Improved prostate cancer detection with anterior apical prostate biopsies

PURPOSE: Research to improve prostate cancer detection with transrectal ultrasound-guided prostate biopsies has focused on increasing the number of cores and the directing of biopsies laterally. In this study, we describe our experience with the addition of anterior apical biopsies. MATERIALS AND METHODS: A total of 164 consecutive patients with an increased or increasing prostate-specific antigen and/or abnormal digital rectal examination underwent transrectal ultrasound and systematic biopsy. We performed our standard laterally directed sextant biopsies plus additional mid parasagittal plane biopsies at the base and mid-gland, and an anteriorly directed biopsy at the apex. Site-specific detection and tumor characteristics are reported. RESULTS: Prostate cancer was detected in 71 patients (43.3%). The most commonly unique site was the anterior apex. Excluding these biopsies would have missed 17% of the cancers detected. The cancers limited to the anterior apex had tumor characteristics similar to all other cancers detected. CONCLUSION: In our experience, the anterior apical biopsies increase the detection of prostate cancer on transrectal ultrasound-guided biopsies. Further study on incorporating this site into the biopsy scheme is indicated.     

Importance of posterolateral needle biopsies in the detection of prostate cancer

Objectives. To determine whether needle biopsy of the posterolateral aspects of the prostate aids in prostate cancer detection. In the routine sextant biopsy strategy, the posterolateral aspects of the prostate are not sampled.Methods. Using an 18-gauge biopsy gun, we performed sextant biopsies and an additional nine needle biopsies in the pathology laboratory on 150 radical prostatectomy specimens performed for Stage T1c prostate cancer. The additional nine biopsies consisted of three midline biopsies and six (three each from the left and right) posterolaterally aimed biopsies from the apex, mid, and base regions of the gland. Significant tumors were defined as those greater than 0.5 cm³, or with a Gleason score of 7 or greater, or non-organ confined.Results. Of the 123 cases with cancer on repeated biopsy, in only 3 (2.4%) was the only cancer found in the midline biopsies. For the following analysis, we analyzed the data as if we had not done the midline biopsies. If one had performed only the routine sextant needle biopsies, in 31 (25.2%) of the 123 cases, tumor would have been missed; 20 of these tumors were significant, including 5 with extraprostatic extension. If one had performed only the more posterolateral six biopsies, in 15 cases (12.2%), tumor would have been missed; 5 of these tumors were significant, all of which were organ confined.Conclusions. Adding routine midline biopsies does not appreciably increase the detection of cancer. If one were to only perform six needle biopsies of the prostate, these biopsies should be aimed more toward the posterolateral aspect of the gland. Maximum cancer detection results from combining both routine sextant and posterolateral needle biopsies.     

Three-dimensional computer-simulated prostate models: lateral prostate biopsies increase the detection rate of prostate cancer

OBJECTIVES: Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. We developed a novel three-dimensional (3D) computer-assisted prostate biopsy simulator based on whole-mounted step-sectioned radical prostatectomy specimens to compare the diagnostic accuracy of various prostate needle biopsy protocols. METHODS: We obtained digital images of 201 step-sectioned whole-mounted radical prostatectomy specimens. 3D computer simulation software was developed to accurately depict the anatomy of the prostate and all individual tumor foci. Additional peripheral devices were incorporated into the system to perform interactive prostate biopsies. We obtained 18 biopsies of each prostate model to determine the detection rates of various biopsy protocols. RESULTS: The 10- and 12-pattern biopsy protocols had a 99.0% detection rate; the traditional sextant biopsy protocol rate was only 72.6%. The 5-region biopsy protocol had a 90.5% detection rate and the 14-pattern, which includes all the biopsies used in the patterns above, only added 1 additional positive case (99.5%). Transitional zone and seminal vesicle biopsies did not result in a significantly increased detection rate when added to the patterns above. Only one positive model was obtained when the transitional zone biopsies were added. The lateral sextant pattern had a detection rate of 95.5%, and the 4-pattern lateral biopsy protocol had a 93.5% detection rate. CONCLUSIONS: Our results suggest that all the biopsy protocols that use laterally placed biopsies based on the 5-region anatomic model are superior to the routinely used sextant prostate biopsy pattern. Lateral biopsies in the mid and apical zones of the gland are the most important.     

