Positive Digital Rectal Examination Research Articles

Abstract 1856: DNA damage and repair markers (H2AX and RAD51) improve accuracy of prostate cancer diagnosis and improve identification of aggressive disease

Abstract Background: Prostate biopsy is the gold standard test for diagnosing prostate cancer. However, due to the sampling error involved, it has low accuracy. Using markers associated with DNA damage and the concept of field effect, this study attempts to improve the diagnostic accuracy of prostate biopsies in men at high risk for this disease. Methods: Data were obtained from men participating in the Negative Biopsy Trial, a randomized multicenter phase 3 chemoprevention trial designed to investigate the effects of selenium supplementation on prostate cancer incidence in men who were at high risk for prostate cancer (PSA (prostate specific antigen) > 4ng/ml &/or PSA velocity (rate of PSA change over time) > 0.75ng/ml/yr &/or positive digital rectal examination) and had a negative prostate biopsy. 699 men were randomized to three treatment arms (placebo, 200ug Se/d, 400ug Se/d) and were followed every 6 months for up to five years. During the course of the study, 73 subjects were diagnosed with prostate cancer on repeat biopsy. For the current study, prostate biopsy samples from 73 subjects and 144 matched controls were stained for RAD51 and H2AX, markers of DNA repair, using immunohistochemistry techniques. Image analysis was conducted using ScanScope and Spectrum software from Aperio Technologies (Vista, California), which provided percentage of positive nuclei. Statistical analysis was conducted using Stata12 statistical software (Statacorp, College station, Texas). Results: Subjects diagnosed with prostate cancer, as compared to controls, demonstrated higher expression levels of both H2AX (mean(SD), 33.8(17.7) and 19.4(14.5)) as well as RAD51 (55.8(24.1) and (44.7(26.5)). As compared to the model containing baseline PSA, age and race (k1), the model containing RAD51 and H2AX data in addition to the data included in k1 showed improved positive predictive value, negative predictive value and area under the curve (70%, 78.9%, 0.77 and 80%, 87.06%, 0.90 respectively, p= 0.025). The above also holds true when data from subjects diagnosed with low grade disease are compared with those having high grade disease (100%, 80%, 0.72 and 100%, 85%, 0.82, p=0.07). Conclusions: Results of this study indicate that DNA damage markers may improve diagnostic accuracy for prostate cancer and also for aggressive disease in both men at high risk, and men diagnosed with prostate cancer. Citation Format: Amit M. Algotar, Anne E. Cress, Raymond B. Nagle, Dan Drinkwitz, Naran S. Lodhia, Patricia A. Thompson, Steven P. Stratton. DNA damage and repair markers (H2AX and RAD51) improve accuracy of prostate cancer diagnosis and improve identification of aggressive disease. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1856. doi:10.1158/1538-7445.AM2014-1856

PROGNOSTIC FACTORS OF BIOCHEMICAL RELAPSE FREE SURVIVAL FOLLOWING SALVAGE RADIOTHERAPY IN MEN WITH BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY

Purpose. To evaluate influence of clinical, biochemical and histological factors to biochemical relapse free survival (BRFS) following salvage radiotherapy (RT) in men with biochemical recurrence after radical prostatectomy. Material and methods. 77 patients with newly diagnosed biochemical recurrence (BR) after RPE were included into retrospective study. All of them underwent local salvage RT. Сlinical variables (age, serum prostate-specific antigen [PSA] level and PSA kinetics, time RPE-BR, Gleason grade, stage after RPE and clinical findings) were evaluated using Cox proportional hazards regression analysis. Results. The median, 1- and 3-year BRFS were 19,9 months, 63,8 ± 6,5 % and 24,7 ± 8,5 % respectively. Significant variables in the multivariable model were age, PSA level before RT, prostatectomy T3b stage, PSA doubling time and positive digital rectal examination findings (p < 0,05). Several clinical parameters help predict the outcomes of men with PSA elevation after radical prostatectomy. These data may be useful in counseling men regarding the timing of administration of adjuvant therapies.

