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Prostate Cancer Detection and Dutasteride: Utility and Limitations of ProstateSpecific Antigen in Men with Previous Negative Biopsies P. J. van Leeuwen, K. Kölble, H. Huland, T. Hambrock, J. Barentsz and F. H. Schröder Department of Urology, Erasmus University Medical Centre, Rotterdam, The Netherlands Eur Urol 2011; 59: 183–190.
Context: We addressed the question whether the change of serum prostate–specific antigen (PSA) in men who use 5␣–reductase inhibitor (5–ARI) dutasteride is sensitive for the detection of aggressive prostate cancer (PCa). Objective: The case of a man using dutasteride diagnosed with Gleason 7 transition zone cancer at biopsy indicated by a rising PSA is described. The following issues are discussed: (1) Is a rise of PSA in patients using dutasteride predictive of aggressive PCa in men with prior negative biopsies? (2) Is it safe not to biopsy men using dutasteride who do not show a rising PSA? (3) How can we avoid potentially unnecessary biopsies in men using dutasteride without a rising PSA? Evidence Acquisition: We reviewed the recent literature addressing our objective that relates to two studies: the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events trial. Evidence Synthesis: In men using dutasteride, the positive predictive value/ detection rate of Gleason 7–10 PCa is 13.2% and 4.0% for men with and without a rising PSA, respectively. However, a substantial proportion of Gleason 7–10 cases (42.9%) would be missed if a rising PSA was used as the only biopsy indication. Currently available data do not provide selective mechanisms to diagnose these cancers. Conclusions: A rising PSA for a patient using dutasteride should be an indication for prostate biopsies. Currently, in the case of stable PSA a biopsy may still be considered. Options for a selective approach are therefore suggested in this review to avoid unnecessary biopsies and to achieve a more selective PCa detection in men on 5-ARI treatment. Editorial Comment: We have been told that dutasteride improves the ability to detect high grade cancer because it lowers the amount of PSA coming from enlarged prostates. It has been suggested that in men taking dutasteride if their PSA ever begins to rise, their risk of aggressive cancer is higher.1 However, van Leeuwen et al are not convinced. Although they agree that a rising PSA is a definite indication for a biopsy, they point out that if one just relied on an increase in PSA to trigger a biopsy, 43% of patients with high grade disease would be missed. Short of biopsying everyone, there are no current data which provide a selective mechanism to identify those patients who need a diagnosis most. Patrick C. Walsh, M.D. 1. Andriole GL, Bostwick D, Brawley OW et al: The effect of dutasteride on the usefulness of prostate specific antigen for the diagnosis of high grade and clinically relevant prostate cancer in men with a previous negative biopsy: results from the REDUCE study. J Urol 2011; 185: 126.
Imaging Prostate Cancer: Differentiation of Central Gland Cancer From Benign Prostatic Hyperplasia by Using Diffusion-Weighted and Dynamic Contrast-Enhanced MR Imaging A. Oto, A. Kayhan, Y. Jiang, M. Tretiakova, C. Yang, T. Antic, F. Dahi, A. L. Shalhav, G. Karczmar and W. M. Stadler Department of Radiology, University of Chicago, Chicago, Illinois Radiology 2010; 257: 715–723.
Purpose: To analyze the diffusion and perfusion parameters of central gland (CG) prostate cancer, stromal hyperplasia (SH), and glandular hyperplasia (GH) and to determine the role of these parameters in the differentiation of CG cancer from benign CG hyperplasia. Materials and Methods: In this institutional review board-approved (with waiver of informed consent), HIPAA-compliant
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study, 38 foci of carcinoma, 38 SH nodules, and 38 GH nodules in the CG were analyzed in 49 patients (26 with CG carcinoma) who underwent preoperative endorectal magnetic resonance (MR) imaging and radical prostatectomy. All carcinomas and hyperplastic foci on MR images were localized on the basis of histopathologic correlation. The apparent diffusion coefficient (ADC), the contrast agent transfer rate between blood and tissue (Ktrans), and extravascular extracellular fractional volume values for all carcinoma, SH, and GH foci were calculated. The mean, standard deviation, 95% confidence interval (CI), and range of each parameter were calculated. Receiver operating characteristic (ROC) and multivariate logistic regression analyses were performed for differentiation of CG cancer from SH and GH foci. Results: The average ADCs (⫻ 10⫺3 mm2/sec) were 1.05 (95% CI: 0.97, 1.11), 1.27 (95% CI: 1.20, 1.33), and 1.73 (95% CI: 1.64, 1.83), respectively, in CG carcinoma, SH foci, and GH foci and differed significantly, yielding areas under the ROC curve (AUCs) of 0.99 and 0.78, respectively, for differentiation of carcinoma from GH and SH. Perfusion parameters were similar in CG carcinomas and SH foci, with Ktrans yielding the greatest AUCs (0.75 and 0.58, respectively). Adding Ktrans to ADC in ROC analysis to differentiate CG carcinoma from SH increased sensitivity from 38% to 57% at 90% specificity without noticeably increasing the AUC (0.79). Conclusion: ADCs differ significantly between CG carcinoma, SH, and GH, and