Multicenter analysis of clinical and MRI characteristics associated with detecting clinically significant prostate cancer in PI-RADS (v2.0) category 3 lesions

ObjectivesWe sought to identify clinical and magnetic resonance imaging (MRI) characteristics in men with the Prostate Imaging - Reporting and Data System (PI-RADS) category 3 index lesions that predict clinically significant prostate cancer (CaP) on MRI targeted biopsy.Materials and MethodsMulticenter study of prospectively collected data for biopsy-naive men (n = 247) who underwent MRI-targeted and systematic biopsies for PI-RADS 3 index lesions. The primary endpoint was diagnosis of clinically significant CaP (Grade Group ≥2). Multivariable logistic regression models assessed for factors associated with clinically significant CaP. The probability distributions of clinically significant CaP based on different levels of predictors of multivariable models were plotted in a heatmap.ResultsMen with clinically significant CaP had smaller prostate volume (39.20 vs. 55.10 ml, P < 0.001) and lower apparent diffusion coefficient (ADC) values (973 vs. 1068 μm²/s, P = 0.013), but higher prostate-specific antigen (PSA) density (0.21 vs. 0.13 ng/ml², P = 0.027). On multivariable analyses, lower prostate volume (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.92–0.97), lower ADC value (OR: 0.99, 95% CI: 0.99–1.00), and Prostate-specific antigen density >0.15 ng/ml² (OR: 3.51, 95% CI 1.61–7.68) were independently associated with significant CaP.ConclusionHigher PSA density, lower prostate volume and ADC values are associated with clinically significant CaP in biopsy-naïve men with PI-RADS 3 lesions. We present regression-derived probabilities of detecting clinically significant CaP based on various clinical and imaging values that can be used in decision-making. Our findings demonstrate an opportunity for MRI refinement or biomarker discovery to improve risk stratification for PI-RADS 3 lesions.     

Clinical validation of IsoPSA,a single parameter,structure-focused assay for improved detection of prostate cancer: A prospective,multicenter study

BackgroundIsoPSA is a blood-based test that assesses prostate cancer (CaP) risk by partitioning and detecting cancer-specific structural isoforms of prostate specific antigen (PSA) with an aqueous 2- phase system.ObjectiveTo validate the diagnostic performance of IsoPSA for High-Grade CaP and Any CaP risk on biopsy in men age ≥ 50 with total PSA ≥ 4 ng/ml.Design, Setting, and ParticipantsProspective, multicenter study of 888 men scheduled for prostate biopsy at 8 academic and community sites between August 2015 and August 2020.InterventionIsoPSA test.Outcome Measurements and Statistical AnalysisReceiver operating characteristic and likelihood ratio analysis used to validate diagnostic performance for previously established IsoPSA Index cutoffs for High-Grade CaP (Gleason Score ≥ 7) and Any CaP (Gleason Score ≥ 6), compare IsoPSA to total PSA and % free PSA, and evaluate subgroups (total PSA 4–10 ng/ml, total PSA > 10 ng/ml, biopsy naïve, prior negative biopsy).Results and LimitationsThe disease prevalence was 35.6% (High-Grade CaP) and 58.9% (Any CaP). The area under the receiver operating characteristic curve was 0.783 (High-Grade CaP) and 0.770 (Any CaP). IsoPSA outperformed total PSA and % free PSA on area under the receiver operating characteristic curve, specificity, positive and negative predictive value at similar sensitivity. Using selected IsoPSA Index cutoffs, an estimated 46% (High-Grade CaP) and 42% (Any CaP) of biopsies could be avoided in low-risk patients. IsoPSA displayed statistically informative likelihood ratio-based predictive characteristics. IsoPSA maintained accuracy in clinically relevant subgroups.ConclusionsIsoPSA diagnostic performance and predictive value is validated for High-Grade CaP and Any CaP in men age ≥ 50 with total PSA ≥ 4 ng/ml undergoing diagnostic biopsy. IsoPSA outperforms total and % free PSA in discriminating the risk of prostate cancer on biopsy.Patient SummaryIsoPSA has the potential to reduce unnecessary biopsies and improve the risk-benefit ratio for CaP early detection.     