Complications of Transrectal Prostate Biopsy

Abstract Objective: The aim of our study is to evaluate complications In patients who underwent a Transrectal Ultrasound Guided Prostate Biopsy (TRUS BP) at the Department of Urology of JFM CU and UHM in 2007-2008 and at the Department of Urology in Bojnice Hospital in 2009-2012. Methodology, disclosures: In our study, patients with positive digital rectal examination (DRE) and/or with hig- her prostate specific antigen (PSA) levels (&gt;4 ng/ml) are included. We excluded patients with PSA levels greater than 50ng/ml. as well as patients with less than 8 biopsy cores. The number of examined patients fulfilling the criteria was 474. An average age of them was 66.3 years (SD±8.3years). As an antibacterial prophylaxis, the patients were given fluoroquinolons in a dose of 500mg twice a day during a 3-day course of antibiotics, while the first dose was given one day before the procedure. In high risk patients, we used a single intramuscular dose of gentamycin 160mg right before the procedure followed by fluoroquinolons for the next five days. Results: The most severe complication was vasovagal reaction, which occurred in 9 (1.9%) cases. Haematuria occurred in 122 (25.7%) cases up to 3 days and in 10 (2.1%) patients up to 7 days. Six patients (1.3%) required hospital admission for severe haematuria. Dysuria occurred in 71 patients (15%). Rectal bleeding occurred in 90 (19%) cases with an average 2 days of bleeding, from which 7 patients were admitted to hospital and administered haemostyptics. From the mentioned count. 2 (0.4%) patients underwent a rectal tamponade and one (0.2%) patient with arterial bleeding underwent an arterial ligation of a stricken artery. Haemospermia occurred in 71 (15%) cases. 23 (4.9%) patients suffered fever above 38°C. within whom in 7 (1.5%) cases was microscopicaly proven uri- nary tract infection requiring hospitalisation lasting 7 days on average. Sepsis occurred in 3 (0.6%) patients, symp- tomatic bacterial prostatitis in 6 (1.2%) cases and urinary retention occurred in one (0.2%) patient. There was not arty significant higher amount of complications in between 8-core and 10-core biopsy (P=0.26), not even in betwe- en 8-core and 12-core biopsy (P=0.32). Conclusion: TRUS PB is a sale procedure with quite a low risk of complications. An important moment is a close monitoring right after the procedure. The most of the complications may persist for around two weeks and are trea- ted conservatively without persistent effects. Prophylaxis with broad spectrum antibiotics may provide an adequa- te coverage and lowers the risk of infectious complications.

Fluctuation in prostate cancer gene 3 (PCA3) score in men undergoing first or repeat prostate biopsies

To evaluate the variability in prostate cancer gene 3 (PCA3) score over time in men with elevated serum prostate-specific antigen (PSA) levels who are undergoing first or repeat prostate biopsy. A total of 360 men from two Italian institutions who had undergone at least two PCA3 assessments were selected. Of these, 97.5% were scheduled for first or repeat prostate biopsy because of elevated PSA level and/or positive digital rectal examination (DRE). We compared the PCA3 scores in men with a negative biopsy (normal parenchyma, benign prostatic hyperplasia [BPH], chronic prostatitis, high-grade prostate intraepithelial neoplasia [HG-PIN]) with those in men with a positive biopsy. We evaluated PCA3 repeated measures biological variability and its possible association with basic patient characteristics (age, family history of prostate cancer, DRE, prostate volume, BPH, prostatitis and HG-PIN). Three different thresholds were used to evaluate the possible changes in risk class: the standard threshold (a PCA3 score of 35), a US Food and Drug Administation-approved PCA3 threshold of 25 and a threshold selected based on our previous research which was a PCA3 score of 50. The PCA3 scores varied significantly (P < 0.001) when comparing men with a negative biopsy with those with a positive biopsy (median [range] PCA3 score: 25 [2-276] vs 43 [7-331]). There was no significant difference in PCA3 scores in men with chronic prostatitis and HG-PIN compared with other men with negative biopsies. The median (range) time between the two PCA3 assessments was 16.2 (3-53.7) months. No association was found between PCA3 repeated measures modifications and age, family history of prostate cancer, DRE, BPH, prostatitis, HG-PIN and use of 5-α-reductase inhibitors. The variability of PCA3 scores on repeated measures confirmed the risk class for about 80% of patients; of the remaining 20% of patients, the risk class was upgraded in two thirds and downgraded in one third. PCA3 score can be considered a stable marker over time in most cases but there is a group of men among whom there is clinically notable risk class change. Further investigation is required to determine the genesis of this phenomenon.

