- Email: [email protected]
Re: Office Based Transrectal Saturation Biopsy Improves Prostate Cancer Detection Compared to Extended Biopsy in the Repeat Biopsy Population
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EUROPEAN UROLOGY 61 (2012) 218–224
[9] Janoff DM, Porra RO. Contemporary appraisal of radical perineal prostatectomy. J Urol 2005;173:1863–70. [10] Wittmann D, He C, Coelho M, et al. Patient preoperative expecta-
Michael Sohn Urologische Klinik, Markus-Krankenhaus, Frankfurt am Main, Germany E-mail address: [email protected]
tions of urinary, bowel, hormonal and sexual functioning do not match actual outcomes 1 year after radical prostatectomy. J Urol 2011;186:494–9.
Re: Office Based Transrectal Saturation Biopsy Improves Prostate Cancer Detection Compared to Extended Biopsy in the Repeat Biopsy Population Zaytoun OM, Moussa AS, Gao T, Fareed K, Jones JS J Urol 2011;186:850–85 Expert’s summary: Urologists at the Cleveland Clinic have performed several studies over the years about the role of extended and saturation needle biopsy in the pursuit of a prostate cancer (PCa) diagnosis. This publication is a retrospective comparison of repeat transrectal extended biopsy (12–14 cores) with officebased transrectal saturation biopsy (20–24 cores) from a prospectively collected database over a period of a decade in a large cohort of men (n = 1056) with numerically adequate initial negative biopsy findings. The authors suggest that saturation biopsy detected almost a third more cancers than did extended biopsy (32.7% and 24.9%, p = 0.0075) on a background of a 29.8% cancer detection rate. Saturation biopsy achieved significantly greater PCa detection than did extended biopsy (33.3% and 25.6%, p = 0.027) in patients with a benign initial biopsy but not in men with previous atypical small acinar proliferation and/or high-grade prostatic intraepithelial neoplasia (31.2% and 23.3%, p = 0.13). Of 315 positive biopsies, 119 (37.8%) revealed clinically insignificant cancer (40.1% and 32.6%, p = 0.2). The authors concluded that compared with extended biopsy, office-based saturation biopsy significantly increased cancer detection on repeat biopsy, and they sensibly commented that the potential for increased detection of clinically insignificant cancer should be weighed against the potential for missing significant cases. Expert’s comments: Do we have a foolproof outpatient repeat biopsy system or a route to find missed clinically significant cancers? The answer is, invariably, no! The majority of men who are biopsied because of a prostate-specific antigen (PSA) abnormality and negative digital rectal examination (DRE) findings have negative results from a numerically adequate first biopsy set. In the absence of affordable and reliable imaging or cancerspecific markers, these men represent a significant diagnostic challenge, and some may then become candidates for repeat biopsy on the basis of previous suggestive pathologic findings (atypical small acinar proliferation of prostate [ASAP]/prostatic intraepithelial neoplasia [PIN]), persistently increased PSA, or PSA velocity (>0.75 ng/ml per year). Periprostatic anesthetic blocks relieve discomfort from extended regimens, but the risks of infection in an age of increasing incidence of quinolone-resistant Escherichia coli, bleeding hemospermia,
DOI: 10.1016/j.eururo.2011.10.017
and voiding morbidity are not inconsiderable. This paper from the United States, where PSA utility among physicians is much greater than in Europe, provides some interesting data and issues for health care systems to consider. The authors report on a large, decade-long cohort (n = 1462) in a university-based setting, having invested prospectively in a comprehensive database. It was interesting that only 406 of these men had a biopsy regimen in which cores were adjusted by prostate size (volume-based sampling), hypoechoic lesions detected on transrectal ultrasonography (TRUS), or suspicious nodules detected on DRE (8% included—Table 1), and these were ‘‘all’’ excluded from the analysis. There was a strong physician bias at this institution toward performing saturation rather than extended repeat biopsy (663 compared with 393) focused on lateral and apical regions using a five-sector schema in each half of the prostate, while anterior targeted biopsy was not mentioned in the schema for either group. We know that anterior cancers are often missed by TRUS biopsy, because despite adequate prostate blocks, it causes pain and greater potential morbidity to drive the biopsy needle transrectally through a large gland several times before firing it to sample the anterior part of the prostate. The majority of men were Caucasian, suggesting that African American men are still underserved in case detection of PCa in major urban conurbations in the United States by university centers. Clinically insignificant cancer was defined as Gleason sum <7, three or fewer positive cores, and a maximum of 50% cancer in any positive core, based on the authors’ previous publication; however, it is not known if all these biopsies had undergone central pathologic review or what pathology reporting quality assurance measures were in place. The median age of the population was close to 65 yr. This fact is relevant, given the age cutoff described in the Scandinavian Prostate Cancer Group-4 [1,2] (in which surgery improved overall mortality, disease-specific mortality, and distant metastases for men aged <65 yr but not for men aged 65 yr with palpable tumors, rather than impalpable ones, as in this study). It was not surprising that more cores meant more cancer detection, but it is important that saturation biopsy yielded no advantage for men with ASAP with or without PIN. In a 29.8% PCa detection rate, there was a finding of significant cancer in only 196 of 1056 men; other words, >4 of 5 men with a negative initial biopsy still had little benefit from extended biopsy, notwithstanding the huge overall cost to payors incurred even in an outpatient setting if saturation biopsy were to become the standard of care. It would have been useful to know the incidence of inflammation in biopsy samples (which could also explain
