The impact of a second MRI and re-biopsy in patients with initial negative mpMRI-targeted and systematic biopsy for PIRADS ≥ 3 lesions.

OBJECTIVE: To evaluate the proportions of detected prostate cancer (PCa) and clinically significant PCa (csPCa), as well as identify clinical predictors of PCa, in patients with PI-RADS > = 3 lesion at mpMRI and initial negative targeted and systematic biopsy (initial biopsy) who underwent a second MRI and a re-biopsy. METHODS: A total of 290 patients from 10 tertiary referral centers were included. The primary outcome measures were the presence of PCa and csPCa at re-biopsy. Logistic regression analyses were performed to evaluate predictors of PCa and csPCa, adjusting for relevant covariates. RESULTS: Forty-two percentage of patients exhibited the presence of a new lesion. Furthermore, at the second MRI, patients showed stable, upgrading, and downgrading PI-RADS lesions in 42%, 39%, and 19%, respectively. The interval from the initial to repeated mpMRI and from the initial to repeated biopsy was 16 mo (IQR 12-20) and 18 mo (IQR 12-21), respectively. One hundred and eight patients (37.2%) were diagnosed with PCa and 74 (25.5%) with csPCa at re-biopsy. The presence of ASAP on the initial biopsy strongly predicted the presence of PCa and csPCa at re-biopsy. Furthermore, PI-RADS scores at the first and second MRI and a higher number of systematic biopsy cores at first and second biopsy were independent predictors of the presence of PCa and csPCa. Selection bias cannot be ruled out. CONCLUSIONS: Persistent PI-RADS ≥ 3 at the second MRI is suggestive of the presence of a not negligible proportion of csPca. These findings contribute to the refinement of risk stratification for men with initial negative MRI-TBx.

Magnetic Resonance Imaging Guided Prostate Biopsy in Patients with ≥ One Negative Systematic Transrectal Ultrasound-Guided Biopsy: A Systemic Review and Meta-Analysis.

The present study aimed to compare prostate cancer (PCa) and clinically significant PCa (csPCa) detection sensitivity between magnetic resonance imaging guided-biopsy (MRI-GB) and transrectal ultrasound-guided biopsy (TRUS-GB) in patients with ≥ 1 negative TRUS-GB, and to explore the additive value of TRUS-GB to MRI-GB. The meta-analysis of 18 studies demonstrated that MRI-GB had a similar sensitivity for PCa detection but a higher sensitivity for csPCa than TRUS-GB. In conclusion, there was limited value in combining TRUS-GB with MRI-GB compared with MRI-GB alone for csPCa detection in patients with one or more negative TRUS-GBs that were suspicious of having PCa.

Utility of serum biomarkers for predicting cancer in patients with previous negative prostate biopsy.

PURPOSE: To review the role of serum biomarkers: prostate-specific antigen (PSA), PSA density (PSAD), free:total PSA ratio, prostate health index (PHI) and PHI density (PHID), along with magnetic resonance imaging (MRI) for identification of clinically significant prostate cancer (PCa), comparing their utility in patients with persistently raised PSA levels after a prior negative prostate biopsy (PNB). METHODS: In this single-centre prospective observational study conducted from September 2015 to October 2020, patients underwent a saturation biopsy via the transperineal route. If a Prostate Imaging Reporting and Data System version 2 (PIRADS) 3 and above lesion was seen on MRI, targeted biopsies were also obtained. Information on clinical history, lesion characteristics, PIRADS classification and follow-up was collected. The sensitivity, specificity and area under curve (AUC) for each of the biomarkers were calculated. RESULTS: 351 men underwent saturation biopsy with or without targeted biopsies. 103 patients had a PNB. Among this PNB cohort, 43 (41.7%) men had a benign outcome, while 60 (58.3%) men had histopathologically diagnosed PCa, of which 41 (39%) were clinically significant. All patients underwent multiparametric MRI scans prior to biopsy. Within this cohort, PHI and PHID had the best abilities to predict for clinically significant PCa with an AUC of 0.73 and 0.70 respectively, compared to 0.65 for PSAD, 0.34 for free:total PSA and 0.56 for PSA. CONCLUSION: A significant proportion of patients are diagnosed with PCa after a PNB. This study shows that PHI and PHI densities may be suitable adjuncts predicting for clinically significant PCa in patients with PNB.

