Prostate CancerProstate-Specific Antigen Improves the Ability of Clinical Stage and Biopsy Gleason Sum to Predict the Pathologic Stage at Radical Prostatectomy in the New Millennium
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)
- et al.
A nomogram for staging of exclusive nonobturator lymph node metastases in men with localized prostate cancer
Eur Urol
(2007) - et al.
Pre-treatment nomogram for disease-specific survival of patients with chemotherapy-naive androgen independent prostate cancer
Eur Urol
(2006) - et al.
Comparison of accuracy between the Partin tables of 1997 and 2001 to predict final pathologic stage in clinically localized prostate cancer
J Urol
(2004) - et al.
Prospective validation of an algorithm with systematic sextant biopsy to predict pelvic lymph node metastasis in patients with clinically localized prostatic carcinoma
J Urol
(2002) - et al.
Pre-operative percent free PSA predicts clinical outcomes in patients treated with radical prostatectomy with total PSA levels below 10 ng/ml
Eur Urol
(2006) - et al.
Validation of a nomogram for prediction of side specific extracapsular extension at radical prostatectomy
J Urol
(2006) - et al.
The prostate specific antigen era in the United States is over for prostate cancer: what happened in the last 20 years?
J Urol
(2004) - et al.
The prostatic specific antigen era is alive and well: prostatic specific antigen and biochemical progression following radical prostatectomy
J Urol
(2005) - et al.
Preoperative serum prostate specific antigen remains a significant prognostic variable in predicting biochemical failure after radical prostatectomy
J Urol
(2006) - et al.
EAU guidelines on prostate cancer
Eur Urol
(2005)
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2008, British Journal of Medical and Surgical UrologyCitation Excerpt :It will be interesting to see over time, with stage migration, whether the UK will follow some US and Australian series where PSA was predictive only in patients with more advanced stage disease (≥pT3a) [20,21]. In other recent series PSA remains an independent predictor of cancer outcome even at levels <10 ng/ml [22,23]. The outcome categories in our series were selected as organ confined disease (pT2), extracapsular extension of tumour (pT3a), and seminal vesicle, bladder neck or lymph node involvement by prostate cancer (pT3b/pT4/N+).
PSA in the New Millennium: A Powerful Predictor of Prostate Cancer Prognosis and Radical Prostatectomy Outcomes - Results from the SEARCH Database
2008, European UrologyCitation Excerpt :Therefore, we did not have sufficient sample size to perform sub-analyses within this group to address the prognostic significance of preoperative PSA values < 4 ng/ml. Although PSA in the new millennium has been shown to help predict pathologic stage [20], to our knowledge this is the first study to examine prostate cancer progression among a cohort of men all operated on in the new millennium. It should be mentioned we have previously reported that within the SEARCH database, lower preoperative PSA values were associated with improved outcomes after radical prostatectomy among all men [6].
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Both authors contributed equally to the manuscript.