224
EUROPEAN UROLOGY 61 (2012) 218–224
persistent PSA abnormalities), mean–median prostate volumes, PSA density, and percentage of free PSA in subgroups of men with negative repeat biopsy, men with extended biopsy, and men with saturation biopsy to see if these statistics could contribute to better selection of men for repeat saturation biopsy in future studies and thereby define a more affordable paradigm, given the challenging economic times we live in. The other important relevant issue is the impact of saturation biopsies (transrectal or transperineal) on the technical ease of apical, nerve-sparing, and anterior mesorectal parts of the dissection of radical prostatectomy, as well as the quality of clinical functional outcomes recovery thereafter. The challenge continues to find curable lethal PCa in the minority of men who may benefit from cure with negative initial biopsies while avoiding unnecessary biopsies in the majority of men who will not benefit from either detection or treatment. Perhaps while we wait for newer, more specific biomarkers to enter the clinical arena, we should test the utility of early PSA testing and PSA kinetics [3] before benign prostatic hyperplasia has set in (ie, in younger men, who have the most to gain from the cure of a lethal
tumor and much better chances of good functional recovery after excisional surgery). Conflicts of interest: The author has nothing to disclose.
References [1] Bill-Axelson A, Holmberg L, Filen F, et al. Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian Prostate Cancer Group-4 randomized trial. J Natl Cancer Inst 2008;100:1144–54. [2] Bill-Axelson A, Holmberg L, Ruutu M, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2011;364:1708–17. [3] Fang J, Metter J, Landis P, et al. Low levels of prostate-specific antigen predict long-term risk of prostate cancer: results from the Baltimore Longitudinal Study of Aging. Urology 2001;58:411–6. Anup Patel St. Mary’s Hospital at Imperial College Healthcare NHS Trust, London, UK E-mail address: [email protected]
DOI: 1016/j.eururo.2011.10.018
EUROPEAN UROLOGY 61 (2012) 218–224
[9] Janoff DM, Porra RO. Contemporary appraisal of radical perineal prostatectomy. J Urol 2005;173:1863–70. [10] Wittmann D, He C, Coelho M, et al. Patient preoperative expecta-
Michael Sohn Urologische Klinik, Markus-Krankenhaus, Frankfurt am Main, Germany E-mail address: [email protected]
tions of urinary, bowel, hormonal and sexual functioning do not match actual outcomes 1 year after radical prostatectomy. J Urol 2011;186:494–9.
Re: Office Based Transrectal Saturation Biopsy Improves Prostate Cancer Detection Compared to Extended Biopsy in the Repeat Biopsy Population Zaytoun OM, Moussa AS, Gao T, Fareed K, Jones JS J Urol 2011;186:850–85 Expert’s summary: Urologists at the Cleveland Clinic have performed several studies over the years about the role of extended and saturation needle biopsy in the pursuit of a prostate cancer (PCa) diagnosis. This publication is a retrospective comparison of repeat transrectal extended biopsy (12–14 cores) with officebased transrectal saturation biopsy (20–24 cores) from a prospectively collected database over a period of a decade in a large cohort of men (n = 1056) with numerically adequate initial negative biopsy findings. The authors suggest that saturation biopsy detected almost a third more cancers than did extended biopsy (32.7% and 24.9%, p = 0.0075) on a background of a 29.8% cancer detection rate. Saturation biopsy achieved significantly greater PCa detection than did extended biopsy (33.3% and 25.6%, p = 0.027) in patients with a benign initial biopsy but not in men with previous atypical small acinar proliferation and/or high-grade prostatic intraepithelial neoplasia (31.2% and 23.3%, p = 0.13). Of 315 positive biopsies, 119 (37.8%) revealed clinically insignificant cancer (40.1% and 32.6%, p = 0.2). The authors concluded that compared with extended biopsy, office-based saturation biopsy significantly increased cancer detection on repeat biopsy, and they sensibly commented that the potential for increased detection of clinically insignificant cancer should be weighed against the potential for missing significant cases. Expert’s comments: Do we have a foolproof outpatient repeat biopsy system or a route to find missed clinically significant cancers? The answer is, invariably, no! The majority of men who are biopsied because of a prostate-specific antigen (PSA) abnormality and negative digital rectal examination (DRE) findings have negative results from a numerically adequate first biopsy set. In the absence of affordable and reliable imaging or cancerspecific markers, these men represent a significant diagnostic challenge, and some may then become candidates for repeat biopsy on the basis of previous suggestive pathologic findings (atypical small acinar proliferation of prostate [ASAP]/prostatic intraepithelial neoplasia [PIN]), persistently increased PSA, or PSA velocity (>0.75 ng/ml per year). Periprostatic anesthetic blocks relieve discomfort from extended regimens, but the risks of infection in an age of increasing incidence of quinolone-resistant Escherichia coli, bleeding hemospermia,
