Local Control in Tumor-Targeted Dose Escalation for Localized Prostate Cancer

Abstract

Tumor-targeted dose escalation may improve biochemical disease-free survival in patients with localized prostate cancer. We report outcomes of dose escalation using a strategy of simultaneous integrated boost or HDR brachytherapy boost.Eighty patients with localized prostate cancer with gross tumor volume (GTV) identified on multiparametric magnetic resonance imaging (mpMRI) were enrolled in this phase 2 non-randomized trial (2012-2016). Patients with GTV > 5mm and less than 33% of total prostate volume were eligible. All patients received whole gland prostate volumetric arc therapy (VMAT), 76 Gy in 38 fractions. GTV dose escalation was delivered by integrated boost VMAT (IB-VMAT) of 95 Gy in 38 fractions (n = 40); or MR-guided HDR boost of 10 Gy in 1 fraction (n = 40). Choice of dose escalation strategy was by physician and/or patient choice. The primary end-point was 3-year local control rates determined by MR-guided biopsy and/or MRI alone. Toxicity data was collected using CTCAE v.4.0. Risk group categorization was similar between the arms; 5% low-, 75% intermediate-, and 20% high-risk. Three patients received 6-months ADT.Median (IQR) follow-up was 55.2 months (48.1-71.4). The overall 5-year biochemical failure-free survival was 92% (95% CI, 85-99), with 5 patients developing biochemical relapse (BCR); 1 IB-VMAT, 4 HDR boost. Local control data was available for 66 patients who agreed to the 3-year post-treatment biopsy (20) or MRI alone (46); 32 in IB-VMAT and 34 in HDR boost. Local control in the boost volume was achieved in 61 patients. One patient in the IB-VMAT arm had persistent disease on biopsy, and subsequently developed late BCR. Intraprostatic relapse outside the GTV was seen in 4 patients at last follow-up; 1 treated with IB-VMAT and 3 with HDR boost. All 4 patients developed BCR. Late G2 genitourinary (GU) toxicity was 22.5% and 27.5% in IB-VMAT and HDR boost, respectively. Late G2 gastrointestinal (GI) toxicity was 5% in each arm. Two G3 (1 GI, 1 GU) toxicities were seen in IB-VMAT.Dose escalation to mpMRI-defined GTV provided high rates of local and biochemical control with limited severe late toxicity. Intraprostatic failures outside the boost volume appeared to correlate with BCR, which suggests that dose escalation to other subclinical intraprostatic regions may be required. Further characterization using molecular classification, beyond usual clinical parameters, may be warranted in order to improve local control.