Cancer of the prostate is the most commonly diagnosed cancer and is the second leading cause of cancer death in American men. The widespread use of serum prostate-specific antigen (PSA), along with digital rectal examination (DRE), transrectal ultrasound (TRUS)-guided biopsies, and greater acceptance of screening led to an abrupt increase in prostate cancer (PC) incidence in the United States beginning in the late 1980s, which has now leveled off. In 2009, approximately 192,280 men in the United States are expected to be diagnosed with PC, and approximately 27,360 are projected to die from the disease. The techniques of PSA, DRE, and TRUS establish an increased likelihood that PC may be present. Diagnosis and prognosis of prostate tumors currently relies on the histopathological evaluation of the biopsy together with clinical findings to determine treatment. Gleason score (GS) is one determinant of a patient's specific risk of dying due to PC, and it strongly influences decisions regarding options for therapy. The majority of PC patients are now diagnosed with moderately malignant tumors of GS 6 and 7 in a 2 to 10 scale. These tumors can take two distinct disease courses -- indolent or highly aggressive, leading to death if not treated. Clinicians and patients daily must choose a primary treatment modality such as surgery, radiation therapy, or cryosurgery, accompanying morbidity and potential for compromised quality of life due to incontinence and/or impotence; or watchful waiting, risking life with delayed treatment. However, the histopathological examination and Gleason grading and scoring is largely subjective. It may be subject to the inter- and intra-personal variability in interpretation, sometimes with discordance in interpretation. Although very good for prognosis, Gleason score ignores nuclear morphology and may not be predictive in all cases, particularly within the largest group of intermediate grade cancer GS 6 cases. Furthermore, an invasive procedure with tissue removal is required to render a Gleason score.

In response to the limits of current pathological evaluations, we here propose to use a specialized optical technique, hyperspectral low coherence enhanced backscattering mesoscopic tomography (LEBT), as a diagnostic and prognostic modality. This method is noninvasive and sensitive to subtle tissue architectural and nuclear structural changes that are known to accompany tumor development and progression. As light scattering is sensitive to sub-wavelength alterations in tissue structure, it is likely to sense these changes much earlier than histopathology. LEBT makes use of unaltered tissue specimens without processing or staining. It scans a narrow low coherence beam across the surface of the specimen, generates a three-dimensional map of tissue architecture and nuclear morphology, and computes an optical risk score for prostate cancer, serving as an objective technique either independent or added to histopathology for predicting prostate tumor aggressiveness. It can therefore help clinicians determine optimal treatments for individual patients.

In this study, we plan to quantify prostate cancer with both LEBT and histopathology in order to establish their correlations and define an optical risk score for prostate cancer that can distinguish prostate cancer from normal prostate and benign prostate hyperplasia (BPH), as well as sub-stratify prognostically heterogeneous GS 6 and 7 tumors. The optical risk scoring system will be validated and its predictive value for patient's outcome will be evaluated on a cohort of approximately thirty patients with known clinical outcome, in collaboration with the well-established NYU prostate tissue bank, which was developed as part of the NCI-supported Cooperative Prostate Cancer Tissue Resource (CPCTR). Since the project will work with fresh cyropreserved tissue specimens that have already been surgically removed, there will be no additional risks to the study participants. By working closely with currently accepted pathology criteria, at the end of this proposed project we will establish the basis for a new, improved grading system for prostate cancer, particularly GS 6 and 7 tumors based on optically probed tissue architecture and nuclear structure, as well as the sensitivity of this new grading system for distinguishing between normal tissue, benign, and malignant lesions and for predicting patient outcome. Our goal is to develop an easy-to-use tool to help clinicians determine the most appropriate treatment strategy for protecting both life and quality of life for individual patients.