Predicting biopsy-proven prostate cancer recurrence following cryosurgery

ObjectivesProstate cancer (CaP) cryosurgery utilizes PSA nadir level and radiotherapy criteria as surrogates for success. We attempted to correlate PSA doubling time (PSAdt) and time of undetectable PSA (TUPSA) with biopsy-proven cancer recurrence (BPR) in men treated with primary third-generation cryotherapy for clinically localized CaP.Materials and methodsDemographic, clinical, and pathologic data was retrieved including age, race, use of preoperative hormones or 5-α reductase inhibitors (5-ARIs), initial biopsy PSA, biopsy Gleason score, cT stage, prostate volume, presence/absence median lobe, and follow-up. Post-cryotherapy biopsy was considered for PSA levels ≥ 0.5 ng/ml. PSAdt was determined by the log-slope method. TUPSA was defined as time from surgery to a PSA value ≥ 0.2ng/ml or most recent follow-up if undetectable.ResultsNinety-seven patients were identified. Preoperative hormonal manipulation was used in 25 (26%); 5 (5%) were using a 5-ARI. Twenty-seven (29%) underwent post-cryotherapy biopsy, 12 (12%) had a BPR. In 41 (42%), PSAdt was calculated (median 11.9 months, IQR 6.6–34.8); no significant difference between patients with BPR and without CaP was found (P = 0.46). TUPSA was a median of 4.9 months (IQR 3.2–9.9) vs. 15.6 months (IQR 6.1–30.3) for BPR or no CaP, respectively (P = 0.005). On proportional hazards regression, TUPSA was the only independent predictor of BPR (P = 0.03, OR 0.91).ConclusionsPost-cryosurgery PSAdt does not appear to be associated with BPR risk, whereas TUPSA reduces the risk of BPR by 9% per month. This may help guide management if local failure is suspected.     

Transition zone PSA density improves the prostate cancer detection rate both in PSA 4.0–10.0 and 10.1–20.0 ng/ml in Chinese men

ObjectivesWe hypothesized the prostate-specific antigen (PSA) “grey zone” in Chinese men was higher than the traditional value (4.0–10.0 ng/ml) since incidence of prostate cancer (CaP) in Chinese men was relative low. We then assessed the efficiencies of transition zone PSA density (TZPSAD) in the diagnosis of CaP in Chinese men with a PSA of both 4.0–10.0 and 10.1–20.0 ng/ml.Materials and methodsMen had a prostatic biopsy for detecting CaP from November 1999 to August 2009 were retrospectively retrieved from our computer center. Those had a document of transrectal ultrasound transition zone measurement with a PSA of 4.0–20.0 ng/ml were included. Receiver-operating characteristic (ROC) curve was used to analyze the efficiencies of PSA and TZPSAD in the diagnosis of CaP.ResultsA total of 189 men were included in the study. Of these men, 78 and 111 had a PSA of 4.0–10.0 and 10.1–20.0 ng/ml, respectively. The rate of CaP in men with a PSA of 4.0–10.0 ng/ml was not statistically significantly different compared with those with a PSA of 10.1–20.0 ng/ml (20.5% vs. 21.6%, P = 0.854). The areas under the ROC curve (AUCs) in diagnosis of CaP for PSA and TZPSAD were 0.569 and 0.702 in men with a PSA of 4.0–10.0 ng/ml and 0.463 and 0.730 in men with a PSA of 10.1–20.0 ng/ml, respectively. The best cut-off of TZPSAD in predicting CaP in men with a PSA of 4.0–10.0 ng/ml was 0.370 ng/ml/ml, the sensitivity of which equaled 68.8%, specificity 72.6%. The best cut-off of TZPSAD in predicting CaP in men with a PSA of 10.1–20.0 ng/ml was 0.500 ng/ml/ml. Its sensitivity equaled 70.8%, specificity 70.1%.ConclusionsUsing TZPSAD can improve the efficiency of PSA in diagnosis of CaP and decreases the unnecessary prostatic biopsy in men with a PSA of both 4.0–10.0 and 10.1–20.0 ng/ml in Chinese men.     

Prostate biopsy in patients with long-term use of indwelling bladder catheter: What is the rationale?

