Rapid On-Site Microscopy and Mapping of Diagnostic Biopsies for See-And-Treat Guidance of Localized Prostate Cancer Therapy

SIMPLE SUMMARY: Localized ablation is an emerging treatment for prostate cancer that minimizes recovery time and improves functional retention. However, standard histological processing of diagnostic prostate biopsies is currently performed too late to inform the treatment of localized lesions at the time of the diagnostic biopsy procedure. We investigated the feasibility of structured illumination microscopy (SIM) as an adjunct tool to confirm malignancy in fresh prostate biopsies for a future “see-and-treat” paradigm of localized prostate cancer. Forty-six biopsies were assessed by two pathologists, resulting in 92% and 87% overall diagnostic accuracies, respectively. In a proposed “clinical decision tree”, urologist predictions from MRI fusion images were compared to diagnoses from SIM images, which demonstrated that SIM feedback would constructively inform on-site intervention of localized prostate cancer and confirm margins. We demonstrated that the process necessary to generate and diagnose pseudo-hematoxylin and eosin biopsy images via SIM can be achieved in well under 15 minutes. ABSTRACT: Prostate cancer continues to be the most diagnosed non-skin malignancy in men. While up to one in eight men will be diagnosed in their lifetimes, most diagnoses are not fatal. Better lesion location accuracy combined with emerging localized treatment methods are increasingly being utilized as a treatment option to preserve healthy function in eligible patients. In locating lesions which are generally <2cc within a prostate (average size 45cc), small variance in MRI-determined boundaries, tumoral heterogeneity, patient characteristics including location of lesion and prostatic calcifications, and patient motion during the procedure can inhibit accurate sampling for diagnosis. The locations of biopsies are recorded and are then fully processed by histology and diagnosed via pathology, often days to weeks later. Utilization of real-time feedback could improve accuracy, potentially prevent repeat procedures, and allow patients to undergo treatment of clinically localized disease at earlier stages. Unfortunately, there is currently no reliable real-time feedback process for confirming diagnosis of biopsy samples. We examined the feasibility of implementing structured illumination microscopy (SIM) as a method for on-site diagnostic biopsy imaging to potentially combine the diagnostic and treatment appointments for prostate cancer patients, or to confirm tumoral margins for localized ablation procedures. We imaged biopsies from 39 patients undergoing image-guided diagnostic biopsy using a customized SIM system and a dual-color fluorescent hematoxylin & eosin (H&E) analog. The biopsy images had an average size of 342 megapixels (minimum 78.1, maximum 842) and an average imaging duration of 145 s (minimum 56, maximum 322). Comparison of urologist’s suspicion of malignancy based on MRI, to pathologist diagnosis of biopsy images obtained in real time, reveals that real-time biopsy imaging could significantly improve confirmation of malignancy or tumoral margins over medical imaging alone.