Review Identifies Factors That Influence Patient Treatment Choice For Localized Prostate Cancer

UroToday.com - Variables that influence a patients' choice of treatment for localized prostate cancer (CaP) are identified in a literature review that is authored by Dr. Zeliadt and colleagues and appears in the on-line version of Cancer, 2006.

Cancer eradication is a primary concern for many men, but perhaps surprisingly not paramount to all patients. One study of 1000 CaP patients found that 42% defined an effective treatment as one that extended survival or delayed disease progression, but 45% defined effectiveness as preservation of quality of life (QOL). This contrasted to physicians, of whom 90% defined effectiveness as extended survival. In another study, only 20% of CaP patients selected either "effect of treatment of length of life" or "chances of dying of cancer" as 1 of the 4 most relevant factors in making a decision.

It is apparent that CaP patients associate cancer eradication with aggressiveness of therapy and radical prostatectomy (RP) was considered the most aggressive. One study found that 98% of RP patients and 50% of brachytherapy patients selected their treatment choice on the basis of evidence that it was the most curative procedure.

Regarding QOL, the issue of incontinence was more concerning than impotence. In fact, urinary and bowel side effects were the only 2 variables found to be important to greater than 50% of patients. Another study found that 49% and 38% of patients were concerned about incontinence and impotence, respectively. However, this must be assessed in the context of their pre-operative functional status. One report found that 55% of spouses reported that side effects were important, but only 6% indicated that side effects were deciding factors.

Only 2% of men indicated that out-of-pocket costs were important in selecting treatment choice. While spouses often are very involved in obtaining treatment information, one study found that only 13% of patients thought they would base their decision on family influence.

Clearly, patients are more involved in the decision making process. The same survey given to 2 cohorts of patients 5 years apart finds that more recently 32% as compared to 58% wanted their physician to make the final decision. Also, patients most commonly rely on the opinion of their urologist. While 37% sought a second opinion, 75% selected the first treatment recommended to them.

Review of studies regarding racial, socioeconomic and cultural factors reveal that African-American men more commonly receive less aggressive therapy. However, more educated men more commonly had watchful waiting presented to them, while higher income patients had surgery or brachytherapy discussed.

Many variables are found to influence a patients' selection of treatment for localized CaP. In addition to cancer eradication and QOL, clearly the initial physician a CaP patient interacts with regarding their new diagnosis of CaP is the most influential.

By Christopher P. Evans, MD

Reference:
Cancer. 2006 May 1;106(9):1865-74.
Link Here. Zeliadt SB, Ramsey SD, Penson DF, Hall IJ, Ekwueme DU, Stroud L, Lee JW

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Common Genetic Prostate Cancer Variant Is Identified

UroToday.com - Prostate cancer (CaP) is a presumed result of both genetic and environmental events. It is known that a positive family history and African-American ancestry will increase the risk of developing CaP 2-4 fold. This strongly supports a genetic alteration as a significant contributing factor. In the online version of Nature Genetics, the group working under Dr. Kari Stefansson in Iceland has reported a genetic variant on chromosome 8q24.

In the report, 3 genome-wide linkage studies were performed. The first used 1.068 microsatellite markers (repetitive stretches of short DNA sequences that occur in increased numbers in cancer cells) were typed for 871 Icelandic men with CaP that grouped into 323 extended families. This identified a suggestive linkage signal on chromosome 8q24. The researchers genotyped an additional 358 microsatellite markers spanning this region in 869 unrelated men with CaP and 596 population case-controls.

A second group of 422 Icelandic men with CaP and 401 controls was studied and the -8 variant was verified with an OR of 1.72 (p=0.0018). Combining the Icelandic groups demonstrated that the DG8S737 -8 allele variant had a frequency of 13.1% in affected men and 7.8% in controls. This corresponded to a population attributable risk of 11%.

Furthermore, 63 single nucleotide pleomorphisms (SNPs or single nucleotide alterations in a short genetic sequence) were geontyped and 37 were found significantly associated with CaP. Most associated were allele A of SNP rs1447295 (OR=1.72) and this correlated with the DG8S737 -8 allele.

The researchers attempted to replicate the findings in 1.435 unrelated men with CaP and 779 controls from Sweden and 458 European America men with CaP and 247 controls from Chicago. The frequency of the DG8S737 -8 allele variant was greater in affected men than in controls for all groups.