ObjectiveAcute urinary retention (AUR) is expected to occur in 2% to 39% men with benign prostatic hyperplasia. To date, no study has elucidated the effect of long-term use of indwelling bladder catheter on serum prostate specific antigen (PSA) levels and on the incidence of prostate cancer (CaP). The aim of the present study is to analyze the incidence of CaP in patients with long-term use of indwelling bladder catheter and determine some practice patterns on this issue.Materials and methodsThe study comprised a retrospective analysis of data from 1,651 patients who had undergone transrectal ultrasound (TRUS)-guided prostate biopsy from July 2004 to June 2009. Among these patients, 198 (12%) were using an indwelling bladder catheter during the biopsy for at least 1 month. The incidence of CaP was recorded according to total PSA levels. Other variables such patient age, free/total PSA rate, PSA density, prostate volume, and duration of catheter use was also analyzed. Men with a digital rectal examination suspicious for cancer were not considered for analysis.ResultsMedian patient age was 71 years (37 to 89 years). Overall, 25% of patients presented a CaP diagnosis. CaP incidence according to the PSA levels was 0%, 18.9%, 24.5%, and 40.6% for patients with PSA ≤4.0, 4.1–10.0, 10.1–20.0, and >20.0 ng/ml, respectively. When prostate volume was analyzed together, we demonstrated that only 1 (2.4%) patient with PSA below 10.0 ng/ml and prostate volume >60 g had CaP. Median total PSA, PSA density, and prostate volume were statistically different between patients with and without CaP.ConclusionsProstate biopsy should not be indicated for all patients with diagnosis of BPH and AUR who present an elevated PSA level. Patients with PSA below 10.0 ng/ml, and prostate volume >60 g should only undergo biopsy in selected cases. Patients with PSA >20.0 ng/ml and a prostate volume ≤60 g are at higher risk of CaP diagnosis.     

8q24 and 17q Prostate cancer susceptibility loci in a multiethnic Asian cohort

ObjectivesRecently, several genome-wide association studies have demonstrated a cumulative association of 5 polymorphic variants in chromosomes 8q24 and 17q with prostate cancer (CaP) risk in Caucasians, particularly those harboring aggressive clinicopathologic characteristics. The purpose of this study was to evaluate the influence of these variants on CaP susceptibility in Singaporean Asian men.Materials and methodsWe performed a case-control study in 289 Chinese CaP patients and 412 healthy subjects (144 Chinese, 134 Malays, and 134 Indians), and examined the association of the 5 single nucleotide polymorphisms (SNPs) with CaP.ResultsIn the healthy subjects, rs16901979 A-allele frequency was highest amongst Chinese (0.32) compared with Malays (0.13; P < 0.0001) or Indians (0.09; P < 0.0001); rs6983267 G-allele was highest in Indians (0.51) compared with Chinese (0.42; P = 0.041) or Malays (0.43; P = 0.077); whereas rs1859962 G-allele frequency was highest amongst Indians (0.56) compared with Chinese (0.40; P = 0.0002) or Malays (0.38; P < 0.0001). Individuals with the rs4430796 TT genotype were at increased CaP risk in the Chinese via a recessive model (odds ratios (OR) = 1.56, 95% CI = 1.04–2.33). Significant associations were observed for rs4430796 TT with Gleason scores of ≥7 (OR = 1.76, 95% CI = 1.14–2.73) and prostate-specific antigen (PSA) levels of ≥10 ng/ml at diagnosis (OR = 1.63, 95% CI = 1.01–2.63), as well as for rs6983267 GG with stage 3–4 CaPs (OR = 1.91, 95% CI = 1.01–3.61). A cumulative gene interaction influence on disease risk, which approximately doubled for individuals with at least 2 susceptibility genotypes, was also identified (OR = 2.18, 95% CI = 1.10–4.32).ConclusionsThis exploratory analysis suggests that the 5 genetic variants previously described may contribute to prostate cancer risk in Singaporean men.     

Serum levels of 17-β-estradiol are not predictive of prostate cancer diagnosis and aggressiveness: Results from an Italian biopsy cohort

ObjectivesTo explore the association between serum levels of 17-β-estradiol (17BE) and prostate cancer (PCa) risk in men undergoing prostate biopsy.Methods and materialsBetween 2006 and 2012, we prospectively enrolled 894 patients, with no history of PCa, undergoing prostate biopsy. Before biopsy was performed, general data, digital rectal examination (DRE), body mass index, 17BE, and prostate-specific antigen (PSA) were recorded. The risk of detecting cancer and high-grade cancer was assessed as a function of 17BE using crude and adjusted logistic regressions.ResultsSerum levels of 17BE were not associated with an increased risk of PCa or high-grade disease. Age (odds ratio [OR] 1.05; 95% confidence interval [CI]: 1.03–1.07; P = 0.000), DRE(OR 2.81; 95% CI: 1.98–4.00; P = 0.000), and PSA(OR 1.07; 95% CI: 1.04–1.10; P = 0.000) were found to be independent predictors of PCa risk. Age (OR 1.05; 95% CI: 1.01–1.09; P = 0.007), DRE (OR 3.04; 95% CI: 1.79–5.17; P = 0.000), body mass index (OR 1.07; 95% CI: 1.01–1.150; P = 0.040), and PSA (OR 1.08; 95% CI: 1.03–1.12; P = 0.000) were found to be independent predictors of high-grade disease.ConclusionIn our cohort of patients, serum levels of 17BE are not predictive of PCa or high-grade disease. In patients at risk of PCa, 17BE should not be considered a reliable marker to predict poorly differentiated PCa in the setting of initial prostate biopsy.     