DOI: 10.1016/j.eururo.2011.10.017
and voiding morbidity are not inconsiderable. This paper from the United States, where PSA utility among physicians is much greater than in Europe, provides some interesting data and issues for health care systems to consider. The authors report on a large, decade-long cohort (n = 1462) in a university-based setting, having invested prospectively in a comprehensive database. It was interesting that only 406 of these men had a biopsy regimen in which cores were adjusted by prostate size (volume-based sampling), hypoechoic lesions detected on transrectal ultrasonography (TRUS), or suspicious nodules detected on DRE (8% included—Table 1), and these were ‘‘all’’ excluded from the analysis. There was a strong physician bias at this institution toward performing saturation rather than extended repeat biopsy (663 compared with 393) focused on lateral and apical regions using a five-sector schema in each half of the prostate, while anterior targeted biopsy was not mentioned in the schema for either group. We know that anterior cancers are often missed by TRUS biopsy, because despite adequate prostate blocks, it causes pain and greater potential morbidity to drive the biopsy needle transrectally through a large gland several times before firing it to sample the anterior part of the prostate. The majority of men were Caucasian, suggesting that African American men are still underserved in case detection of PCa in major urban conurbations in the United States by university centers. Clinically insignificant cancer was defined as Gleason sum <7, three or fewer positive cores, and a maximum of 50% cancer in any positive core, based on the authors’ previous publication; however, it is not known if all these biopsies had undergone central pathologic review or what pathology reporting quality assurance measures were in place. The median age of the population was close to 65 yr. This fact is relevant, given the age cutoff described in the Scandinavian Prostate Cancer Group-4 [1,2] (in which surgery improved overall mortality, disease-specific mortality, and distant metastases for men aged <65 yr but not for men aged 65 yr with palpable tumors, rather than impalpable ones, as in this study). It was not surprising that more cores meant more cancer detection, but it is important that saturation biopsy yielded no advantage for men with ASAP with or without PIN. In a 29.8% PCa detection rate, there was a finding of significant cancer in only 196 of 1056 men; other words, >4 of 5 men with a negative initial biopsy still had little benefit from extended biopsy, notwithstanding the huge overall cost to payors incurred even in an outpatient setting if saturation biopsy were to become the standard of care. It would have been useful to know the incidence of inflammation in biopsy samples (which could also explain
224
EUROPEAN UROLOGY 61 (2012) 218–224
persistent PSA abnormalities), mean–median prostate volumes, PSA density, and percentage of free PSA in subgroups of men with negative repeat biopsy, men with extended biopsy, and men with saturation biopsy to see if these statistics could contribute to better selection of men for repeat saturation biopsy in future studies and thereby define a more affordable paradigm, given the challenging economic times we live in. The other important relevant issue is the impact of saturation biopsies (transrectal or transperineal) on the technical ease of apical, nerve-sparing, and anterior mesorectal parts of the dissection of radical prostatectomy, as well as the quality of clinical functional outcomes recovery thereafter. The challenge continues to find curable lethal PCa in the minority of men who may benefit from cure with negative initial biopsies while avoiding unnecessary biopsies in the majority of men who will not benefit from either detection or treatment. Perhaps while we wait for newer, more specific biomarkers to enter the clinical arena, we should test the utility of early PSA testing and PSA kinetics [3] before benign prostatic hyperplasia has set in (ie, in younger men, who have the most to gain from the cure of a lethal
tumor and much better chances of good functional recovery after excisional surgery). Conflicts of interest: The author has nothing to disclose.
References [1] Bill-Axelson A, Holmberg L, Filen F, et al. Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian Prostate Cancer Group-4 randomized trial. J Natl Cancer Inst 2008;100:1144–54. [2] Bill-Axelson A, Holmberg L, Ruutu M, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2011;364:1708–17. [3] Fang J, Metter J, Landis P, et al. Low levels of prostate-specific antigen predict long-term risk of prostate cancer: results from the Baltimore Longitudinal Study of Aging. Urology 2001;58:411–6. Anup Patel St. Mary’s Hospital at Imperial College Healthcare NHS Trust, London, UK E-mail address: [email protected]
DOI: 1016/j.eururo.2011.10.018