# Increasing nerve-sparing radical prostatectomy rates using intraoperative nonlinear microscopy

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $466,284

## Abstract

Prostate cancer is the most common cancer in the US male population, with an estimated 160,000 new cases
in 2018. Treatment with radical prostatectomy (RP), complete surgical excision of the prostate, results in
favorable oncologic outcomes with long-term survival benefits. Nerve-sparing RP is favored if cancer does not
involve the neurovascular bundles since patients have better recovery of sexual function and continence, major
factors determining postoperative quality of life. However current preoperative methods do not accurately identify
patients who could be treated by nerve-sparing RP. The NeuroSAFE study, Schlomm, et al., 2012 demonstrated
that comprehensive intraoperative frozen section analysis (FSA) of margins near the neurovascular bundles
increased the rate of nerve-sparing RPs. However comprehensive intraoperative FSA required extensive time
and personnel, which is impractical for most hospitals. Nonlinear microscopy (NLM) can generate images of
freshly excised tissue resembling H&E histology, without freezing or microtoming, reducing the time and labor
required for pathology evaluation. We developed custom NLM technology and specimen handing/staining
protocols for rapid, high-throughput evaluation of prostatectomy specimens. Our preliminary data demonstrates
that NLM detects prostate cancer with 97% sensitivity and 100% specificity compared to formalin fixed paraffin
embedded (FFPE) H&E in a study of 122 RP specimens from 40 patients with blinded reading by three
pathologists. NLM promises to enable intraoperative evaluation of RP specimens with a simplified workflow that
is practical for widespread clinical adoption. Our hypothesis is: NLM can be used to rapidly assess prostate
surgical specimens and increase nerve-sparing RP rates without increasing positive margin rates. This is a
collaborative, multidisciplinary program with investigators at the Massachusetts Institute of Technology and Beth
Israel Deaconess Medical Center (BIDMC), Harvard Medical School. Aim 1 will develop next generation NLM
technology and clinical workflow for rapid, comprehensive evaluation of prostate specimens in RP. These
advances will enable a two person team (histotech/resident and pathologist) to perform comprehensive NLM of
RP margins adjacent to the neurovascular bundles, faster and with much fewer personnel than NeuroSAFE.
Aim 2 will perform a randomized controlled trial with patients undergoing robotic RP. The primary endpoints will
be the rate of nerve-sparing RPs and rate of positive surgical margins in areas adjacent to the neurovascular
bundles in a study group receiving intraoperative NLM margin assessment and standard-of-care postoperative
FFPE histology versus a control group receiving standard-of-care FFPE postoperative histology. The secondary
endpoints will be agreement between intraoperative NLM versus postoperative histology in the study arm and
surgical times in the study arm versus control arm. Aim 3 will develop NLM technology and wo...

## Key facts

- **NIH application ID:** 10121810
- **Project number:** 1R01CA249151-01A1
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** JAMES G FUJIMOTO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $466,284
- **Award type:** 1
- **Project period:** 2021-02-05 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121810

## Citation

> US National Institutes of Health, RePORTER application 10121810, Increasing nerve-sparing radical prostatectomy rates using intraoperative nonlinear microscopy (1R01CA249151-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10121810. Licensed CC0.

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