## 2 Materials and Methods  
Using Cox regression analysis, with time to BCR as the outcome for prostate cancer patients who underwent SBRT, a model was developed that calculates a PCO score based on (1) age at diagnosis, (2) clinical-radiological staging, and (3) the modified risk level based on a combination of pretreatment prostate specific antigen (PSA) and the Gleason score. We studied the outcomes of 809 prostate cancer patients at MedStar-Georgetown University Hospital's Department of Radiation Medicine between August 2007 and November 2016. They were treated with SBRT after being diagnosed with prostate cancer and undergoing follow-up management. The patients were seen for follow-up examinations and blood sample collection at 3-month intervals for 2 years and then 6-month intervals for the remaining 3-year follow-up period. We focused on BCR at 5 years after SBRT. The patients were enrolled in an IRB (Institutional review board)-approved study (#12-1175). The analysis was performed on de-identified, HIPAA-compliant data. The PCO score was calculated using a nomogram. The three predictors we used for the PCO classifier application were as follows: (1) age at diagnosis, (2) clinical-radiological staging, and (3) modified risk level, which is the combination of pretreatment PSA and the Gleason score. These were selected and modified based on one physician's comments and fed into the application. We used age, clinical-radiological staging, and modified risk level as independent variables in the regression analysis. For input into our PCO classifier application, patients were grouped into four age categories: 59 and under, 60-69, 70-79, and over 80 years. After an initial data review of tumor staging, only three patients presented with T3 tumors; a number were considered inadequate for separate analysis. Therefore, based on standard t-stage classification [14], the patients were assigned into the following groups: T1 (T1a, T1b, T1c), T2a, T2b, and T2c + T3. Recent studies have categorized a Gleason 7 tumor as two types: 7a (primary 3 + secondary 4) and 7b (4 + 3) [4; 15]. Thus, the PCO classifier application divided the Gleason score into four grades (Table 1). Pretreatment PSA scoreswere divided into three categories: \(\leq\)10.0 ng/mL, \(>\)10.0 and \(\leq\)20.0 ng/mL, and \(>\)20.0 ng/mL (Table 1). We used a modified risk level based on a combination of the Gleason score and pretreatment PSA (Table 1) [16] and determined five classifications for the modified risk level. Using a total score range based on BCR-free survival rate at 4 years, the patients were classified into one of three groups: 99%, 90%, and 80%. We determined three risk-groups based on patient distribution and the range of the total score (Appendices). Finally, the three risk-groups were validated by physician comments. The BCR-free survival rate at 4 years was used to calculate PCO scores. Because prostate cancer treated with SBRT has the lowest recurrence rate, there were not enough BCR rates to calculate the risk score using the BCR-free survival rate at 5 years. To determine the accuracy of the PCO classifier application, we computed the concordance index (c-index). The 95% CI of the c-index was calculated by K-folder cross-validation. K-folder cross-validation is an effective validation procedure for classification [17; 18]; we used 5-folder cross-validation in this study. To obtain balanced statistical power, we divided the data into two sets: training and test data [18]. We matched seven training datasets (\(n=570\)) to four test datasets (\(n=239\)). In addition, the PCO classifier application and classifications according to the D'Amico and Kattan nomogram risk groups were compared. Survival data analyses were used to find the disease-free survival rates. We used the Kaplan-Meier estimator and Cox multivariable regression analysis to determine the risk factors significantly associated with BCR. In this study, we used the American Society of Therapeutic Radiology and Oncology (ASTRO) definitions for BCR [19].