Comparison of systematic sextant and lesion directed biopsies in prostate cancer detection

This study was designed to determine the value of performing separate lesion directed biopsies in addition to systematic random sextant biopsies for the detection, grading, and assessment of bilaterality of prostate cancer. A prospective study of 82 consecutive patients who had peripheral zone hypoechoic regions visualized on transrectal ultrasound was performed. All patients had either an abnormal prostate-specific antigen or an abnormal digital rectal examination and underwent random systematic and lesion directed biopsies. Cancer detection, laterality, and histologic grade of lesion directed biopsies were compared with those from systematic random biopsies. Prostate cancer was detected in 35 (40%) of 82 patients who had a hypoechoic lesion visualized. Three (9%) cancers would have been missed if only systematic biopsies had been performed, while nine (26%) cancers would have been missed if only lesion directed biopsies had been performed. In all but one patient, the Gleason score of the lesion directed biopsy was equal to or within one grade of the highest Gleason score determined from systematic biopsy. Systematic random biopsies detected cancer on the opposite side of a positive lesion directed biopsy in 48% of patients. In no case did a lesion directed biopsy add to the detection of bilateral disease. In conclusion, lesion directed biopsies increase the detection of prostate cancer when performed in addition to systematic random sextant biopsies. However, lesion directed biopsies alone would result in a substantial miss rate of prostate cancer. They do not add to the determination of bilateral disease, nor do they add to the pathologic grading of the detected cancer.     

The utility of ERG/P63 double immunohistochemical staining in the diagnosis of limited cancer in prostate needle biopsies

Diagnosis of limited cancer can be challenging in prostate needle biopsies, and immunohistochemistry is commonly used in such settings. Recently, TMPRSS2:ERG gene rearrangement was found to be highly specific for and detected in approximately 50% of prostate cancer. Positive immunohistochemical staining with a novel anti-ERG antibody highly correlated with TMPRSS2:ERG gene rearrangement status. We developed a double immunohistochemical staining containing both erythroblastosis virus E26 oncogen (ERG) and basal cell marker P63 antibodies and evaluated its use in the diagnosis of limited cancer in prostate needle biopsies. A total of 77 prostate needle biopsies containing cancer occupying <1 mm of the length of only 1 core of the entire biopsy set were stained with the double stain containing ERG and P63 antibodies. ERG positivity and its staining intensity in cancerous and other noncancerous lesions were evaluated. ERG expression was detected in 42% (32 of 77) of cases, with strong, moderate, and weak staining intensity in 72%, 16%, and 12% of cases. The staining was uniform in 84% of cases and heterogeneous in 16% of cases with different staining intensities in >10% of cancerous cells. High-grade prostatic intraepithelial neoplasia was present in 17 cases, and in 5 (29%) cases ERG was positive in high-grade prostatic intraepithelial neoplasia glands, which were all immediately adjacent to or intermingled with ERG-positive cancerous glands. In 4 additional cases, positive ERG staining was found in morphologically benign glands, which were also immediately adjacent to or intermingled with ERG-positive cancerous glands. All other benign lesions distant from cancerous glands, including simple and partial atrophy, were negative for ERG. P63 was negative in all cancerous glands and positive in noncancerous lesions. The P63/ERG double immunostain combines the high sensitivity of P63 and the high specificity of ERG and may be potentially useful in the work-up of difficult prostate biopsies. The high specificity of ERG for the presence of cancer may have important implications for prostate biopsy interpretation and needs to be further validated in larger prospective studies.     

Prediction of prostate cancer in extended-field biopsies of the prostate

OBJECTIVES: To assess the prediction of prostate cancer using extended-field prostatic biopsies (8-11 cores), as such biopsy protocols are recommended to increase the detection of prostate cancer, and as fewer cancers are missed this should improve the prediction of biopsy outcome from the patients' history, transrectal ultrasonography (TRUS) and serum markers. PATIENTS AND METHODS: In all, 260 patients were prospectively evaluated and 206 with a total prostate-specific antigen (PSA) level of < 20 ng/mL were included. All patients were evaluated for age, family history, lower urinary tract symptoms (LUTS), medication for LUTS, previous prostate biopsy, the presence of cysts, a digital rectal examination, calcifications or hypoechoic lesions on TRUS, total and transitional zone volume, total PSA (tPSA), PSA density (tPSAD), total PSA transition zone density (tPSATZD), complexed PSA (cPSA), cPSA density (cPSAD), cPSA transitional zone density (cPSATZD), free/total (f/t)PSA ratio and free/complexed PSA ratio (f/cPSA). Logistic regression was used to predict the outcome; 80% of the patients were used to generate the models and 20% to test the prediction. RESULTS: Two models were constructed; the most accurate contained family history, cPSA, cPSAD, cPSATZD, f/cPSA, PSAD and tPSATZD (sensitivity 91%, specificity 70%). A workable and concise model contained tPSATZD, cPSATZD and f/cPSA, and had a sensitivity of 93% and a specificity of 60%. The best single predictor was tPSATZD with a sensitivity of 92% and a specificity of 55%. Using regression models can produce considerable gains in specificity. This would allow unnecessary prostate biopsies to be avoided for a third of patients compared with tPSA alone. CONCLUSIONS: The present analysis for PSA indices appeared to be slightly more accurate than those in previously published studies. Most of this improvement in diagnostic accuracy was ascribed to the use of an extended-field biopsy protocol. Prostate cancer in a first-degree relative was the only variable that contributed significantly to the regression model. tPSATZD was the best volume-adjusted PSA index. The f/tPSA appeared to be the best test with no volume adjustment, followed by f/cPSA and cPSA. Although the models are cumbersome and expensive for use in general urological practice they could be used to optimize biopsy strategies on the basis of predicted cancer probabilities in screening studies. The cost of the models may compare favourably with tPSA because of the high specificity that can be achieved.     