Detailed biopsy pathologic features as predictive factors for initial reclassification in prostate cancer patients eligible for active surveillance

ObjectiveTo evaluate the impact of detailed biopsy characteristics such as positive cores location or multifocality on the risk of initial reclassification in prostate cancer (CaP) patients eligible for active surveillance (AS).Materials and methodsWe reviewed data from 300 consecutive men eligible for AS (PSA ≤ 10 ng/ml, clinical stage T1c, Gleason score ≤6, <3 positive cores, extent of cancer in any core < 50%) who have undergone a radical prostatectomy (RP). Reclassification was defined as upstaged disease and/or upgraded disease in RP specimens.ResultsBiopsy features showed 36% of CaP involving 2 cores and a mean total tumor length of 2.63 mm. The 2 most frequently positive sites were base and apex. Mean total tumor length was significantly associated with upgraded disease (P = 0.025). In a multivariate model taking into account PSA, PSAD, number of positive cores and total tumor length, a total tumor length > 5 mm were independently predictor for a upgraded disease (OR 1.93, P = 0.046). The number, the multifocality and the bilaterality of positive cores were not associated with reclassification. Upgraded disease was significantly less reported in case of positivity at midline zone compared with positivity at base, apex, or transition zone (P = 0.013).ConclusionsDetailed biopsy data provide additional information on the initial risk of reclassification in AS patients. Patients having a total tumor length < 5 mm and positive cores at midline zone are more likely to have favorable pathologic characteristics at diagnosis. These variables can be used for selection and monitoring improvement in AS programs.     

Micropapillary bladder cancer: a review of Léon Bérard Cancer Center experience

Background

High-grade prostatic intraepithelial neoplasia (HGPIN) is a precursor lesion to prostate cancer (CaP). UK-based studies examining the occurrence of isolated HGPIN and subsequent risk of CaP are lacking. Our aim was to assess the occurrence of HGPIN in a regional UK population and to determine whether in a retrievable cohort of such patients that had repeat extended core biopsies, there was an elevated risk of CaP.

Methods

A retrospective analysis of the pathology database was conducted at our institution (Lancashire Teaching Hospitals NHS Foundation Trust) for prostate biopsies recorded between January 2001 and December 2005 (all extended core biopsies). Those patients with isolated HGPIN on 1^st set of biopsies were identified and, their clinical characteristics and pathological findings from subsequent biopsies (if any) were determined. The risk of CaP on subsequent biopsies based on presenting baseline PSA was stratified.

Results

Of 2,192 biopsied patients, there were 88 cases of isolated HGPIN of which 67 patients underwent one or more repeat biopsies. In this repeat-biopsy group, 28 CaP diagnoses were made. Age at first biopsy (P < 0.001), higher mean baseline prostate-specific antigen (PSA) (P < 0.005) and higher mean change in PSA (P < 0.05) were predictive of CaP detection on repeat biopsies. PSA ranges and their associated predictive values for cancer were: 0 to 5 ng/ml – 11%; 5 to 10 ng/ml – 34%; 10 to 20 ng/ml – 50%; and > 20 ng/ml – 87.5%.

Conclusion

Based on our results, we recommend delaying the 1st repeat biopsy at low PSA range but to have a shorter interval to repeat biopsies at intermediate and higher PSA ranges.     

