Biopsy Strategy Research Articles

3D modelling of radical prostatectomy specimens: Developing a method to quantify tumor morphometry for prostate cancer risk prediction

Prostate cancer displays a wide spectrum of clinical behaviour from biological indolence to rapidly lethal disease, but we remain unable to accurately predict an individual tumor’s future clinical course at an early curable stage. Beyond basic dimensions and volume calculations, tumor morphometry is an area that has received little attention, as it requires the analysis of the prostate gland and tumor foci in three-dimensions. Previous efforts to generate three-dimensional prostate models have required specialised graphics units and focused on the spatial distribution of tumors for optimisation of biopsy strategies rather than to generate novel morphometric variables such as tumor surface area. Here, we aimed to develop a method of creating three-dimensional models of a prostate’s pathological state post radical prostatectomy that allowed the derivation of surface areas and volumes of both prostate and tumors, to assess the method’s accuracy to known clinical data, and to perform initial investigation into the utility of morphometric variables in prostate cancer prognostication. Serial histology slides from 21 prostatectomy specimens covering a range of tumor sizes and pathologies were digitised. Computer generated three-dimensional models of tumor and prostate space filling models were reconstructed from these scanned images using Rhinoceros 4.0 spatial reconstruction software. Analysis of three-dimensional modelled prostate volume correlated only moderately with weak concordance to that from the clinical data (r = 0.552, θ = 0.405), but tumor volume correlated well with strong concordance (r = 0.949, θ = 0.876). We divided the cohort of 21 patients into those with features of aggressive tumor versus those without and found that larger tumor surface area (32.7 vs 3.4cc, p = 0.008) and a lower tumor surface area to volume ratio (4.7 vs 15.4, p = 0.008) were associated with aggressive tumor biology.

A cost-effectiveness analysis of the diagnostic strategies for differentiating focal nodular hyperplasia from hepatocellular adenoma.

We evaluated the cost-effectiveness of a gadoxetic acid-enhanced MRI (EOB-MRI) strategy compared with conventional MRI strategy and biopsy to differentiate focal nodular hyperplasia (FNH) from hepatocellular adenoma (HCA). A decision tree model was constructed to compare the cost-effectiveness of EOB-MRI, conventional MRI with extracellular contrast agents, and biopsy as the initial diagnostic modality in patients with incidentally detected focal liver lesions suspected of being FNH or HCA. We analysed the cost and effectiveness, i.e. probability of successful diagnosis of each strategy. Costs were based on utilisation rates and Medicare reimbursements in the USA and South Korea. In the base case analysis of our decision tree model, the effectiveness of the three strategies was similar. The cost of the EOB-MRI strategy ($1283 in USA, $813 in South Korea) was lowest compared with the biopsy strategy ($1725 in USA, $847 in South Korea) and the conventional MRI strategy ($1750 in USA, $962 in South Korea). One-way, two-way and probabilistic sensitivity analysis showed unchanged results over an acceptable range. EOB-MRI strategy is the most cost-effective strategy for differentiating FNH from HCA in patients with incidentally detected focal liver lesions in a non-cirrhotic liver. • The effectiveness of the three strategies was similar. • The cost of the EOB-MRI strategy was lowest. • EOB-MRI strategy is the most cost-effective for differentiating FNH from HCA.

Evaluation of Prostate HistoScanning as a Method for Targeted Biopsy in Routine Practice

