Impact of radiation dose on achieving nadir PSA levels after 3-dimensional conformal radiotherapy for patients with localized prostate cancer

Purpose: Several reports have documented the prognostic value of a post-irradiation nadir PSA of ≤1 ng/ml in prostatic cancer patients. The purpose of this study was to determine which pre-treatment and treatment-related variables impact upon achieving such nadir levels. Materials and Methods: Between January 1987 and June 1995, 740 patients with clinically localized prostate cancer were treated with 3-dimensional conformal radiotherapy (3D-CRT). 214 (29%) patients were treated with neo-adjuvant androgen ablation prior to therapy and were excluded from this analysis. Among the 526 evaluable patients, the clinical stage were as follows: T1C=128 (24%); T2A=76 (14%); T2B=116 (22%); T2C=99 (19%) and T3=107 (21%). The prescription dose to the planning target volume (PTV) was 64.8-68.4 Gy in 87 patients (17%); 70.2 Gy in 191 (36%); 75.6 Gy in 209 (40%) and 81 Gy in 39 (7%). The median pre-treatment PSA value was 11.2 ng/ml (range 0.3-114). The median follow-up was 20 months (range: 6-76 months). Results: 242 patients (46%) had PSA levels which declined to ≤1.0 ng/ml. The median time to a nadir level of ≤1.0 was 15.6 months (range: 1-43 months) from completion of 3D-CRT. 154 (29%) patients continued to show declining PSA levels within the first 2 years after therapy, and 130 patients (25%) failed to nadir at PSA levels of ≤1.0 ng/ml. Among patients with nadir PSA levels ≤1, the 3 year PSA relapse-free survival was 91% compared to 29% for patients with nadir PSA levels >1 ng/ml (p<0.0001). A Cox-regression analysis demonstrated that nadir PSA ≤1 was the strongest predictor of PSA relapse-free survival (p<0.001) followed by Gleason score ≤ 6 (p<0.001) and stage<T3 (p=0.004). Among patients who received doses of ≥75.6 Gy, the likelihood of achieving PSA nadir levels ≤1.0 at 24 and 36 months was 86% and 93%, respectively, compared to 74 and 80%, respectively, among those who received lower doses (p<0.001). Doses of ≥75.6 Gy was the strongest independent predictor for a nadir PSA level of ≤1.0 (p<0.001) followed by pre-treatment PSA levels ≤10 ng/ml (p<0.001) and stage (p=0.01), while the Gleason score had no significant impact. Conclusion: Nadir PSA levels of ≤ 1.0 ng/ml after radiotherapy for localized prostate cancer is the strongest predictor of PSA relapse-free survival. Higher radiation doses are associated with an increased likelihood of achieving post-treatment nadir PSA levels of ≤1.0 ng/ml. Further follow-up is needed to determine whether higher doses will also translate into improved long-term outcome for these patients