High Prevalence of Screen Detected Prostate Cancer in West Africans: Implications for Racial Disparity of Prostate Cancer

To our knowledge the reasons for the high rates of prostate cancer inblack American men are unknown. Genetic and lifestyle factors have been implicated. Better understanding of prostate cancer rates in West African men would help clarify why black American men have such high rates since the groups share genetic ancestry and yet have different lifestyles and screening practices. To estimate the prostate cancer burden in West African men we performed a population based screening study with biopsy confirmation in Ghana. We randomly selected 1,037 healthy men 50 to 74 years old from Accra, Ghana for prostate cancer screening with prostate specific antigen testing and digital rectal examination. Men with a positive screen result (positive digital rectal examination or prostate specific antigen greater than 2.5ng/ml) underwent transrectal ultrasound guided biopsies. Of the 1,037 men 154 (14.9%) had a positive digital rectal examination and 272 (26.2%) had prostate specific antigen greater than 2.5 ng/ml, including 166 with prostate specific antigen greater than 4.0 ng/ml. A total of 352 men (33.9%) had a positive screen by prostate specific antigen or digital rectal examination and 307 (87%) underwent biopsy. Of these men 73 were confirmed to have prostate cancer, yielding a 7.0% screen detected prostate cancer prevalence (65 patients), including 5.8% with prostate specific antigen greater than 4.0ng/ml. In this relatively unscreened population in Africa the screen detected prostate cancer prevalence is high, suggesting a possible role of genetics in prostate cancer etiology and the disparity in prostate cancer risk between black and white American men. Further studies are needed to confirm the high prostate cancer burden in African men and the role of genetics in prostate cancer etiology.

Fecal occult blood testing as a diagnostic test in symptomatic patients is not useful: a retrospective chart review.

The fecal occult blood test (FOBT) is a screening tool designed for the early detection of colorectal cancer in primary care. Although not validated for use in hospitalized patients, it is often used by hospital physicians for reasons other than asymptomatic screening. To profile the in-hospital use of the FOBT and assess its impact on patient care. Patient charts were retrospectively reviewed for all FOBTs conducted over a three-month period in 2011 by the central laboratory supporting the three acute care campuses of Hamilton Health Sciences (Hamilton, Ontario). A total of 229 patients underwent 351 tests; 52% were female and the mean age was 49 years (range one to 104 years). A total of 80 (34.9%) patients had at least one positive test. The most common indications for testing were anemia (51.0%) and overt gastrointestinal bleeding (19.2%). Only one patient had testing performed for asymptomatic colorectal cancer screening. In only 20 (8.7%) cases medications were modified before testing and diet was modified in only 21 (9.2%) cases. Most patients (85.2%) were taking one or more medications that could result in a false-positive result. Only 18 (7.9%) patients had a digital rectal examinations documented, of which seven were positive. All patients with a positive digital rectal examination underwent endoscopic procedures that revealed a source of bleeding. Among 44 patients with overt gastrointestinal bleeding, 12 (27.3%) had endoscopic investigations delayed to await results of the FOBT. Four patients were referred despite a negative FOBT due to a high degree of suspicion of gastrointestinal bleeding. The FOBT is often used inappropriately in the hospital setting. Confounding factors, such as diet and medication use, which may lead to false positives, are often ignored. Use of the FOBT in-hospital may lead to inappropriate management of patients, increased length of stay and increased direct medical costs. Use of the FOBT should be limited to validated indications only.

Histological inflammation and risk of subsequent prostate cancer among men with initially elevated serum prostate‐specific antigen (PSA) concentration in the Finnish prostate cancer screening trial

To assess whether histological signs of inflammation are associated with an increased risk of subsequent prostate cancer (PCa) in men with elevated serum prostate-specific antigen (PSA) concentrations and benign initial biopsy. Study subjects were men aged 54-67 years with an elevated PSA (≥4 ng/mL or 3-4 ng/mL and free to total PSA ratio ≤0.16 or positive digital rectal examination), but a benign biopsy result within the Finnish population-based randomised screening trial for PCa, which started in 1996. A total of 293 prostate biopsies without PCa or suspicion of malignancy from the first screening round in the Tampere centre were re-evaluated by a uropathologist to assess histological inflammation. Results of the subsequent screening rounds were obtained from the trial database and PCa diagnoses made outside the screening were obtained from the Finnish Cancer Registry. The median length of follow-up was 10.5 years. Cox regression analysis was used to assess PCa risk after the initial benign biopsy. Histological inflammation was found in 66% of the biopsies. Subjects with inflammation at the biopsy had a slightly lower PCa risk in the second screening round (18 vs 27%, rate ratio 0.69, 95% confidence interval [CI] 0.35-1.34) relative to men without inflammation. In further follow-up, the PCa risk remained nonsignificantly lower (hazard ratio [HR] 0.71, CI 0.46-1.10; P = 0.13). The risk was not appreciably affected by adjustment for age, PSA, prostate volume and family history of PCa (HR 0.67, CI 0.42-1.07; P = 0.092). Histological inflammation in a prostate biopsy among men with an initial false-positive screening test was not associated with an increased risk of subsequent PCa, but instead with a decreased risk which was of borderline significance. Inflammation in prostate biopsy is not a useful risk indicator in PCa screening.

