Benign Prostatic Hyperplasia – Prostate Cancer – Prostatitis

Archive for the ‘Prostate Cancer’ Category

Endocrine Therapy and Observation

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Outcome variables in treating node-positive prostate cancer have traditionally included local progression (bladder outlet obstruction, ureteral obstruction, impotence), biochemical recurrence or progression, development of distant metastasis, and disease-specific survival. More recently, the issue of quality of life as an outcome measure has surfaced. When reviewing the literature of immediate versus deferred hormonal therapy, that is, observation, for advanced prostate cancer, it is important to be aware of the specific outcome variables being measured and compared. Moul provides an excellent definition of this clinical scenario as well as a review of the hormonal management of advanced prostate cancer, employing data recently published in Britain by the Medical Research Council Prostate Cancer Working Party Investigators Group. The literature examined in Moul's review clearly and unequivocally confirms that early hormonal therapy delays the time to progression (biochemical and symptomatic), a result that has been confirmed by several authors. The rates of pathologic bone fracture, spinal cord Read more [...]

Screening for Prostate Cancer

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Screening for Prostate Cancer: the Case for Screening The American Cancer Society estimates that there will be 179,300 new cases of prostate cancer diagnosed in 1999, making it the most commonly diagnosed malignancy among men in the United States. In addition, a projected 37,000 men will die this year secondary to prostate cancer. As a result, the American Cancer Society and the American Urological Association (AUA) have put forth guidelines recommending that annual serum prostate-specific antigen (prostate-specific antigen) testing and digital rectal examination be offered to men aged 50 and older who have at least a 10-year life expectancy. The prostate-specific antigen and digital rectal examination should also be offered to younger men at high risk for developing prostate cancer, such as African American men or men with a strong family predisposition to the disease (two or more affected first-degree relatives, e.g., father, brother). Information should be provided to patients regarding the risks and benefits of intervention. In order for prostate cancer screening to be deemed a successful Read more [...]

Screening by Digital Rectal Examination

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Before the widespread clinical use of prostate-specific antigen, digital rectal examination was the most common initial test for the diagnosis of prostate cancer. While several earlier reports have concluded that annual screening using digital rectal examination leads to improved early detection of disease and prolonged survival, other studies contradicted these findings. The limitation of digital rectal examination as a screening test appears to be its poor sensitivity in detecting curable (i.e., pathologically organ-confined) disease. In fact, approximately 40 to 60% of men with clinically localized prostate cancer detected by annual digital rectal examination have local or systemic spread of disease when pathologic staging is available. In addition, a study by Gerber and colleagues that evaluated disease-specific survival following routine screening by digital rectal examination in over 4000 men suggests that this approach will not decrease the mortality rate from prostate cancer. The investigators compared cancers diagnosed during the initial screen (prevalence group) with those identified Read more [...]

Prostate-specific antigen Derivatives

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The sensitivity of prostate-specific antigen has never been questioned. It is the test's lack of specificity (i.e., the number of false-positives that result in invasive evaluations) that has caused most concern. In an attempt to improve specificity, several investigators have tried to modify the interpretation of prostate-specific antigen values. These modifications have been termed prostate-specific antigen derivatives. Numerous prostate-specific antigen derivatives have been developed and tested clinically with the purpose of optimizing the use of prostate-specific antigen as a screening tool. This can only be achieved by increasing the test's specificity while preserving its sensitivity. Prostate-specific antigen Density Prostate-specific antigen density is one such variation and is defined mathematically as total prostate-specific antigen (ng/mL) divided by the volume of the prostate gland (cc). The concept of Prostate-specific antigen density is based on the assumption that the Prostate-specific antigen density calculation would standardize the amount of prostate-specific antigen produced Read more [...]

The Status of Screening

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There are reports that support the notion that since the introduction of prostate-specific antigen in the late 1980s, prostate-specific antigen-based prostate cancer screening has led to dramatic changes in the epidemiology of the disease, which are suggestive of effective screening. Data supplied by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 1994 have shown a substantial increase in the number of newly diagnosed cases of prostate cancer. This trend accelerated when prostate-specific antigen use became widespread in the late 1980s. New prostate cancer cases peaked in 1992 and have since declined. However, the incidence has not fallen back to pre-prostate-specific antigen screening levels. TABLE. Percent of Free to Total prostate-specific antigen Ratio and Cancer Probability Ratio (%) Probability of Cancer (%) 0-10 56 10-15 28 15-20 20 20-25 16 >25 8 In addition to the drastic changes in the number of cases of prostate cancer during the prostate-specific antigen-testing era, there has Read more [...]