BackgroundProstate HistoScanning (PHS) is a tissue characterization system used to enhance prostate cancer (PCa) detection via transrectal ultrasound imaging. ObjectiveTo assess the impact of supplementing systematic transrectal biopsy with up to three PHS true targeting (TT) guided biopsies on the PCa detection rate and preclinical patient assessment. Design, setting, and participantsThis was a prospective study involving a cohort of 611 consecutive patients referred for transrectal prostate biopsy following suspicion of PCa. PHS-TT guided cores were obtained from up to three PHS lesions of ≥0.5cm3 per prostate and only one core per single PHS lesion. Histological outcomes from a systematic extended 12-core biopsy (Bx) scheme and additional PHS-TT guided cores were compared. Outcome measurements and statistical analysisComparison of PHS results and histopathology was performed per sextant. The χ2 and Mann-Whitney test were used to assess differences. Statistical significance was set at p<0.05. Results and limitationsPHS showed lesions of ≥0.5cm3 in 312 out of the 611 patients recruited. In this group, Bx detected PCa in 59% (185/312) and PHS-TT in 87% (270/312; p<0.001). The detection rate was 25% (944/3744 cores) for Bx and 68% (387/573 cores) for PHS-TT (p<0.001). Preclinical assessment was significantly better when using PHS-TT: Bx found 18.6% (58/312) and 8.3% (26/312), while PHS-TT found 42.3% (132/312) and 20.8% (65/312) of Gleason 7 and 8 cases, respectively (p<0.001). PHS-TT attributed Gleason score 6 to fewer patients (23.4%, 73/312) than Bx did (32.4%, 101/312; p=0.0021). ConclusionsPatients with a suspicion of PCa may benefit from addition of a few PHS-TT cores to the standard Bx workflow. Patient summaryTargeted biopsies of the prostate are proving to be equivalent to or better than standard systematic random sampling in many studies. Our study results support supplementing the standard schematic transrectal ultrasound-guided biopsy with a few guided cores harvested using the ultrasound-based prostate HistoScanning true targeting approach in cases for which multiparametric magnetic resonance imaging is not available.

Safety of transrectal ultrasound-guided prostate biopsy in patients affected by Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract. It is usually considered a contraindication to transrectal ultrasound-guided prostate biopsy (TRUSBx). The aim of this study was to investigate the safety of TRUSBx in a small cohort of patients with CD. We queried our institutional database clinical data of patients with a diagnosis of CD undergoing TRUSBx, and a retrospective prospective study of 5 patients was planned. All patients enrolled were in the remission phase of CD and asymptomatic. They received the same antibiotic prophylaxis and a povidone-iodine aqueous solution enema before the procedure. A standardized reproducible technique was used with using a ultrasound machine equipped with a 5-9 MHz multifrequency convex probe "end-fire". The patients were treated under local anaesthesia, and a 14-core biopsy scheme was performed in each patient as first intention. After the procedure each patient was given a verbal numeric pain scale to evaluate tolerability of TRUSBx. TRUSBx was successfully completed in all patients. The number of biopsy cores was 14 (12-16). Of the 5 biopsy procedures performed 40% revealed prostatic carcinoma (PCa) with a Gleason score 6 (3+3). No patients required catheterization or admission to the hospital for adverse events after the procedure. The most frequent adverse event was hematospermia (60%), while hematuria was present in 20% of patients and a minimal rectal bleeding in 20% of the patients. No patients reported severe or unbearable pain (score ≥ 8). This study suggests that CD may not be an absolute contraindication to TRUSBx for prostate cancer detection, but still requires a careful patients selection.

Cost-effectiveness of MR Imaging-guided Strategies for Detection of Prostate Cancer in Biopsy-Naive Men.

Purpose To evaluate the cost-effectiveness of multiparametric diagnostic magnetic resonance (MR) imaging examination followed by MR imaging-guided biopsy strategies in the detection of prostate cancer in biopsy-naive men presenting with clinical suspicion of cancer for the first time. Materials and Methods A decision-analysis model was created for biopsy-naive men who had been recommended for prostate biopsy on the basis of abnormal digital rectal examination results or elevated prostate-specific antigen levels (age groups: 41-50 years, 51-60 years, and 61-70 years). The following three major strategies were evaluated: (a) standard transrectal ultrasonography (US)-guided biopsy; (b) diagnostic MR imaging followed by MR imaging-targeted biopsy, with no biopsy performed if MR imaging findings were negative; and (c) diagnostic MR imaging followed by MR imaging-targeted biopsy, with a standard biopsy performed when MR imaging findings were negative. The following three MR imaging-guided biopsy strategies were further evaluated in each MR imaging category: (a) biopsy with cognitive guidance, (b) biopsy with MR imaging/US fusion guidance, and (c) in-gantry MR imaging-guided biopsy. Model parameters were derived from the literature. The primary outcome measure was net health benefit (NHB), which was measured as quality-adjusted life-years (QALYs) gained or lost by investing resources in a new strategy compared with a standard strategy at a willingness-to-pay (WTP) threshold of $50 000 per QALY gained. Probabilistic sensitivity analysis was performed by using Monte Carlo simulations. Results Noncontrast MR imaging followed by cognitively guided MR biopsy (no standard biopsy if MR imaging findings were negative) was the most cost-effective approach, yielding an additional NHB of 0.198 QALY compared with the standard biopsy approach. Noncontrast MR imaging followed by in-gantry MR imaging-guided biopsy (no standard biopsy if MR imaging findings were negative) led to the highest NHB gain of 0.251 additional QALY compared with the standard biopsy strategy. All MR imaging strategies were cost-effective in 94.05% of Monte Carlo simulations. Analysis by age groups yielded similar results. Conclusion MR imaging-guided strategies for the detection of prostate cancer were cost-effective compared with the standard biopsy strategy in a decision-analysis model. © RSNA, 2017 Online supplemental material is available for this article.