Prostate-specific antigen density during dutasteride treatment for 1 year predicts the presence of prostate cancer in benign prostatic hyperplasia after the first negative biopsy (PREDICT study).

OBJECTIVES: To prospectively evaluate the detection rate of prostate cancer, and to identify the risk factors of prostate cancer detection after a 1-year administration of dutasteride and first negative prostate biopsy. METHODS: Patients with benign prostatic hyperplasia who presented high prostate-specific antigen levels after the first negative prostate biopsy were administered 0.5 mg dutasteride daily for 1 year. They underwent a repeat prostate biopsy after 1 year. The primary end-point was the detection rate of prostate cancer. The secondary end-point was the ability of prostate-specific antigen kinetics to predict prostate cancer detection. Prostate-specific antigen was measured before the initial prostate biopsy and at 6, 9 and 12 months after starting dutasteride. Patients were classified into a prostate cancer and a non-prostate cancer group. RESULTS: Prostate cancer was detected in 15 of 149 participants (10.1%). The total prostate-specific antigen change between the prostate cancer and non-prostate cancer group at 1 year was significantly different (P = 0.002). Although prostate-specific antigen levels at baseline did not significantly differ between study groups (P = 0.102), prostate-specific antigen levels at 6, 9 and 12 months were significantly different (P = 0.002, P = 0.001 and P < 0.001, respectively). The mean reduction rate of prostate-specific antigen density between the prostate cancer and non-prostate cancer group at 1 year was significantly different (-4.25 ± 76.5% vs -38.0 ± 28.7%, P = 0.001). Using a multivariate analysis, a >10% increase of prostate-specific antigen density at 1 year post-dutasteride treatment was the only predictive risk factor for prostate cancer after the first negative prostate biopsy (odds ratio 11.238, 95% confidence interval 3.112-40.577, P < 0.001). CONCLUSION: In the present study cohort, >10% increase in prostate-specific antigen density represented the only significant predictive risk factor for prostate cancer diagnosis in patients with elevated prostate-specific antigen after the first negative prostate biopsy.

Evaluation of Transperineal Magnetic Resonance Imaging/Ultrasound-Fusion Biopsy Compared to Transrectal Systematic Biopsy in the Prediction of Tumour Aggressiveness in Patients with Previously Negative Biopsy.

OBJECTIVES: We compared the transperineal MRI/ultrasound-fusion biopsy (fusPbx) to transrectal systematic biopsy (sysPbx) in patients with previously negative biopsy and investigated the prediction of tumour aggressiveness with regard to radical prostatectomy (RP) specimen. MATERIAL AND METHODS: A total of 710 patients underwent multiparametric magnetic resonance imaging (mpMRI), which was evaluated in accordance with Prostate Imaging Reporting and Data System (PI-RADS). The maximum PI-RADS (maxPI-RADS) was defined as the highest PI-RADS of all lesions detected in mpMRI. In case of proven prostate cancer (PCa) and performed RP, tumour grading of the biopsy specimen was compared to that of the RP. Significant PCa (csPCa) was defined according to Epstein criteria. RESULTS: Overall, scPCa was detected in 40% of patients. The detection rate of scPCa was 33% for fusPbx and 25% for sysPbx alone (p < 0.005). Patients with a maxPI-RADS ≥3 and a prostate specific antigen (PSA)-density ≥0.2 ng/mL2 harboured more csPCa than those with a PSA-density < 0.2 ng/mL2 (41% [33/81] vs. 20% [48/248]; p < 0.001). Compared to the RP specimen (n = 140), the concordance of tumour grading was 48% (γ = 0.57), 36% (γ = 0.31) and 54% (γ = 0.6) in fusPbx, sysPbx and comPbx, respectively. CONCLUSIONS: The combination of fusPbx and sysPbx outperforms both biopsy modalities in patients with re-biopsy. Additionally, the PSA-density may represent a predictor for csPCa in patients with maxPI-RADS ≥3.

