Nadir PSA is a Strong Predictor of Treatment Outcome in Intermediate and High Risk Localized Prostate Cancer Patients Treated by Definitive External Beam Radiotherapy and Androgen Deprivation.
Jamal Khader, M.D(1). Fady Geara, M.D,PhD (2); Muhammad Bulbul, M.D(3); Raja B. Khauli, M.D(3) ; Nasim Sarhan, MD(1); Maya Charafeddine, M.P.H(4); ; Ali Shamseddine, M.D(4)
- Department of Radiation Oncology, King Hussein Cancer Center, Amman, Jordan ,
- Department of Radiation Oncology, The Naef K. Basile Cancer Institute at the American University of Beirut Medical Center, Beirut, Lebanon
- Division of Urology, the American University of Beirut Medical Center, Beirut, Lebanon
- Division of Medical Oncology, The Naef K. Basile Cancer Institute at the American University of Beirut Medical Center, Beirut, Lebanon
Background
Localized prostate cancer is effectively treated by definitive external beam radiation therapy (EBRT) in combination with androgen deprivation therapy (ADT). The aim of this study is to investigate the effect of known tumor characteristics and parameters of treatment response in predicting biochemical disease-free survival (BFS) for patients with intermediate or high risk prostate cancer treated by combined EBRT and ADT.
Hypothesis
Single or composite variables combining tumor characteristics and tumor response, could improve our ability to predict biochemical free survival.
Methods
Between June 1995 and January 2015, 509 patients with localized prostate cancer were treated at The American University of Beirut Medical Center (AUBMC) and King Hussein Cancer Center (KHCC) by definitive EBRT. Of those, 375 with a National Comprehensive Cancer Network (NCCN) intermediate or high risk categories received both ADT and EBRT and were retained for this study. Median duration of androgen blockade was 10 months (range: 3-36 months); Median radiation dose was 72 Gy (Range: 70-78 Gy). Median follow-up time was 5.8 years (range: 0.8-16.39 years). The main study endpoint was BFS.
Results
The median age was 71 years (range: 51-92). One hundred forty-three patients (38.1%) had intermediate and 232 (61.9%) had high risk disease. Forty seven patients (12.5%) developed biochemical recurrence (BCR) during the observation period. Monovariate analysis identified baseline PSA (bPSA) (p =0.024), T-stage (p=0.001), Gleason’s score (GS) (p= 0.042), radiation dose (p=0.045), PSA pre-radiation therapy (p=0.048), and nadir PSA (nPSA), (p <0.001) as significant variables affecting BCR, while age (p=0.148), ADT duration (p=0.784), and time to nadir (p=0.965) did not have significant impact. BFS was significantly higher in the intermediate vs. high risk group with a 10-year rate of 79.6% vs 58.4% (p=0.001). The receiver operating characteristic (ROC) curve identified a bPSA of 14.55 ng/ml and a nPSA of 0.059 ng/ml as optimal cut off values significantly predicting the patients’ risk of BCR (p=0.006 and <0.001 respectively). Multivariate cox regression analysis revealed T-stage and nPSA as independent variable affecting BFS, while bPSA, GS, age and radiation dose were not. Patient grouping using these 2 variables identified 3 risk groups with regard to their risk of BFS: A favorable group with a combination of nPSA <0.059 ng/ml, and T1-T2 stage disease; an unfavorable group with nPSA ≥ 0.059 ng/ml, and T3-T4 stage disease and an intermediate group containing one unfavorable variable. Ten-year BFS rates were 84.9% for the favorable group, 59.5% for the intermediate, and 0% for the unfavorable group (p<0.001).
Conclusion
Nadir PSA at 0.059 is a strong independent predictor of BFS in patients with intermediate or high risk prostate cancer treated by definitive EBRT and ADT. Using this treatment outcome variable in combination with T-stage, improves our ability to predict BFS in these groups of patients, which might help initiate early and more individualized therapy for those who have a high predicted risk of recurrence.