In the final study, 246 African-American men with CaP and 352 controls were genotyped and the frequency of the DG8S737 -8 allele variant was 23.4% in African American men with CaP and 16.1% in controls with an OR of 1.6. Of the SNPs evaluated in this study, rs1447295 gave the lowest, but not significant result suggesting that DG8S737 -8 rather than the SNPs is either itself a functional variant or is tightly associated with a presently unknown risk variant. In African-American men the association for affected individuals was 41% and 30% in the population, with a population attributable risk of 16% that may contribute to the higher incidence of CaP in African-American men.

An analysis of 510 Icelandic men with BPH did not show a significant excess of either the DG8S737 -8 allele or allele A of re1447295.

By Christopher P. Evans, MD

Reference:
Nat Genet. 2006 Jun;38(6):652-8. Epub 2006 May 7.
Link Here (PDF)

Amundadottir LT, Sulem P, Gudmundsson J, Helgason A, Baker A, Agnarsson BA, Sigurdsson A, Benediktsdottir KR, Cazier JB, Sainz J, Jakobsdottir M, Kostic J, Magnusdottir DN, Ghosh S, Agnarsson K, Birgisdottir B, Le Roux L, Olafsdottir A, Blondal T, Andresdottir M, Gretarsdottir OS, Bergthorsson JT, Gudbjartsson D, Gylfason A, Thorleifsson G, Manolescu A, Kristjansson K, Geirsson G, Isaksson H, Douglas J, Johansson JE, Balter K, Wiklund F, Montie JE, Yu X, Suarez BK, Ober C, Cooney KA, Gronberg H, Catalona WJ, Einarsson GV, Barkardottir RB, Gulcher JR, Kong A, Thorsteinsdottir U, Stefansson K

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Establishing An Integrated Molecular Signature Model For Metastatic Prostate Cancer

UroToday.com - Genomic and proteomic profiling has attempted to link patients with the likelihood for advanced disease progression. Approaches to do this are reviewed by Dr. Taylor and associates in the June 1, 2006 issue of Cancer Research.

Integrated approaches are of three types. One uses data available in the public domain rather than experimental, patient derived data and uses data-mining and bioinformatics. A second model integrates experimental data with heterogeneous public data sources. The third approach integrates multifaceted genomic and proteomic data for analysis of metastatic risk.

The paper reviews the integrated approach from the laboratory of Dr. Arul Chinnaiyan at the University of Michigan. Specimens from patients include benign, localized malignant and metastatic tissues that undergo direct proteomic analysis by an antibody-based high-throughput immunoblot approach. This methodology was validated with traditional immunoblotting and tissue microarray-based immunohistochemical staining. Correlation was also performed with prostate cancer transcriptomes to include publicly available genes expression studies and microarrays. Mapping between genes and dysregulated proteins resulted in data for meta-analysis by statistical procedures.

A 50-gene ensemble was identified that served as a multiplex signature of CaP progression when it was applied to patient primary disease specimens. The 50-gene signature was tested with two CaP gene expression studies and demonstrated strong concordance. The data suggests that mRNA transcripts that correlate with protein levels in metastatic disease could be applied as a multiplex gene predictor of CaP progression in localized disease. Application to other primary tumor types also supported relevance.

The integration of high-throughput data could also be extended to other proteomic platforms, such as mass spectrometry or array-based platforms.

By Christopher P. Evans, MD

Reference:
Cancer Res 2006;66:5537-39
Link Here.
Taylor BS, Varambally S, Chinnaiyan AM

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Symptom Severity Of PBS/IC Difficult To Predict Based On Medical History And Demographics

UroToday.com - The association, if any, between medical or demographic characteristics and symptom severity in chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS) and PBS/IC patients has not been well studied. Clemens and colleagues from Northwestern University reviewed their patient database covering 1999 to 2002 to identify patients diagnosed with CP/CPPS and IC. Questionnaires were mailed to these patients, and nonresponders were followed up 6 months later. The questionnaires asked for information on demographics, medical history, and smoking and alcohol intake. A standardized mental health questionnaire was administered, and females were sent the O'Leary Sant Symptom and Problem Indexes as well as the AUA Symptom Index. Men were sent the NIH chronic prostatitis symptom index.

Self-reported urinary urgency and frequency, depression and lower education level were independent predictors of symptom severity in men with CP/CPPS and women with PBS/IC. Self-reported pelvic pain, fibromyalgia and a previous heart attack predicted symptom severity in men and postmenopausal status predicted symptom severity in women. The authors conclude that although several common medical conditions are associated with urological pelvic pain syndromes in men women, few of them were predictive of symptom severity in this analysis.

By Philip M Hanno, MD, MPH
Reference:
Journal of Urology, 175:963-967, 2006
Link Here.
Clemens JQ, Brown SO, Kozloff L, Calhoun EA

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