic malignancy.