Patterns of local relapse following tumor-targeted dose escalation for localized prostate cancer

Abstract

Purpose or Objective Tumor-targeted dose escalation may improve local control rates in patients with prostate cancer, leading to improved biochemical failure-free survival (bFFS). We report outcomes of dose escalation using a strategy of simultaneous integrated boost or HDR brachytherapy boost. Materials and Methods Eighty patients with localized prostate cancer with GTV identified on multiparametric MRI (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 VMAT, 76 Gy in 38 fractions. Choice of GTV dose escalation was by physician and/or patient choice and delivered by integrated boost VMAT (IB-VMAT) of 95 Gy in 38 fractions (n=40); or MRI-guided HDR boost of 10 Gy in 1 fraction (n=40). The primary endpoint was 3-year local control rates determined by MRI-guided biopsy and/or MRI alone. Toxicity data was collected using CTCAE v.4.0. Risk group categorization was comparable between the arms; 5% low-, 75% intermediate-, and 20% high-risk. Three patients received 6-months of concurrent/adjuvant ADT. Results Median (IQR) follow-up was 55.2 months (48.1-71.4). The overall 5-year bFFS was 92% (95% CI, 85-99). Late G2 GU toxicity was 22.5% and 27.5% in IB-VMAT and HDR boost arms, respectively. Late G2 GI toxicity was 5% in each arm. Two G3 (1 GI, 1 GU) toxicities were seen in IB-VMAT. 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 within the boost volume was achieved in 61 patients. One patient in the IB-VMAT arm had persistent disease on biopsy, and subsequently met criteria for biochemical relapse (BCR). At last follow-up of the 66 patients, 4 developed BCR with evidence of intraprostatic relapse outside the boost volume; 1 treated with IB-VMAT and 3 with HDR boost. The spatial distribution of these relative to the boost volume were: ipsilateral lobe (IB-VMAT), marginal/contralateral/bilateral (HDR boost). These relapses appeared to correlate to sites of known microscopic disease at original diagnosis. Conclusion Dose escalation to mpMRI-defined GTV provided high rates of local and biochemical control with a favorable late toxicity profile. The majority of local treatment failures developed beyond the tumor-targeted volume, suggesting that other treatment intensification strategies may be required to further improve outcomes.