Anterior apical biopsy: Is it useful for prostate cancer detection?

Objectives: To evaluate the utility of a 12‐core prostate biopsy protocol including apical anterior peripheral zone (AAPZ) cores. Methods: Between February 2002 and October 2006, 10‐core and 12‐core initial transrectal prostate biopsies were performed on 164 and 549 men, respectively. Two AAPZ‐directed biopsies were included in the 12‐core biopsy. During the same period, 12‐core repeat biopsies including six AAPZ sites were performed on 118 men. Results: Cancer was found in 66 cases (40.2%) in the 10‐core biopsy group and in 252 (45.9%) in the 12‐core biopsy group. In this latter group, 13 (5.2%) of the 252 men with positive biopsy had cancer exclusively in the AAPZ cores. When the cancer detection rate at initial biopsy in AAPZ alone was compared according to the digital rectal examination (DRE) findings, it was significantly higher in men with normal rather than abnormal DRE: 12/250 (3.4%) vs 1/185 (0.5%) (P < 0.01). In repeat 12‐core biopsies, cancer was detected in 25 (21.2%) men and 9 of them (36.0%) had cancer exclusively in the AAPZ cores. The cancer detection rate from AAPZ sites was significantly higher in repeat biopsy than that in initial biopsy (P < 0.01). Conclusions: Addition of the AAPZ site‐directed biopsy had greater utility in men with normal DRE and particularly in patients with a prior negative biopsy.     

Ultrasound-guided seminal vesicle biopsies in prostate cancer

Invasion of prostatic adenocarcinoma into the seminal vesicles (SV) is generally accepted as an index of poor prognosis. The pre-operative identification of SV invasion is an important element in staging since it may alter subsequent treatment decisions. We studied the possibility of diagnosing SV invasion with two biopsies from the junction between the prostate and seminal vesicles. Also we studied the correlation of several prognostic factors with the risk of clinical stage T(1,2,3) prostate cancer patients of having cancer growth into the seminal vesicles. Consecutive patients referred for transrectal ultrasound (TRUS) and biopsy because of clinical suspicion of prostate cancer were examined. This staging procedure was evaluated in patients who underwent a pelvic lymphadenectomy and radical retropubic prostatectomy (RRP). In 83 out of 138 patients prostate cancer was detected whereas 55 patients had benign disease. In 44% of prostate cancer patients a positive SV biopsy was found. The accuracy of the biopsies adjacent to the junction of the SV and the prostate was 91%. The best predictors for SV invasion were tumor grade of the biopsy sample (P<0.001), serum prostate-specific antigen (PSA) (P<0.0005), PSA density (P<0.0005) and clinical stage (P<0.0005). No significance was found in the relation to seminal vesicle involvement with free/total (f/t) PSA ratio (P=0.588) for the prostate cancer group (SV+ and SV-). In a receiver operating characteristic curves analysis, PSA density was significantly more accurate for prediction of SV invasion than PSA or f/t PSA ratio. In five prostatectomized patients (and negative SV biopsy) no SV invasion was found in the final pathologic examination either. SV biopsy at the junction of the SV and prostate is accurate for staging with high efficacy and low morbidity. To predict SV invasion in prostate cancer patients, PSA density was more accurate than PSA or f/t PSA ratio. The determination of the f/t PSA ratio in patients with low and intermediate PSA levels (eg <15 &mgr;g/L) is not useful to estimation of the risk of seminal vesicle involvement. The combination of serum PSA concentration, PSA density, tumor grade from the biopsy specimens ad clinical stage provides the best prediction of SV invasion. These parameters are identical to the conventional predictors of pathology after RRP. SV biopsies may provide additional information; if one or both basal biopsies are positive, a clinical T(1,2) disease is altered to T(3). Hence SV biopsy is useful for selection of patients who might obtain good results from RRP for prostate cancer. Prostate Cancer and Prostatic Diseases (2000) 3, 100-106     