The role of mpMRI and PSA density in patients with an initial negative prostatic biopsy.

INTRODUCTION: While an elevated PSA significantly increases the risk of men harboring prostate cancer, many men with a persistently elevated PSA have negative prostate biopsies. More recently, multiparametric MRI (mpMRI) has had promising implications for the diagnosis of prostate cancer. We aim to investigate the diagnostic role of mpMRI in predicting the future diagnosis of prostate cancer in patients with an initial negative biopsy. METHODS: This study included all men with negative biopsies, elevated PSA and mpMRI. All patients had their age, PSA, and PSAd recorded. mpMRI lesions were classified using the PI-RADS 2 scoring system. RESULTS: mpMRI imaging was performed in 336 men with an initial negative biopsy, of whom 108, 111, 76 and 41 men underwent single, two, three and four biopsies, respectively. Of the 228 men with more than one biopsy, 115 patients were diagnosed with prostate cancer on further biopsies. Older patients and men with higher PSA, PSAd and PIRADS score had a significant risk to progress to cancer but only higher PSAd and higher PI-RADS score were significantly associated with clinically significant cancers. For clinically significant cancer; sensitivity and specificity of PI-RADS scoring was 86 and 45%, respectively, and a NPV of 87.6%. When combined with PSAd, NPV was 93%. CONCLUSION: Men with benign prostatic biopsy and both PSAd < 0.15 and low PI-RADS score may avoid second biopsy. PI-RADS scoring system has a high sensitivity to diagnose clinically significant prostate cancer and repeat biopsy should be recommended in men with benign biopsy and high score.

Prostate cancer rates in patients with initially negative elastography-targeted biopsy vs. systematic biopsy.

PURPOSE: To assess whether real-time elastography-targeted biopsy (RTE-bx) is superior to the standard systematic transrectal ultrasound (TRUS)-guided biopsy in predicting subsequent prostate cancer (PCa) rates in patients with initially negative biopsy and to specifically reveal differences in the occurrence of high-grade (Gleason ≥ 4 + 3) PCa by comparing both biopsy methods. PATIENTS AND METHODS: Overall, 630 patients had an initially negative prostate biopsy between 2007 and 2015, either RTE targeted (n = 213) or systematically (n = 417). Follow-up data, ascertained by a questionnaire, of patients receiving RTE-bx were compared to data of patients receiving systematic biopsy (sbx) using Mann-Whitney-U test and Chi-square test. We performed logistic regression analyses to assess any association with PCa or high-grade PCa occurrence. RESULTS: In total, 258 (41%) patients were diagnosed with PCa at repeat biopsy whereof 54 (8.6%) harboured high-grade PCa. PCa occurred in 95 (44.6%) patients with initially negative RTE-bx and in 163 (39.1%) patients with initially negative sbx (p = 0.003). 24 (11.3%) patients receiving RTE-bx and 30 (7.2%) patients receiving sbx were diagnosed with high-grade PCa (p = 0.095). Logistic regression analyses showed that patients with the initial RTE-bx vs. those with the initial sbx neither resulted in a significant higher risk for PCa occurrence (OR 1.35 [CI 0.87-2.1]; p = 0.2) nor for high-grade PCa occurrence (OR 1.52 [CI 0.66-3.35]; p = 0.3). CONCLUSIONS: We found no statistically significant association of prior biopsy method to subsequent PCa or high-grade PCa occurrence. Referring to our analyses, RTE is not superior to sbx in predicting subsequent PCa rates and, therefore, not eligible to decide on repeat biopsy.

