The Association between Dose Escalation and Risk of Developing Metastases in Intermediate and High-Risk Prostate Cancer Patients Treated with Radiotherapy

Abstract

<h3>Purpose/Objective(s)</h3> Radiotherapy dose escalation through brachytherapy or simultaneous integrated boost have been successfully introduced to clinical practice, facilitating improved local control of the tumor in intermediate and high-risk prostate cancer (PCa) patients, but not necessarily improved metastasis-free survival. Moreover, the improvement in clinical endpoints is often associated with increased risk of adverse effects. In this article, we analyzed effect of high dose-rate (HDR) brachytherapy boost (BT) dose escalation on freedom from metastases (FFM), based on real-world data. <h3>Materials/Methods</h3> The analysis was based on a multi-institutional retrospective database of 1641 consecutive intermediate (30%) or high risk (70%) prostate cancer patients treated with external beam radiotherapy (EBRT; 70.9%) or EBRT, combined with single or double fraction BT boost (29.1%). The majority of the patients (95%) received anti-androgen therapy (ADT). The biologically effective dose was calculated using α/β of 3 Gy. The follow-up data was acquired from institutional databases. The analysis included the Kaplan-Meier method and Cox regression models. A multivariable model was constructed utilizing backward stepwise feature selection based on Akaike information criterion. The model presented adjusted hazard ratios (HR) in multivariable analysis, and was further used to create a nomogram. C-index was used to assess the model. <h3>Results</h3> The median age was 63.8 years (IQR 62.9 – 73.5). Median FFM was not achieved, metastasis occurred in 234 patients (14.1%) over the course of follow up. The univariate analysis showed that BED was significantly associated with FFM (HR 0.99; CI 95% 0.98-0.99; p<0.001), along with Gleason grade group, PSA density, maximum PSA, pre-treatment PSA, T and N stage according to TNM, previous transurethral resection of the prostate, and NCCN risk group. Backward stepwise feature selection allowed to create multivariable model which included BED, prostate volume, Gleason grade group and NCCN risk groups. This model presented c-index of 0.665 and 5-fold cross-validation-corrected c-index of 0.652. The results are presented in Table 1. This model was used to create a clinical nomogram for FFM. <h3>Conclusion</h3> Biologically effective dose is an independent prognostic factor for developing metastases in patients treated with radiotherapy for intermediate or high-risk group prostate cancer. Dose escalation through brachytherapy boost can be used to decrease the risk of developing metastases in patients with adverse features.