Implant Shows Promise for Tumor-Specific Treatment in Prostate Cancer

An implantable, drug-eluting microdevice showed promise for informing decisions about systemic therapy for prostate cancer prior to radical prostatectomy for high-risk disease, according to results of a pilot study.

Percutaneously inserted directly into a prostate cancer lesion, the implantable microdevice (IMD) caused no severe adverse events. Pathology studies of tumor and adjacent tissue showed differential responses to the same drug within and between patients. All 14 patients underwent uneventful, successful, robot-assisted prostatectomy.

The study showed the feasibility of simultaneous assessment of tumor-specific responses to multiple drugs to guide targeted systemic therapy for high-risk prostate cancer, reported Benjamin V. Stone, MD, of the Medical University of South Carolina in Charleston, and co-authors in the Journal of Urology.

“Our ability in this study to place the IMD preoperatively using MR-guided percutaneous methods represents an important innovation and is critical to assessing drug response,” the authors stated in their discussion of the study. “Given the safety and feasibility demonstrated in this pilot study, next steps include assessment of the feasibility of MR-guided percutaneous IMD retrieval, which would enable use in patients not undergoing surgery. The results could then be used to guide neoadjuvant systemic therapy and inform treatment choices in men undergoing radiation or no local treatment.”

The prostate cancer study followed a similar one in non-small cell lung cancer, wherein an IMD was placed intraoperatively into tumors, they noted.

Despite marked expansion of systemic therapy options for prostate cancer over the past 20 years, genomic variation and the multifocal nature of prostate cancer continue to pose a challenge to optimizing systemic therapy, noted Madison K. Krischak, MD, and Arnav Srivastava, MD, both of the University of Michigan in Ann Arbor, in an accompanying commentary.

“In this context, there is a growing need to tailor systemic therapy regimens to the genomic signatures of a patient’s tumor,” they stated.

Despite the small sample size and logistical issues that may limit applicability, “this study holds tremendous promise,” Krischak and Srivastava added. “As the prostate cancer field moves toward precision medicine, future work is needed to inform IMD length of exposure, evaluation of biomarker response, and IMD retrieval techniques to expand this technology’s utility.”

Need for Better Treatment Options

As the incidence of prostate cancer has increased in the U.S., so has the need for better options for patients at high risk of treatment failure. The rationale for systemic therapy in high-risk localized disease revolves around the hypothesis that many patients likely harbor micrometastatic disease that eventually will require systemic drug combinations, Stone and colleagues pointed out.

“Earlier treatment should improve survival while tumor burden is low,” they wrote. “However, given the genomic and epigenetic heterogeneity of prostate cancer and the mixed treatment responses to systemic agents, the optimal therapy for each individual patient with newly diagnosed high-risk disease remains unknown.”

Recent studies have shown that specific mutations and gene expression profiles correlate with differential response to systemic therapies, they continued. As an example, BRCA mutations correlate with sensitivity to platinum chemotherapy and PARP inhibitors.

Preclinical studies of several tumor types, including prostate cancer, have shown that local response to chemotherapy correlates with systemic response. The observations imply that identifying patient-specific local response to systemic agents might inform treatment sequence in neoadjuvant, adjuvant, and salvage settings.

Stone and colleagues evaluated the feasibility of using an IMD to assess in situ intratumoral response to therapeutic agents in intermediate- and high-risk localized prostate cancer. Information gleaned from the pilot study might offer guidance toward development of individualized therapy and simultaneously facilitate testing of novel agents.

Investigators enrolled men with intermediate- or high-risk localized prostate cancer (defined as ≥Gleason score 3 + 4, >3 positive biopsy cores, and >50% positivity in a single core). All patients underwent multiparametric MRI that detected at least one lesion in the region of a positive biopsy.

Device, Study Characteristics

The IMD consists of a biocompatible cylinder with 20 drug reservoirs, each of which releases a unique drug or drug combination into non-overlapping regions of the tumor, enabling assessment of activity in the native microenvironment, the authors noted. Drugs used in the study included second-generation androgen inhibitors, PARP inhibitors, PD-1 inhibitors, and chemotherapy.

Each IMD has a fluorescent-tagged marker to aid orientation in postoperative analysis and is implanted via transperineal insertion of an 18-gauge biopsy needle. Radical prostatectomy occurred 2 days after IMD placement. Investigators inserted a total of 53 IMDs and retrieved 49. Missing IMDs were thought to have been displaced during specimen handling or transport.

A variety of pharmacodynamic assessments were performed and demonstrated differential tumor responses across treatments. The authors noted both intra- and inter-patient variability in response to the different therapies evaluated. They also used pathway signaling markers to study the drugs’ effects on known prostate cancer-specific signaling pathways.

“A clear strength of this technique is to evaluate tumor response to systemic therapy in situ,” the authors stated. “Therapeutic response from all agents is likely a complex interaction between the normal stroma, immune system, and tumor.”

“Placing multiple IMDs into multiple MRI-visible tumors, if present, enables us to assess both intertumor and intratumor drug response across different regions of the same tumor and between different tumor foci,” they added. “Importantly, the IMD may facilitate a safe and novel methodology for drug discovery with intratumor testing of new and emerging therapies using microdoses that are a small fraction of therapeutic systemic doses with no apparent systemic toxicity.”

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