Prostate cancer risk prediction in a urology clinic in Mexico

ObjectivesTo evaluate factors affecting the risk of prostate cancer (CaP) and high-grade disease (HGCaP, Gleason score ≥ 7) in a Mexican referral population, with comparison to the Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (PCPTRC).Methods and materialsFrom a retrospective study of 826 patients who underwent prostate biopsy between January 2005 and December 2009 at the Instituto Nacional de Cancerología, Mexico, logistic regression was used to assess the effects of age, prostate-specific antigen (PSA), digital rectal exam (DRE), first-degree family history of CaP, and history of a prior prostate biopsy on CaP and HGCaP, separately. Internal discrimination, goodness-of-fit, and clinical utility of the resulting models were assessed with comparison to the PCPTRC.ResultsRates of both CaP (73.2%) and HGCaP (33.3%) were high among referral patients in this Mexican urology clinic. The PCPTRC generally underestimated the risk of CaP but overestimated the risk of HGCaP. Four factors influencing CaP on biopsy were logPSA, DRE, family history and a prior biopsy history (all P < 0.001). The internal AUC of the logistic model was 0.823 compared with 0.785 of the PCPTRC for CaP (P < 0.001). The same 4 factors were significantly associated with HGCaP as well and the AUC was 0.779 compared with 0.766 of the PCPTRC for HGCaP (P = 0.13).ConclusionsLack of screening programs or regular urologic checkups in Mexico imply that men typically first reach specialized clinics with a high cancer risk. This renders diagnostic tools developed on comparatively healthy populations, such as the PCPTRC, of lesser utility. Continued efforts are needed to develop and externally validate new clinical diagnostic tools specific to high-risk referral populations incorporating new biomarkers and more clinical characteristics.     

Prostate carcinoma spatial distribution patterns in Chinese men investigated with systematic transperineal ultrasound guided 11-region biopsy

ObjectivesTo evaluate prostate cancer spatial distribution patterns with transperineal ultrasound navigated 11-region prostate biopsy template in a Chinese screening population.MethodsFrom May 2004 to December 2007, 215 patients with a median prostate-specific antigen (PSA) level of 21.0 ng/ml were diagnosed with prostate cancer through transperineal ultrasound guided 11-region template prostate biopsy at Peking Union Medical College Hospital. The characteristics of our sample cancer spatial distribution were assessed in relation with different PSA levels.ResultsThe mean positives for the cancer of regions 1–10 and region 11 (the apical region) were 61.2% vs. 66.4% in patients whose PSA > 20 ng/ml (P = 0.29), and 35.7% vs. 47.6% in patients with PSA ≤ 20 ng/ml (P = 0.001). The positives for cancer contained within the anterior and posterior parts were 96.5% vs. 90.9% (P = 0.10) in patients with PSA > 20 ng/ml and 75.2% vs. 75.2% in patients with PSA ≤ 20 ng/ml (P = 1.00).ConclusionsThe current study suggests that prostate carcinoma foci are more frequently localized in the apical region in patients with normal to moderately increased PSA. Special attention should be paid to the apical region during the selection process of biopsy regions for this group of patients.     

PCA3 sensitivity and specificity for prostate cancer detection in patients with abnormal PSA and/or suspicious digital rectal examination. First Latin American experience

IntroductionProstate Cancer Gene 3 (PCA3) is a recently described and highly specific urinary marker for prostate cancer (CaP). Its introduction in clinical practice to supplement low specificity of prostate specific antigen (PSA) can improve CaP diagnosis and follow-up. However, before its introduction, it is necessary to validate the method of PCA3 detection in distinct geographic populations.ObjectivesOur aim was to describe for the first time in Latin America, the application of the PROGENSA PCA3 assay for PCA3 detection in urine in Chilean men and its utility for CaP diagnosis in men with an indication of prostate biopsy.Materials and methodsSixty-four Chilean patients (mean age, 64 years) with indication of prostate biopsy because of elevated PSA and/or suspicious digital rectal examination (DRE) were prospectively recruited. PCA3 scores were assessed from urine samples obtained after DRE, before biopsy, and compared with PSA levels and biopsy outcome.ResultsThe median PSA value and mean PCA3 score were 5.8 ng/ml and 31.7, respectively. Using a cutoff PCA3 score of 35, the sensitivity and specificity for detecting CaP were 52% and 87%, respectively. The receiver operating characteristic (ROC) curve analysis showed an area under the curve of 0.77 for PCA3 and 0.57 for PSA, for the same group of patients. In patients with previous negative biopsy, PCA3 specificity increased by 2.2%.ConclusionsThis is the first report in Latin America on the use of PCA3 in diagnosing CaP. Our results are comparable to those reported in other populations in the literature, demonstrating the reproducibility of the test. PCA3 score was highly specific and we specially recommend its use in patients with persistent elevated PSA and prior negative biopsies.     