Prostate Biopsies Can Be Omitted in Most Patients with a Positive Stockholm3 Test and Negative Prostate Magnetic Resonance Imaging.

BACKGROUND: Magnetic resonance imaging (MRI) combined with the Stockholm3 test can be used to inform biopsy decision-making in patients with a suspicion of prostate cancer. OBJECTIVE: To determine the consequence of omitting biopsies in men with a positive Stockholm3 test and a negative MRI. DESIGN, SETTING, AND PARTICIPANTS: In a real-life setting, 438 men with a positive Stockholm3 test and a negative MRI underwent systematic biopsies from 2017 to 2020. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The Stockholm3 test result is a percentage risk score with or without a prostate volume cutoff. The main outcomes were the number of clinically significant (Gleason grade group [GG] ≥2) and nonsignificant (GG 1) prostate cancers. RESULTS AND LIMITATIONS: Median prostate-specific antigen was 4.5 ng/ml (interquartile range 2.8-6.4 ng/ml) and the median age was 69 yr. Systematic biopsies detected grade group (GG) ≥2 disease in 48 men (11%, 95% confidence interval [CI] 8.4-14.2%) and GG 1 disease in 94 men (21.5%, 95% CI 17.9-25.6%). Of 256 patients without a volume cutoff in the test report, GG ≥2 was detected in 37 men (14.5%, 95% CI 10.7-19.3%). Omitting biopsies in patients with a volume cutoff would miss 11 GG ≥2 cases (6%, 95% CI 3.4-10.5%), reduce the number of GG 1 cases detected by 37 (39.4%, 95% CI 30.1-49.5%), and avoid a total of 182 biopsies (41.6%, 95% CI 37.0-46.2%). Limitations include the lack of follow-up data. CONCLUSIONS: Systematic biopsies can be omitted in patients with a positive Stockholm3 test and a negative MRI when there is a volume cutoff in the test report. With no volume cutoff, biopsies can be considered with shared decision-making. PATIENT SUMMARY: When investigated on suspicion of prostate cancer with a positive Stockholm3 test and a negative MRI (magnetic resonance imaging), prostate biopsies are only necessary for a subgroup of patients. This can spare some men from undergoing biopsies and reduce the detection of clinically insignificant cancers.

Combining targeted and systematic prostate biopsy improves prostate cancer detection and correlation with the whole mount histopathology in biopsy naïve and previous negative biopsy patients.

Objective: Guidelines for previous negative biopsy (PNB) cohorts with a suspicion of prostate cancer (PCa) after positive multiparametric (mp) magnetic-resonance-imaging (MRI) often favour the fusion-guided targeted prostate-biopsy (TB) only approach for Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesions. However, recommendations lack direct biopsy performance comparison within biopsy naïve (BN) vs. PNB patients and its prognostication of the whole mount pathology report (WMPR), respectively. We suppose, that the combination of TB and concomitant TRUS-systematic biopsy (SB) improves the PCa detection rate of PI-RADS 2, 3, 4 or 5 lesions and the International Society of Urological Pathology (ISUP)-grade predictability of the WMPR in BN- and PNB patients. Methods: Patients with suspicious mpMRI, elevated prostate-specific-antigen and/or abnormal digital rectal examination were included. All PI-RADS reports were intramurally reviewed for biopsy planning. We compared the PI-RADS score substratified TB, SB or combined approach (TB/SB) associated BN- and PNB-PCa detection rate. Furthermore, we assessed the ISUP-grade variability between biopsy cores and the WMPR. Results: According to BN (n = 499) vs. PNB (n = 314) patients, clinically significant (cs) PCa was detected more frequently by the TB/SB approach (62 vs. 43%) than with the TB (54 vs. 34%) or SB (57 vs. 34%) (all p < 0.0001) alone. Furthermore, we observed that the TB/SB strategy detects a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports, both in BN and PNB men. In contrast, applied biopsy techniques were equally effective to detect csPCa within PI-RADS 2 lesions. In case of csPCa diagnosis the TB approach was more often false-negative in PNB patients (BN 11% vs. PNB 19%; p = 0.02). The TB/SB technique showed in general significantly less upgrading, whereas a higher agreement was only observed for the total and BN patient cohort. Conclusion: Despite csPCa is more frequently found in BN patients, the TB/SB method always detected a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports of our BN and PNB group. The TB/SB strategy predicts the ISUP-grade best in the total and BN cohort and in general shows the lowest upgrading rates, emphasizing its value not only in BN but also PNB patients.

