The Optimal Rebiopsy Prostatic Scheme Depends on Patient Clinical Characteristics: Results of a Recursive Partitioning Analysis Based on a 24-Core Systematic Scheme

doi:10.1016/j.eururo.2011.07.036

European Urology

Volume 60, Issue 4, October 2011, Pages 834-841

https://doi.org/10.1016/j.eururo.2011.07.036 Get rights and content

Abstract

Background

The most beneficial number and the location of prostate biopsies remain matters of debate, especially after an initial negative biopsy.

Objective

To identify the optimal combination of sampling sites (number and location) to detect prostate cancer (PCa) in patients previously submitted to an initial negative prostatic biopsy.

Design, setting, and participants

A transrectal ultrasound–guided systematic 24-core prostate biopsy (24PBx) was performed prospectively in 340 consecutive patients after a first negative biopsy (at least 12 cores).

Measurements

We relied on a classification and regression tree analysis to identify three clinically different subgroups of patients at dissimilar risk of harboring PCa at second biopsy. Subsequently, we set the cancer-positive rate of the 24PBx at 100% and calculated PCa detection rates for 255 possible combinations of sampling sites. We selected the optimal biopsy scheme (defined as the combination of sampling sites that detected 95% of all the cancers with the minimal number of biopsy cores) for each patient subgroup.

Results and limitations

After an initial negative biopsy, cancer was detected at rebiopsy in 95 men (27.9%). At a given number of cores, the cancer detection rates varied significantly according to the different combination of sites considered. Three different PCa risk groups were identified: (1) previous report of atypical small acinar proliferation of the prostate (ASAP), (2) no previous ASAP and ratio of free prostate-specific antigen (fPSA) to total PSA (%fPSA) ≤10%, and (3) no previous ASAP and %fPSA >10%. For patients with previous ASAP or patients with no previous ASAP and %fPSA ≤10%, two schemes with different combinations of 14 cores were most favorable. The optimal sampling in patients with no previous ASAP and %fPSA >10% was a scheme with a combination of 20 cores.

Conclusions

Both the number and the location of biopsy cores taken affect cancer detection rates in a repeated biopsy setting. We developed an internally validated flowchart to identify the most advantageous set of sampling sites according to patient characteristics.

Introduction

Patients with a prior negative prostate biopsy but a persistent suspicion of prostate cancer (PCa) on the basis of abnormal digital rectal examination (DRE), prostate-specific antigen (PSA) measurements, and histologic findings, namely, atypical small acinar proliferation of prostate (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN), should be considered for a repeated biopsy [1]. Because initial 10- to 12-core biopsy schemes may miss almost a third of cancers [1], [2], a saturation prostate biopsy (SPBx) has been adopted to improve PCa detection rate in the repeat setting. Several authors showed that SPBx increases the detection rate of PCa in patients with suspicious clinical findings following previous negative standard prostate biopsy compared with repeat standard biopsy strategies using up to 12 cores [1], [2], [3], [4], [5], [6].

Nevertheless, the most efficient scheme with the optimal number and location of the cores has not yet been defined [1]. It is not clear whether it is critical to perform the same sampling protocol in each patient or to modify the protocol according to the different clinical parameters, such as PSA value, DRE findings, or prostatic volume [7]. It is still contentious whether the detection rate may vary simply with additional biopsies or it is due to the different locations from which the cores are taken [1], [2], [4].

We evaluated cancer detection rates on an individual-core basis after a 24-core prostate biopsy (24PBx) and investigated the ability of various biopsy regimens, which are characterized by the number and anatomic location of cores taken, to detect PCa. We also attempted to identify the optimal number and location of the cores to detect the maximum number of PCas with the minimum number of cores according to different clinical parameters.

Section snippets

Procedure

Following institutional review board approval, from September 2005 to June 2008 we prospectively performed a saturation 24PBx in 340 consecutive patients suspected of harboring PCa after a first negative biopsy sampling (at least 12 cores taken) [8]. The indications to perform a rebiopsy were PSA >4.0 ng/ml and/or abnormal DRE (n = 229) and/or initial HGPIN (n = 78) or ASAP (n = 33). Five dedicated urologists performed the procedures during this period.

Each physician used a TRUS (transrectal

Results

In all cases, the planned numbers of cores were obtained (Table 1). After an initial negative biopsy with at least 12 cores, cancer was detected in 95 men (27.9%) at rebiopsy. The cancer detection rate was significantly higher in patients with ASAP (17 of 33; 51.5%) than in patients with an initial benign diagnosis (55 of 229; 24.0%; p = 0.002) or in patients with HGPIN (23 of 78, 29.5%; p = 0.04). No significant difference was found between patients without or with HGPIN at initial biopsy (p = 0.4).