Original Paper Inflammatory changes in biopsy specimens from patients with suspected prostate cancer

IntroductionProstate cancer (PCa) is one of the most commonly diagnosed cancers in elderly men, and accounts for 30% of all newly diagnosed cases of cancer. The development of the ‘clinically insignificant’ prostate cancer into its invasive form is still unclear, and it is believed that chronic inflammation may play its role, as proposed by De Marzo in 1999. However, there is no clear opinion on the subject of existence of dependencies between changes of the inflammatory type and PCa.Material and methodsThe study involved 1,010 men, suspected of prostate cancer development by positive digital rectal examination (DRE) and/or elevated PSA value. The 10 cores, TRUS guided biopsy was performed. In those with ASAP, HG–PIN or inflammation the second biopsy was proposed.ResultsIn the first biopsy PCa was diagnosed in 336 patients (33.27%). ASAP was found in 58 (5.74%), HG–PIN in 82 (8.11%), and the coexistence of both was found in 19 (1.88%). Chronic prostatitis was diagnosed in 101 (10%) men. Of those who underwent second biopsy, PCa was diagnosed in six of 19 patients (31.57%) who were diagnosed with HG–PIN in the first biopsy, in four of 40 (10%) with BPH in the first biopsy, in four of 18 (22.22%) with ASAP or LG–PIN together with ASAP, and in two out of five (40%) with the coexistence of ASAP and HG–PIN. Malignancy was not confirmed in any of the patients in whom the diagnosis of BPH, HG–PIN, or ASAP was accompanied by chronic prostatitis.ConclusionsChronic prostatitis does not significantly increase the value of PSA in patients with benign changes (BPH). The presence of prostatitis in the first biopsy did not predict cancer in subsequent biopsy, because the second biopsy did not reveal prostate cancer in any of the patients in whom prostatitis was diagnosed in the first biopsy.

WHAT WOULD HAVE HAPPENED IF NEUROVASCULAR BUNDLES WERE LEFT BEHIND AT RADICAL RETROPUBIC PROSTATECTOMY?

To evaluate whether nerve-sparing radical prostatectomy (NSRP) results in a residual tumor in the remaining neurovascular bundle (NVB). Materials and methods: A total of 88 patients underwent bilateral NSRP. The ipsilateral NVB was excised uni-/bilaterally on the tumor side, separately. Factors affecting NVB involvement were evaluated. Results: The mean patient age and preoperative serum prostate specific antigen (PSA) were 63.8 ± 6.2 years (49-76) and 12.9 ± 9.4 ng/mL (2.4-45.5), respectively. Digital rectal examination (DRE) suggested nodules in 34 patients (38.6%). Uni- and bilateral NVB resections were performed on 40 (45.5%) and 48 patients (54.5%), respectively, according to transrectal ultrasound-guided prostate biopsy (TRUS-Bx) pathology findings. NVB dissection was performed easily in all patients. The only factors correlated with tumor presence in the remaining NVB were a positive DRE finding (85.7% vs. 34.6%, P = 0.012), final pathology Gleason score (P = 0.016), capsular penetration/extracapsular extension (P = 0.001), and seminal vesicle invasion (P = 0.002). NVB involvement was detected in only 7 (8%) patients (6 had bilateral NVB resections), and the mean PSA was 19 ± 14.3 ng/mL in this group. The number of biopsy cores ranged between 6 and 27. In 15 patients, prostate cancer was diagnosed on repeat biopsies, and none had NVB invasion on pathology. Conclusion: NVBs seem to have been excised unnecessarily on the tumor side (81 out of 88 patients). No preoperative parameter other than DRE status was correlated with NVB involvement. Further criteria should be evaluated in performing NSRP.

Clinicopathologic analysis of prostate biopsy in men younger than 50 years of age with prostate-specific antigen 4-10 μg/L

Objective To discuss the prostate biopsy results in young men with age less than 50 years and with PSA 4-10 μg/L.Methods From January 2006 to December 2011,22 patients with PSA 4-10 μg/L underwent prostate biopsy for free/total PSA ≤ 0.16 (20 cases) and/or positive digital rectal examination (DRE) (4 cases).The nean age was 43 years (range,24-49 years),the mean PSA level was 7.08 μg/L (range,4.17-9.74 μg/L),the mean free/total PSA level was 0.11 (range,0.03-0.53).Radiologic suspicious lesion was founded in 13 cases.Clinicopathological data from these patients were reviewed.Results The results of the biopsy were 1 (4.5％) case of prostate cancer,2 cases (9.1％) with tuberculosis,9 cases (40.9％) with inflammation,10 cases (45.5％) with benign tissue.In 20 cases with free/total PSA ≤0.16,only 1 case was diagnosed as prostate cancer.In 4 cases with positive DRE,tuberculosis (2 cases) and inflammation (1 case) were diagnosed.Conclusions The prostate cancer detection was rare in young men less than 50 years of age with PSA 4-10 μg/L.The most common cause was prostate hyperplasia with inflammation. Key words: Prostate-specific antigen; Digital rectal examination; Biopsy, needle; Prostatic neoplasms

