A Comprehensive Assessment of the Prognostic Utility of the Stephenson Nomogram for Salvage Radiation Therapy Postprostatectomy

Abstract

To investigate the prognostic utility of the Stephenson nomogram for clinically relevant endpoints, freedom from metastasis (FFM) and prostate cancer-specific survival (PCSS), in patients treated with salvage external beam radiation therapy (SRT) following a rising prostate specific antigen (PSA) after radical prostatectomy (RP). From an institutional cohort of 575 patients treated with SRT between 1986 and 2010, the Stephenson nomogram variables were retrospectively collected and available for 179 patients. The prognostic impact of the Stephenson nomogram on 6-year freedom from biochemical failure (FFBF), FFM, and PCSS was assessed on univariate and multivariate analysis using Kaplan-Meier, and Cox proportional hazards models. The prognostic utility of the Stephenson nomogram was compared to individual pre-treatment, treatment and clinical characteristics using concordance indices. In the 179 patients with all available nomogram variables, median follow-up was 85.0 months (IQR, 52.8-113.2) and 6-year FFBF, FFM and PCSS were 38% (95% Confidence Interval [CI]:30.2-45.8), 79% (95% CI:73.1-84.9) and 96% (95% CI:92.1-99.9), respectively. Univariate analysis, demonstrated that the Stephenson nomogram, as a continuous variable and as a risk stratified group, was prognostic of FFBF (both, p<0.0001), FFM (both, p<0.0001) and PCSS (both, p≤0.0005). When analyzing individual Stephenson nomogram variables, multivariate analysis revealed that positive surgical margins (p = 0.02,HR0.4,95% CI:0.2-0.8) and pre-RT PSA (p = 0.0001,HR1.6,95% CI:1.3-2.0) were prognostic for FFM, while pre-RT PSA (p = 0.03,HR1.2,95% CI:1.0-1.4) was the only prognostic variables for PCSS. Concordance indices revealed the Stephenson nomogram to have superior prognostic capability for biochemical failure (0.71), distant metastasis (0.75) and prostate cancer-specific mortality (0.75) when compared to individual variables (BF all≤0.65, DM all≤0.67, PCSM all≤0.71). For patients treated with SRT for a rising PSA post-prostatectomy, the Stephenson nomogram is an appropriate prognostic tool for estimating the response to treatment; however there remains a need for improvement in current and future nomograms.