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Significance

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    The biology and natural history of prostate cancer is not completely understood. Rigorous evaluation of any prostate cancer screening modality is desirable because the natural history of the disease is variable, and appropriate treatment is not clearly defined. Although the prevalence of prostate cancer and preneoplastic lesions found at autopsy steadily increases for each decade of age, most of these lesions remain clinically undetected.[28]

    There is an association between primary tumor volume and local extent of disease, progression, and survival.[29] A review of a large number of prostate cancers in radical prostatectomy, cystectomy, and autopsy specimens showed that capsular penetration, seminal vesicle invasion, and lymph node metastases were usually found only with tumors larger than 1.4 cc.[30] Furthermore, the semiquantitative histopathologic grading scheme proposed by Gleason is reasonably reproducible among pathologists and correlates with the incidence of nodal metastases and with patient survival in a number of reported studies.[31]

    Cancer statistics from the American Cancer Society and the National Cancer Institute indicated that between 2002 and 2008, the proportion of disease diagnosed at a locoregional stage and at a distant stage was 93% and 4% for whites, compared with 91% and 6% for African Americans, respectively.[10] Stage distribution of prostate cancer is affected substantially by the intensity of early detection efforts.

    Pathologic stage does not always reflect clinical stage and upstaging (owing either to extracapsular extension, positive margins, seminal vesicle invasion, or lymph node involvement) occurs frequently. Of the prostate cancers detected by digital rectal exam (DRE) in the pre-PSA era, 67% to 88% were at a clinically localized stage (T1–2, NX, M0 [T = tumor size, N = lymph node involvement, and M = metastasis]).[32,33] However, in one of those series of 2,002 patients undergoing annual screening DRE, only one-third of men proved to have pathologically organ-confined disease.[33]

    With the proliferation of PSA for early detection, reviews of large numbers of asymptomatic men with prostate cancer found that most have organ-confined disease. One study found that 63% of cancers detected in men undergoing their first screening PSA were pathologically organ-confined cancers; the percentage increased to 71% if cancer was detected on a subsequent examination.[34] In a series of 2,999 men undergoing screening with PSA, DRE, and transrectal ultrasound, 62% of the tumors detected were reported to be pathologically organ-confined.[35] While the proportion of node-positive cancers in the pre-PSA era were in the range of 25% for patients with ostensibly localized disease, current series report proportions as low as 3%.[36] Stage T1c tumors detected by serial PSA and removed by radical prostatectomy are organ-confined in 79% of cases.[37]

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