Prospective Randomized Multicenter Study Comparing Prostate Cancer Detection Rates of End-fire and Side-fire Transrectal Ultrasound Probe Configuration

To prospectively test the hypothesis that end-fire transrectal ultrasound prostate biopsy probes have greater cancer detection rates than side-fire probes. Retrospective studies have suggested that such probes might have greater cancer detection rates. The present prospective randomized multicenter trial aimed to compare the prostate cancer detection rates of the end-fire versus side-fire probe configuration during transrectal ultrasound-guided 12-core prostate biopsy. Patients were randomized according to age, prostate-specific antigen level and prostate volume. An interim analysis was planned after the inclusion of 300 patients. At the interim analysis after the inclusion of 297 patients, no differences were found in the mean prostate-specific antigen level (P = .412), mean age (P = .519), mean prostate volume (P = .730), and positive digital rectal examination findings (P = .295). The prostate cancer detection rate did not differ between the end-fire and side-fire probe (34.3% vs 34.4%, P = .972). On multivariate analysis, suspicious digital rectal examination findings (relative risk 8.185, P < .001), prostate-specific antigen level (relative risk 1.051, P = .041), and prostate volume (relative risk 0.973, P < .001), but not probe configuration (relative risk 0.942, P = .831), were independent predictive factors for the detection of prostate cancer. The interim analysis committee suggested that, because no difference of 5 absolute percent was achieved after 300 patients, no additional recruitment was necessary. Therefore, the study was terminated early. The results of the present study have shown that the transrectal ultrasound probe configuration does not affect the prostate cancer detection rate during transrectal ultrasound-guided prostate biopsy.

Prostate Cancers Detected During 5α-Reductase Inhibitor Use Are Smaller, De-Differentiated, But Confined when Compared To Controls

Rationale: To compare cancers detected during use of 5α-reductase inhibitors (5αRI) with cancers detected in untreated controls stratified for tumor size.Methods: Prostate biopsies were performed on 235 consecutive patients “for cause” (elevated or rising PSA, positive digital rectal examination, or focal hypoechoic lesion). Fifty patients were excluded for a prior diagnosis of cancer, leaving 185 as the study group (5αRI=41, control=144). Patients in the 5αRI group had been treated for a mean of 3.5 years. Cancer was ultimately diagnosed in 114/185 patients.Results: Cancer was diagnosed in 31/41 (76%) of patients treated with 5αRI and 83/144 (58%) of the control group (p=0.04). Control tumors were larger (14.3 mm) than those in 5αRI treated patients (9.4 mm, p=0.0007). No differences in mean PSA or PSA kinetics were detected between groups. For tumors less than 1.0 cm, the proportion of high grade cancers (Gleason 7-10 and Gleason 4+3-10) was higher in 5αRI subjects than in controls (p<0.05). Fewer 5αRI patients had proven extracapsular extension than controls, but this difference did not reach statistical significance (p=0.13). Normal DNA ploidy was more likely to be diagnosed in the 5αRI group versus controls, but this difference was not statistically significant (81% vs. 65%, p=0.14).Conclusions: Cancers diagnosed in patients presenting “for cause” treated with 5αRI drugs are more likely to be de-differentiated compared to controls. However, these tumors are also smaller and less likely to have extracapsular extension and abnormal DNA ploidy than controls.

The uncertain relationship between obesity and prostate cancer: An Italian biopsy cohort analysis

BackgroundThe study aims to investigate the relationship between obesity and prostate cancer diagnosis at biopsy. MethodsFrom 2005 onwards, a consecutive series of patients undergoing 12-core prostate biopsy for PSA value ≥ 4 ng/ml and/or positive digital rectal examination (DRE) were enrolled. Before the biopsy, patients underwent a physical examination, including height and weight measurement. Obesity was defined as body mass index (BMI) ≥30 kg/m2. Blood samples were drawn from all patients and analyzed for total PSA and testosterone. Results885 patients were enrolled with a median age and PSA of 67 years (range 37–95) and 6.4 ng/ml (range 1–30) respectively. Median BMI was 27.1 kg/m2 (range 18–46.6) with 185 patients classified as obese. 363 patients had cancer at biopsy; 76 were obese. PSA was independently associated with a higher risk of cancer (OR 1.09 per 1 unit PSA, p = 0.01). On multivariate analysis, the BMI was not significantly associated with an increased prostate cancer risk (p = 0.19). Out of 363 patients with prostate cancer, 154 had a Gleason score 6 (23 were obese) and 209 a Gleason score ≥7 (53 were obese). Among men with cancer, a higher BMI on univariate (p = 0.001) and multivariate analysis (p = 0.005) was associated with high-grade disease (Gleason ≥ 7). ConclusionsIn our single center study and less aggressively screened cohort, obesity is associated with an increased risk of a high-grade Gleason score when prostate cancer is diagnosed at biopsy.

