THE "NEW" PROSTATE CANCER INFOLINK

Several years ago, it was shown that there are, in fact, three forms of free PSA (as opposed to the bound or complexed form)  in the bloodstream: B-PSA, I-PSA, and pro-PSA. B-PSA and I-PSA are reduced relative to normal levels in the blood of prostate cancer patients; by contrast the levels of pro-PSA are increased. 

In an abstract presented at the annual meeting of the American Urological Association Meeting in 2003, Catalona et al. presented early data suggesting that pro-PSA could distinguish better than other forms of PSA between cancer and benign conditions in men with PSA values from 2.5-10 ng/ml. They also suggested that pro-PSA was capable of selectively identifing the more aggressive forms of prostate cancer. These data were published in the Journal of Urology in 2004, but there has been little published on this topic since then.

Makharov et al. have now reported data on the association between quantitative clinical and pathologic information, including serum and tissue levels of pro-PSA, and outcomes among men with prostate cancer in an expectant management (active surveillance) program.

They identified 71 patients enrolled in expectant management the expectant management program for whom frozen serum and tissue was available going back to the time of their initial diagnosis. Of these 71 patients, 39 (54.9 percent) subsequently developed unfavorable biopsies (with a Gleason score ≥ 7 or ≥ 3 cores positive for cancer or >50 percent of any core involved with cancer), whereas 32 ( 45.1 percent) maintained favorable biopsies (median follow-up, 3.93 years).

The patients’ total serum PSA, free serum PSA (fPSA), and [-2]pro-PSA levels were all measured by immunoassay, and their [-5/-7]pro-PSA level was evaluated in cancer and benign-adjacent areas (BAA) by quantitative immunohistochemistry.

The results of this analysis showed the following:

• The ratio of the [-2]pro-PSA level to the % fPSA level in serum ([-2]pro-PSA/% fPSA) was significantly higher at diagnosis in men developing unfavorable biopsies(0.87 ± 0.44 pg/ml) than it was in men with continuously favorable biopsy results (0.65 ± 0.36 pg/ml).
• [-5/-7]pro-PSA tissue staining was more intense (4104.09 ± 3033.50 vs 2418.06 +/- 1606.04) and encompassed a greater fractional area (11.58 ±7.08% vs 6.88 ± 5.20%) in the BAA of these men.
• The serum [-2]proPSA/% fPSA ratio, the BAA [-5/-7]proPSA % area, and the BAA [-5/-7]proPSA stain intensitywere all significantly associated with the occurrence of unfavorable biopsy.
• The serum [-2]proPSA/% fPSA ratio correlated significantly with the BAA [-5/-7]proPSA % area and the BAA [-5/-7]pro-PSA stain intensity.

Now it will be apparent that this is a technically complex paper. However, as expressed by the authors, in their group of expectant management patients, they were able to show that serum and tissue levels of pro-PSA at diagnosis are “associated with the need for subsequent treatment.” They go on to state that the apparent increase in serum proPSA/% fPSA might be driven by increased pro-PSA production from “premalignant” cells in the prostate BAA.

It is hard to know exactly what to make of this paper. It seems as though there may be something to the potential of pro-PSA as a better means to identify patients at higher need for treatment, but on the other hand there is certainly no “ringing endorsement” based on these data. The question is going to be (as it still is with PSA velocity) whether assessment of pro-PSA levels (or some ratio based on pro-PSA levels) actually provides more accurate prognostic information than the standard PSA level at a point in time. Another paper, by Hull et al., published earlier this year, also seems to imply that the value of pro-PSA may be rather less significant that originally thought.

Filed under: Diagnosis, Management, Risk, Treatment | Tagged: pro-PSA