Diffuse reflectance spectroscopy can differentiate high grade and low grade prostatic carcinoma.

Prostate tumors are graded by the revised Gleason Score (GS) which is the sum of the two predominant Gleason grades present ranging from 6-10. GS 6 cancer exclusively with Gleason grade 3 is designated as low grade (LG) and correlates with better clinical prognosis for patients. GS >7 cancer with at least one of the Gleason grades 4 and 5 is designated as HG indicate worse prognosis for patients. Current transrectal ultrasound guided prostate biopsies often fail to correctly diagnose HG prostate cancer due to sampling errors. Diffuse reflectance spectra (DRS) of biological tissue depend on tissue morphology and architecture. Thus, DRS could potentially differentiate between HG and LG prostatic carcinoma. A 15-gauge optical biopsy needle was prototyped to take prostate biopsies after measuring DRS with a laboratory fluorometer. This needle has an optical sensor that utilizes 8×100 µm optical fibers for tissue excitation and a single 200 µm central optical fiber to measure DRS. Tissue biopsy cores were obtained from 20 surgically excised prostates using this needle after measuring DRS at 5 nm intervals between 500-700 nm wavelengths. Tissue within a measurement window was histopathologically classified as either benign, LG, or HG and correlated with DRS. Partial least square analysis of DRS identified principal components (PC) as potential classifiers. Statistically significant PCs (p<;0.05) were tested for their ability to classify biopsy tissue using support vector machine and leave-one-out cross validation method. There were 29 HG and 49 LG cancers among 187 biopsy cores included in the study. Study results show 76% sensitivity, 80% specificity, 93% negative predictive value, and 50% positive predictive value for HG versus benign, and 76%, 73%, 84%, and 63%, for HG versus LG prostate tissue classification. DRS failed to diagnose 7/29 (24%) HG cancers. This study demonstrated that an optical biopsy needle guided by DRS has sufficient accuracy to differentiate HG from LG carcinoma and benign tissue. It may allow precise targeting of HG prostate cancer providing more accurate assessment of the disease and improvement in patient care.

Systematic diagnosis of prostate cancer using an optical biopsy needle adjunct with fluorescence spectroscopy.

Transrectal ultrasound guided prostate biopsies often fail to diagnose prostate cancer with 90% of cores reported as benign. Thus, it is desirable to target prostate cancer lesions while reducing the sampling of benign tissue. The concentrations of natural fluorophores in prostate tissue fluctuate with disease states. Hence, fluorescence spectroscopy could be used to quantify these fluctuations to identify prostate cancer. An optical biopsy needle with a light sensitive optical probe at the tip of the inner needle was developed to take prostate biopsies after measuring tissue fluorescence with a laboratory fluorometer. The optical probe consists of eight 100 µm fibers for tissue excitation and a single 200 µm fiber to capture fluorescence spectra. Random biopsy cores were taken from 20 surgically excised prostates after measuring fluorescence spectra of tissue between 295-550nm for several excitations between 280-350nm. Each biopsy core was histopathologically classified and correlated with corresponding spectra. Prostate biopsies were grouped into benign or malignant based on the histological findings. Out of 187 biopsy cores, 109 were benign and 78 were malignant. Partial least square analysis of tissue spectra was performed to identify diagnostically significant principal components as potential classifiers. A linear support vector machine and leave-one-out cross validation method was employed for tissue classification. Study results show 86% sensitivity, 87% specificity, 90% negative predictive value, and 83% positive predictive value for benign versus malignant prostate tissue classification. This study demonstrates potential clinical applications of fluorescence spectroscopy guided optical biopsy needle for prostate cancer diagnosis with the consequent improvement of patient care.

Anterior tumors of the prostate: diagnosis and significance.