Detection of prostate cancer with three-dimensional transrectal ultrasound: correlation with biopsy results

The aim of this study was to evaluate the role of three-dimensional transrectal ultrasound in the diagnosis of prostate cancer. A total of 112 patients with elevated serum prostate-specific antigen (PSA) or a positive digital rectal examination were evaluated using three-dimensional greyscale transrectal ultrasound (3D-GS TRUS) and three-dimensional power Doppler sonography (3D-PDS). Target biopsies were obtained together with 12 core systematic biopsies. Pathological results were correlated with the imaging data. Cancers were detected in 269 biopsy sites from 41 patients. 229 sites of cancer were depicted by 3D-GS TRUS and 213 sites were depicted by 3D-PDS. 30 sites were missed by both 3D-GS TRUS and 3D-PDS. Abnormal prostate images depicted by 3D-GS TRUS and 3D-PDS were associated with lesions with a Gleason score of 6.9 or higher. The detection rates of prostate cancer were significantly improved with 3D-GS TRUS and 3D-PDS on serum PSA levels >10 ng ml(-1) or 20 ng ml(-1). 3D-GS TRUS and 3D-PDS may improve the biopsy yield by determining appropriate sites for target and systematic biopsies. The abnormalities detected by 3D ultrasound were associated with moderate- and high-grade prostate cancers. However, based on the number of false-negative TRUS results, the use of systematic prostate biopsies should not be eliminated.

2030 THE ADDED VALUE OF DIGITAL RECTAL EXAMINATION IN PROSTATE CANCER SCREENING AND OUTCOMES

You have accessJournal of UrologyProstate Cancer: Detection and Screening1 Apr 20112030 THE ADDED VALUE OF DIGITAL RECTAL EXAMINATION IN PROSTATE CANCER SCREENING AND OUTCOMES Phillip Pierorazio, and Patrick Walsh Phillip PierorazioPhillip Pierorazio Baltimore, MD More articles by this author , and Patrick WalshPatrick Walsh Baltimore, MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2259AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The role of digital rectal examination (DRE) in prostate cancer (PC) screening has been called into question. The American Cancer Society (ACS) recommends PC screening with serial PSA with or without DRE. We evaluate the influence of DRE on outcomes of men with PC undergoing radical prostatectomy (RP) in low to normal ranges of PSA testing. METHODS The Johns Hopkins RP Database was queried for men in the PSA era (1993-present) with a PSA in the “low-normal” range (0–4.0 ng/mL) with a documented DRE; 4,270 men were identified. Cancer diagnosis was prompted by clinical examination (DRE) or PSA kinetics with consideration for patient age and family history of PC. Patient demographic and PC characteristics were compared between those men with a normal DRE (cT1c) and those with palpable disease (≥cT2) and those with cT2a disease only. Biochemical-free (BFS) and cancer-specific survival (CSS) were calculated using the Kaplan-Meier method and log-rank test. Analyses were repeated for those men with a PSA 0–2.5 and from 2.5–4.0. RESULTS 2,495 (64.0%) men were cT1c. 1,405 (36.0%) men had palpable DRE: 1,066 (75.9%) cT2a, 291 (20.7%) cT2b, 34 (2.4%) cT2c and 14 (0.4%) were cT3. Men with palpable DRE (≥cT2) had a greater proportion of Gleason 7–10 on biopsy (28.6 vs. 14.9%, p<0.001) and at RP (35.8 vs. 21.6%, p<0.001); fewer men with organ-confined PC (71.6% vs. 86.3%, p<0.001) and more positive surgical margins (10.0 vs. 6.7%, p<0.001) when compared to cT1c. Differences in biopsy and RP Gleason sum, pathological stage and surgical margin status were preserved when PSA was restricted from 0–2.5ng/mL and from >2.5–4.0ng/mL (p<0.001 for all interactions). 10-year BFS for men with cT1c, ≥cT2 and cT2a was 93.5, 85.8 and 91.1% respectively (p≤.04). 10-year CSS for men with cT1c, ≥cT2 and cT2a was 98.8, 93.8 and 96.8% (p0.01) respectively. There was no difference in BFS or CSS based on clinical stage for men with PSA 0–2.5. For men with PSA >2.5–4.0, 10-year BFS for men with cT1c, ≥cT2 and cT2a was 94.9, 84.2 and 90.3% (p≤.005) respectively. For men with PSA >2.5–4.0, 10-year CSS for men with cT1c, ≥cT2 and cT2a was 100, 94.1 and 95.2% (p≤0.002) respectively. CONCLUSIONS For men with a PSA 0–4.0ng/mL, a positive DRE was associated with a higher Gleason sum at biopsy and at RP; higher pathological stage and more positive surgical margins. In addition, men with cT1c had a better BFS and CSS at 10-years when compared to all men with a palpable DRE abnormality and those with cT2a only. DRE provides important information regarding grading, staging and outcome following RP in men with a PSA ≤4.0 ng/mL. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e812 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Phillip Pierorazio Baltimore, MD More articles by this author Patrick Walsh Baltimore, MD More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Metabolic syndrome is associated with high grade gleason score when prostate cancer is diagnosed on biopsy

