Platinum Priority – Prostate CancerEditorial by Leah Gerber, Lionel L. Bañez and Stephen J. Freedland on pp. 8–9 of this issueOutcome Predictors of Radical Prostatectomy in Patients With Prostate-Specific Antigen Greater Than 20 ng/ml: A European Multi-Institutional Study of 712 Patients
Introduction
There is no consensus about the optimal treatment of the 20–35% of prostate cancer (PCa) patients classified as high risk based on the presence of prostate-specific antigen (PSA) >20 ng/ml, biopsy Gleason score (bGS) ≥8, or an advanced clinical stage [1]. Androgen-deprivation therapy (ADT) plus external-beam radiation therapy (EBRT) are most often recommended by urologists and, despite little data to support any particular treatment option, only about 36% of high-risk cases are initially treated with radical prostatectomy (RP) [2].
Initial PSA has long been recognised as an important risk indicator. D’Amico et al defined high-risk PCa as stage T2c or greater or PSA >20 ng/ml or Gleason score (GS) 8–10; the National Comprehensive Cancer Network and European Association of Urology guidelines use stage T3 or greater or PSA >20 ng/ml or GS 8–10 [3], [4], [5], [6], [7].
Yossepowitch et al recently demonstrated that the 10-yr prostate cancer–specific mortality (PCSM) was 9% in patients with a PSA >20 ng/ml, compared with only 3% in those with PSA ≤20 ng/ml (hazard ratio: 3.4; 95% confidence interval [CI], 2.3–5.4) [8]. Similarly, Stephenson et al found that the 15-yr PCSM was 22% in patients with PSA of 20.1–50 ng/ml and 4–11% in those with PSA <20 ng/ml [9]. These data suggest that a PSA >20 ng/ml may indeed be considered a high-risk factor.
Classifying patients as high risk on the basis of a PSA >20 ng/ml alone is questionable because it does not consider the total number of risk factors. The only study with a validated nomogram allowing personalised predictions of death from PCa in this specific risk group is that of Stephenson et al. [9].
The aim of this study was to identify pretreatment outcome predictors in a large cohort of PCa patients with a PSA >20 ng/ml and to provide an easy-to-use risk substratification using the cumulative number of high-risk factors.
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Patient population
We identified 712 men with a preoperative PSA level >20 ng/ml who had undergone RP between 1987 and 2005. At all six centres, clinical stage was assigned according to the 2002 TNM system, prostate biopsy cores were obtained under transrectal-ultrasound guidance, and pretreatment PSA was measured before digital rectal examination (DRE) or prostate ultrasound (US). Biopsy and pathologic grading was assessed according to the Gleason grading system by dedicated genitourinary pathologists. All
Results
There were 345 patients (48.5%) in risk group 1, 227 in risk group 2 (31.9%), 52 in risk group 3 (7.3%), and 88 in risk group 4 (12.4%). BP was known for 684 patients (96.1%) and CF for 581 patients (81.5%), while PCSM and overall mortality were known for all patients.
Discussion
Currently, urologists face the dilemma of how to treat PCa patients with PSA >20 ng/ml; ADT, radiotherapy (RT), RP, or a combined therapeutic approach have all been proposed [12], [13], [14], [15], [16], and most patients undergo ADT plus EBRT [2], [17].
Conclusions
PCa patients with PSA >20 ng/ml are a heterogeneous group. An elevated PSA in isolation is not sufficient to define a patient as high risk. Considering PSA, clinical stage, and GS allows us to distinguish four risk groups to select the most appropriate treatment.
A higher number of risk factors at diagnosis is significantly correlated to unfavourable pathology, clinical progression, and PCSM. Men with PSA >20 ng/ml and GS ≤7 are at minimal risk for PCSM, so they are good candidates for surgery.
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Martin Spahn and Steven Joniau contributed equally to this work.