the use of them can improve the differentiation of CG cancer from SH and GH. Combining Ktrans with ADC can potentially improve the detection of CG cancer. Editorial Comment: Evaluation of the central gland of the prostate has been problematic. Central gland benign prostatic hyperplasia (BPH) is heterogeneous and discerning central gland tumors is difficult. Approximately 30% of all prostate cancers involve the central gland of the prostate, which is irregular and often corrugated or lumpy in appearance. MR spectroscopy can be difficult in the central gland because of overlapping ranges of metabolic ratios due to its histological heterogeneity. The benign central gland is composed of tissue that exhibits high signal intensity on T2-weighted images and stromal tissue that exhibits decreased signal intensity on T2-weighted images (this can mimic central gland cancer). This study compares diffusion weighted imaging and dynamic contrast enhancement in an attempt to distinguish BPH of the central gland from central gland prostatic carcinoma. All patients in this study underwent radical prostatectomy and the surgical specimens were matched to the corresponding T2-weighted MR images for analysis. All prostate cancers larger than 5 mm that were confidently matched with the T2-weighted MR images (by consensus of the radiologist and pathologist) were included in the analysis. The authors found that the performance of diffusion and perfusion in differentiating central gland BPH from central gland tumor varied depending on histological BPH subtype. All of the central gland tumors showed low signal intensity on the T2-weighted images and the majority had ill defined margins. The glandular hyperplasia foci were easy to distinguish, as they exhibit high signal intensity on T2-weighted images and are encapsulated. The stromal hyperplasia had T2 imaging characteristics that were indistinguishable from the central gland tumors (decreased signal intensity, ill defined margins and no capsule). The authors suggest that the combination of diffusion weighting and dynamic contrast enhancement will improve differentiation of central gland cancer from BPH of the central gland. Unfortunately significant overlap persists. When looking for subtle or stealth prostate cancer, evaluation would optimally include examination of the central gland and diffusion imaging. Cary Siegel, M.D.
IMAGING
Prostate Cancer Detection and Dutasteride: Utility and Limitations of ProstateSpecific Antigen in Men with Previous Negative Biopsies P. J. van Leeuwen, K. Kölble, H. Huland, T. Hambrock, J. Barentsz and F. H. Schröder Department of Urology, Erasmus University Medical Centre, Rotterdam, The Netherlands Eur Urol 2011; 59: 183–190.
Context: We addressed the question whether the change of serum prostate–specific antigen (PSA) in men who use 5␣–reductase inhibitor (5–ARI) dutasteride is sensitive for the detection of aggressive prostate cancer (PCa). Objective: The case of a man using dutasteride diagnosed with Gleason 7 transition zone cancer at biopsy indicated by a rising PSA is described. The following issues are discussed: (1) Is a rise of PSA in patients using dutasteride predictive of aggressive PCa in men with prior negative biopsies? (2) Is it safe not to biopsy men using dutasteride who do not show a rising PSA? (3) How can we avoid potentially unnecessary biopsies in men using dutasteride without a rising PSA? Evidence Acquisition: We reviewed the recent literature addressing our objective that relates to two studies: the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events trial. Evidence Synthesis: In men using dutasteride, the positive predictive value/ detection rate of Gleason 7–10 PCa is 13.2% and 4.0% for men with and without a rising PSA, respectively. However, a substantial proportion of Gleason 7–10 cases (42.9%) would be missed if a rising PSA was used as the only biopsy indication. Currently available data do not provide selective mechanisms to diagnose these cancers. Conclusions: A rising PSA for a patient using dutasteride should be an indication for prostate biopsies. Currently, in the case of stable PSA a biopsy may still be considered. Options for a selective approach are therefore suggested in this review to avoid unnecessary biopsies and to achieve a more selective PCa detection in men on 5-ARI treatment. Editorial Comment: We have been told that dutasteride improves the ability to detect high grade cancer because it lowers the amount of PSA coming from enlarged prostates. It has been suggested that in men taking dutasteride if their PSA ever begins to rise, their risk of aggressive cancer is higher.1 However, van Leeuwen et al are not convinced. Although they agree that a rising PSA is a definite indication for a biopsy, they point out that if one just relied on an increase in PSA to trigger a biopsy, 43% of patients with high grade disease would be missed. Short of biopsying everyone, there are no current data which provide a selective mechanism to identify those patients who need a diagnosis most. Patrick C. Walsh, M.D. 1. Andriole GL, Bostwick D, Brawley OW et al: The effect of dutasteride on the usefulness of prostate specific antigen for the diagnosis of high grade and clinically relevant prostate cancer in men with a previous negative biopsy: results from the REDUCE study. J Urol 2011; 185: 126.