To evaluate the association between metabolic syndrome (MS) and prostate cancer diagnosis and grade in patients undergoing prostate biopsy. From 2009 onwards, a consecutive series of patients undergoing 12-core prostate biopsy for PSA value ≥4 ng/ml and/or positive digital rectal examination (DRE) were prospectively enrolled. Body mass index (BMI), waist circumferences, and blood pressure were measured before the biopsy. Blood samples were tested for: PSA, fasting glucose, triglycerides, and cholesterol HDL. MS presence was defined according to Adult Treatment Panel III criteria. One hundred ninety five patients were enrolled with a median age and PSA of 69 years and 5.6 ng/ml respectively. Median BMI was 27.6 kg/m(2) with 64 patients (33%) being classified as obese (BMI ≥ 30 kg/m(2) ). Eighty-six patients (44%) had MS. Eighty-three patients (43%) had cancer on biopsy; 37 (45%) with MS and 46 (55%) without (P = 0.48). PSA was independently associated with higher risk of cancer (OR 1.12/1 U PSA, P = 0.01). Out of 83 patients with prostate cancer, 42 (51%) had Gleason score 6 (12 (28.5%) presented a MS) and 41 (49%) a Gleason score ≥7 (25 (61%) presented a MS). The presence of MS was not associated with an increased risk prostate cancer (OR: 0.97, P = 0.94) but with an increased risk of Gleason ≥7 (OR: 3.82; P = 0.013). In our single center study, MS is associated with an increased risk of high grade Gleason score when prostate cancer is diagnosed on biopsy. However, these results should be confirmed in a larger multicenter study. .

Does the criterion for prostate biopsy indication impact its accuracy? A prospective population-based outpatient clinical setting study

IntroductionProstate specific antigen (PSA) and digital rectal examination (DRE) are the main tests for initial prostate investigation; there is no consensus about the best criterion for prostate biopsies. We aim to check the accuracy of different criteria in this context including PSA derivatives to detect prostate cancer. Material and methodsFour different criteria for indication of prostate biopsy were compared: (A) PSA-density (>15ng/mL/cc); (B) PSA>2.5ng/mL; (C) PSA-velocity (>0.7ng/mL/year); (D) free/total PSA ratio (<15%). All biopsies and histopathological examinations were performed by the same urologist and pathologist, respectively. ResultsThe study was performed on 180 consecutive biopsies with 37.7% overall cancer detection rate: 29 (16.1%) performed following criterion A, 42 (23.3%) criterion B, 65 (36.1%) criterion C and 44 (24.4%) criterion D. Based on PSA criteria alone, the predictive positive value (PPV) was 37.9% for criterion A, 33.3% for B, 32.3% for C and 50.0% for criterion D, respectively, (p>0.05). Associating positive DRE with changed PSA, the PPV increased to 50%, 50%, 43.9% and 68.2% for criteria A, B, C and D, respectively (p>0.05). In univariate analysis, DRE (positive versus negative), PSA level (>10ng/mL versus <4.0ng/mL), free/total PSA ratio (<10% versus >15%) and age were associated with PC. In multivariate analysis only positive DRE was associated with prostate cancer. ConclusionsAll the criteria of PSA derivatives are complementary and useful predictors of cancer risk. However, a positive DRE increased the PPV of PSA derivatives. New tools are needed to improve the accuracy of prostate cancer detection.

