Original Paper Curr Urol 2013;7:24–27 DOI: 10.1159/000343548

Received: September 26, 2012 Accepted: November 19, 2012 Published online: July 28, 2013

Pathological Correlation between Number of Biopsies and Radical Surgery: Does It Make a Difference to Final Pathology? Tahir Qayyuma Jennifer M. Willdera Paul G Horganb Joanne Edwardsa Mark A. Underwoodc Unit of Experimental Therapeutics, Institute of Cancer, College of MVLS, University of Glasgow, Western Infirmary; School of Medicine, College of MVLS, University of Glasgow, Royal Infirmary; cDepartment of Urology, Royal Infirmary, Glasgow, UK

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Abstract Aims: To evaluate whether the number of biopsies performed via transrectal ultrasound (TRUS) accurately predicts pathological parameters such as Gleason sum, prostatic intraepithelial neoplasia and perineural invasion of the final prostatectomy specimen. Materials and Methods: The cohort consisted of 99 patients whom had undergone radical prostatectomy. Comparisons were made between the number of biopsies utilised and the presence of the pathological parameters from tissue at time of diagnosis and tissue from the final prostatectomy. Results: A significant difference was noted between Gleason sum, prostatic intraepithelial neoplasia and perineural invasion from tissue at time of diagnosis irrespective of the number of biopsies utilised and tissue from the radical specimen (p < 0.001, p < 0.001, p < 0.001 respectively). No difference was noted in the mean Gleason sum when 11–14 biopsies were utilised at TRUS and the Gleason sum from the radical specimen. Conclusion: We have demonstrated that the number of biopsies utilised at time of TRUS for diagnosis predicts the accuracy of pathological parameters in the final radical prostatectomy specimen. We believe that 11–14 biopsies should be utilised at time of TRUS as this allows a higher accuracy in the Gleason sum and therefore allows optimum treatment plans to be devised. Copyright © 2013 S. Karger AG, Basel © 2013 S. Karger AG, Basel 1015–9770/13/0071–0024$26.00/0 Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com

Accessible online at: www.karger.com/cur

Introduction

Prostate cancer is now recognised as a major burden on the global health-care system. In the United States and in Europe, it is the most common neoplasm diagnosed in men and is responsible for 11% of all male cancer deaths [1, 2]. After a diagnosis of prostate cancer is made, a number of treatments may be considered depending on the information provided by staging investigations. In patients who are thought to have organ confined prostate cancer treatment options include radical prostatectomy, external beam radiation therapy, brachytherapy and active monitoring. The Gleason score is utilised to grade adenocarcinoma of the prostate [3]. The Gleason score is the sum of the 2 most common patterns of tumor growth found with the score ranging from 2 to 10. Tissue is either analysed from core needle biopsies performed with the aid of a transrectal ultrasound (TRUS) probe or from specimens retrieved at time of surgery. The Gleason score is a prognostic factor for tumor behavior and treatment response [4] and is incorporated into prognostic algorithms predicting risk of recurrence following radical surgery [5]. The need to perform biopsies using TRUS often arises depending on the findings at time of digital rectal examination and/or prostate specific antigen (PSA) measurement. The question arises regarding how many biopsies should be performed and whether the number of biopsies has an impact on the final Gleason grade from the surgical specimen. There have been various reports regarding Tahir Qayyum Institute of Cancer, College of MVLS University of Glasgow, Western Infirmary G11 6NT Glasgow (UK) E-Mail [email protected]

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Key Words Radical prostatectomy • Prostate cancer • Transrectal ultrasound biopsy

Correlation between Number of Biopsies and Radical Surgery

Materials and Methods This was a single centre retrospective study. Patients diagnosed with prostate cancer following TRUS guided biopsy in North Glasgow NHS Trust and who subsequently underwent radical prostatectomy was included. Patients were staged according to the TNM classification and had organ confined disease. All patients had at least 6 core biopsies. All biopsies were performed utilising TRUS guidance. All patients had retropubic, nerve sparing (when appropriate) radical prostatectomy. No patient received preoperative hormone therapy. The surgical specimens were whole mount sectioned. The Research Ethics Committee of North Glasgow NHS Trust approved the study. Statistical analysis was undertaken using SPSS. Significant differences were calculated using Wilcoxon and Fischer tests.

