• Byron H Lee, Adam S Kibel, Jay P Ciezki, Eric A Klein, Chandana A Reddy, Changhong Yu, Michael W Kattan, and Andrew J Stephenson.
• Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
• Eur. Urol. 2015 Feb 1; 67 (2): 204-9.

BackgroundDue to the protracted natural history of the clinical progression of prostate cancer, biochemical recurrence (BCR) is often used to compare treatment modalities. However, BCR definitions and posttreatment prostate-specific antigen kinetics vary considerably among treatments, calling into the question the validity of such comparisons.ObjectiveTo analyze prostate cancer-specific mortality (PCSM) according to treatment-specific nomogram-predicted risk of BCR for men treated by radical prostatectomy (RP), external-beam radiation therapy (EBRT), and brachytherapy.Design, Setting, And ParticipantsA total of 13 803 men who underwent RP, EBRT, or brachytherapy at two US high-volume hospitals between 1995 and 2008.InterventionRP, EBRT, and brachytherapy.Outcome Measurements And Statistical AnalysisThe 5-yr progression-free probability (5Y-PFP) was calculated for each patient based on the treatment received using a validated treatment-specific nomogram. Fine and Gray competing risk analysis was then used to estimate PCSM by a patient's predicted 5Y-PFP. Multivariable competing risk regression analysis was used to determine the association of treatment with PCSM after adjusting for nomogram-predicted 5Y-PFP.Results And LimitationsMen receiving EBRT had higher 10-yr PCSM compared with those treated by RP across the range of nomogram-predicted risks of BCR: 5Y-PFP >75%, 3% versus 0.9%; 5Y-PFP 51-75%, 6.8% versus 5.9%; 5Y-PFP 26-50%, 12.2% versus 10.6%; and 5Y-PFP ≤25%, 26.6% versus 21.2%. After adjusting for nomogram-predicted 5Y-PFP, EBRT was associated with a significantly increased PCSM risk compared with RP (hazard ratio: 1.5; 95% confidence interval, 1.1-2.0; p=0.006). No statistically significant difference in PCSM was observed between patients treated by brachytherapy and RP, although patient selection factors and lack of statistical power limited this analysis.ConclusionsEBRT patients with similar nomogram-predicted 5Y-PFP appear to have a significantly increased risk of PCSM compared with those treated by RP. Comparison of treatments using nomogram-predicted BCR end points may not be valid.Patient SummaryBiochemical recurrence (BCR) outcomes after external-beam radiation therapy and radical prostatectomy are associated with different risks of subsequent prostate cancer-specific mortality. Physicians and patients should cautiously interpret BCR end points when comparing treatments to make treatment decisions.Copyright © 2014. Published by Elsevier B.V.

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