The clinical potential of pretreatment serum testosterone level to improve the efficiency of prostate cancer screening

OBJECTIVES: The aim of the present study was to evaluate the clinical value of the pretreatment serum testosterone (T) level as a potential predictor of prostate cancer risk in screening for prostate cancer. MATERIALS AND METHODS: The subjects were 420 patients suspected of having prostate cancer who underwent prostate biopsy, and whose pretreatment T levels were recorded. We checked for association between the presence of prostate cancer and the following clinical factors: pretreatment serum T level, age, pretreatment prostate-specific antigen (PSA) level, digital rectal examination findings, ratio of free to total PSA, prostate volume, and PSA density (PSAD). RESULTS: Overall, there was no significant difference in mean pretreatment T level between patients diagnosed with cancer (3.9+/-2.4 ng/ml) and patients diagnosed with benign prostate disease (BPD; 3.7+/-1.7 ng/ml); diagnosis was based on prostate biopsy. However, among patients with PSA <10 ng/ml, the pretreatment T level was significantly higher in patients diagnosed with prostate cancer (4.2+/-2.6 ng/ml) than in patients diagnosed with BPD (3.6+/-1.4 ng/ml) (p=0.007); a similar trend was observed among patients with PSAD <0.15 ng/ml/cc. Multivariate analysis indicated that pretreatment T level was an independent significant predictor of positive prostate biopsy (p=0.020). Additionally, the serum T level was significantly lower in patients with a Gleason score >or=7 (3.7+/-2.1 ng/ml) versus a score <7 (4.2+/-1.7 ng/ml) (p=0.030). Also, serum T levels were significantly higher in well-differentiated prostate cancer (4.8+/-2.1 ng/ml) versus moderately differentiated (3.8+/-1.3 ng/ml) or poorly differentiated (3.7+/-1.4 ng/ml) (p<0.01). CONCLUSIONS: Among relatively low-risk patients, serum T level was an independent significant predictor of positive prostate biopsy, suggesting that the efficiency of prostate cancer screening can be improved by including measurement of serum T level.     

The impact of pretreatment PSA on risk stratification in men with Gleason 6 prostate cancer: Implications for active surveillance

BackgroundThere are limited data to support the safety of active surveillance in men with favorable-intermediate risk prostate cancer due only to a prostate specific antigen (PSA) above 10 ng/ml. We therefore evaluated the impact of pretreatment PSA on risk-stratification in men with Gleason 6 prostate cancer.MethodsWe identified men aged 18 to 75 with cT1-2cN0cM0, pre-treatment PSA < 20 ng/ml, Gleason 6 prostate cancer diagnosed from 2010 to 2016 in the National Cancer Database who underwent radical prostatectomy. The associations of patient and disease features with Gleason score upgrading or adverse pathologic features at prostatectomy were evaluated using logistic regression. To evaluate for non linear relationships between PSA and each outcome, we examined predicted marginal event rates standardized for baseline characteristics with PSA modeled using restricted cubic splinesResultsA total of 75,566 patients were included in the cohort. In unadjusted analyses, patients with pretreatment PSA ≥ 10 ng/ml had higher rates of Gleason core upgrading (58.8% vs. 47.9%; P< 0.001) and adverse pathologic features (19.7% vs. 10.0%; P< 0.001) compared to patients with PSA < 10 ng/ml. In multivariable analyses, PSA ≥ 10 ng/ml was associated with statistically significantly increased risks of Gleason score upgrading (OR 1.47;95%CI 1.39 – 1.55) and adverse pathologic features (OR 2.15;95%CI 2.01 – 2.30). When modeled as a non linear continuous covariate, PSA was associated with increased adjusted rates of Gleason score upgrading and adverse pathologic features without a clear dichotomization at a threshold of 10 ng/ml.ConclusionHigher pretreatment PSA was independently associated with increased risks of Gleason score upgrading and adverse pathologic features at prostatectomy. Flexible modeling of the relationship between PSA and each outcome did not support dichotomization at a threshold of 10 ng/ml. These results can be used to improve patient risk-stratification for active surveillance.     

Impact of immediate TRUS rebiopsy in a patient cohort considering active surveillance for favorable risk prostate cancer

