Dataset Information

Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer.

ABSTRACT:

Objectives

To examine whether prostate-specific antigen doubling time (PSADT) correlates with metastases, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) and to identify PSADT thresholds that can be used clinically for risk stratification in men with M0 castration-resistant prostate cancer (CRPC).

Materials and methods

We collected data on 441 men with M0 CRPC in 2000-2015 at five Veterans Affairs hospitals. Cox models were used to test the association between log-transformed PSADT and the development of metastasis, ACM and PCSM. To identify thresholds, we categorized PSADT into 3-month groups and then combined groups with similar hazard ratios (HRs).

Results

The median (interquartile range) follow-up was 28.3 (14.7-49.1) months. As a continuous variable, PSADT was associated with metastases, ACM and PCSM (HR 1.40-1.68, all P < 0.001). We identified the following PSADT thresholds: <3 months; 3-8.9 months; 9-14. months; and ?15 months. As a categorical variable, PSADT was associated with metastases, ACM and PCSM (all P < 0.001). Specifically, PSADT <3 months was associated with an approximately ninefold increased risk of metastases (HR 8.63, 95% CI 5.07-14.7) and PCSM (HR 9.29, 95% CI 5.38-16.0), and a 4.7-fold increased risk of ACM (HR 4.71, 95% CI 2.98-7.43) on multivariable analysis compared with PSADT ?15 months. The median times to metastasis for patients with PSADT <3, 3-8.9, 9-14.9 and ?15 months were 9, 19, 40 and 50 months, respectively.

Conclusion

Prostate-specific antigen doubling time was a strong predictor of metastases, ACM and PCSM in patients with M0 CRPC. As with patients at earlier disease stages, <3, 3-8.9, 9-14.9 and ?15 months are reasonable PSADT thresholds for risk stratification in men with M0 CRPC. These thresholds can be used for selecting high-risk men for clinical trials.

SUBMITTER: Howard LE

PROVIDER: S-EPMC5617753 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Publications

Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer.

Howard Lauren E LE Moreira Daniel M DM De Hoedt Amanda A Aronson William J WJ Kane Christopher J CJ Amling Christopher L CL Cooperberg Matthew R MR Terris Martha K MK Freedland Stephen J SJ

BJU international 20170430 5B

<h4>Objectives</h4>To examine whether prostate-specific antigen doubling time (PSADT) correlates with metastases, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) and to identify PSADT thresholds that can be used clinically for risk stratification in men with M0 castration-resistant prostate cancer (CRPC).<h4>Materials and methods</h4>We collected data on 441 men with M0 CRPC in 2000-2015 at five Veterans Affairs hospitals. Cox models were used to test the association bet ...[more]

PMID: 28371163

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Project description:Exposure measurement error is a pervasive problem for epidemiology research projects designed to provide valid and precise statistical evidence supporting postulated exposure-disease relationships of interest. The purpose of this commentary is to highlight an important real-life example of this exposure measurement error problem and to provide a simple and useful diagnostic tool for physicians and their patients that corrects for the exposure measurement error. More specifically, prostate-specific antigen doubling time (PSADT) is a widely used measure for guiding future treatment options for patients with biochemically recurrent prostate cancer. Numerous papers have been published claiming that a low calculated PSADT value (denoted PSADT^) is predictive of metastasis and premature death from prostate cancer. Unfortunately, none of these papers have adjusted for the measurement error in PSADT^, an estimator that is typically computed using the popular Memorial Sloan Kettering website very often visited by both physicians and their patients. For this website, the estimator PSADT^ of the true (but unknown) PSADT for a patient (denoted PSADT∗) is computed as the natural log of 2 (i.e., 0.6931) divided by the estimated slope of the straight-line regression of the natural log of PSA (in ng/mL) on time. We utilize PSADT^ to derive an expression for the probability that the unknown PSADT∗ for a patient is below a specified value C (>0) of concern to both the physician and the patient. This probability is easy to interpret and takes into account the fact that PSADT^ is a statistical estimator with variability. This variability introduces measurement error, namely, the difference between a computed value PSADT^ and the true, but unknown, value PSADT∗. We have developed an Excel calculator that, once the [time, ln(PSA)] values are entered, outputs both the value of PSADT^ and the desired probability. In addition, we discuss problematic statistical issues attendant with PSADT∗ estimation typically based on at most three or four PSA values. We strongly recommend the use of this probability when physicians are discussing PSADT^ values and associated treatment options with their patients. And, we stress that future epidemiology research projects involving PSA doubling time should take into account the measurement error problem highlighted in this Commentary.

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Dataset Information

Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer.

Objectives

Materials and methods

Results

Conclusion

Publications

Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer.

Similar Datasets

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