Platinum Priority – Prostate Cancer
Editorial by Leah Gerber, Lionel L. Bañez and Stephen J. Freedland on pp. 8–9 of this issue
Outcome Predictors of Radical Prostatectomy in Patients With Prostate-Specific Antigen Greater Than 20 ng/ml: A European Multi-Institutional Study of 712 Patients

https://doi.org/10.1016/j.eururo.2010.03.001Get rights and content

Abstract

Background

Prostate cancer (PCa) patients with pretreatment prostate-specific antigen (PSA) >20 ng/ml have a high risk of biochemical and clinical failure and even cancer-related death after local therapy. Pretreatment predictors of outcome after radical prostatectomy (RP) in this patient group are necessary.

Objective

Our aim was to assess how the use of additional high-risk factors (biopsy Gleason score [bGS] ≥8 or clinical stage 3–4) can improve prediction of treatment failure and cancer-related death after RP in patients with PSA >20.

Design, setting, and participants

In a retrospective multicentre cohort study from six European centres between 1987 and 2005, 712 patients with PSA >20 ng/ml underwent RP and bilateral pelvic lymphadenectomy.

Measurements

Subgroups were analysed to determine the relationship between the number of high-risk factors and histopathology, biochemical progression-free survival, clinical evidence of progressive disease, prostate cancer–specific mortality (PCSM), and overall mortality. Kaplan-Meier analysis with log-rank test and Cox multivariable analysis were applied.

Results and limitations

Median follow-up was 77 mo. The number of high-risk factors was significantly associated with unfavourable histopathology. Among patients with only PSA >20 ng/ml, 33% had pT2 PCa, 57.9% had bGS <7, 54% had negative surgical margins, and 85% were lymph node negative (pN0), whereas among patients with all three high-risk factors, 4.5% had pT2 PCa, 2.3% had bGS <7, 20.5% had negative margins, and 49% were pN0 (p < 0.001). The strongest predictor of progression and mortality was bGS. PSA >20 ng/ml associated with bGS ≤7 resulted in 10-yr PCSM of 5%; when associated with bGS ≥8, PCSM was 35%. The main limitations of the study were retrospective design and varying treatment modalities.

Conclusions

PCa patients with PSA >20 ng/ml have varying risk levels of disease progression and PCSM. Considering additional risk factors further stratifies this group into four subgroups that can guide the clinician in preoperative patient counselling.

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.

Section snippets

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.

References (24)

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1

Martin Spahn and Steven Joniau contributed equally to this work.

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