Discussion

Although SPBx has been shown to be appropriate in the rebiopsy setting in men with an initial negative extended biopsy, its regular use in clinical practice is not approved [1], [2], [4], [5], [14]. The National Comprehensive Cancer Network (NCCN) suggests performing a second extended protocol after an initial negative extended protocol and suggests considering SPBx only in patients with a high risk of cancer after multiple negative biopsies [14]. Thus the ideal strategy for prostate biopsy

Conclusions

Both the number and the location of biopsy cores taken affect cancer detection rates in a repeated biopsy setting. The optimal scheme varies according to the clinical characteristics of the patients. Our analysis revealed that for patients with previous ASAP diagnosis or no previous ASAP diagnosis and %fPSA ≤10%, two different combinations of a 14-core biopsy scheme were most advantageous. The optimal sampling in patients with no previous ASAP diagnosis and %fPSA>10% was a combination of a

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Cited by (32)

Repeat Prostate Biopsy: Rationale, Indications, and Strategies
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Citation Excerpt :
For patients with no previous ASAP diagnosis and %fPSA ≤10%, the most advantageous scheme was a 14-core biopsy (including transitional area). Finally, the most advantageous sampling scheme for patients with no previous ASAP and %fPSA >10% was a saturation combination of a 20-core biopsy [28]. These data confirm that cancer detection is influenced not only by the number of cores sampled but also by the exact location of the cores [1–3,34].
The inaccuracy of prostate biopsy in detecting and characterising prostate cancer (PCa) has led to a widespread use of repeat biopsy (RB).
To summarise the most recent data regarding indication, techniques, and clinical implications of RB.
A search of Medline, PubMed, and Scopus identified articles published in the last 7 yr (2008–2014) addressing the role of RB in the PCa setting. Abstracts deemed relevant to the defined review question were screened, and the data were extracted, analysed, and summarised.
RB can be considered either in patients with persistent PCa suspicion after a first negative systematic biopsy or during active surveillance (AS), either to confirm patient enrolment or to monitor the natural progression of the disease. Indication and biopsy techniques differ according to each PCa scenario. Magnetic resonance imaging (MRI)-guided RB has been gaining popularity because of its accuracy in detecting and characterising PCa. Indications for multiple RBs (eg, AS setting) should be carefully evaluated because of the cumulative risk of complications, especially infection. In the next few years, clinical and genetic markers are expected to further improve the ability to determine the need for RB.
RB indications and techniques in persistent PCa suspicion and AS should take into account the evolving field of imaging, management options, and the risk of possible complications. In an RB setting, the introduction in daily clinical practice of MRI-guided targeted biopsy has improved the accuracy in detecting PCa without significantly increasing the risk of finding indolent, low-risk PCa. Referral to specialised care centres should be considered in patients with persistent PCa suspicion to provide the most rationalised management in terms of indication, biopsy technique, complications, pathologic assessment, and, finally, clinical implications of the findings.
A man may require a second prostatic biopsy for a number of reasons. In the current report, we describe why, when, and how a patient should undergo rebiopsy of the prostate.
Transrectal prostate biopsy
2013, Urologic Clinics of North America
Citation Excerpt :
The NCCN guidelines suggest performing a second extended protocol and considering saturation biopsies only in patients with high risk of cancer after multiple negative biopsies.6 Several studies support the hypothesis that saturation biopsy (>20 cores) seems appropriate in the repeat biopsy setting.76,83,84 In a study from Italy,84 the best rebiopsy scheme varied according to the clinical characteristics of the patients.
Head-to-head comparison of prostate health index and urinary PCA3 for predicting cancer at initial or repeat biopsy
2013, Journal of Urology
Citation Excerpt :
Urine samples were processed and tested to quantify PCA3 and PSA mRNA concentrations using the Progensa® PCA3 assay. Patients in the initial and repeat biopsy settings underwent ambulatory transrectal ultrasound guided PBx according to a standardized institutional saturation scheme consisting of at least 14 to 24 biopsy cores obtained from the prostate to achieve the highest detection rate.15 This saturation biopsy protocol is routinely used at the 2 institutions in daily clinical practice.
We performed a head-to-head comparison of the PHI (Prostate Health Index) and PCA3.
We evaluated PHI and PCA3 performance in 211 patients undergoing initial (116) or repeat (95) prostate biopsy. Multivariable logistic regression analysis was done using the AUC to test the accuracy of PHI and PCA3 for predicting prostate cancer in the overall population and in each setting. Decision curve analysis was used to compare the clinical benefit of different models.
