Novel Intraprostatic Magnetic Resonance-Guided Implantation of Multidrug-Eluting Microdevice for Testing of Systemic Therapy Agents In Situ: Proof of Concept in Intermediate-Risk and High-Risk Prostate Cancer.

Abstract

The purpose of this study was to assess safety and feasibility of percutaneous magnetic resonance-guided placement of an implantable microdevice (IMD) to evaluate in situ intratumor response to multiple pharmacologic agents in men with intermediate-risk and high-risk localized prostate cancer. Biocompatible IMDs measuring 750 µm in diameter and 5 mm in length were prepared with 20 reservoirs containing candidate drug and drug combinations including second-generation androgen inhibitors, PARP inhibitors, PD-1 inhibitors, and conventional chemotherapy. Men with intermediate-risk or high-risk localized prostate cancer and MRI-visible lesions were enrolled. Up to 4 IMDs were placed using a transperineal approach into MRI-visible tumors 2 days before planned radical prostatectomy. After radical prostatectomy, the IMDs and a small segment of surrounding tumor tissue were removed and sectioned, stained, and analyzed for tissue drug response by a variety of pharmacodynamic markers. Fourteen patients were enrolled: 7 (50%) with intermediate-risk and 7 (50%) with high-risk localized prostate cancer. A total of 53 IMDs were implanted (mean 3.8 per patient), and 49 IMDs (92%) were successfully retrieved. All men underwent uncomplicated robotic-assisted radical prostatectomy and bilateral pelvic lymph node dissection 2 days after IMD placement. There were no severe adverse events. Pathological examination of the tissues adjacent to the IMDs demonstrated differential drug response within patients and between patients. Limitations include small sample size. A multidrug IMD can be safely placed percutaneously into MRI-visible lesions before radical prostatectomy, enabling assessment of tumor-specific local response to multiple agents simultaneously within the tumor's normal stromal environment to guide targeted systemic therapy. ClinicalTrials.gov identifier: NCT04399876.