Combined Use of Prostate-specific Antigen Density and Magnetic Resonance Imaging for Prostate Biopsy Decision Planning: A Retrospective Multi-institutional Study Using the Prostate Magnetic Resonance Imaging Outcome Database (PROMOD).

BACKGROUND: Previous studies suggested that prostate-specific antigen (PSA) density (PSAd) combined with magnetic resonance imaging (MRI) may help avoid unnecessary prostate biopsy (PB) with a limited risk of missing clinically significant prostate cancer (csPCa; Gleason grade group [GGG] >1). OBJECTIVE: To define optimal diagnostic strategies based on the combined use of PSAd and MRI in patients at risk of prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of the international multicenter Prostate MRI Outcome Database (PROMOD), including 2512 men having undergone PSAd and prostate MRI before PB between 2013 and 2019, was performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Rates of avoided PB, missed GGG 1, and csPCa according to 10 strategies based on PSAd values and MRI reporting scores (Prostate Imaging Reporting and Data System [PI-RADS]/Likert/IMPROD biparametric prostate MRI Likert). Decision curve analysis (DCA) was used to statistically compare the net benefit of each strategy. Combined systematic and targeted biopsies were used for reference. RESULTS AND LIMITATIONS: According to DCA, the best strategy in biopsy-naive patients was #7 (PI-RADS/Likert 4-5 or PI-RADS/Likert 3 if PSAd >0.2), which avoided 41.2% PBs while missed 44% of GGG 1 and 10.9% of csPCa cases. From a clinical standpoint, however, strategies with a lower risk of missing csPCa included #10 (PI-RADS/Likert 4-5 or PI-RADS 3 if PSAd >0.10 or PSAd >0.2), which avoided 27% PBs while missing 24.4% GGG 1 and 4% csPCa cases, or #5 (PI-RADS/Likert 3-5 or PSAd>0.15), which avoided 14.7% PBs while missing 9.3% GGG 1 and 1.7% csPCa cases. Similar results were found in patients with a previous negative biopsy. This study is limited by its retrospective nature, and no central review of MRI and histopathological findings. CONCLUSIONS: Combined PSAd and MRI findings allows individualization of the decision to perform PB on the basis of the risk of missing PCa that both patients and clinicians are ready to accept to avoid this procedure. PATIENT SUMMARY: We compared several biopsy strategies based on a combination of prostate magnetic resonance imaging findings and prostate-specific antigen density, providing a readily available tool for each center and practicing urologist to counsel patients about their individual risk of significant prostate cancer.

Predicting Benign Prostate Pathology on Magnetic Resonance Imaging/Ultrasound Fusion Biopsy in Men with a Prior Negative 12-core Systematic Biopsy: External Validation of a Prognostic Nomogram.