Overall, the AUC of the PHI (0.70) was significantly higher than the AUC of PCA3 (0.59), total prostate specific antigen (0.56) and free-to-total prostate specific antigen (0.60) (p = 0.043, 0.002 and 0.037, respectively). PHI was more accurate than PCA3 for predicting prostate cancer in the initial setting (AUC 0.69 vs 0.57) and in the repeat setting (AUC 0.72 vs 0.63), although no statistically significant difference was observed. Including PCA3 in the base multivariable model (prostate specific antigen plus free-to-total prostate specific antigen plus prostate volume) did not increase predictive accuracy in either setting (AUC 0.79 vs 0.80 and 0.75 vs 0.76, respectively). Conversely, including PHI in the base multivariable model improved predictive accuracy by 5% (AUC 0.79 to 0.84) and 6% (AUC 0.75 to 0.81) in the initial and repeat prostate biopsy settings, respectively. On decision curve analysis the highest net benefit was observed when PHI was added to the base multivariable model.
PHI and PCA3 provide a significant increase in sensitivity and specificity compared to all other examined markers and they may help guide biopsy decisions. PCA3 does not increase the accuracy of predicting prostate cancer when PHI is assessed.
Contemporary role of systematic prostate biopsies: Indications, techniques, and implications for patient care
2013, European Urology
Citation Excerpt :
In a repeat PB setting, to minimise sampling error, the office-based transrectal saturation biopsy technique with a number of biopsy cores ≥20 has gained interest in some academic circles to enhance the detection of PCa by approximately 30%. Complication rates have not been higher than for standard biopsy [61,62,10,123]. The optimal repeat PB technique is more controversial than initial PB, requiring further consideration of the risk for clinically significant versus insignificant cancer based on the results of initial biopsy as well as biopsy-related morbidity.
Prostate cancer (PCa) screening to detect early stage PCa has resulted in increased identification of small-volume, low-grade PCa, many of which meet criteria for clinically indolent disease. Nevertheless, there remains some degree of underdetection of high-risk PCa in substantial numbers of men despite current diagnostic strategies.
To discuss the contemporary role of prostate biopsy (PB), focusing on the indications, techniques, and limitations of current PB techniques and evolving techniques affecting patient care.
A comprehensive Medline search was performed using the medical subject heading search terms prostate cancer, detection, prostate biopsy, significant cancer, and diagnosis, with restriction to the English language. Emphasis was given to publications within the past 5 yr.
Because abnormal digital rectal examination (DRE) and prostate-specific antigen (PSA) tests alone lack specificity for cancer, there is no universal indication for PB. This lack has inspired exploration for a cancer-specific biomarker and prediction tools such as risk calculators. Indication for biopsy should involve a balance between the underdiagnosis of high-risk cancers and the potential risks for the overdetection of clinically insignificant cancers as well as biopsy-related morbidity. Evidence supports the inclusion of laterally directed cores during transrectal ultrasound (TRUS) PB in addition to the traditional sextant pattern, which significantly improves cancer detection without a demonstrable increase in morbidity. These data indicate that such PB templates, typically 12 cores, represent the optimal template in initial PB. Optimised techniques and templates for repeat PB remain controversial. However, debate continues regarding indications, sampling number, and location as well as on the potential of modern image-guided approaches or three-dimensional (3D) mapping biopsy in this unique setting. Additional limitations of repeat PB techniques include associated procedural risks if general anaesthesia is required and inherent sampling errors of template-based techniques that are not targeted to the specific tumour site.
Current data support the utility of extended PB templates for initial TRUS PB intended to detect clinically significant PCa. Repeat PB in the setting of prior negative PB on the grounds of clinical suspicion or for risk-stratified approaches to management of low risk PCa requires balancing overdetection of low-risk cancer with the potential to miss significant cancer. Several options, including modern image-guided targeting, biomarker development, transrectal saturation PB, and 3D template mapping PB, are changing the clinical paradigms for evaluation and management. Evidence to support adopting approaches other than the current established standards should be tested through appropriately designed prospective studies.
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Published by Elsevier B.V.

Prostate CancerThe Optimal Rebiopsy Prostatic Scheme Depends on Patient Clinical Characteristics: Results of a Recursive Partitioning Analysis Based on a 24-Core Systematic Scheme

Abstract

Background

Objective

Design, setting, and participants

Measurements

Results and limitations

Conclusions

Introduction

Section snippets

Procedure

Results

Discussion

Conclusions

Eur Urol

Eur Urol

Urology

Eur Urol

Eur Urol

Urology

Eur Urol

Urology

Eur Urol

Eur Urol

Urol Oncol

Eur Urol

Urology

Eur Urol

Prostate Cancer
The Optimal Rebiopsy Prostatic Scheme Depends on Patient Clinical Characteristics: Results of a Recursive Partitioning Analysis Based on a 24-Core Systematic Scheme