New prospective for non-invasive detection, grading, size evaluation, and tumor location of prostate cancer.

BACKGROUND: PSA blood test and other present screening tools fail to provide the required sensitivity and specificity and, at early stages, lack correlation with tumor grade, volume, and location. Thus alternative approaches are highly desired. We present and assess a novel method for PCa detection, grading, volume evaluation and tumor location, based on non-invasive zinc concentration mapping in the gland by means of a dedicated rectal probe. METHODS: Zinc-concentration values measured in histologically examined tissue fragments from needle biopsy of 598 patients were analyzed. They were used to generate computer simulated zinc-concentration maps, further analyzed with image-processing tools. The tumor detection performances versus Gleason grade were assessed. RESULTS: A significant increase of zinc depletion with increasing Gleason pattern (grade) classification was established. Tumor detection performance in zinc-concentration maps progressively improves with the cancer's first component score. Reliable information on the location, size and Gleason-grade combination of the lesion can be extracted for clinically relevant volumes. CONCLUSIONS: Zinc depletion in the prostate peripheral zone is the basis for a novel, non-invasive PCa detection, localization, volume evaluation and grading method. Its realization and application as a pre-biopsy and pre-treatment examination, or a follow-up tool, relies on the development of a dedicated transrectal probe. It should have significant impact on biopsy effectiveness, point at a possible extraprostatic extension and provide critical data for focal treatment. The information on tumor grade and distribution may have an important impact on disease management.

Clinical assessment of the cancer diagnostic value of prostatic zinc: a comprehensive needle-biopsy study.

BACKGROUND: The correlation between Zinc concentration in the prostate's peripheral zone to the onset or presence of malignant process needs to be evaluated in detail. METHODS: Zinc concentration was measured in approximately 1-4 mm3 segments of fresh needle-biopsy cores, with X-ray fluorescence, and correlated with the histological findings of these tissue segments. RESULTS: Local Zinc concentration is correlated with the presence of cancer (PCa); the higher the Gleason score the greater the Local Zinc depletion. The Zinc value averaged over the entire extracted tissue is specific only to Gleason score 8-9 PCa. The results refer to patients avoiding Zinc-rich supplements since those show elevated prostatic Zinc concentration in identified cancer tissue. A computer simulation analysis of randomly located 0.03-3.3 cm3 lesions, with particular Gleason score and the measured Local Zinc concentration, revealed a potential diagnostic approach definitely superior to PSA, with sensitivity to the tumor grade and with excellent detection capability for Gleason score >6. Further clinical studies have been designed, both on full prostates after radical prostatectomy as well as on biopsy cores at higher resolution, to establish the accuracy of the method for Gleason score = 6. CONCLUSIONS: The PCa diagnostic potential of Local Zinc concentration is confirmed and there is indication that the amount of Zinc depletion could be used as a measure of the Gleason score of the tumor. Local Zinc concentration mapping has the potential to improve patient selection for biopsy, biopsy site selection and local therapy (e.g., Cryotherapy, Brachytherapy) site selection.

Prostatic Zn determination for prostate cancer diagnosis.

We present our studies of prostatic Zn concentration measurements, carried out in the light of a novel prostate cancer (CAP) diagnosis method proposed by us. The method is based on in vivo prostatic Zn mapping by XRF trans-rectal probe. We report on the extensive clinical studies, intended to assess the validity of the novel proposed diagnostic method. Zn content was measured in vitro in needle-biopsy samples from several hundreds of patients, and was correlated with histological findings and other patient parameters. For this purpose, a technique of absolute Zn content determination in approximately 1mm(3) fresh tissue samples by XRF was developed. The experimental details and the main clinical-evaluation results are presented. We further outline the suggested design of the XRF trans-rectal probe for an efficient in vivo detection and mapping of the Zn fluorescence radiation from the prostate through the rectal wall. Laboratory phantom studies, a preliminary design concept and its expected performance are also reported.

In vivo determination of prostatic zinc: phantom feasibility study.

This paper describes a phantom-based feasibility study for a potential in vivo determination of zinc in prostate, which could bring about improved diagnosis of prostate cancer. An x-ray fluorescence topographic technique was developed, which will permit determination of the Zn content in the prostate through the rectum, namely behind a 2-3 mm thick layer of the rectal wall. The topographic approach, together with a reconstruction method developed here, minimizes the interference of Zn from non-prostatic tissue. The phantom studies show that it will be possible to determine Zn in a prostatic compartment behind a few mm thick layer of tissue using a specially designed transrectal probe. Such a probe is currently under development in our laboratories.