Tumor Control Probability Modeling and Systematic Review of Oligometastatic Prostate Cancer Treated with Stereotactic Ablative Radiotherapy

Abstract

<h3>Purpose/Objective(s)</h3> Oligometastatic prostate adenocarcinoma is increasingly treated with stereotactic ablative body radiotherapy (SABR), and treatment efficacy requires achieving adequate local control (LC). Reported dose and fractionation schemes vary and evidence supporting a consensus treatment schema is lacking. We sought to define a dose-response curve based on meta-analysis of reported SABR regimens for prostate cancer oligometastases. <h3>Materials/Methods</h3> A systematic literature review was performed through PubMed using MESH terms "neoplasm metastasis," "radiotherapy," and "prostatic neoplasms." Inclusion criteria included radiologically- or biopsy- identified prostate cancer metastases, histologically confirmed prostate cancer diagnosis, metastasis-directed treatment with SABR, follow-up with radiologic assessment of treated metastases, and reporting of SABR dose and fractionation. Review articles were excluded. Doses were converted to equivalent doses of 2 Gy per fraction (EQD₂) with alpha/beta ratio of 1.5. 90% and 95% tumor control probability (TCP) at 6 months, 1 year, and 2 years was calculated using the Poisson model, with TCP = (1/2)<i>^e</i>^{[2γ50 (1-D/D50)/ln2]} and fit determined by least squares analysis in Proc NLIN of a data management and decision management software. The basic parameters of each model are D₅₀, which is the equivalent dose for a LC rate of 50%; and γ, which is the maximum normalized slope (gradient) of the dose response curve. <h3>Results</h3> We screened 733 studies and 16 studies met inclusion criteria. 1,214 metastatic prostate lesions were treated with SABR. The median EQD₂ was 230 Gy (IQR 202.9-286.7) with a median prescription dose of 30 Gy (IQR 24-33.8) in 3 fractions (range 1-10). There was poor model fit at 6 months and 1 year (p>0.05). At 2 years, the median LC was 95.7% (IQR 93.3%-100%). Chi-square test for our model fit was <0.0001, with estimated D₅₀ of 56.35 (95% CI 12.18-100.50) and γ of 0.30 (95% CI -0.05-0.65). TCP of 90% may be achieved with EQD₂ of 179.0 Gy, and TCP of 95% with EQD₂ of 225.8 Gy. This corresponds to a prescription of 41.1 Gy in 3 fractions or 52.3 Gy in 5 fractions for 90% TCP and 46.5 Gy in 3 fractions or 59.2 Gy in 5 fractions for 95% TCP at 2 years. <h3>Conclusion</h3> Although significant dose and fractionation variation is present, excellent TCP for oligometastatic prostate cancer treated with SABR was reported. Our study was limited by availability of prescription doses, rather than dosimetric data, and an individual patient-level meta-analysis to expand on this work is planned. There are many areas of need for continued research as SABR is increasingly utilized for oligometastatic prostate cancer, including durability of LC with longer follow-up, integration of novel imaging techniques into disease assessment, and the impact of systemic therapy on LC assessment.