Abstract
The risk of biochemical recurrence of prostate cancer among individuals who undergo radical prostatectomy for treatment is around 25%. Current clinical methods often fail at successfully predicting recurrence among patients at intermediate risk for recurrence. We used a label-free method, spatial light interference microscopy, to perform localized measurements of light scattering in prostatectomy tissue microarrays. We show, for the first time to our knowledge, that anisotropy of light scattering in the stroma immediately adjoining cancerous glands can be used to identify patients at higher risk for recurrence. The data show that lower value of anisotropy corresponds to a higher risk for recurrence, meaning that the stroma adjoining the glands of recurrent patients is more fractionated than in non-recurrent patients. Our method outperformed the widely accepted clinical tool CAPRA-S in the cases we interrogated irrespective of Gleason grade, prostate-specific antigen (PSA) levels and pathological tumor-node-metastasis (pTNM) stage. These results suggest that QPI shows promise in assisting pathologists to improve prediction of prostate cancer recurrence.
Highlights
A method capable of forecasting recurrence is highly desirable
Normal prostate stroma is composed of collagen fibers, smooth muscle cells and fibroblasts, unlike breast and ovarian stroma, which are not smooth muscle-rich[26]
We believe that the changes in anisotropy of scattering detected by quantitative phase imaging (QPI) are consistent with current understanding of prostate cancer biology
Summary
A method capable of forecasting recurrence is highly desirable. The commonly used tools to predict biochemical prostate cancer recurrence after prostatectomy, Kattan nomogram and Cancer of the Prostate Risk Assessment (CAPRA-S score), have c-index values ranging from 0.76–0.81 (see Supplemental Information for a review of this metric)[6,7]. Scattering differences measured using optical coherence tomography have been used as a diagnostic measure for in-vivo cancer diagnosis in bladder, esophagus, skin, uterus, stomach and breast[8,9,10,11,12,13,14] These studies concluded that scattering was stronger in cancerous regions when compared to normal tissue. The resulting SLIM image contains rich information about tissue morphology, with the glandular epithelium and stroma structures clearly resolved (Fig. 3). This allows us to interrogate scattering changes specific to prostate stroma. We used an unstained prostate tissue microarray containing prostatectomy samples of patients with and without biochemical recurrence of cancer, and studied changes in scattering signatures to identify patients at higher risk for recurrence
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