Purpose/Objective: Accumulating evidence demonstrates that prostate cancer has a low α/β ratio. However, several challenging issues have been raised from previous studies. These issues include the biological equivalence between external-beam radiotherapy (EBRT) and brachytherapy, the effect of relative biological effectiveness (RBE) for permanent implantation, and the systematic uncertainties of multi-institutional and multi-modality clinical data. The purpose of this study is to address these issues via reexamining a reported clinical outcome of high dose rate (HDR) brachytherapy and to confirm the low α/β ratio for prostate cancer. Materials/Methods: The generalized linear-quadratic (LQ) model, which was extended to include the repair of sub-lethal damage and clonogen repopulation, was used to calculate the cell-killing efficiency of radiotherapy treatments for prostate cancer. Standard models of tumor cure based on Poisson statistics were used to bridge cell killing to treatment outcome. The data collected in a clinical trial using EBRT plus HDR brachytherapy boost for prostate cancer at William Beaumont Hospital (WBH) ( 1Brenner DJ, Martinez AA, Edmundson GK, et al. Int J Radiat Oncol Biol Phys 2002;52:6–13.) was re-analyzed. The endpoint of 4-year post-treatment time, instead of the 3-year used in the previous analysis ( 1Brenner DJ, Martinez AA, Edmundson GK, et al. Int J Radiat Oncol Biol Phys 2002;52:6–13.), was chosen because of better maturity and stability. The least Chi-square method was employed to fit the clinical data to estimate the LQ parameters as well as their confidence intervals. The clonogen numbers of prostate tumors derived in a separate study ( 2Wang JZ, Guerrero M, Li XA. Int J Radiat Oncol Biol Phys 2003;55:194–203.), which was based on the EBRT dose-escalation study from Memorial Sloan-Kettering Cancer Center (MSKCC) ( 3Levegrun S, Jackson A, Zelefsky MJ, et al. Int J Radiat Oncol Biol Phys 2001;51:1064–1080.), was used as a constraint for the data modeling to improve the confidence level. Results: Our analysis demonstrates that only relationships among the LQ parameters, not their definitive and unique values, can be derived from the WBH data set alone. This is due to the large statistical uncertainties, i.e., the small number of sampled patients. By combining with the results obtained with MSKCC clinical data ( 2Wang JZ, Guerrero M, Li XA. Int J Radiat Oncol Biol Phys 2003;55:194–203.), a new set of LQ parameters (α = 0.14±0.05 Gy−1, α/β = 3.1−1.6+2.6 Gy) was obtained from the current analysis of the WBH clinic data without dealing with data from permanent implants. These results are consistent with a previous study based on the biological equivalence between EBRT and permanent implants with consideration of tumor repopulation ( 2Wang JZ, Guerrero M, Li XA. Int J Radiat Oncol Biol Phys 2003;55:194–203.). This set of LQ parameters provides a consistent interpretation of clinical data currently available for prostate cancer. Conclusions: This study provides further evidence to support that prostate cancer has a low α/β ratio of about 3.1 Gy. This study shows that the RBE effect in the permanent implant may not be clinically significant for prostate cancer. The consistency found between this analysis and the previously reported study ( 2Wang JZ, Guerrero M, Li XA. Int J Radiat Oncol Biol Phys 2003;55:194–203.) based on EBRT and permanent brachytherapy data supports the general biological equivalence between EBRT and brachytherapy treatments for prostate cancer. The low α/β ratio opens the door for searching alternative or more effective radiotherapy for prostate cancer, e.g., hypofractionation radiotherapy. 1Brenner DJ, Martinez AA, Edmundson GK, et al. Int J Radiat Oncol Biol Phys 2002;52:6–13. 2Wang JZ, Guerrero M, Li XA. Int J Radiat Oncol Biol Phys 2003;55:194–203. 3Levegrun S, Jackson A, Zelefsky MJ, et al. Int J Radiat Oncol Biol Phys 2001;51:1064–1080.