In patients with prostate cancer, measures of PSA kinetics are proving to be accurate predictors of outcomes as well as treatment efficacy in those patients who are receiving systemic therapy. This, along with reports about the use of traditional and nontraditional agents for slowing the progression of PSA rise and the effects of androgen deprivation on bone, headed the key take-home messages in advanced prostate cancer presented at this year's AUA annual meeting.
PSA kinetics calculations are replacing absolute PSA levels as more meaningful and predictive estimates of outcomes; specifically, the most meaningful outcome of prostate cancer death.
Researchers from Northwestern University, Chicago, reported an increase in prostate cancer death among patients with a pretreatment PSA velocity of greater than 2.0 ng/mL in the year preceding definitive external beam radiation. This affirmed a prior database analysis that demonstrated the same predictive role of a 2.0-ng/mL PSA rise in the year preceding radical prostatectomy.
A PSA failure study from Johns Hopkins, Baltimore, used PSA doubling time intervals (<3 months, 3 to 8 months, 9 to 14.5 months, and >15 months) combined with Gleason grade (≤8 vs. >8) and time to failure after surgery (≤3 years vs. >3 years) to establish prostate cancer mortality risks ranging from <1% to 94% during a 15-year follow-up interval after biochemical failure. For patients with high-risk profiles, clinical trials applying aggressive therapies are appropriate to explore quality of life and survival benefits. Patients with low-risk profiles may be followed without immediate intervention.
In addition to PSA doubling time, other parameters that might point to treatment efficacy include depth of PSA nadir, PSA nadir response duration, and PSA half-time response.
As noted, biochemical failure and myriad available treatment options present a dilemma for the physician and the patient. Favorable alteration of PSA kinetics presumes, but as yet does not prove delay in disease progression. Pharmaceutical or "natural" agents provide attractive strategies to reverse or slow the progression of PSA rise.
The COX-2 inhibitor celecoxib (Celebrex) was employed in a study from the University of North Carolina, Chapel Hill. It was administered in doses ranging from 400 to 800 mg per day to 40 patients with rising PSA (32 patients after radical prostatectomy and eight after external beam radiation). Of these patients, 11 showed falling PSA and eight showed PSA stabilization. Significantly, at 1-year follow-up, all but one of 19 patients with rapid PSA doubling times (6 to 12 months) experienced lengthened doubling times.
Pomegranate juice is available at health food stores and, although somewhat cloying, is quite palatable. In a study of 48 patients by UCLA researchers, 8 ounces of pomegranate juice daily significantly lengthened PSA doubling time from 14 months to 26 months (p<.048). In addition, the serum of these patients decreased in vitro proliferation of LNCAP cells. Polyphenols, which pomegranate juice contains in abundance, were measurable in patients' urine. While celecoxib carries the issue of expense and the potential worry of cardiac events associated as a class effect with the nonsteroidal COX-2 inhibitors, pomegranate juice provides an inexpensive, side-effect-free approach to reversing or forestalling a rising PSA profile.
Previously noted was evidence that PSA doubling time is a marker for disease progression, morbidity, and mortality. Intuitively, lengthened PSA doubling time promises to delay these outcomes. Time will tell if these and other strategies will play a role in the paradigm to convert prostate cancer to a chronic disease with lessened morbidity and lower mortality.