BACKGROUND: Magnetic resonance imaging (MRI) of the prostate after a prior negative biopsy may reduce the need for unnecessary repeat biopsies. OBJECTIVE: To externally validate a previously developed nomogram predicting benign prostate pathology on MRI/ultrasound (US) fusion-targeted biopsy in men with a Prostate Imaging Reporting and Data System (PI-RADS) 3-5 region of interest and a prior negative 12-core systematic biopsy, and update this nomogram to improve its performance. DESIGN, SETTING, AND PARTICIPANTS: A total of 2063 men underwent MRI/US fusion-targeted biopsy from April 2012 to September 2017; 104 men with a negative systematic biopsy followed by MRI-US fusion-targeted biopsy of a PI-RADS 3-5 region of interest (58%) met the study inclusion criteria. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: An MRI-based nomogram that had previously been developed in a multi-institutional clinical setting was externally validated. Predictive characteristics were age, prostate volume, MRI PI-RADS score, and prostate-specific antigen (PSA). Bayesian logistic regression was used to update the previous model. RESULTS AND LIMITATIONS: Median age of the external validation cohort was 68 yr, PSA was 7.2ng/ml, and biopsy confirmed benign pathology in 30% (n=31), suggesting a lower baseline risk compared with the nomogram development cohort. Receiver operating characteristic curve analysis showed areas under curve (AUCs) from 0.77 to 0.80 for nomogram validation. An updated model was constructed with improved calibration and similar discrimination (AUC 0.79). CONCLUSIONS: Age, prostate volume, PI-RADS, and PSA predict benign pathology on MRI/US fusion-targeted biopsy in men with a prior negative 12-core systematic biopsy. The validated and updated nomogram demonstrated high diagnostic accuracy and may further aid in the decision to avoid a biopsy in men with a prior negative biopsy. PATIENT SUMMARY: We externally validated a clinically useful tool that predicts benign prostate pathology on magnetic resonance imaging/ultrasound fusion-targeted biopsy in men with a prior negative 12-core systematic biopsy and updated this predictive tool to improve its performance in patient counseling regarding the need for a repeat biopsy.

Remaining challenges in the diagnosis of early stage cardiac sarcoidosis.

Despite the requirement for histopathological evidence to make a definite diagnosis of cardiac sarcoidosis, the sensitivity of endomyocardial biopsy is still low. Recently, Japanese Circulation Society suggests a new strategy that patients diagnosed clinically do not require the endomyocardial biopsy evidence. Physicians should familiarize themselves with such paradigm shifts.

Fusion prostate biopsy outperforms 12-core systematic prostate biopsy in patients with prior negative systematic biopsy: A multi-institutional analysis.

INTRODUCTION AND OBJECTIVES: Patients with persistently elevated prostate specific antigen (PSA) and prior negative 12-core TRUS prostate biopsy (or biopsies) (systematic biopsy-SBx) are a diagnostic challenge. Repeat SBx or saturation biopsy in this cohort has been shown to have an even lower yield. The aim of our study is to compare the prostate cancer yield of magnetic resonance imaging (MRI) fusion biopsy (FBx) to SBx in a multi-institutional cohort comprised of patients with prior negative biopsies. METHODS: A multi-institutional review was performed on patients with a history of one or more prior negative SBx who underwent multiparametric MRI (mpMRI), followed by FBx and SBx in the same session. Imaging protocol was standardized across institutions and institutional genitourinary radiologists and pathologists reviewed mpMRI and pathology, respectively. Gleason score (GS) distribution and risk classifications were recorded. Prostate cancer with GS ≥3 + 4 was defined as clinically significant (CS). Univariate and multivariable logistic regression was done to identify predictors of cancer detection on SBx and FBx. RESULTS: Seven-hundred seventy-nine patients from four institutions were included in the study. Median age and prostate specific antigen (IQR) were 63.1 (58.5-68.0) years and 8.5 (5.9-13.1)ng/dl, respectively. Median number of prior negative biopsies (range) was 2.0 (1-16). The cancer detection rate (CDR) in the cohort was 346/779 patients (44.4%). Total CS CDR was 30.7% (239/779 patients), with FBx detecting 26.3% (205/779) of patients with CS disease and SBx diagnosing an additional 4.4% (34/779) of patients (P<0.001). Furthermore, of all cancers detected by each modality, FBx detected a higher proportion of CS cancer compared to SBx (one negative biopsy: 75 vs. 50%, P<0.001, 2-3 negative biopsy: 76 vs. 61%, P = 0.006, 4 or more negative biopsies: 84 vs. 52%, P = 0.006). As such, SBx added a relatively small diagnostic value to FBx for detecting CS disease (one negative biopsy 3.5%, 2-3 negative biopsies 5%, 4 or more negative biopsies: 1%). FBx also outperformed SBx for upgrading patients to an intermediate or high-risk cancer category (GS>6) (one negative biopsy 11.5% vs. 3.6%, 2-3 negative biopsy 10.3% vs. 5.3%, 4 or more negative biopsies 19.1% vs. 1.1%). On multivariable analysis, the number of prior negative biopsies was a significant negative predictor of CS CDR on SBx (P = 0.006), but not on FBx (P = 0.151). CONCLUSIONS: Using a large multi-institutional cohort, we were able to demonstrate that FBx outperformed SBx in patients with prior negative systematic biopsy. This was due, in part, to the decreasing CS CDR by SBx with increased number of prior biopsies. The yield of FBx stayed constant and did not decrease with increased number of prior negative biopsies. Therefore, repeat SBx alone in patients with multiple prior negative biopsies will be hindered by lower yield and FBx should be utilized concurrently in these patients.