Epidemiology of Prostate Cancer in Hispanic Americans

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Definition of Hispanics The United States Bureau of the Census established the term "Hispanic" in 1970 to identify people of Spanish origin. The Hispanic population is very heterogeneous, including Mexicans, Puerto Ricans, Cubans, Dominicans, individuals from Central and South America within its subgroups, as well as those originating from the Iberian peninsula. Hispanics may be identified by their surnames as well as use of the Spanish language. However, Swallen and his colleagues demonstrated that this practice could potentially lead to ethnic misclassification which, in turn, could lead to false conclusions. In spite of these limitations, when considering Hispanics as a distinct ethnic group, several generalizations can be made. Hispanics constitute one of the fastest growing minority groups in the United States, mostly due to high immigration and fertility rates. The number of Hispanics in the United States increased by 265% from 1950 to 1980, compared to a 50% increase in the general population. By 1990, Hispanics made up approximately 9% of the United States population and could potentially Read more [...]

Pathologic Outcome

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In a retrospective review of 336 men (24 Hispanics, 33 African Americans, 279 non-Hispanic Caucasians) who did not receive neoadjuvant hormonal therapy and were treated at the authors' institution with radical prostatectomy for clinically localized prostate cancer, the incidence of extraprostatic extension of the disease was confirmed in the pathologic specimen of 67% of Hispanics, 61% of African Americans, and 52% of non-Hispanic Caucasians. The incidence of seminal vesicle involvement among Hispanics was 25%, compared to 12% and 11% in African American and non-Hispanic Caucasian patients, respectively. The status of lymphnode involvement was available for 226 patients (13 Hispanics, 24 African Americans, and 189 non-Hispanic Caucasians). Among these patients, 31% of Hispanics had positive lymph nodes on pathologic evaluation whereas no African Americans and only 3% of non-Hispanic Caucasians had evidence of nodal involvement. Friedrichs and associates included patients from two additional institutions for a total of 1026 patients and found that, after controlling for grade, clinical stage, Read more [...]

Hormonal Therapies

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Overview. Several hormonal therapies are in development for CaP. Baxter Oncology's D-63153 and teverelix (Ardana's Antaralix) are decapeptide luteinizing hormone-releasing hormone (LHRH) antagonists in Phase II development. Lack of data precludes further discussion of them. Toremifene (GTx's Acapodene) is a nonsteroidal selective estrogen-receptor modulator (SERM) in Phase Ilb / III development. It is being tested for the prevention of CaP among patients with high-grade prostatic intraepithelial neoplasia and for the prevention and treatment of osteoporosis caused by adjuvant LHRH analogues. This agent falls outside the scope of this study. In late-stage development for CaP are finasteride. Mechanism Of Action. Finasteride is a steroid analogue of testosterone that treats benign prostatic conditions by blocking the activity of the enzyme 5-alpha reductase and obstructing the conversion of testosterone to dihydrotestosterone, a hormone that plays a role in benign prostatic growth and is believed to contribute to the development of CaP. Histrelin hydrogel implant is an LHRH antagonist. Unlike Read more [...]

Epidermal Growth Factor Receptor Inhibitors

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Overview. A vast amount of R&D has been committed to the study of epidermal growth factor receptor (EGFR) inhibition. Although several EGFR inhibitors have been launched for other solid tumor types, results for CaP have been very disappointing. The two main approaches researchers have investigated are the specific inhibition of EGFR tyrosine kinase (e.g., gefitinib [AstraZeneca's Iressa]) and MAbs directed at the external domain of the EGFR (e.g., trastuzumab [Genen-tech / Roche's Herceptin] and, initially, panitumumab). Both approaches have failed to deliver results in CaP. The following sections discuss only trastuzumab and gefitinib because of their success in treating other tumor types. Please note that Panitumumab, has now been discontinued. One agent targeting the EGFR pathway that is in earlier-stage development is pertuzumab (Genentech / Roche / Chugai's Omnitarg). This next-generation, humanized, anti-HER / neu MAb is in Phase II development. Enrollment for the trial, which recruited men with hormone-refractory CaP who had received a taxane or epothilone, has been completed. Read more [...]

Antisense Therapies

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Overview. Despite its promise, no antisense therapy for the treatment of cancer has yet been approved. Genta (in collaboration with Sanofi-Aventis) and Isis are the main players in antisense approaches. This section focuses on Genta's agent, oblimersen (Genasense), because it has been the most extensively investigated for CaP. Another antisense oligonucleotide in development is Lorus Therapeutics' GTI-2501, which is targeted to the Rl component of ribonucleotide reductase, a highly regulated enzyme in the cell cycle of mammalian cells that plays an essential role in DNA synthesis and cell proliferation. The lack of published data precludes further discussion of it. Antisense oligonucleotides are short sequences of single-stranded DNA that can bind to a specific region of corresponding messenger RNA (mRNA) sequence, thereby blocking both the expression and translation of the mRNA itself and the generation of the corresponding protein encoded by the mRNA. In this way, antisense molecules can block the expression of undesirable genes and their proteins. Mechanism of Action. Oblimersen. Read more [...]