NEW YORK (Reuters Health) – Mounting evidence suggests that preoperative prostate specific antigen (PSA) kinetics are a poor marker of disease progression.
During active surveillance for low-risk, low-volume prostate cancer, instead of relying on PSA doubling time or velocity, “careful follow-up with annual surveillance biopsy to trigger intervention within the window of curability” is preferable, the authors of a recent study say.
Dr. Ashley E. Ross, from Johns Hopkins in Baltimore, and associates evaluated 290 men who opted for active surveillance of their prostate cancer (diagnosed between 1994 and 2008). At baseline, each had a PSA density < 0.15 ng/mL/cm3 and a Gleason score of 6 or less. The men received twice-yearly digital rectal exams and PSA measurements and annual surveillance biopsy. The timing of treatment initiation was based on biopsy progression.
At a median follow-up of 2.9 years, 102 (35%) had had biopsy proven disease progression.
There was a nonsignificant trend toward a higher PSA velocity in patients with progression (p = 0.06), but PSA doubling time was similar in men whose disease did and did not progress (p = 0.83).
No cut point for either PSA velocity or doubling time “provided both high sensitivity and specificity to correctly classify those with and without adverse histology on repeat biopsy,” Dr. Ross and colleagues report.
Biopsy progression rates were similar with PSA levels above or below 4 ng/mL. Forty-five men had radical prostatectomy; neither PSA velocity nor doubling time was linked with unfavorable surgical pathology.
The authors conclude that postdiagnostic PSA kinetics do not reliably predict adverse pathology and should not be used to replace annual surveillance biopsy” in these patients.
“The results of this study are somewhat unexpected in light of the existing (prostate cancer) literature,” Dr. Jared M. Whitson and Dr. Peter R. Carroll, from the University of California San Francisco, write in an editorial. For example, in other studies of men undergoing treatment an elevated PSA velocity predicts prostate cancer-specific mortality.
They blame selection bias for their finding, and note that Dr. Ross and associates did not perform multivariable analysis to at least limit confounding.
But in a study published in the May issue of the Journal of Urology, a separate team reported a somewhat similar finding regarding preoperative PSA doubling times. Specifically, the other team found, PSA doubling time as measured before radical prostatectomy does not predict biochemical progression after surgery (see Reuters Health story, Apr 15 2010).
The senior author of that study told Reuters Health that PSA doubling time is a relative change, useful for assessing prognosis "only among men who begin with the same initial PSA level." It's not a good parameter for assessing the aggressiveness of prostate cancer in men with newly diagnosed, untreated prostate cancer, he said.
J Clin Oncol 2010.