What is an acceptable false negative rate in the detection of prostate cancer?

BACKGROUND: In prostate cancer (PCa) screening men and their physicians aim to rule out the presence of potentially life threatening PCa. To date, prostate specific antigen (PSA) testing and systematic prostate biopsy (Bx)-in case of an elevated PSA-are still the main modes of PCa detection. Often uncertainty remains when a PSA-test is <3.0 ng/mL or a Bx shows a benign result, leading to the continuous repeating of procedures. Here we assess the potential consequences of false negatives by studying follow-up data of a purely PSA-based approach with applying sextant Bx, an approach considered to have a high risk of missing PCa diagnosis. METHODS: Our study population consisted of 19,970 men from the ERSPC project section Rotterdam, initially screened in 1993-1999. We assessed clinically significant Gleason ≥3+4 PCa (csPCa) diagnosis within the 4-year screening interval and subsequent screening round 4 years later in men having a PSA <3.0 ng/mL at initial screening (no Bx) and men with Bx (PSA >3.0 ng/mL), but no PCa detected at that time. In addition, we addressed PCa mortality and PCa diagnosis for men with a negative PSA test and negative Bx, who were retested every 4 years covering a 15-year follow-up. RESULTS: A total of 14,935 men had PSA <3.0 ng/mL in the initial screening round, of whom 75 (0.5%) were diagnosed with csPCa at a subsequent screening examination and 2 (<0.1%) in the 4-year screening interval. For 2,260 men with a previously negative Bx at first screening, the figures were 17 (0.8%) and 2 (0.1%) respectively. Indolent PCa (Gleason ≤3+3) was diagnosed in 312 (2%) men with PSA <3.0 ng/mL initially and 115 (5%) men with initial negative Bx. After a 15-year follow-up, 45 (0.3%) PCa deaths occurred in men with initially low PSA, and 29 men (0.2%) had metastasis. For men with negative Bx, 11 (0.5%) PCa deaths occurred and 4 (0.2%) experienced metastasis. CONCLUSIONS: The false negative rates for men with PSA <3.0 ng/mL and negative sextant Bx are extremely low but not negligible. Proper risk stratification before deciding to biopsy is expected to hardly miss any clinical significant PCa diagnosis. This is especially relevant with the increased use of the relatively expensive multi-parametric magnetic resonance imaging (mpMRI) guided targeted Bx procedures.

A Promising Method for Tumor Localization during Total Laparoscopic Distal Gastrectomy: Preoperative Endoscopic Clipping based on Negative Biopsy and Selective Intraoperative Radiography Findings.

