Dr. Catalona – Quest – Spring 2010
Dr. Catalona wishes to keep his patients and research participants updated on the findings of his prostate cancer research group by providing brief lay summaries in QUEST.
These summaries are from studies prepared by Dr. Catalona and his research collaborators for presentation at annual meetings of the American Urological Association (AUA), which is the world’s largest meeting of urologic professionals.
Some of the information has practical applications now. Some of these findings will need to be replicated by other researchers before being applied in clinical settings.
Some show beginning research with exploration or new understanding as the main purpose, and hopefully, practical applications will follow.
Surely, though, this research will help define how prostate cancer is diagnosed, treated and hopefully prevented in generations to come.
How Long Do Men Need Pads After a Radical Retropubic Prostatectomy (RRP)?
Aprime concern of men considering a RRP is how long they are likely to require pads for urinary incontinence after surgery.
Patients (Catalona) in our study of 335 were a median age of 59 and 90% had organ-confined disease in their radical prostatectomy specimen.
We define continence as requiring “no pads” or other protection to keep clothing dry.
With respect to continence: 14% never wore pads; 50% were continent one month after surgery; 63% by two months; 75% by 3 months; 84% by six months; 86% by nine months; 89% by 12 months; and 90% by 18 months.
Among the 10% who did not become pad free in the 18-month follow-up, 6.5% required a “precautionary” pad for rare leakage of a few drops of urine; 1.8% reported mild stress incontinence; and 0.6% had severe stress incontinence. No patient required artificial urinary sphincter implantation.
In summary, three-fourths of patients no longer required pads after less than 3 months and 90% required no pads by 18 months.
Previous studies from other institutions find a connection between continence after a radical prostatectomy and the surgeon’s experience regarding number and frequency of surgeries.
It is reasonable to ask surgeons how many and how often they perform radical prostatectomy and to request their patients’ continence rates after the operation.
Using Genetic Information to Detect CaP in Men with “Normal” PSA and DRE
Several reports suggest that a combintion of genetic prostate cancer (CaP) variants may independently predict CaP risk and tumor features. However, the ability to detect CaP in patients with a “normal” PSA and nonsuspicious digital rectal examination (DRE) remains to be determined.
It would be reasonable to ask why a man with a “normal” PSA and a nonsuspicious DRE would or should be concerned about having prostate cancer.
The response is that a substantial proportion of biopsy-detected CaP occurs in men with PSA levels lower than 4 ng/mL and a non-suspicious DRE.
We found that in this population, genetic risk variants are significantly associated with prostate cancer risk and may guide in the prediction of aggressive disease.
Future studies are needed to determine the usefulness of incorporating genetic risk factors into prostate cancer screening programs.
Associating Prostate Cancer Aggressiveness With New Genetic Research Findings
Genome-wide association studies (GWAS) have identified numerous common risk alleles that are associated with prostate cancer (CaP) susceptibility.
Recently, six additional genetic susceptibility variants (along chromosomes 3, 5, 8, 11 and 19) were identified, but little is known about the relationship of these risk alleles with tumor aggressiveness.
Knowing whether prostate cancer tumors are slow growing or aggressive is important but not predictable at the present time. We would very much like to be able to predict tumor aggressiveness from looking at a man’s genetic make-up because it would affect treatment options and treatment decisions.
In our study of 938 RP patients (Catalona), we determined the genotypes for genetic variants among these newly identified areas. We compared pathology tumor features between those who carried these risk alleles and those who did not.
What we found is that the newly described prostate cancer susceptibility alleles on chromosomes 3q21, 8q24, and 19q13 were significantly associated with specific adverse patholody features.
The other risk alleles (genetic markers) had no apparent association with tumor aggressiveness.
Because being able to predict tumor aggressiveness is so important, further study into the combined contribution of genetic variants to the prediction of prostate cancer prognosis is warranted.
Use of PSA Derivatives to Determine the Need for Repeat Biopsy
When men have an initial negative prostate biopsy, the decision on when and/or whether to repeat biopsy is not standard.
The 1010 NCCN Guidelines (National Comprehensive Cancer Network) recommend the use of PSA derivatives to evaluate the need for repeat biopsy.
Our study looked at how, or if, PSA derivatives – %Free PSA, PSA velocity (PSAV) and PSA density(PSAD) – could be useful in assigning risk of possible prostate cancer detection with more biopsies.
(More information about these derivatives is on our website: www.drcatalona.com)
What we found is that PSA derivatives are useful for identifying risk following an initial negative prostate biopsy.
Men with a % free PSA less than 10; with a PSAD more than 0.10; and PSAV greater than 0.35 ng/mL/year are at significantly greater risk of subsequent prostate cancer detection.
This information could help with the recommendation for when or whether to repeat a negative biopsy.
How Long Can Surgery Be Delayed in Men with Low-Risk Prostate Cancer?
With increased acceptance of active surveillance for lowrisk prostate cancer (CaP), patients often ask how long is it safe to delay treatment.
To further evaluate the effect of delay on treatment outcomes, we compared the outcomes between patients with low-risk prostate cancer who delayed treatment for more than 6 months versus those who did not delay treatment.
Of the 331 men (Catalona), 21 patients delayed treatment for more than 6 months.
Patients with delayed treatment had a lower rate of organ-confined disease, a significantly greater proportion with high-grade disease in the prostatectomy specimen, and a higher rate of recurrence.
In some patients with low-risk prostate cancer, a 6-month delay in treatment might compromise pathology outcomes and recurrence-free survival.
This study addressed the question of delaying surgery but has clear implications for potential consequences of “watchful waiting,” referred to as “wishful waiting” by Dr. Catalona in a previous QUEST article.