© The Author 2007. Published by Oxford University Press.
CORRESPONDENCE |
Re: Detection of Life-Threatening Prostate Cancer With Prostate-Specific Antigen Velocity During a Window of Curability
Affiliations of authors: Fred Hutchinson Cancer Research Center, Program in Biostatistics, Seattle, WA (RDE); Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX (DPA, IMT)
Correspondence to: Ian M. Thompson, MD, Department of Urology, University of Texas Health Science Center at San Antonio, MC 7845, 7703 Floyd Curl, San Antonio, TX 78229-3900 (e-mail: thompsoni{at}uthscsa.edu).
Carter et al. (1) suggest that prostate-specific antigen velocity (PSAV, change in PSA over a defined interval) is a useful measure to detect life-threatening prostate cancer during a window of curability 10–15 years before diagnosis. They recommend that a PSAV greater than 0.35 ng/mL per year should be used to refer men with a PSA concentration less than 4.0 ng/mL for biopsy. This recommendation is based on two findings in their study: 1) a nearly fourfold increase in the hazard ratio for prostate cancer mortality associated with a unit increase in PSAV and 2) an area under the receiver operating characteristics curve for PSAV of 0.75 compared with 0.74 for PSA.
The recommendation that PSAV be used as a trigger for biopsy runs counter to the evidence from a variety of large prospective and retrospective studies, including our own (2). We found that after taking the level of PSA into account, the hazard ratio for PSAV either dropped to marginal or statistically nonsignificant (close to 1.0) or flips direction (<1.0), implying a decreased risk of prostate cancer for higher velocity.
PSAV, PSA density (PSA divided by volume of the prostate), and complexed PSA concentration are some of the PSA-related markers that have been proposed as providing more useful information than PSA concentration; however, all face the challenges that they correlate highly with PSA and are harder to measure. The correlation between PSA and PSAV was .70 in the Carter et al. study, so the incremental information provided by PSAV is questionable. Studies assessing independent prognostic information of markers should provide adjusted hazard ratios for both markers and should put both markers on the same scale (continuous or dichotomized at a cut point) for a fair and equally powerful comparison. Moreover, PSAV is both more subjective and difficult to standardize than PSA. To truly assess whether a change in PSA concentration of 0.35 ng/mL per year improves detection, even in men who have low (
4 ng/mL) PSA concentrations, the sensitivity, specificity, and positive predictive value of the test at this threshold should be assessed and compared with tests using only PSA concentrations, which was not done in the study by Carter et al.
We have shown (3) that even among men who have PSA concentrations less than 4.0 ng/mL, risk of prostate cancer and of high-grade disease are on a continuum with PSA concentration; thus, no threshold exists that simultaneously achieves sufficiently high sensitivity and specificity for superior performance of this screening test. Without the sensitivity and specificity table for PSAV, and based on only 20 prostate cancer deaths, we cannot infer that any specific PSAV threshold provides incremental value in detection of disease, whether potentially fatal or otherwise.
REFERENCES
(1) Carter HB, Ferrucci L, Kettermann A, Landis P, Wright EJ, Epstein JI, et al. (2006) Detection of life-threatening prostate cancer with prostate-specific antigen velocity during a window of curability. J Natl Cancer Inst 98:1521–7.
(2) Thompson IM, Ankerst DP, Chi C, Goodman PJ, Tangen CM, Lucia MS, et al. (2006) Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial. J Natl Cancer Inst 98:529–34.
(3) Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, et al. (2004) Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med 350:2239–46.
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J Natl Cancer Inst 2007 99: 490.
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  H. B. Carter, L. Ferrucci, A. Kettermann, P. Landis, J. Wright, J. I. Epstein, B. J. Trock, and E. J. Metter Response: Re: Detection of Life-Threatening Prostate Cancer With Prostate-Specific Antigen Velocity During a Window of Curability J Natl Cancer Inst, March 21, 2007; 99(6): 490 - 490. [Full Text] [PDF]
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