Introduction and ObjectiveActive surveillance (AS) is an option for the management of favorable risk prostate cancer (CaP) in the PSA era. Published studies have reported variable inclusion criteria for cohort selection. Accurate assessment of individual patient risk in AS is dependent not only upon rigorous selection criteria, but also reliability of diagnosis at tissue biopsy. To date, the impact of immediate transrectal ultrasound (TRUS) rebiopsy in confirming candidates for AS has been incompletely defined.MethodsFrom a total of over 567 men, 67 met criteria for AS (Gleason <7, PSA <10, PSAD <0.15, <3 cores with <50% involvement of any 1 core). Fifty-two men agreed to a 12-core TRUS rebiopsy within 6 months of first diagnosis performed in clinic. Statistical analysis was performed using Wilcoxon signed rank test and logistic regression to determine predictors of rebiopsy characteristics, histopathologic outcomes, and impact on treatment choice.ResultsMean cohort age was 63.9 years (range 56–72 years), PSA 5.9 ng/ml (4.1–10), and PSA density 0.12 ng/ml/cc at initial biopsy. Tumor involved 1.1 cores and 3.2% (range 1%–5%) of the total tissue. Average time to rebiopsy was 2.7 months. Notably, 29 of 52 men (56%) demonstrated no evidence of CaP on repeat biopsy; 14 of 23 men with a positive repeat biopsy showed either an increase in cancer volume (2.8% mean increase) and 9 (18%) were upgraded to Gleason pattern 3+4 = 7. Rebiopsy demonstrated 9 (17%) patients exceeded AS criteria. Nine patients chose curative surgical intervention (radical prostatectomy) based on increased cancer volume or grade (4) or an elective desire for treatment (5). All had organ confined disease with negative margins on final pathologic analysis. Statistical review revealed that initial Gleason score, PSA density, and number of positive cores at first biopsy were not predictive of men with higher volume/grade on re-biopsy.ConclusionsImmediate TRUS repeat biopsy after diagnosis frequently fails to redemonstrate prostate cancer confirming the favorable-risk nature of disease burden in this group being considered for AS. A subset of patients are upgraded (17%) leading to reconsideration of AS. We conclude this clinic-based approach provides valuable additional information to discriminate appropriate AS candidates.     

Potential predictive factors of positive prostate biopsy in the Japanese population

Introduction There are numerous arguments for the predictive factors of positive prostate biopsies, differing according to race and region. This study aimed to determine predictive factors for a positive prostate biopsy in East Asian, especially Japanese men, using clinical, laboratory, and transrectal ultrasound (TRUS) findings. Methods Data were collected from 466 men who underwent a prostate biopsy for suspected prostate cancer. Variables analyzed including age, digital rectal examination (DRE) findings, prostate-specific antigen (PSA) level, PSA density, prostate volume, and TRUS findings. Logistic regression analysis and the Mann–Whitney U test were used for this study. Results Logistic regression analysis showed that significant predictors for a positive prostate biopsy for all patients were positive DRE results, prostate volume, and hypoechoic lesions on TRUS. Especially in the patients with PSA levels <10 ng/ml, the significant predictor for positive biopsy was prostate volume. The Mann–Whitney U test showed that significant predictors for a positive prostate biopsy in all patients were PSA density >0.15, positive DRE results, and prostate volume <25 cm³. Especially in patients with PSA levels <10 ng/ml, significant predictors for a positive prostate biopsy were prostate volume <25 cm³ and PSA density >0.15. Additionally, even if the data were confined to those patients with seven or more core biopsies, all the predictive factors shown in all patients were significant predictors in this category. Conclusion This study investigated potential predictors for positive prostate biopsy and demonstrated that prostate volume was an independent predictive factor for positive prostate biopsy in patients with PSA levels <10 ng/ml. In the future, we may be able to use our findings to create a nomogram for predicting positive prostate biopsy in Japanese men.     

The risk of death from prostate cancer in men with Gleason score 3+4 prostate cancer treated using brachytherapy with or without a short course of androgen deprivation therapy

ObjectiveWe evaluated whether intermediate-risk factors, in addition to age, were associated with risk of prostate cancer-specific mortality (PCSM) among men with Gleason 3+4 prostate cancer.Materials and methodsWe conducted a prospective cohort study of 1,920 men with Gleason 3+4 adenocarcinoma of the prostate who received brachytherapy (BT) or BT and a median of 4 months of androgen deprivation therapy (ADT). Separate multivariable Fine and Gray competing risks regression models among men treated with BT or BT and ADT were used to assess whether percentage of positive biopsies (PPB), cT2b-T2c stage, prostate-specific antigen (PSA) of 10.1-20.0 ng/ml, and age >70 years (median) were associated with risk of PCSM after adjustment for comorbidity.ResultsAfter median follow-up of 7.8 years, 284 men (14.8%) had died (31 from prostate cancer). For BT alone, increasing PPB, PSA of 10.1–20.0 vs. 4.0–10.0 ng/mL, and age >70 vs. ≤70 were significantly associated with increased risk of PCSM (adjusted hazard ratio 1.015, 95% confidence interval 1.000–1.031, P = 0.048; 5.55, 2.01-15.29, P<0.001; and 3.66, 1.16–11.56, P = 0.03, respectively). The respective results for BT and ADT were 1.009, 0.987-1.031, P = 0.44; 4.17, 1.29–13.50, P = 0.02; and 3.74, 0.87–16.05, P = 0.08.ConclusionAmong men with Gleason score 3+4 prostate cancer treated with BT, the risk of PCSM was elevated in those with PSA of 10.1–20.0 ng/mL and possibly age >70 years, despite the addition of ADT. Should these findings be validated in future studies, then advanced imaging and targeted biopsy of suspicious areas should be investigated in an effort to personalize treatment and minimize the risk of PCSM in these men.     

