PROSTATE SPECIFIC ANTIGEN VARIATION AND NO CLINICALLY EVIDENT PROSTATE CANCER 1313

measurements and changes (time adjusted or not) in PSA values, as opposed to Carter et a1.6 Of note, any comparison between “short” and “long” intervals should be interpreted with caution, because intervals were long, with most ranging from 2 to 5 years. This difference could explain the discrep- ancies between our study and that of Carter et al. On the other hand, a third PSA sample reduced substantially the variability in almost all indexes except for coefficient of vari- ation which showed only a nearly significant trend. This last point is consistent with the findings of Carter et a1.6 Thus, PSA changes depend more on the number of samples rather than the time between measurements when long sampling intervals are provided. This within individual variability, which is high with only 2 and reduced when a third meas- urement is considered, could be explained by some individual benign conditions that are not time dependent (sudden ap- pearing and self-limited), such as prostatitis, infarct, reten- tion and so forth.

CONCLUSIONS

PSA velocity is within normal limits in more than 95% of men without clinically relevant prostate cancer. When long intervals between measurements are provided, PSA individ- ual variability is not fully dependent on the time elapsed. Long-term within individual variability can be high and per- haps be explained due to benign and self-limited conditions other than prostate cancer. It can be substantially decreased with a third PSA sample.

REFERENCES

1. Chan, D. W., Bruzek, D. J., Oesterling, J . E., Rock, R. C. and Walsh, P. C.: Prostate-specific antigen as a marker for pros- tate cancer: a monoclonal and polyclonal immunoassay com- pared. Clin. Chem., 33 1916, 1987.

2. Lilja, H.: Significance of different molecular forms of serum PSA. The free, noncomplexed form of PSA versus that complexed to alpha 1-antichymotrypsin. Urol. Clin. N. Amer., 2 0 681,1993.

3. Oesterling, J. E., Jacobsen, S. J., Chute, C. G., Guess, H. A,, Girman, C. J., Panser, L. A. and Lieber, M. M.: Serum prostate-specific antigen in a community-based population of healthy men: establishment of age-specific reference ranges. J.A.M.A., 2 7 0 860, 1993.

4. Benson, M. C., Whang, I. S., Olsson, C. A,, McMahon, D. J. and Cooner, W. H.: Use of prostate specific antigen density to enhance the predictive value of intermediate levels of prostate specific antigen. J. Urol., 147: 817, 1992.

5. Carter, H. B., Pearson, J. D., Metter, J . E., Brant, L. J., Chan, D. W., Andres, R., Fozard, L. and Walsh, P. C.: Longitudinal evaluation of prostate-specific antigen levels in men with and without Drostate disease. J.A.M.A., 267: 2215, 1992.

D. W., Guess, H. A. and Walsh, P. C.: Prostate-specific antigen variability in men without prostate cancer: effect of sampling interval on prostate-specific antigen velocity. Urology, 4 5 591, 1995.

7. Riehmann, M., Rhodes, P. R., Cook, T. D., Grose, S. and Bruskewitz, R. C.: Analysis of variation in prostate-specific antigen values. Urology, 42: 390. 1993.

8. Prestigiacomo, A. F. and Stamey, T. A,: Physiological variation of serum prostate specific antigen in the 4.0 to 10.0 nglml. range in male volunteers. J . Urol., 155 1977, 1996.

9. Kadmon, D., Weinberg, D., Williams, R. H., Pavlik, V. N., Cooper, P. and Migliore, P. J.: Pitfalls in interpreting prostate specific antigen velocity. J . Urol., 155 1655, 1996.

EDITORIAL COMMENT

The authors evaluated the within individual variability of PSA among men without evidence of prostate cancer from a screening study. There are several important points with regard to clinical practice. There is substantial variability between PSA meas- urements from the same individual as shown by the coefficient of variation (mean, 95% CI) in table 2. It has previously been shown that this variability or deviation between measurements is similar when PSA is sampled at 3-month or 2-year intervals (reference 6 in article). This variability in PSA can be adjusted for the time between measurements to derive PSA velocity (ng./ml. per year), a method of considering the within individual PSA variability. In the present study 95% of the population thought to be cancer-free had a PSA velocity of 0.6 ng./ml. per year or less with an average time between PSA measurements of 1.8 years (table 2).

In a case control study of men with and without prostate cancer we found that the average PSA velocity for 3 measurements was pre- dictive of cancer (reference 5 in article). In that study PSA velocity was less than 0.75 ng./ml. per year in 95% of the men without prostate cancer and 0.75 ng./ml. per year or more in 72%, of those with cancer. Others (present study, references 6 and 9 in article) have also noted that when changes in PSA are adjusted for long periods (2 or more years), 9 5 8 or more of men without prostate cancer have PSA velocities less than 0.75 nglml. per year. Thus, if a man has a 2-year PSA history with an average PSA velocity of 0.75 ng./ml. per year or more based on 3 PSA measurements, it is not likely that this rate of change in PSA is caused by benign disease. A PSA velocity of less than 0.75 ng./ml. per year does not exclude the presence of significant cancer. Early diagnosis of prostate cancer involves assessing the risk that cancer is present and recommending further evaluation when appropriate. In an era when men commonly have PSA histories spanning many years and often a history of negative biopsies, PSA velocity is a method of assessing the risk that cancer is present, with age, family history, race, PSA density and free PSA.

H. Ballentine Carter Department of Urology The Johns HoDkins HosDital

6. Carter, H. B., Pearson, J . D., Waclawiw, Z., Metter, E. J., Chan, Baltimore, Mdryland .