PURPOSE: Precise localization of tumors and creation of sufficient proximal resection margins are complicated processes during total laparoscopic distal gastrectomy (TLDG) for clinical T1/T2 gastric cancers. Various solutions to this problem have also yielded many disadvantages. In this study, we reviewed a preoperative endoscopic clipping method based on the results of negative biopsy and selective intraoperative radiography. MATERIALS AND METHODS: A retrospective review of 345 consecutive patients who underwent TLDG and preoperative endoscopic clipping for tumor localization was conducted. During preoperative endoscopy, the endoscopists performed negative biopsies just 1-2 cm selectively above the tumor's upper limit. After confirming the biopsy results, endoscopic metal clips were applied just proximal to the negative biopsy site the day before surgery. Selective intraoperative tumor localization using portable abdominal radiography was performed only when we could not ensure a precise resection line. RESULTS: Negative biopsy was performed in 244 patients. Larger tumor size (P=0.008) and more distally located tumors (P=0.052) were observed more frequently in the negative biopsy group than in the non-negative biopsy group. The non-negative biopsy group had significantly higher frequencies of differentiated tumor types than the negative biopsy group (P=0.003). Of the 244 patients who underwent negative biopsies, 6 had cancer cells in their biopsy specimens. We performed intraoperative radiography in 12 patients whose tumors had difficult-to-determine proximal margins. No tumors were found in the proximal resection margins of any patients. CONCLUSIONS: Our tumor localization method is a promising and accurate method for securing a sufficient resection margin during TLDG.

Commercialized biomarkers: new horizons in prostate cancer diagnostics.

Limitations with current clinical tools available for diagnosis and prognosis of prostate cancer (PCa) have resulted in overdiagnosis and costly overtreatment, which is affecting the outcomes and quality of life of men. The biotech industry is investing significant resources into developing more specific biomarkers for PCa detection and patient stratification that would greatly advance the decision-making processes behind PCa management and treatment. In this review, we focus on those biomarkers that have been translated into commercial tests available to clinicians. Since these tests aim to fill specific gaps during the decision-making process of PCa management, we have grouped them based on the clinical question they claim to address, that is, improved PCa screening, false-negative biopsy dilemma, prognostic tests following a positive biopsy and tests predicting relapse/metastases after surgery. We evaluate each test with respect to its development, platform, clinical validation, biomatrix, regulatory approval status and cost.

The accuracy of multiparametric MRI in men with negative biopsy and elevated PSA level--can it rule out clinically significant prostate cancer?

PURPOSE: To assess the performance of multiparametric magnetic resonance imaging (mp-MRI) in patients with previous negative transrectal ultrasound (TRUS) guided prostate biopsy. MATERIALS AND METHODS: Fifty-four patients with at least 1 previous negative TRUS prostate biopsy underwent mp-MRI in the form of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging. This was followed by transperineal template systematic prostate biopsies. Analysis was done based on 2 sectors per prostate, right and left (108 sectors out of 54 prostates). mp-MRI was scored using an ordinal scale 1 to 5 based on the suspicion of the presence of clinically significant disease. We used 6 different definitions for clinically significant disease and tested the performance of mp-MRI at each single definition. RESULTS: Median age was 64 (range, 39-75), median PSA level was 10 (range, 2-23), and median number of biopsies was 45 (range, 21-137). Cancer of any volume and any grade was detected in 34 of 54 (63%) patients. mp-MRI accuracy at detection of clinically significant cancer using University College London (UCL) definition 2 (any Gleason score of 4 or maximum cancer core length of ≥ 4 mm or both) showed sensitivity of 76%, specificity of 42%, positive predictive value of 38%, and negative predictive value of 79%. For a different definition of significant tumor (UCL definition 1; dominant Gleason score 4 or maximum cancer core length ≥ 6 mm or both), the sensitivity was 90%, specificity 42%, positive predictive value 26%, and negative predictive value 95%. CONCLUSIONS: mp-MRI showed good performance at both detection and ruling out clinically significant disease, according to the definition used. mp-MRI can then be used as a triage test in the population with persistently elevated or rising PSA levels to select patients that can avoid unnecessary prostate biopsy.