Platinum Priority – Prostate Cancer
Editorial by Anthony V. DAmico on pp. 903–904 of this issue

A New Risk Classification System for Therapeutic Decision Making with Intermediate-risk Prostate Cancer Patients Undergoing Dose-escalated External-beam Radiation Therapy eulogo1

By: Zachary S. Zumsteg a , Daniel E. Spratt a , Isaac Pei a , Zhigang Zhang b , Yoshiya Yamada a , Marisa Kollmeier a and Michael J. Zelefsky a

European Urology, Volume 64 Issue 6, December 2013, Pages 895-902

Published online: 01 December 2013

Keywords: Prostate cancer, Intermediate risk, Dose escalation, Androgen deprivation, Risk stratification

Abstract Full Text Full Text PDF (889 KB)



The management of intermediate-risk prostate cancer (PCa) is controversial, in part due to the heterogeneous nature of patients falling within this classification.


We propose a new risk stratification system for intermediate-risk PCa to aid in prognosis and therapeutic decision making.

Design, setting, and participants

Between 1992 and 2007, 1024 patients with National Comprehensive Cancer Network intermediate-risk PCa and complete biopsy information were treated with definitive external-beam radiation therapy (EBRT) utilizing doses ≥81 Gy. Unfavorable intermediate-risk (UIR) PCa was defined as any intermediate-risk patient with a primary Gleason pattern of 4, percentage of positive biopsy cores (PPBC) ≥50%, or multiple intermediate-risk factors (IRFs; cT2b–c, prostate-specific antigen [PSA] 10–20, or Gleason score 7).


All patients received EBRT with ≥81 Gy with or without neoadjuvant and concurrent androgen-deprivation therapy (ADT).

Outcome measurements and statistical analysis

Univariate and multivariate analyses were performed using a Cox proportional hazards model for PSA recurrence-free survival (PSA-RFS) and distant metastasis (DM). PCa-specific mortality (PCSM) was analyzed using a competing-risk method.

Results and limitations

Median follow-up was 71 mo. Primary Gleason pattern 4 (hazard ratio [HR]: 3.26; p < 0.0001), PPBC ≥50% (HR: 2.72; p = 0.0007), and multiple IRFs (HR: 2.20; p = 0.008) all were significant predictors of increased DM in multivariate analyses. Primary Gleason pattern 4 (HR: 5.23; p < 0.0001) and PPBC ≥50% (HR: 4.08; p = 0.002) but not multiple IRFs (HR: 1.74; p = 0.21) independently predicted for increased PCSM. Patients with UIR disease had inferior PSA-RFS (HR: 2.37; p < 0.0001), DM (HR: 4.34; p = 0.0003), and PCSM (HR: 7.39; p = 0.007) compared with those with favorable intermediate-risk disease, despite being more likely to receive neoadjuvant ADT. Short follow-up and retrospective study design are the primary limitations.


Intermediate-risk PCa is a heterogeneous collection of diseases that can be separated into favorable and unfavorable subsets. These groups likely will benefit from divergent therapeutic paradigms.

Take Home Message

Intermediate-risk prostate cancer can be stratified into favorable and unfavorable subgroups based on primary Gleason pattern, percentage of positive biopsy cores, and number of intermediate-risk factors.

Keywords: Prostate cancer, Intermediate risk, Dose escalation, Androgen deprivation, Risk stratification.


a Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

b Department of Epidemiology-Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Corresponding author. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 22, New York, NY 10065, USA. Tel. +1 212 639 6802; Fax: +1 212 639 8876.

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