Prostate Cancer Detection

To date, needle biopsy is the best method to confirm if a malignant prostate tumor is present. However, studies show that current biopsy techniques miss up to 20 % of all prostate cancers, leaving many men with false negative results [9,10]. In these cases, the tumor will go undetected. Left untreated, it may be too late to successfiilly treat, especially if the cancer has spread beyond the prostate. 

Accurate biopsies are vital to prostate cancer detection and, hence, treatment. Early stage detection requires accurate imaging systems and precise needle insertion techniques to probe small potential tumors. Currently, ultrasound imaging is used to manually insert a biopsy needle to the prostate. Unfortunately, the biopsy needle often misses the tumor because ultrasound images are too low resolution to see small, early stage, tumors. Tumors smaller than 5 mm are not detected by ultrasound imaging [ 11 ]. Only about 20 % of tumors between 5 and 10 mm are detected by ultrasound. Even large tumors, of the order of 20-25 mm, are only detected 79 % of the time. 

Given the unique imaging capabilities of MRI, it is possible to diagnose and treat small, millimeter size tumors that cannot be detected otherwise [13, 14]. 

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Prostate cancer evaluation/Effects on PSA Finasteride causes a decrease in serum PSA levels in patients with BPH even in the presence of prostate cancer. Consider this reduction when evaluating PSA laboratory data it does not suggest a beneficial effect of finasteride on prostate cancer. In controlled clinical trials, finasteride did not appear to alter the rate of prostate cancer detection. 

The presence of the different suPAR variants in EDTA plasma from a prostate cancer patient was analyzed by size exclusion chromatography and measurement of the fractions obtained with the three different TR-FIAs. This EDTA plasma contained detectable amounts of uPAR(I) in contrast to an EDTA plasma pool from healthy donors. The levels of suPAR measured with TR-FIA 2 were considerably higher and eluted at a later position in the patient sample than in the donor plasma, thus indicating the presence of suPAR(II nf) in the patient sample [108], In a recent study, the concentrations of uPAR(I) as well as the calculated suPAR(II-III) were found to be significantly elevated in serum samples from patients with prostate cancer compared to the concentrations in serum from men with benign prostatic conditions. Specific measurements of uPAR(I) were found to improve specificity of prostate cancer detection [142],... 

In addition to the approaches described above, a number of algorithms using PSA and other analytes have been developed to increase the sensitivity of prostate cancer detection, They include logistic regression and artificial neural networks. 

Partin AW, Brawer MK, Bartscli G, et al Complexed prostate specific antigen improves specificity for prostate cancer detection Results of a prospective multicenter clinical trial. J Urology 2003 170 ... 

Partin AW, Catalona WJ, Southwick PC, et al. Analysis of percent free prostate specific antigen (PSA) for prostate cancer detection Influence of total PSA, prostate volume and age. Urology 1996 48 55-61. 

Stephan C, Cammann H, Semjonow A, et al. Multicenter evaluation of an artificial neural network to increase the prostate cancer detection rate and reduce unnecessary biopsies. Cfin Chem 2002 48 1279-87. 

Ross KS, Carter HB, Pearson JD, Guess HA. Comparative efficacy of prostate specific antigen screening strategies for prostate cancer detection. JAMA 2000 284 1399-1405. 

Gretzer MB, Partin AW. PSA markers in prostate cancer detection. Urol Clin North Am. 2003 30 677. 

Bill of Rights , state lawmakers are enacting laws in response to more specific concerns about managed care cost containment efforts. These new state laws cover such topics as requiring health plans to allow women specified minimum hospital stays after childbirth or mastectomy, or requiring physicians to inform certain male patients of specified diagnostic procedures for prostate cancer detection. 

Margreiter M, Stangelberger A, Valimberti E et al. (2008) Biomarkers for early prostate cancer detection. Minerva Urol Nefrol 60 51-60... 

Soh S, Kattan MW, Berkman S, Wheeler TM, Scardino PT (1997) Has there been a recent shift in the pathological features and prognosis of patients treated with radical prostatectomy J Urol 157 2223-2224 Takenaka A, Hara R, Hyodo Y, Ishimura T, Sakai Y, Fujioka H, Fujii T, Jo Y, Fujisawa M (2006) Transperineal extended biopsy improves the clinically significant prostate cancer detection rate a comparative study of 6 and 12 biopsy cores. Int J Urol 13 10-14... 

This chapter presents a binary manipulator for MRI guided prostate cancer biopsies and brachytherapies using a transperineal approach (Figure 22.2). The problem of prostate cancer detection and treatment is exposed along with a review of alternative approaches. The proposed manipulator concept is presented and an analytical model of its performance is developed. Model predictions are compared with experimental data. Results show that... 

Devita, L.M., An MRI Compatible Manipulator for Prostate Cancer Detection and Treatment, M.S. Thesis, Massachusetts Instimte of Technology, 2007. 

