First Results for Nanosphere Focal Therapy in Prostate Cancer

Alexander M. Castellino, PhD

August 28, 2019

When imaging of the prostate shows only one small area of cancer, "why can't you treat just that spot, instead of the whole prostate?" frustrated patients keep asking.

This is what a new approach now being tested aims to do, says Ardeshir R. Rastinehad, DO, director of focal therapy and interventional urologic oncology at the Icahn School of Medicine at Mount Sinai, New York City.

His team has just reported early results from a small trial of focal therapy for discrete lesions in the prostate using gold-silica nanoshell (GSN)–directed laser technology (also called AuroLase Therapy, developed by Nanospectra).

The study was conducted in 15 patients who had low- to intermediate-risk prostate cancer.

There were no serious side effects after 90 days, which was the primary endpoint of the study.

At 12 months, 87.5% of the lesions tested negative for tumor in the ablation zone.

"This current pilot device study demonstrates that GSN-directed laser excitation and ablation is a safe and technically feasible procedure for the targeted destruction of prostate cancer," the study authors conclude.

The study was published online August 26 in the Proceedings of the National Academy of Sciences.

Another study is currently in progress. That study, which involves 45 patients, is assessing efficacy at a 12-month follow-up.

To grant approval of devices, the US Food and Drug Administration (FDA) requires data for 100 patients. This nanoshell technology may therefore be closer to approval than most believe — "2 years, more or less," Nanospectra's chief executive officer, David Jorden, MBA, told Medscape Medical News.

Accrual for a study involving 65 patients will begin in September 2019. Jorden indicated that Nanospectra will be in a position to submit its data to the FDA in early 2021. "AuroLase Therapy should be commercially available in less than 2 years," he said.

"Our study shows that for low- to intermediate-risk prostate cancer, photothermal ablation provides the ability to avoid overtreatment as well as to avoid the deleterious effects of radical treatment options," Jenson noted.

Approached for comment, Anthony V. D'Amico, MD, PhD, from the Dana-Farber Cancer Institute, Boston, Massachusetts, who was not involved in the study, told Medscape Medical News that efficacy needs to be established in future studies in more men with longer follow-up to assess cancer control and toxicity.

How Nanoshells Work

Nanoshells comprise a silica core and a gold shell. They measure 150 nm in diameter. They are designed to absorb near-infrared light and convert it to heat. They accumulate at high levels at tumor sites, owing to their leaky vascular architecture. When near-infrared light from a laser is targeted in a pinpoint manner at the lesion, the nanoshells absorb the light. The tumor then undergoes photothermal heating, resulting in cell death.

Rastinehad explained that healthy tissue is spared. In healthy tissue, the concentration of nanoshells is low, and so only mild, reversible hyperthermia occurs there.

Study Details

The safety study enrolled 16 men aged 58 to 79 years with low- to intermediate-risk prostate cancer (Gleason score, 4+3 or less).

The patients were diagnosed and underwent staging that employed high-resolution multiparametric MRI (mpMRI). The regions of interest were overlaid on live ultrasound images. These images guided placement of the laser trocar, which houses a laser catheter, so as to deliver near-infrared light in a pinpoint manner at the site of the lesions, thereby heating the nanoshells.

The procedure was carried out in two stages on consecutive days. On the first day, patients received an intravenous infusion of 7.5 mL/kg of nanoshells. On the second day, patients underwent laser excitation of the nanoshells under general anesthesia.

The median time under anesthesia, which included patient positioning and equipment preparation, was nearly 4 hours (230 minutes; range: 115 – 345).

Patients were discharged on the same day after several hours of monitoring and a successful voiding trial. Five patients required a Foley catheter post ablation.

After 48 to 72 hours, patients underwent mpMRI for evaluation of radiologic treatment response at the planned ablation zone. At 3 and 12 months, patients underwent repeat mpMRI and MR/ultrasound targeted biopsy.

Patients were followed for 1, 3, 6, and 12 months for adverse events. Patients' International Prostate Symptom Score, urinary quality of life, and Sexual Health Inventory for Men score were assessed. The scores at 3, 6, 12 months were similar to baseline values.

Study Results

Fifteen patients completed the study. One patient experienced epigastric pain during the nanoshell infusion and did not undergo laser treatment on day 2.

At 3 months (the primary endpoint time point), median prostate volume had decreased by 7 cm3 (49 cm3 at baseline), and the median prostate-specific antigen (PSA) level had decreased by 2.8 ng/mL (6.7 ng/mL at baseline). Decreases in PSA were sustained through 12 months of observation.

No grade 3/4 adverse events occurred during the procedure. Grade 1/2 hematuria was reported for all 15 patients at 90 days post ablation.

Two occurrences of residual disease were reported at 3 months. According to the investigators, these occurrences may have been due to the positioning of the laser catheter. At 3 and 12 months, residual disease was observed in two patients. The investigators attribute this to incomplete treatment resulting from an underestimation of the lesion volume during procedure planning.

"Pretreatment planning is crucial," Rastinehad said. He pointed out that if the region of interest is not drawn correctly, the laser light will miss its target. "The placement of the trocars is important," he said.

In a comment to Medscape Medical News, D'Amico said, "One issue is that any form of focal ablation (even if mpMRI directed) does not ensure cure, because mpMRI can miss lesions that are grade 4 and that are <0.5 cm3 in size, and certainly misses microscopic disease.

"So the question remains as to whether, by missing such disease even in carefully selected men, they are at risk for worse outcomes than if they are treated when and if their PSA subsequently rises," he added.

Rastinehad emphasized that the objective of focal ablation therapy is to control cancer and reduce the undesirable side effects that men experience with other approaches that are currently in use.

He noted that pinpoint, tumor-specific ablation ensures less inflammation of prostatic tissue so that patients can undergo surgery successfully, if needed. Indeed, one patient in the study has subsequently undergone robotic prostatectomy successfully, Rastinehad said.

The study was sponsored by Nanospectra Biosciences, Inc. Rastinehad is the national principal investigator for the multi-institutional trial of GSN-directed ablation funded by Nanospectra Biosciences, with whom he also consults. Two coauthors cofounded Nanospectra Biosciences and have an equity stake in the company but have indicated that are not involved with the company's business or strategic decisions.

Proc Natl Acad Sci. Published online August 26, 2019. Full text

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