INTRODUCTION: Prostate biopsies are usually taken from the peripheral rather than anterior region of the prostate. Consequently, tumors originating from the anterior apical region and transition zones may be under-sampled. We examined whether addition of transrectal anterior biopsy (TAB) would improve efficacy of prostate biopsies. MATERIALS AND METHODS: Simulations of TAB and sextant biopsy (SB) were performed using computer models of 86 autopsy prostates (AP) and 40 radical prostatectomy (RP) specimens. TAB was obtained bilaterally from apex, mid, and base regions by advancing the biopsy needle 5 mm-35 mm beyond the prostatic capsule. A phase I clinical trial with 114 patients was conducted to determine the performance of an extended biopsy protocol consisting of TAB, SB, and laterally-directed biopsy (LDB). RESULTS: The overall cancer detection rates of SB and TAB were 33% and 55% for AP series (p = 0.00003); 60% and 88% for RP series (p = 0.006). Alternatively, SB + bilateral apical TAB and SB + bilateral mid TAB had cancer detection rates of 45% and 42% for AP series; 80% and 78% for RP series. The extended biopsy protocol detected cancer in 33% (38/114) of patients with 29, 25, and 15 diagnosed by SB, LDB, and bilateral apical TAB, respectively. Patients diagnosed by bilateral apical TAB versus SB (p = 0.01) and LDB (p = 0.02) were statistically significant. Without bilateral apical TAB, the overall cancer detection rate decreased to 30% (34/114). CONCLUSIONS: Inclusion of bilateral TAB from apical region for first time and repeat prostate biopsies may increase diagnosis of prostate cancer. The clinical significance of these findings needs further investigations and clinical follow up.

Optimization of prostate cancer diagnosis by increasing the number of core biopsies based on gland volume.

In this prospective, non-randomized phase-I clinical trial, we comparatively studied the performance of six laterally-directed biopsies or the modified fan-shaped biopsies (MFSB), midline sextant biopsies (MB), and transition zone biopsies (TZB) and examine their prostate cancer (PCa) detection rates. A total of 114 patients received combinations of MFSB, MB, and TZB based on prostate gland volume: those ≤15 cc received 8 biopsies; those >15 cc but ≤ 50 cc received 14 biopsies; and those >50 cc received 20 biopsies. The mean prostate-specific antigen (PSA) level, Gleason score, and prostate volume were 8.0 ng/ml, 6.4, and 47 cc, respectively. PCa detection rate of the MB was 25% while the MFSB was 22%. The overall PCa detection rate was 33.3% with all biopsies. PCa and high-grade prostatic intraepithelial neoplasia (HG-PIN) detection rates decrease as the size of the prostate increases. PCa detection rates were 50.0% for volumes ≤19.9 cc and volumes of >50 cc had a detection rate of 25.8%. PSA levels of <3.0 had PCa detection rates of 15% which increased to 58% with PSA levels >9.0. In a multivariate analysis, only TZB was significant for PCa diagnosed by PSA (ß=7.4, p<0.01). Our study showed that it is important to perform both the lateral MFSB and the MB to improve overall PCa detections rates. Thus, we recommend performing MB, MFSB, and TZB based on prostate volume, as follows: 8 biopsies for ≤15 cc; 14 for those >15 cc but ≤50 cc, and 14-20 for those >50 cc.

Proliferative tumor doubling times of prostatic carcinoma.

Prostate cancer (PCa) has a variable biology ranging from latent cancer to extremely aggressive tumors. Proliferative activities of cancers may indicate their biological potential. A flow cytometric assay to calculate maximum proliferative doubling times (T(max)) of PCa in radical prostatectomy specimens after preoperative in vivo bromodeoxyuridine (BrdU) infusion is presented. Only 4/17 specimens had tumors large enough for flow cytometric analysis. The T(max) of tumors was similar and ranged from 0.6 to 3.6 months. Tumors had calculated doubling times 2- to 25-fold faster than their matched normal tissue. Variations in labeling index and T(max) were observed within a tumor as well as between different Gleason grades. The observed PSA doubling times (PSA-DT) ranged from 18.4 to 32.0 months, considerably slower than the corresponding T(max) of tumors involved. While lack of data for apoptotic rates is a limitation, apparent biological differences between latent versus aggressive PCa may be attributable to variations in apoptotic rates of these tumors rather than their cell proliferative rates.