By Laszlo Dosa
ORLANDO—The value of the prostate-specific antigen (PSA) test in the diagnosis of prostate cancer (PC) has been in question often in the past. Recent advances may offer help and preserve the value of the PSA. A gene-based assay of high specificity and sensitivity has been shown helpful in the diagnosis of suspected PC in men with elevated PSA and a negative biopsy, according to data presented at the 2005 Multidisciplinary Prostate Cancer Symposium, which was sponsored by the American Society of Clinical Oncology.
The test, called uPM3 (Bostwick), simultaneously detects the RNA expression of the PCA3 gene, which is only produced by the prostate tissue. PCA3 is 70 times more abundant in cancerous tissue than in benign tissue and may therefore be a new marker for PC.
“The concept is that with this marker and sensitive technology, which is nucleic acid amplification that multiplies 1-million-fold the signal, we could detect the presence of this rare cancer cell,” said Yves Fradet, MD, of Laval University, Quebec City. With the help of a digital rectal examination (DRE) of the prostate, and then palpating the area to push the cells into the urethra, the cell is shed into the urine, and a sample can then be collected from the next voided urine.
In a previous study (Urol. 2004;64:311-315) by Dr Fradet and colleagues, 517 patients at 5 different sites who were about to undergo a transrectal ultrasonography of the prostate (TRUSP) first underwent the uPM3 test, which showed that the uPM3 led to a correct positive or negative result for the presence of PC in 81% of cases. “The test was done before that [the TRUSP] and the result of the biopsy was used as the gold standard,” said Dr Fradet, who is associated with GenProbe, the company that makes the gene-based assay. Of the 443 evaluable samples that were taken, the test showed a 90% specificity and 70% sensitivity to detect cancer.
The specificity and predictive value of the test were high even in the 91 men who had normal PSA values and negative biopsies. Because of the limited number of patients, if the test is positive, the probability of cancer would be about 75%, in which case the patient should undergo further biopsy, Dr Fradet said.
At the meeting, Joseph C. Presti Jr, MD, of Stanford University School of Medicine, and colleagues presented data showing that extended-core or needle-biopsy modalities increase cancer detection rates. The increasing use of extended-core biopsies, which typically involve 10 to 12 cores from the prostate, in the past several years has improved the PC detection rate in the United States.
“It also shows that PSA is not as bad a test as we thought. It used to be that in a normal digital rectal exam with a PSA between 4 and 10, or if you did a biopsy of that prostate, you found cancer about 25% of the time. Now if we do an extended-core biopsy on a patient who has a PSA value between 4 and 10 and a normal digital exam, 40% of the men [will have] cancer,” said Dr Presti. “So PSA has a positive predictive value. It’s 40%, if the PSA value is between 4 and 10.”
Although some of Dr Presti’s patients presented with an abnormality on their DRE, the majority had just a slight elevation of their PSA test. However, false-positive PSA results still occur, he noted. If a normal DRE and a PSA between 4 and 10 show that 40% of the men have cancer, that means that 60% do not have cancer. “We use the core exam to determine the presence of cancer. The needle biopsy is the gold standard to determine whether or not cancer is present,” he added.