Significance of cancer detection in the anterior lateral horn on systematic prostate biopsy: the effect on pathological findings of radical prostatectomy specimens

OBJECTIVE: To clarify the significance of cancer detection in the anterior lateral horn (ALH) on systematic prostate biopsy in relation to its effect on the pathological findings from retropubic radical prostatectomy (RRP) specimens. PATIENTS AND METHODS: The study included 84 consecutive patients who underwent RRP at our institution between January 1999 and December 2002, after being diagnosed as having prostate cancer, based on systematic prostate biopsies that included the areas taken by standard sextant biopsies and the bilateral ALHs. Several clinicopathological factors of these patients were analysed in relation to the presence or absence of cancer in the ALH on systematic biopsy. RESULTS: Of the 84 patients, cancer was detected in the ALH in 44 (group A), but not in the remaining 40 (group B). There were no significant differences in age, preoperative serum prostate-specific antigen level, or prostate volume between the groups. However, the incidence of bilateral positive cores and the percentage of positive biopsy cores in group A were significantly higher than those in group B. Pathological examinations of RRP specimens showed no significant differences in the incidence of lymphatic invasion, vascular invasion and perineural invasion, or Gleason score between the groups, but group A had a significantly larger tumour volume and higher incidence of extraprostatic disease than group B. CONCLUSIONS: Despite similar biological tumour characteristics and irrespective of the cancer location in the ALH, advanced and extensive disease frequently involves the ALH. Therefore, more aggressive treatment should be considered if cancer is detected in the ALH by systematic prostate biopsy.     

Computer simulated additional deep apical biopsy enhances cancer detection in palpably benign prostate gland

OBJECTIVES: The objective of this study was to use computer simulation to investigate the optimal biopsy scheme for enhancing the detection of cancer in palpably benign prostate glands. METHODS: The predominant distribution of palpably benign prostate cancer is anterior apex to mid-prostate. We used computer simulation to optimize apical samplings and to simulate the biopsy procedure, including angle and length. A total of 254 consecutive patients with palpably benign prostate glands underwent sextant biopsy plus two additional deep apical biopsies. RESULTS: Based on the computer simulation, lateral sextant and two additional medially located deep apical cores with a sagittal penetration angle of 80 degrees had the maximum cancer detection. Of the 254 patients, 58 (22.8%) had prostate cancer: 28 (48.3%) were positive only at the standard sextant sites, 12 (20.7%) were positive exclusively at the deep apical sites, and the remaining 18 (31.0%) were positive at both sites. Patients with gray-zone prostate-specific antigen (PSA) ranges of 4.1-10.0 ng/mL had increased cancer detection rates of 24% compared to sextant biopsy. Enhanced cancer detection by the deep apical biopsy was also evident in patients with a prostatic volume >40 cm3 (by 36.4%) and PSA 2.1-4.0 ng/mL (by 13.3%). CONCLUSIONS: Using a computer simulation-based biopsy scheme with deep apical sampling cores enhanced the detection of prostate cancer in palpably benign glands, especially in men with PSA ranges of 4.1-10.0 ng/mL or a gland volume of >40 cm3. Our approach with fewer sampling cores may have been more cost-effective than other extensive biopsy schemes, but further studies with larger samples are warranted.     

Lateral biopsies added to the traditional sextant prostate biopsy pattern increases the detection rate of prostate cancer

Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error and data based upon whole-mounted step-sectioned radical prostatectomy specimens using a three-dimensional computer-assisted prostate biopsy simulator suggests that an increased detection rate is possible using laterally placed biopsies. The simulated 10-core biopsy pattern (traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland) was shown to be superior to the traditional sextant biopsy. The objective of this pilot study was to confirm the higher prostate cancer detection rate obtained using the 10-core biopsy pattern in patients. We reviewed data on 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core biopsy pattern. The frequency of positive biopsy was determined for each core. Additionally, the sextant and 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. Of the 35 patients diagnosed with prostate cancer, 54.3%(19/35) were diagnosed by the sextant biopsy only. The 10-core pattern resulted in an additional 45.7%(16/35) of patients being diagnosed solely with the laterally placed biopsies. The laterally placed biopsies had the highest frequency of positive biopsies when compared to the sextant cores. In conclusion, biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern. Prostate Cancer and Prostatic Diseases (2000) 3, 43-46     