Clinical analysis of systematic 12+ 1-core biopsy of prostate cancer detected by transrectal ultrasound resonance guided prostate system

Objective To compare the difference of prostate cancer detection rate (PCDR) between 12+ 1-core biopsy and 6-core biopsy of the prostate system guided by transrectal ultrasonography (TRUS). Methods The clinical data of 2 707 patients with prostate biopsy from July 1999 to June 2012 were retrospectively analyzed. These patients were 54 to 92 years old, mean age was 69 years old. The range of PSA was 0.02-158.56 ng/ml, with an average of 16.97 ng/ml. People in the range of PSA 0-4.00, 4.01-10.00, 10.01-20.00, 20.01-30.00, and >30.00 were 161, 826, 827, 312, 581, respectively. The volume of the prostate ranged from 14.1 to 82.6 cm3, mean 47.9 cm3. The 1 603 cases before the July 2009 were performed 6-core biopsy guided by the finger, followed by 1104 TRUS-guided 12+ 1-core biopsy. In addition, after March 2012, 60 patients accepeted the MRI examination before prostate biopsy. The strategy of prostate biopsy was medial 6-core, lateral 6-core, the 13th core was positioned at abnormal signal area of TRUS and MRI. Explore the difference of PCDR medial 6-core, lateral 6-core, systematic 12-and 12+ 1-core, and the difference of 13th core and the other 12 cores, with the cut off value of PSA quartile of 30 ng/ml and PV quartile of 46 cm3. Results Comparison of clinical characteristics of prostate biopsy between positive group and negative group was performed, and the result suggested that The positive outcome of prostate cancer biopsy was related with element such as high PSA, old age[(71.7±7.1 )vs.(68.3±8.1), P=0.008], large fPSA[(8.5±36.4) vs.(2.3±3.4), P 46 cm3[30.0%(254/846)vs.22.2%(284/1 280), P<0.001; 31.7%(124/391)vs.18.1%(131/723), P<0.001]. PCDR of the 13th core positioned at abnormal signal area of TRUS and MRI was higher than the average PCDR of other 12 cores [70.9%(107/151)vs.56.6%(3 109/5 496), P<0.001]. Conclusion PCDR of TRUS-guided biopsy was higher than that of finger-guided biopsy in patients with PSA≤30 ng/ml and PV>46 cm3.PCDR of 12+ 1-core biopsy was significantly higher than that of lateral 6-core biopsy . However, PCDR of 12-core biopsy had no statistical differences with that of 6-core biopsy. PCDR of the 13th core positioned at abnormal signal area of TRUS was higher than the average PCDR of other 12 cores. Key words: Prostate cancer; Prostate biopsy; Transrectun ultrasound; Magnetic resonance imaging

Does early resection of presumed low-grade glioma improve survival? A clinical perspective

Early resection is standard of care for presumed low-grade gliomas. This is based on studies including only tumors that were post-surgically confirmed as low-grade glioma. Unfortunately this does not represent the clinicians’ situation wherein he/she has to deal with a lesion on MRI that is suspect for low-grade glioma (i.e. without prior knowledge on the histological diagnosis). We therefore aimed to determine the optimal initial strategy for patients with a lesion suspect for low-grade glioma, but not histologically proven yet. We retrospectively identified 150 patients with a resectable presumed low-grade-glioma and who were otherwise in good clinical condition. In this cohort we compared overall survival between three types of initital treatment strategy: a wait-and-scan approach (n = 38), early resection (n = 83), or biopsy for histopathological verification (n = 29). In multivariate analysis, no difference was observed in overall survival for early resection compared to wait-and-scan: hazard ratio of 0.92 (95% CI 0.43–2.01; p = 0.85). However, biopsy strategy showed a shorter overall survival compared to wait-and-scan: hazard ratio of 2.69 (95% CI 1.19–6.06; p = 0.02). In this cohort we failed to confirm superiority of early resection over a wait-and-scan approach in terms of overall survival, though longer follow-up is required for final conclusion. Biopsy was associated with shorter overall survival.