Results

Ninety-nine patients were studied for whom all clinical data was available and had undergone radical prostatectomy. Median age of diagnosis was 62 years (range 43–73 years), and 37% (n = 36) of patients had between 6 and 8 biopsies, 26% (n = 26) had 9–10 biopsies and 37% (n = 37) had 11–14 biopsies. No patient experienced significant post biopsy related morbidity including urinary tract infection or urinary retention. On analysis of Gleason sum, presence of PIN and PNI, there was a significant difference in these pathological parameters from tissue at time of diagnosis via TRUS irrespective of the number of biopsies utilised and tissue from the radical specimen (p < 0.001, p < 0.001, p < 0.001 respectively). Upon further analysis, of those patients that had undergone 6–8 biopsies, the median Gleason sum was 6 at time of TRUS and this was upgraded to 7 following radical prostatectomy. Wilcoxon test analysis demonstrated this to be a significant difference (p = 0.04). Fischer test analysis demonstrated a significant difference in the presence PIN and PNI from initial diagnosis when 6–8 cores were utilised in comparison to the final pathological specimen (p = 0.0064, p < 0.001 respectively). Of those that underwent 9–10 biopsies, median Gleason sum was 6 at time of diagnosis and was upgraded to 7 after surgery. This was noted to be a significant difference (p < 0.001). Analysis demonstrated no significant difference between PIN and PNI. In those that underwent 11–14 biopsies, no difference between the median Gleason sum at time of diagnosis and after radical surgery was demonstrated. Despite no difference in the median, an overall significant difference in Gleason sum was demonstrated (p = 0.029). A signifi-

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the optimal number biopsies performed at time of TRUS which allows accurate assessment of pathological parameters. There have been reports that 4–6 biopsies at time of TRUS yield the best results [6] and 6 biopsies are sufficient as there was no difference in the Gleason sum from the final surgical specimen [7] and taking more than 6 biopsies has no further benefit [8]. Others have reported that 10 biopsies are sufficient [9] whilst in comparison to 6 biopsies, 10 biopsies increases the concordance of the Gleason sum from the final pathological specimen [10]. It has also been reported that 6 biopsies are no longer adequate and taking more than 12 biopsies in comparison to 8 is not significantly more conclusive [11]. Furthermore, there have been reports that 18 biopsies poorly predict Gleason scores from radical prostatectomy specimens [12] and that the incidence of prostate cancer in those undergoing saturation biopsies is between 30 and 40% but this cohort of patients had previous negative biopsies [13]. In a specific subset of patients with Gleason 4+3 disease, nearly 50% had their disease downgraded following surgery where at least 12 biopsies were taken [14] and two-thirds of patients with unilateral disease on biopsies had bilateral disease on final specimen [15]. There are other well known pathological parameters that are often reported upon when analysing prostate cancer such as prostatic intraepithelial neoplasia (PIN) and perineural invasion (PNI). PIN represents the pre-invasive end of the continuum of cellular proliferation within the lining of prostatic ducts and acini. The presence of PIN is often deemed a precursor of malignancy and it has been reported that its presence is a strong predictor of carcinoma and these patients should be closely followed-up [16–18]. Despite its presence, it is not thought that PIN should influence treatment options [19, 20]. PNI has been related to worse prognostic factors in radical prostatectomy specimens [21] and has also been demonstrated to predict local/regional recurrence following radiotherapy [22] and radical surgery [21, 23] and its presence at biopsy is an independent factor in correlation with high grade disease following radical prostatectomy [24]. Despite the association of PNI with a worse prognosis, it has also been reported that its presence should not be a deterrent for patients who otherwise meet the criteria for active surveillance [25]. The aim of this study was to assess whether the number of biopsy samples accurately predicted presence of PIN, PNI and final Gleason sum in those undergoing radical prostatectomy for localised prostate cancer.