Several studies have investigated the role of dietary factors in prostate cancer risk, but results appear inconsistent. Significant effects have not been detected for dietary soya products certain vegetables, beans, fruit, rice and seaweed appear to be protective in some studies, while another has shown no protective effect from seaweed or vegetable consumption. In addition, a number of other risk factors have been shown to be associated with an increased risk of this cancer, including meat and dairy products and carotenoids. 

An evaluation of the Health Professionals Follow-Up Study (Giovannucci et al., 1995) has detected a lower prostate cancer risk associated with the greater consumption of tomatoes and related food products. Tomatoes are the primary dietary source of lycopene and lycopene concentrations are highest in testis and adrenal tissue (Clinton, 1998). In paired benign and malignant prostate tissue from 25 American men, 53-74 yrs, undergoing... 

Prostate-specific antigen (PSA) is a useful marker for detecting prostate cancer at early stages, predicting outcome for localized disease, defining disease-free status, and monitoring response to... 

Neither DRE nor PSA is sensitive or specific enough to be used alone as a screening test.12 Although the relative predictability of DRE and PSA is similar, the tumors identified by each method are different. Catalona and associates13 confirmed that the combination of a DRE and a PSA determination is a better method of detecting prostate cancer than DRE alone. 

Increased diagnosis of prostate cancer is attributed in part to the increased utilization of PSA testing. In fact, the American Cancer Society (ACS) now recommends measurement of PSA in addition to digital rectal examinations (DREs) in men over 50 years of age. Early detection of clinically localized prostate cancer can potentially result in a cure with radical prostatectomy or other treatments. PSA tests are used to monitor therapeutic efficacy and detect recurrent disease in patients with prostate cancer. 

Patients must be monitored to assess their response to treatment and to detect recurrent diseases. PSA as a specific marker for prostate cancer is most useful in monitoring patients who have been treated with radical prostatectomy, radiation therapy, or endocrine therapy. The concentration of PSA falls to undetectable levels following a radical prostatectomy because all prostate tissue has been removed. Generally, PSA is measured at periodic intervals. In studies, the extent of disease at the time of surgery correlated well with the postoperative PSA concentration. A significant measurable PSA concentration after prostatectomy indicates that residual tumor may be present. PSA concentrations decline gradually after radiation therapy (36). 

It has been reported that PSA exists in multiple isoforms in serum free PSA (30-kDa protease) and complexed PS A (100-kDa complex between PSA and A1 ACT). While the PSA in the prostate is in the free form, when the PSA enters the blood stream, the majority binds to A1 ACT. Recent studies have shown that PSA in serum occurs in two molecular forms, free (f-PSA) and bound both PSAs gave equal detectable signals ( equimolar ). Most of the PSA in serum is complexed with either A1 ACT or A2 MG. Different proportions of free and complex isoforms have been detected in the sera of prostate cancer and BPH patients. The fraction... 

Ultrasensitive assays for PSA contribute to the earlier detection of prostate cancer relapse and (or) residual disease in prostatectomized patients as well as the more timely evaluation of response to current therapies. PSA determinations can be useful in detecting metastatic or persistent disease in patients following surgical or medical treatment of prostate cancer. Persistent elevation of PSA following treatment, or an increase in the pretreatment PSA concentrations, is indicative of recurrent or residual disease. Hence, PSA is widely accepted as an aid in the management of prostate cancer patients, and serum levels are most useful when sequential values are obtained and monitored over time. After complete removal of the prostate gland (radical prostatectomy), PSA levels should become very low or undetectable. A rise of the serum PSA level in prostatectomy patients indicates residual prostate tissue, recurrence, or metastasis of the disease (13, 16, 24, 36). 

Carter, H. B., Epstein, J. I., Chen, D. W., et al. Recommended prostate-specific antigen testing intervals for the detection of curable prostate cancer. JAMA 227,1456-1460 (1997). 

Stamey, T. A. Lower limits of detection, biological detection limits, functional sensitivity, or residual cancer detection limit/sensitivity reports on prostate-specific antigen assays mislead clinicians. Clin. Chem. 42, 849-850 (1996). 

Wright, G. L., Cazares, L. H., Leung, S.-M., Nasim, S., Adam, B.-L., Yip, T.-T., Schellhammer, P. F., Gong, L., and Vlahou, A. (2000). ProteinChip surface enhanced laser desorption/ionization (SELDI) mass spectrometry a novel protein biochip technology for detection of prostate cancer biomarkers in complex protein mixtures. Prostate Cancer and Prostatic Diseases 2, 264-276. 

Oliver, SE, D Gunnell, J Donovan et al. 2004. Screen-detected prostate cancer and the insulin-like growth factor axis results of a population-based case-control study (United States). Int J Cancer 108(6) 887-892. 

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