Elsevier

European Urology

Volume 52, Issue 4, October 2007, Pages 1067-1075
European Urology

Prostate Cancer
Prostate-Specific Antigen Improves the Ability of Clinical Stage and Biopsy Gleason Sum to Predict the Pathologic Stage at Radical Prostatectomy in the New Millennium

https://doi.org/10.1016/j.eururo.2007.03.018Get rights and content

Abstract

Objectives

The contemporary ability of prostate-specific antigen (PSA) to predict pathologic stage in men with localized prostate cancer was recently questioned.

Methods

We quantified the added value related to the addition of pretreatment PSA to established pathologic stage predictors (namely clinical stage and biopsy Gleason sum) in 5921 consecutive radical prostatectomy (RP) patients. Univariable and multivariable logistic regression analyses predicting pathologic stage (extracapsular extension [ECE], seminal vesicle invasion [SVI], lymph node invasion [LNI], and organ-confined disease [OC]) were stratified according to four time quartiles. The gain in predictive accuracy (PA) related to the inclusion of PSA to multivariable models was quantified by using the area under the curve method.

Results

Temporal analyses showed a decrease in PSA levels over the study years (p < 0.001). Conversely, the rate of nonpalpable disease and the rate of biopsy Gleason sum ≤6 increased over time (all p < 0.001). At RP, the rate of OC increased over time, while the rate of ECE and SVI decreased over time (all p < 0.001). The rate of LNI remained stable (p = 0.1). In multivariable models, PSA represented an independent predictor of all pathologic stages over time (all p < 0.03), except for ECE in the first and last time quartiles. The addition of PSA significantly increased the multivariable PA of all models predicting pathologic stages over time (all p < 0.03), except for ECE predictions in the first quartile (p = 0.1).

Conclusions

In the new millennium, PSA has not lost its ability to accurately predict the pathologic stage in contemporary patients.

Introduction

Along with clinical stage and biopsy Gleason sum, pretreatment prostate-specific antigen (PSA) represents one of three key determinants of prostate cancer stage. Since the late 1990s, PSA’s ability to predict pathologic stages at radical prostatectomy (RP) has been corroborated on numerous occasions. In 1997, Partin and colleagues [1] published the most widely used staging tool for men with clinically localized prostate cancer, namely the Partin tables. Within the Partin tables, PSA occupies a central role alongside biopsy Gleason sum and clinical stage. Several new models have been developed since the advent of the original Partin tables [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]. In all these, PSA plays a crucial role. Despite PSA’s central role in virtually all predictive tools, Stamey and colleagues [12] criticized the ability of PSA to distinguish between prostate cancer and benign prostatic hyperplasia (BPH). Their argument against PSA hinged on the stage shift of prostate cancer, in which an increasingly larger proportion of clinically localized prostate cancer are nonpalpable, are of low volume, and are associated with lower PSA values. Stamey et al argue that PSA is unable to accurately predict the pathologic stage, expressed as index (largest) tumor volume, in contemporary patients. Their hypothesis states that the ability of PSA to distinguish between prostate cancer and BPH gradually decreased with time.

On the basis of this criticism, we decided to assess the ability of PSA to predict Partin stages over a period of 14 yr in a large multi-institutional cohort of 5921 men treated with RP. Our analysis tested not only PSA’s multivariable ability to predict prostate cancer expressed as a p value, but also its ability to increase the predictive accuracy (PA) of multivariable models that include other established predictors, such as clinical stage and biopsy Gleason sum [13].

Section snippets

Methods

Between January 1992 and July 2005, data were prospectively collected in 5921 men treated with RP for localized prostate cancer at two European centers and one North American center. Patients with unavailable date of surgery, preoperative PSA, clinical stage, biopsy Gleason sum, or pathologic stage information (organ-confined disease [OC], extracapsular extension [ECE], seminal vesicle invasion [SVI], and lymph node invasion [LNI]), were excluded. Cohorts used for univariable and multivariable

Results

Clinical and pathologic patient characteristics are shown in Table 1. Patient age ranged from 39 to 85 yr (mean: 62.5; median: 63.1). Preoperative PSA ranged from 0.1 to 50 ng/ml (mean: 8.7; median: 6.7). The majority had clinical stage T1c (63.5%) and biopsy Gleason sum of 6 (64.4%). Overall, ECE was present in 19.7%, SVI in 11%, LNI in 4.9%, and 67.2% had OC disease.

Fig. 1 graphically displays temporal trends for PSA, clinical stage, biopsy Gleason sum, and pathologic stages. A significant

Discussion

The performance characteristics of serum PSA have been criticized [12]. The criticism stems from increasing homogeneity of contemporary prostate cancers in which the majority of patients present with low serum PSA values. This limitation of PSA range at presentation may undermine the ability of this serum marker to predict pathologic stage. On the basis of this consideration, we tested the hypothesis stating that PSA is still capable of predicting pathologic stage at RP. Our findings confirmed

Conclusions

PSA’s accuracy in prediction of pathologic stages has not decreased over time. PSA improves the PA of clinical stage and biopsy Gleason in historic as well as in contemporary patients. Moreover, stage migration, which resulted in narrowing of the range of biopsy Gleason sums and in predominance of nonpalpable disease, has not resulted in a lower accuracy of PSA when it is used to predict pathologic stages. Taken together, these results indicate that the contribution of PSA to predict disease

Conflicts of interest

Pierre I. Karakiewicz is partially supported by the Fonds de la Recherche en Santé du Québec, the CHUM Foundation, the Department of Surgery, and Les Urologues Associés du CHUM.

References (20)

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Both authors contributed equally to the manuscript.

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