Assessing the diagnostic performance of systematic freehand PrecisionPoint transperineal prostate biopsy: Comparison of observed outcomes to PBCG nomogram predictions

ObjectiveWe assessed the diagnostic performance of freehand systematic transperineal biopsy (fTPb) by using the Prostate Biopsy Collaborative Group (PBCG) nomogram, which is a contemporary update to the PCPT nomogram.MethodsFrom 1/2012 to 12/2018, fTPb was performed on consecutive men with clinical suspicion of prostate cancer. Patients included in this study had no previous diagnosis of prostate cancer, PSA between 2.5 ng/ml and 20 ng/ml, and underwent at least 12 core biopsies. In addition, those men who underwent pre-biopsy multiparametric magnetic resonance imaging of the prostate were considered separately from those without prebiopsy imaging. Biopsies were performed by a single urologist who developed the needle guidance device used in the procedure. Clinical and pathological data were collected retrospectively. We compared observed biopsy outcomes with those predicted by PBCG nomogram utilizing chi-square statistical analysis.ResultsSystematic fTPb (without pre-biopsy MRI) was performed in 301 men (median age 67, mean PSA 6.9 ng/mL). These men had a median of 20 biopsy cores. Clinically significant cancer (ISUP 2 or greater) was found in 33.9% of men. In men without pre-biopsy MRI, using PBCG Nomogram, we found no significant difference between the expected and observed number of clinically significant cancer (96 vs. 102; P = 0.09). An additional 73 men (median age 67, mean PSA 7.8 ng/ml) underwent pre-biopsy MRI imaging. The addition of MRI targets to systematic sampling resulted in a median of 25 cores. Clinically significant cancer was found in 49.3%. Using the PBCG Nomogram, in the men with pre-biopsy MRI we found clinically significant cancer in significantly more men than was expected by PBCG nomogram predictions (36 vs. 20; P = <0.01). There were no biopsy-related infectious complications.ConclusionThe fTPb technique is a promising method to sample the prostate which provides cancer detection that is comparable to that expected from systematic TRUS biopsy. We found that pre-biopsy mpMRI resulted in greater than expected detection of clinically significant cancer when utilizing this technique.     

The prognostic value of transrectal ultrasound guided biopsy in patients over 70 years old with a prostate specific Antigen (PSA) level ≤15 ng/ml and normal digital rectal examination: A 10-year prospective follow-up study of 427 consecutive patients

IntroductionAs a urologist, it is common to review a patient above the age of 70 being referred to a prostate assessments clinic with an elevated PSA. We evaluate the prognosis of these patients clinically as there is no international consensus on the exact PSA cutoff level or a single international guideline as to when these patients should be offered a prostate biopsy.Patients and methodsOn receiving ethic committee approval, we recruited 427 consecutive patients aged 70 years and above referred with a PSA of ≥4 ng/ml, from January 1996 to December 2000, into our study. All patients were assessed, examined with a digital rectal examination (DRE) of the prostate, and a subsequent prostate biopsy. We followed up on their histologic diagnosis for up to 10 years and analyzed their outcome. The main outcome measures were disease-free survival and overall survival, stratified according to the PSA level (≤15 vs. >15 ng/ml) and DRE findings (normal vs. sbnormal).ResultsThere was a statistically significant difference in the overall survival (P value < 0.011) and disease specific survival (P value < 0.0001) of cancer patients with a PSA was >15 ng/ml and an abnormal DRE. However, in patients with a PSA ≤15 ng/ml and normal DRE, the incidence of cancer was low and they had no disease-specific or overall survival benefit.ConclusionsA policy of deferring prostate biopsy in patients with a PSA ≤15 ng/ml and normal DRE (Group A) would significantly decrease the need of unnecessary prostate biopsies. Within this group, patients did not have any survival advantage compared with those without cancer. We conclude that up to 20% of the prostate biopsies performed in this age group could have been avoided.