Assessing Clinical and Dosimetric Predictors For Low PSA Nadir after Stereotactic Body Radiation Monotherapy with Intraprostatic Dose Escalation

Abstract

Definitive Stereotactic Body Radiation Therapy (SBRT) has become a standard treatment option for men with low to intermediate risk prostate cancer. Several studies have characterized the importance of low PSA nadir for sustained disease control post radiation. Dose response parameters are well-established for low dose rate (LDR) brachytherapy, and remain emerging for prostate SBRT. Due to heterogeneity of treatment platforms and prescription nomenclature, it remains challenging to apply dose-response data with SBRT in an ecumenical fashion. This study assesses clinical and dosimetric factors associated with a low PSA nadir post prostate SBRT. 852 patients with NCCN low (39.0%), favorable intermediate (26.6%) and unfavorable intermediate (34.4%) risk disease were treated with, inhomogeneous non-coplanar SBRT, allowing for intraprostatic dose escalation. Treatment was delivered at an academic institution from June 21, 2006 to January 3, 2018 and consisted of a 5-fraction regimen of 35.0-36.25 Gy. The mean age was 66.6 years (41-87). 77.9% of patients were Caucasian and 17.4% African American. The mean follow-up time was 46.3 months (24-155). In order to distill predictive correlates for post-treatment PSA decline, patients receiving ADT or who experienced biochemical failure were omitted a priori. Correlation analyses were performed using Pearson chi-square testing and odds ratios were assessed with binary logistic regression. After a minimum of 24 months post SBRT monotherapy, the mean PSA nadir was 0.39ng/ml (0-2.72), with 56.0% of patients experiencing a nadir ≤0.3ng/ml. Patients with a nadir ≤0.3ng/ml were more likely to be age ≥65 years (68.1% vs. 52.8%, p<.001), and to be Caucasian (80.7% vs. 74.4%, p = .007). They were more likely to have clinical T2b/T2c disease (11.6% vs. 6.7%, p = .031) and less likely to have a pre-treatment PSA >10ng/ml (9.6% vs. 15.2%, p = .014). They more often were treated with anti-coagulation medicine (12.0% vs. 6.5%, p = .01). Those with a nadir ≤0.3ng/ml had no difference in overall NCCN risk grouping, use of 5-alpha reductase inhibitor, metformin, or statin medication use. Dosimetric parameters that portended for nadir ≤0.3ng/ml included CTV D70 ≥37.75Gy (82.6% vs. 70.5%, p<.001), CTV D80≥ 37.5Gy (70.0% vs. 57.8%, p = .003), and CTV mean dose ≥38.5Gy (57.1% vs. 43.8%, p = .002). On multivariate analysis, predictors for long-term PSA nadir ≤0.3ng/ml were age ≥65 (OR 1.78, CI 1.20-2.64, p = .004) and CTV D70 ≥37.75Gy (OR 2.52, CI 1.10-5.79, p = .029). Patients with localized prostate cancer can experience low PSA nadirs post SBRT monotherapy. Consistent with previous studies, older age appears to correlate with lower nadir values. CTV D70 ≥37.75Gy predicts for PSA nadir ≤0.3ng/ml. Longer follow-up is warranted to assess for durability of these findings and future inquiry should involve correlation between D70 and long-term disease-free endpoints.