Imaging Prostate Cancer: Differentiation of Central Gland Cancer From Benign Prostatic Hyperplasia by Using Diffusion-Weighted and Dynamic Contrast-Enhanced MR Imaging A. Oto, A. Kayhan, Y. Jiang, M. Tretiakova, C. Yang, T. Antic, F. Dahi, A. L. Shalhav, G. Karczmar and W. M. Stadler Department of Radiology, University of Chicago, Chicago, Illinois Radiology 2010; 257: 715–723.
Purpose: To analyze the diffusion and perfusion parameters of central gland (CG) prostate cancer, stromal hyperplasia (SH), and glandular hyperplasia (GH) and to determine the role of these parameters in the differentiation of CG cancer from benign CG hyperplasia. Materials and Methods: In this institutional review board-approved (with waiver of informed consent), HIPAA-compliant
IMAGING
107
study, 38 foci of carcinoma, 38 SH nodules, and 38 GH nodules in the CG were analyzed in 49 patients (26 with CG carcinoma) who underwent preoperative endorectal magnetic resonance (MR) imaging and radical prostatectomy. All carcinomas and hyperplastic foci on MR images were localized on the basis of histopathologic correlation. The apparent diffusion coefficient (ADC), the contrast agent transfer rate between blood and tissue (Ktrans), and extravascular extracellular fractional volume values for all carcinoma, SH, and GH foci were calculated. The mean, standard deviation, 95% confidence interval (CI), and range of each parameter were calculated. Receiver operating characteristic (ROC) and multivariate logistic regression analyses were performed for differentiation of CG cancer from SH and GH foci. Results: The average ADCs (⫻ 10⫺3 mm2/sec) were 1.05 (95% CI: 0.97, 1.11), 1.27 (95% CI: 1.20, 1.33), and 1.73 (95% CI: 1.64, 1.83), respectively, in CG carcinoma, SH foci, and GH foci and differed significantly, yielding areas under the ROC curve (AUCs) of 0.99 and 0.78, respectively, for differentiation of carcinoma from GH and SH. Perfusion parameters were similar in CG carcinomas and SH foci, with Ktrans yielding the greatest AUCs (0.75 and 0.58, respectively). Adding Ktrans to ADC in ROC analysis to differentiate CG carcinoma from SH increased sensitivity from 38% to 57% at 90% specificity without noticeably increasing the AUC (0.79). Conclusion: ADCs differ significantly between CG carcinoma, SH, and GH, and the use of them can improve the differentiation of CG cancer from SH and GH. Combining Ktrans with ADC can potentially improve the detection of CG cancer. Editorial Comment: Evaluation of the central gland of the prostate has been problematic. Central gland benign prostatic hyperplasia (BPH) is heterogeneous and discerning central gland tumors is difficult. Approximately 30% of all prostate cancers involve the central gland of the prostate, which is irregular and often corrugated or lumpy in appearance. MR spectroscopy can be difficult in the central gland because of overlapping ranges of metabolic ratios due to its histological heterogeneity. The benign central gland is composed of tissue that exhibits high signal intensity on T2-weighted images and stromal tissue that exhibits decreased signal intensity on T2-weighted images (this can mimic central gland cancer). This study compares diffusion weighted imaging and dynamic contrast enhancement in an attempt to distinguish BPH of the central gland from central gland prostatic carcinoma. All patients in this study underwent radical prostatectomy and the surgical specimens were matched to the corresponding T2-weighted MR images for analysis. All prostate cancers larger than 5 mm that were confidently matched with the T2-weighted MR images (by consensus of the radiologist and pathologist) were included in the analysis. The authors found that the performance of diffusion and perfusion in differentiating central gland BPH from central gland tumor varied depending on histological BPH subtype. All of the central gland tumors showed low signal intensity on the T2-weighted images and the majority had ill defined margins. The glandular hyperplasia foci were easy to distinguish, as they exhibit high signal intensity on T2-weighted images and are encapsulated. The stromal hyperplasia had T2 imaging characteristics that were indistinguishable from the central gland tumors (decreased signal intensity, ill defined margins and no capsule). The authors suggest that the combination of diffusion weighting and dynamic contrast enhancement will improve differentiation of central gland cancer from BPH of the central gland. Unfortunately significant overlap persists. When looking for subtle or stealth prostate cancer, evaluation would optimally include examination of the central gland and diffusion imaging. Cary Siegel, M.D.