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      Characterizing Clinically Significant Prostate Cancer Using Template Prostate Mapping Biopsy

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          Abstract

          Definitions of prostate cancer risk are limited since accurate attribution of the cancer grade and burden is not possible due to the random and systematic errors associated with transrectal ultrasound guided biopsy. Transperineal prostate mapping biopsy may have a role in accurate risk stratification. We defined the transperineal prostate mapping biopsy characteristics of clinically significant disease. A 3-dimensional model of each gland and individual cancer was reconstructed using 107 radical whole mount specimens. We performed 500 transperineal prostate mapping simulations per case by varying needle targeting errors to calculate sensitivity, specificity, and negative and positive predictive value to detect lesions 0.2 ml or greater, or 0.5 ml or greater. Definitions of clinically significant cancer based on a combination of Gleason grade and cancer burden (cancer core length) were derived. Mean±SD patient age was 61±6.4 years (range 44 to 74) and mean prostate specific antigen was 9.7±5.9 ng/ml (range 0.8 to 36.2). We reconstructed 665 foci. The total cancer core length from all positive biopsies for a particular lesion that detected more than 95% of lesions 0.5 ml or greater and 0.2 ml or greater was 10 mm or greater and 6 mm or greater, respectively. The maximum cancer core length that detected more than 95% of lesions 0.5 ml or greater and 0.2 ml or greater was 6 mm or greater and 4 mm or greater, respectively. We combined these cancer burden thresholds with dominant and nondominant Gleason pattern 4 to derive 2 definitions of clinically significant disease. Transperineal prostate mapping may provide an effective method to risk stratify men with localized prostate cancer. The definitions that we present require prospective validation. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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          Most cited references22

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          Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer.

          PURPOSE We assessed the outcome of a watchful-waiting protocol with selective delayed intervention by using clinical prostate-specific antigen (PSA), or histologic progression as treatment indications for clinically localized prostate cancer. PATIENTS AND METHODS This was a prospective, single-arm, cohort study. Patients were managed with an initial expectant approach. Definitive intervention was offered to those patients with a PSA doubling time of less than 3 years, Gleason score progression (to 4 + 3 or greater), or unequivocal clinical progression. Survival analysis and Cox proportional hazard model were applied to the data. Results A total of 450 patients have been observed with active surveillance. Median follow-up was 6.8 years (range, 1 to 13 years). Overall survival was 78.6%. The 10-year prostate cancer actuarial survival was 97.2%. Overall, 30% of patients have been reclassified as higher risk and have been offered definitive therapy. Of 117 patients treated radically, the PSA failure rate was 50%, which was 13% of the total cohort. PSA doubling time of 3 years or less was associated with an 8.5-times higher risk of biochemical failure after definitive treatment compared with a doubling time of more than 3 years (P < .0001). The hazard ratio for nonprostate cancer to prostate cancer mortality was 18.6 at 10 years. CONCLUSION We observed a low rate of prostate cancer mortality. Among the patients who were reclassified as higher risk and who were treated, PSA failure was relatively common. Other-cause mortality accounted for almost all of the deaths. Additional studies are warranted to improve the identification of patients who harbor more aggressive disease despite favorable clinical parameters at diagnosis.
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            Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer.

            We examined preoperative clinical and pathologic parameters in men with clinical stage T1c disease who underwent radical prostatectomy and correlated these findings with the pathologic extent of disease in the surgical specimen in an attempt to identify a subset of patients with potentially biologically insignificant tumor who might be followed up without immediate treatment. A case series of 157 consecutive men who underwent radical prostatectomy for clinical stage T1c disease compared with 64 similarly treated clinical stage T1a cancers (incidental minimal cancers found on transurethral resection of prostate) and 439 clinical stage T2 (palpable) cancers. Pathologic stage, grade, and margins; tumor volume; and tumor location. Sixteen percent of tumors were insignificant ( 0.5 cm3 or capsular penetration, with a Gleason score or = 7 or positive margins, seminal vesicles, or lymph nodes). These findings are intermediate between those found in clinical stage T1a and stage T2 disease. The following parameters were not predictive of tumor extent: age, reason for evaluation, method of detection, and transrectal ultrasound. The best model predicting insignificant tumor was prostate-specific antigen (PSA) density less than 0.1 ng/mL per gram and no adverse pathologic findings on needle biopsy, or PSA density of 0.1 to 0.15 ng/mL per gram, with a low- to intermediate-grade cancer smaller than 3 mm found in only one needle biopsy core specimen. The positive predictive value of the model was 95%, with a negative predictive value of 66%. We accurately predicted 73% of cases with insignificant tumor. Eighty-four percent of nonpalpable prostate cancers diagnosed by screening techniques are significant tumors and warrant definitive therapy. However, 16% are insignificant. Serum PSA level, PSA density, and needle biopsy pathologic findings are accurate predictors of tumor extent. It may be reasonable to follow up some patients whose tumors are most likely insignificant with serial PSA measurements and repeated biopsies.
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              Rethinking screening for breast cancer and prostate cancer.

              After 20 years of screening for breast and prostate cancer, several observations can be made. First, the incidence of these cancers increased after the introduction of screening but has never returned to prescreening levels. Second, the increase in the relative fraction of early stage cancers has increased. Third, the incidence of regional cancers has not decreased at a commensurate rate. One possible explanation is that screening may be increasing the burden of low-risk cancers without significantly reducing the burden of more aggressively growing cancers and therefore not resulting in the anticipated reduction in cancer mortality. To reduce morbidity and mortality from prostate cancer and breast cancer, new approaches for screening, early detection, and prevention for both diseases should be considered.
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                Author and article information

                Journal
                Journal of Urology
                Journal of Urology
                Elsevier BV
                0022-5347
                1527-3792
                August 2011
                August 2011
                : 186
                : 2
                : 458-464
                Affiliations
                [1 ]Division of Surgery and Interventional Science, University College London, London, United Kingdom
                [2 ]Centre for Medical Image Computing, University College London, London, United Kingdom
                [3 ]Service d'Urologie, Hôpital Claude Huriez, Centre Hospitalier Régional Universitaire de Lille, Lille, France
                [4 ]Department of Histopathology, University College London Hospitals National Health Service Foundation Trust, London, United Kingdom
                [5 ]University College Hospital/University College London National Institute for Health Research Comprehensive Biomedical Research Centre and Clinical Effectiveness Unit, Royal College of Surgeons of England, London, United Kingdom
                Article
                10.1016/j.juro.2011.03.147
                21679984
                1e260b43-9c61-4dbf-a749-7a7641c00af1
                © 2011

                https://www.elsevier.com/tdm/userlicense/1.0/

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