The diagnostic utility of novel immunohistochemical marker ERG in the workup of prostate biopsies with "atypical glands suspicious for cancer"

A diagnosis of "atypical glands suspicious for cancer" (ATYP) in prostate needle biopsy is associated with a 40% to 50% risk of finding prostate carcinoma (PCa) in subsequent biopsies. Many studies have attempted to identify clinical, histologic, or molecular characteristics of ATYP that correlated with the risk of PCa in follow-up biopsies. TMPRSS2:ERG gene rearrangement is the most common chromosomal alteration and is highly specific for PCa. Recently, 2 studies reported that positive immunohistochemical (IHC) stains with an ERG antibody highly correlated with the TMPRSS2:ERG gene rearrangement status. We evaluated the use of this antibody as an IHC marker on prostate biopsies with an initial ATYP diagnosis to determine whether positive ERG IHC was associated with increased PCa detection in subsequent biopsies, which therefore might be useful for stratifying ATYP prostate biopsies. ERG IHC was performed on 103 biopsies with initial ATYP diagnosis. Positive ERG IHC staining was detected in 16 of the 103 cases (15.5%) of the ATYP prostate biopsies. Of these 16 ERG-positive cases, the atypical glands were positive for ERG in 9 cases. In the remaining 7 cases, positive ERG staining was found in glands other than ATYP glands, including high-grade prostatic intraepithelial neoplasia and morphologically benign glands. ERG IHC was negative in other benign prostate lesions, including simple atrophy, partial atrophy, proliferative inflammatory atrophy, basal cell hyperplasia, postatrophic hyperplasia, and squamous metaplasia. In subsequent follow-up biopsies, PCa was detected in 7 of the 16 (43.8%) ERG-positive cases and in 42 of the 87 (48.3%) ERG-negative cases (P=0.952 by χ test). In biopsies with ERG-positive ATYP glands, cancer was found in 5 of 9 (55.6%) cases in subsequent biopsies. This is the first study to investigate the use of ERG IHC in difficult prostate biopsies. ERG IHC was positive in a small percentage (15.5%) of the ATYP prostate biopsies, and positive ERG staining did not correlate with the increased cancer detection in subsequent prostate biopsies. Therefore, ERG IHC is not useful for stratifying ATYP prostate biopsies to identify patients who have increased risk for PCa in repeat biopsies. Furthermore, positive ERG staining is not entirely specific for PCa and can occasionally be found in high-grade prostatic intraepithelial neoplasia and benign glands that are not associated with PCa in prostate biopsies.     

Prostate cancer detection and complication rates with transrectal ultrasound-guided prostate biopsies among different operators

ObjectiveTo evaluate interoperator differences in cancer detection and complication rates using transrectal ultrasound (TRUS)-guided prostate biopsies. We also analyzed whether there was a correlation between the experience of the operator and the cancer detection rate.Materials and methodsMedical records of 1879 patients who underwent a TRUS-guided prostate biopsy between 2005 and 2009 were retrospectively reviewed. Among them, 1496 patients who underwent a first biopsy without previous prostate surgery were selected for the analysis. Five urology residents performed 327, 351, 218, 332, and 268 biopsies, respectively. Cancer detection rates were analyzed by comparing the initial 20 and 100 patients with the final 20 and 100 patients. Patients were subdivided into two groups: prostate-specific antigen (PSA) of approximately 4–10 and >10 ng/mL. Prostate cancer (CaP) detection and complication rates were compared among operators.ResultsCancer was detected in 541 patients (36%). The operators performed a median of 403 (range: approximately 277–436) transrectal sono-guided prostate biopsies with CaP detection rates of approximately 33.9–42.2% (p = 0.243). Among different operators, we found no differences in cancer detection rates for the initial 100 or final 100 patients, even when separating patients into PSA > 10 ng/mL and 4 < PSA < 10 ng/mL groups. But significant individual variations in CaP-positive rates (p = 0.046) were observed in the first 20 biopsies for patients with PSA > 10 ng/mL receiving a TRUS biopsy; however, variable PSA levels in different groups of patients may have been responsible for this finding. There were no differences in complication rates among the different operators for the initial 20 and final 20 biopsies or for the initial 50 and final 50 biopsies.ConclusionNo clinically significant differences in CaP detection existed among operators performing TRUS-guided prostate biopsies. Complication rates did not differ among the operators. A TRUS-guided prostate biopsy is a rapidly learned technique and is a good diagnostic tool for CaP detection.