cant difference of the presence PIN and PNI from initial diagnosis in comparison to the final pathological specimen was also demonstrated (p < 0.001, p < 0.001). Discussion

We have demonstrated that there is a significant difference between Gleason sum, PIN and PNI from tissue at time of diagnostic at TRUS irrespective of the number of biopsies utilised and the final radical specimen. When this is further sub-divided into various biopsy categories, 6–8 biopsies, 9–10 biopsies and 11–14 biopsies there is still a significant difference in the Gleason sum. Various studies have reported that 4–6 biopsies are sufficient [6, 7] and more than 6 biopsies reaps no further benefit [8]. We have reported that there is a significant difference not only in Gleason sum but PIN and PNI status when taking 6–8 biopsies and 11–14 biopsies in comparison to the pathology from the radical specimen. This discordance can be related due to the heterogeneous natures of prostate cancer resulting in sampling areas which are over or under-represented with high or low grade disease [11]. There have also been reports that taking more biopsies results in a greater yield of cancer [26, 27] but increasing the number of biopsies is not more conclusive and does not increase the accuracy of the Gleason sum [11, 12].

From this current study, there was a significant difference in the Gleason sum in all biopsy categories but no actual difference in the mean Gleason sum from biopsy and the radical specimen when 11–14 biopsies were utilised. Given this category of biopsies also demonstrated the least significant difference in Gleason sum, it would suggest that 11–14 biopsies maybe the optimum number of biopsies. No statistical difference was demonstrated in the presence of PIN and PNI when 9–10 biopsies were used for diagnosis. Whilst these pathological characteristics are known to correlate with other recognised prognostic factors, their presence should not dictate treatment options and should be closely followed-up in certain circumstances [19, 20, 25]. Limitations of this study include patient numbers and no assessment of core lengths when biopsies were taken as core volume would impact on the area being analysed and therefore accuracy. Other limitations include that it was a retrospective study and there was no standard protocol for the number of biopsies obtained at time of diagnosis. We have reported that utilising 11–14 biopsies at time of TRUS has a higher accuracy of determining the final Gleason sum from the radical specimen and 9–10 biopsies has a higher accuracy of determining the presence of PIN and PNI. Given that PIN and PNI will not dictate treatment options and Gleason sum will, we believe that taking 11–14 biopsies for diagnosis will allow a higher degree of accuracy for the Gleason sum and therefore determine the optimum treatment option.

1 Boyle P, Ferlay J: Cancer incidence and mortality in Europe, 2004. Ann Oncol 2005;16: 481–488. 2 Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin 2010;60:277– 300. 3 Gleason DF, Mellinger GT: Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol 1974;111:58–64. 4 Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL: The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol 2005;29:1228– 1242. 5 Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI, Pearson JD: Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology 2001;58:843–848.

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6 Thickman D, Speers WC, Philpott PJ, Shapiro H: Effect of the number of core biopsies of the prostate on predicting Gleason score of prostate cancer. J Urol 1996;156:110–113. 7 Hsieh TF, Chang CH, Chen WC, Chou CL, Chen CC, Wu HC: Correlation of Gleason scores between needle-core biopsy and radical prostatectomy specimens in patients with prostate cancer. J Chin Med Assoc 2005; 68:167–171. 8 Grossklaus DJ, Coffey CS, Shappell SB, Jack GS, Cookson MS: Prediction of tumour volume and pathological stage in radical prostatectomy specimens is not improved by taking more prostate needle-biopsy cores. BJU Int 2001;88:722–726. 9 Donovan J, Hamdy F, Neal D, Peters T, Oliver S, Brindle L, Jewell D, Powell P, Gillatt D, Dedman D, Mills N, Smith M, Noble S, Lane A: Prostate Testing for Cancer and Treatment (ProtecT) feasibility study. Health Technol Assess 2003;7:1–88.

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Correlation between Number of Biopsies and Radical Surgery

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Pathological Correlation between Number of Biopsies and Radical Surgery: Does It Make a Difference to Final Pathology?

To evaluate whether the number of biopsies performed via transrectal ultrasound (TRUS) accurately predicts pathological parameters such as Gleason sum...
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