Elsevier

Urology

Volume 80, Issue 6, December 2012, Pages 1319-1327
Urology

Oncology
NADiA ProsVue Prostate-specific Antigen Slope Is an Independent Prognostic Marker for Identifying Men at Reduced Risk of Clinical Recurrence of Prostate Cancer After Radical Prostatectomy

https://doi.org/10.1016/j.urology.2012.06.080Get rights and content

Objective

To validate the hypothesis that men displaying serum prostate-specific antigen (PSA) slopes ≤2.0 pg/mL/mo after prostatectomy, measured using a new immuno-polymerase chain reaction diagnostic test (NADiA ProsVue), have a reduced risk of clinical recurrence as determined by positive biopsy, imaging findings, or death from prostate cancer.

Materials and Methods

From 4 clinical sites, we selected a cohort of 304 men who had been followed up for 17.6 years after prostatectomy for clinical recurrence. We assessed the prognostic value of a PSA slope cutpoint of 2.0 pg/mL/mo against established risk factors to identify men at low risk of clinical recurrence using uni- and multivariate Cox proportional hazards regression and Kaplan-Meier analyses.

Results

The univariate hazard ratio of a PSA slope >2.0 pg/mL/mo was 18.3 (95% confidence interval 10.6-31.8) compared with a slope ≤2.0 pg/mL/mo (P <.0001). The median disease-free survival interval was 4.8 years vs >10 years in the 2 groups (P <.0001). The multivariate hazard ratio for PSA slope with the covariates of preprostatectomy PSA, pathologic stage, and Gleason score was 9.8 (95% confidence interval 5.4-17.8), an 89.8% risk reduction for men with PSA slopes ≤2.0 pg/mL/mo (P <.0001). The Gleason score (<7 vs ≥7) was the only other significant predictor (hazard ratio 5.4, 95% confidence interval 2.1-13.8, P = .0004).

Conclusion

Clinical recurrence after radical prostatectomy is difficult to predict using established risk factors. We have demonstrated that a NADiA ProsVue PSA slope of ≤2.0 pg/mL/mo after prostatectomy is prognostic for a reduced risk of prostate cancer recurrence and adds predictive power to the established risk factors.

Section snippets

Study Design

The required sample size was determined to be 262, assuming a type I error rate of 5%, 80% power, and a univariate hazard ratio (HR) for a PSA slope of 1.4 (as estimated from pilot studies) using a 2-sided test. Assuming a 20% prevalence for recurrence, a minimum of 52 men with recurrence was required. A cohort random sampling of eligible men was performed within 4 strata arising from categorization of older than or younger than the median patient age (61.4 years) and median sample storage time

Study Population

The patient characteristics are listed in Table 1. For discrete covariates, category frequencies are provided, and for continuously valued covariates, the mean, median, and interquartile ranges (IQRs) are given. Overall, 56.1% of men had organ-confined disease, and 3% had evidence of nodal spread. Also, 46% had a Gleason score of ≤6 and 76.6% had a PSA value of ≤10 ng/mL at RP. Comparing the recurrent and nonrecurrent groups, the pre-RP PSA level, tumor volume, presence of stage pT3-pT4

Comment

Prostate cancer is a complex disease, and it has proved difficult to predict the clinical outcome accurately in individual men after RP.8 Previous studies have linked undetectable PSA levels of <0.01 ng/mL (<10 pg/mL) after RP to biochemical relapse-free survival12 and nadir values to a lower likelihood of BCR.14 However, the risk of BCR is not informative as a predictor of clinical endpoints because of the unpredictable kinetics of post-RP PSA values after a BCR event occurs.19, 20, 21, 22, 23

Conclusion

This is the first study of a prognostic assay for risk stratification of clinical prostate cancer recurrence with >10 years of median follow-up. NADiA ProsVue is also the first assay based on the linear slope of tumor marker concentrations over time to receive Food and Drug Administration clearance. A ProsVue result was the most powerful indicator of a reduced risk of clinical recurrence and added prognostic value to established risk factors. ProsVue testing could possibly reduce healthcare

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    Financial Disclosure: Hans Lilja holds patents for free PSA, intact PSA, and hK2 assays and has stock or other ownership interests in Arctic Partners; Mark J. Sarno is a consultant to IRIS International, Inc.; Barbara Stevens is a consultant of IRIS International, Inc.; Robert E. Klem is employed by IRIS International, Inc. and has stock in IRIS International, Inc.; Jonathan E. McDermed is employed by IRIS International, Inc. and has stock in IRIS International, Inc.; Melissa T. Triebell is employed by IRIS International, Inc. and has stock in IRIS International, Inc.; Thomas H. Adams is Chief Technology Officer for, and has stock in, IRIS International, Inc.; remaining authors have no disclosures.

    Funding Support: Patient samples from the University of Washington were collected in part using funding from the National Institutes of Health NW Prostate Cancer SPORE (grant CA-097186) and National Institutes of Health PO1 (grant CA-085859). Funding support to Memorial Sloan-Kettering Cancer Center was provided in part from the National Cancer Institute (grant P50-CA92629); Sidney Kimmel Center for Prostate and Urologic Cancers; David H. Koch through the Prostate Cancer Foundation.

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