Evidence for a Biopsy Derived Grade Artifact Among Larger Prostate Glands

Kulkarni, Girish S.; Al-Azab, Rami; Lockwood, Gina; Toi, Ants; Evans, Andrew; Trachtenberg, John; Jewett, Michael A.S.; Finelli, Antonio; Fleshner, Neil

doi:10.1016/s0022-5347(05)00236-3

Cited by 115 publications

(89 citation statements)

References 18 publications

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“…Cancer usually involves only a small fraction of the total gland, and proportionately smaller tissue is collected from a large prostate at biopsy, decreasing the chance of sampling from the cancer site(s). 12,13 This may be particularly true for high-grade cancer, which often represents only a fraction of the total cancer content. Thus, the negative biopsy group favors men who may be most susceptible to prostate enlargement, and perhaps the effects of obesity on prostate volume may be more easily detected within this group.…”

Section: Discussionmentioning

confidence: 99%

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The association between body size, prostate volume and prostate-specific antigen

Fowke

Motley

Cookson

et al. 2006

Prostate Cancer Prostatic Dis

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Increasing prostate volume contributes to urinary tract symptoms and may obscure prostate cancer detection. We investigated the association between obesity and prostate volume, prostate-specific antigen (PSA) and PSA density among 753 men referred for prostate biopsy. Among men with a negative biopsy, prostate volume significantly increased approximately 25% from the lowest to highest body mass index (BMI), waist or hip circumference or height categories. PSA was 0.7 ng/ml lower with a high waist-to-hip ratio. These associations were less consistent among subjects diagnosed with high-grade prostatic intraepithelial neoplasia or cancer. Our data suggest that obesity and height are independently associated with prostate volume.

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Section: Discussionmentioning

confidence: 99%

“…Prostate cancer may be more difficult to detect as prostate volume increases, 12,13 leading to un-or under-diagnosed prostate cancer among obese men with a greater prostate volume.…”

Section: Introductionmentioning

confidence: 99%

The association between body size, prostate volume and prostate-specific antigen

Fowke

Motley

Cookson

et al. 2006

Prostate Cancer Prostatic Dis

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“…The relevance of this finding, however, has been called into question by concerns that the biopsy Gleason score may be affected by volume or other artifacts induced by exposure to finasteride. Because finasteride is known to shrink the prostate, it has been argued that biopsy Gleason scores may be more accurate in the finasteride arm than in the placebo arm because a greater proportion of the prostate is being sampled (2,3). Accordingly, there may be less upgrading of Gleason score from biopsy to radical prostatectomy (RP) in men on finasteride.…”

mentioning

confidence: 99%

Estimating Rates of True High-Grade Disease in the Prostate Cancer Prevention Trial

Pinsky

Parnes

Ford

2008

Cancer Prevention Research

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The Prostate Cancer Prevention Trial (PCPT) showed a decreased prostate cancer rate but an increased rate of high Gleason grade disease on biopsy for finasteride versus placebo. The results from radical prostatectomy (RP) on 25% of the men undergoing RP have recently been reported and suggest that grading artifacts in biopsy Gleason scoring may have occurred. We used a statistical model to extrapolate the RP Gleason results to all men in the PCPT using a missing-at-random assumption. We estimated the rates of true high-grade (Gleason 7-10) and true low-grade disease, where true Gleason grade is what is (or would have been) found on RP. We also estimated misclassification rates on biopsy of true high-grade and low-grade disease. We show that the rate of upgrading of biopsy lowgrade disease to high-grade on RP is a function of misclassification rates as well as the ratio of true low-grade to high-grade disease. The estimated relative risks for true low-grade and true high-grade disease for finasteride compared with placebo were 0.61 (95% confidence interval, 0.51-0.71) and 0.84 (95% confidence interval, 0.68-1.05), respectively. The misclassification rate of true high-grade disease (to low-grade disease on biopsy) was significantly lower for finasteride (34.6%) than for placebo (52.6%). Although misclassification rates differed, upgrading rates were similar in each arm due to the different ratios of true low-grade to high-grade disease in each arm. Results from RP show that misclassification rates on biopsy were higher in the placebo arm and that the rate of true high-grade disease may have been lower in the finasteride arm.

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“…Some observers suggest that the likely cause of the bias could be that finasteride decreased PSA to a lesser extent in men with high-grade cancer, given that the sensitivity of PSA for detecting prostate cancer in the finasteride arm compared to the placebo arm was statistically significantly better (12). Another cause of the bias is likely due to the sampling density of a small gland volume and number of cores in the finasteride group, resulting in disproportionate sampling of the gland upon random needle biopsy as compared with the placebo group (13)(14)(15). Recently, in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, there was no significant increase in incidence of high-grade prostate cancer in the dutasteride arm, as compared with the placebo arm (1).…”

Section: Discussionmentioning

confidence: 99%

Five-alpha Reductase Inhibitor Influences Expression of Androgen Receptor and HOXB13 in Human Hyperplastic Prostate Tissue

et al. 2013

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Objectives: Five-alpha reductase inhibitors (5ARIs) are known as chemopreventive agents in prostate cancer with a risk of high-grade disease. This study evaluated the effects of 5ARI on androgen receptor (AR) and proteins involved in prostate cell growth such as HOXB13 expression in human prostate tissue and LNCaP prostate cancer cells. Materials and Methods:We retrospectively selected 21 patients who underwent TURP between March 2007 and February 2010 for previously confirmed BPH by prostate biopsy. They were grouped into control (group 1, n = 9) and 5ARI treatment (group 2, n = 12) before TURP. AR and HOXB13 expression in prostate tissue was evaluated by immunohistochemical staining. We tested the effect of 5ARI on the expression of AR, prostate specific antigen (PSA) and HOXB13 in LNCaP cells. Cells were assessed by Western blot analysis, MTT in vitro proliferation assay, and ELISA. Results: Group 2 showed stronger reactivity for AR and HOXB13 than those of the group 1. MTT assay showed death of LNCaP cells at 25uM of 5ARI. At the same time, ELISA assay for PSA showed that 5ARI inhibited secretion of PSA in LNCaP cells. Western blot analysis showed that 5ARI did not greatly alter AR expression but it stimulated the expression of HOXB13. Conclusions: These results demonstrated that 5ARI influences AR and HOXB13 expression in both LNCaP cells and human prostate tissue. In order to use 5ARI in chemoprevention of prostate cancer, we still need to clarify the influence of 5ARI in ARs and oncogenic proteins and its regulation pathway. Five-alpha

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Evidence for a Biopsy Derived Grade Artifact Among Larger Prostate Glands

Cited by 115 publications

References 18 publications

The association between body size, prostate volume and prostate-specific antigen

The association between body size, prostate volume and prostate-specific antigen

Estimating Rates of True High-Grade Disease in the Prostate Cancer Prevention Trial

Five-alpha Reductase Inhibitor Influences Expression of Androgen Receptor and HOXB13 in Human Hyperplastic Prostate Tissue

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