¿Impacta el criterio para indicar la biopsia prostática sobre su exactitud? Estudio prospectivo llevado a cabo sobre una población de pacientes ambulantes

Introduction Prostate specific antigen (PSA) and digital rectal examination (DRE) are the main tests for initial prostate investigation; there is no consensus about the best criterion for prostate biopsies. We aim to check the accuracy of different criteria in this context including PSA derivatives to detect prostate cancer. Material and methods Four different criteria for indication of prostate biopsy were compared: (A) PSA-density (>15 ng/ ml/ cc); (B) PSA > 2,5ng/ml; (C) PSA-velocity (> 0.7 ng/ ml/ year); (D) free/total PSA ratio (<15%). All biopsies and histopathological examinations were performed by the same urologist and pathologist, respectively. Results The study was performed on 180 consecutive biopsies with 37.7% overall cancer detection rate: 29 (16.1%) performed following criterion A, 42 (23.3%) criterion B, 65 (36.1%) criterion C and 44 (24.4%) criterion D. Based on PSA criteria alone, the predictive positive value (PPV) was 37.9% for criterion A, 33.3% for B, 32.3% for C and 50.0% for criterion D, respectively, (p > 0.05). Associating positive DRE with changed PSA, the PPV increased to 50%, 50%, 43.9% and 68.2% for criteria A, B, C and D, respectively (p > 0.05). In univariate analysis, DRE (positive versus negative), PSA level (>10 ng/ ml versus <4.0 ng/ ml), free/total PSA ratio (<10% versus >15%) and age were associated with PC. In multivariate analysis only positive DRE was associated with prostate cancer. Conclusions All the criteria of PSA derivatives are complementary and useful predictors of cancer risk. However, a positive DRE increased the PPV of PSA derivatives. New tools are needed to improve the accuracy of prostate cancer detection.

Expanding the Criteria of Organ Procurement from Donors with Prostate Cancer: The Application of the New Italian Guidelines

Prostate cancer (CaP) represents the most prevalent malignancy in men more than 60-year-old, posing a problem in organ procurement from elderly subjects. However, most of the currently diagnosed CaP are low-grade and intraprostatic, with low metastatic risk, and there is recent evidence that most patients are overdiagnosed. The Italian National guidelines about organ acceptance from neoplastic donors changed in March 2005, extending the pool of potential candidates with CaP and introducing the function of a second opinion expert. Between 2001 and February 2005, 40 candidate donors with total PSA>/=10 and/or positive digital rectal examination underwent histopathological analysis of the prostate: 15 (37.5%) donors harboured CaP, and 25 (62%) were judged at 'standard risk'. After the introduction of the new guidelines in 2005, the second opinion expert judged at 'standard risk' 48 of 65 donors, while 17 of 65 needed histopathological analysis. Four (6.2%) donors harboured CaP, and 61 (94%) where judged at 'standard risk', with a significant increase of donated and actually transplanted organs. The application of the new guidelines and the introduction of a second opinion expert allowed a significant extension of the 'standard risk' category also to CaP patients, decreasing the histopathological examinations and expanding the donor pool.

Community‐based prostate cancer screening in Japan: Predicting factors for positive repeat biopsy

To assess possible predictors in determining criteria for repeat biopsy in a prostate cancer screening population. A total of 50 207 men over 55 years-of-age have participated in a prostate cancer screening program in Otokuni, Kyoto, Japan for 12 years. Transperineal systematic biopsy was carried out in case of positive digital rectal examination (DRE) or positive transrectal ultrasonography (TRUS) or a prostate-specific antigen (PSA) value greater than 10.0 ng/mL. For those with a PSA level from 4.1 to 10.0 ng/mL, and negative DRE and TRUS findings, biopsy was indicated only when PSA density (PSAD) was greater than 0.15. The same indication was applied for the repeat biopsy. A repeat biopsy after an interval of more than 2 years was carried out in 140 patients and was positive in 50 (36%) patients. The PSA value at the diagnosis of cancer declined from the initial value in six (12%) patients. On multivariate logistic regression analysis, PSA velocity (PSAV) as well as PSAD and DRE findings at latest screening were independent predictors for positive repeat-biopsy outcome. The odds ratio (95% confidence intervals) of PSAV >0.48, latest PSAD >0.33 and positive latest DRE were 4.17 (1.05-18.5), 4.15 (1.31-14.0), and 3.62 (1.06-13.2), respectively. A combination of three variables defined as positive if any of these were positive, reduced 31% of unnecessary biopsies while missing 8% of low volume, low grade cancers. A combination of latest PSAD, PSAV and positive DRE at latest screening might help to reduce unnecessary repeat biopsies in high-risk patients with an initial negative biopsy.