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

Abstract Background The management of intermediate-risk prostate cancer (PCa) is controversial, in part due to the heterogeneous nature of patients falling within this classification. Objective 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 ≥81Gy. 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). Intervention All patients received EBRT with ≥81Gy 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 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 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 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. Conclusions 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.