MP33-20 THE SMARTTARGET BIOPSY TRIAL: A PROSPECTIVE PAIRED BLINDED TRIAL WITH RANDOMISATION TO COMPARE VISUAL-ESTIMATION AND IMAGE-FUSION TARGETED PROSTATE BIOPSIES

You have accessJournal of UrologyProstate Cancer: Detection & Screening III1 Apr 2017MP33-20 THE SMARTTARGET BIOPSY TRIAL: A PROSPECTIVE PAIRED BLINDED TRIAL WITH RANDOMISATION TO COMPARE VISUAL-ESTIMATION AND IMAGE-FUSION TARGETED PROSTATE BIOPSIES Ian Donaldson, Sami Hamid, Dean Barratt, Yipeng Hu, Rachel Rodell, Barbara Villarini, Ester Bonmati, Paul Martin, David Hawkes, Neil McCartan, Ingrid Potyka, Norman Williams, Chris Brew-Graves, Caroline Moore, Mark Emberton, and Hashim Ahmed Ian DonaldsonIan Donaldson More articles by this author , Sami HamidSami Hamid More articles by this author , Dean BarrattDean Barratt More articles by this author , Yipeng HuYipeng Hu More articles by this author , Rachel RodellRachel Rodell More articles by this author , Barbara VillariniBarbara Villarini More articles by this author , Ester BonmatiEster Bonmati More articles by this author , Paul MartinPaul Martin More articles by this author , David HawkesDavid Hawkes More articles by this author , Neil McCartanNeil McCartan More articles by this author , Ingrid PotykaIngrid Potyka More articles by this author , Norman WilliamsNorman Williams More articles by this author , Chris Brew-GravesChris Brew-Graves More articles by this author , Caroline MooreCaroline Moore More articles by this author , Mark EmbertonMark Emberton More articles by this author , and Hashim AhmedHashim Ahmed More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1016AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Multi-parametric MRI targeted prostate biopsies can improve detection of clinically significant prostate cancer and decrease the diagnosis of clinically insignificant cancers. There is debate whether visual estimated targeting is sufficient or whether image-fusion software is required. We conducted an ethics committee approved, prospective, blinded, paired validating clinical trial of visual estimated targeted biopsies compared to non-rigid MR/US image-fusion using an academically developed fusion system (SmartTarget®). METHODS 141 men requiring targeted transperineal biopsies for accurate risk stratification were enrolled following written informed consent (August2014-September2016). Entry required prior trans-rectal ultrasound biopsy, a discrete lesion on mpMRI (PIRADS 3-5) and no previous prostate cancer treatment. All men underwent a targeted transperineal biopsy of a single lesion using visual estimation (3 cores) and image-fusion (3 cores). Two different urologists independently conducted the targeting strategies with each urologist assigned a strategy and order by randomised. Only one urologist was permitted to be present for each biopsy strategy and did not communicate with the other about any aspect of the procedure (blinded). 14 urologists of varying levels of experience participated. All were competent in transperineal targeting. UCL definition 2 clinically significant prostate cancer was used as the target condition for the primary outcome (>/= G3+4 and or MCCL >/= 4mm). RESULTS 129 men completed both biopsy strategies. Median age (IQR) was 65 years (58-70) and median PSA was 8.5ng/ml (5.6-12.1). 94 (72.8%) had clinically significant prostate cancer; 81/94 (86.2%) were identified on visual estimation targeting and 81/94 (86.2%) on image-fusion targeting. Fusion biopsy and visual estimation targeting each identified clinically significant cancers that the other missed, 13 and 13 respectively. We found no statistically significant difference between visual estimation and image-fusion (McNemar, p=1.00). CONCLUSIONS Our prospective, paired blinded trial demonstrates that there is no overall difference in detection of clinically significant prostate cancer between visual estimation and image-fusion targeted biopsies. Our results suggest that both techniques should be used together for optimal cancer detection. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e425 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Ian Donaldson More articles by this author Sami Hamid More articles by this author Dean Barratt More articles by this author Yipeng Hu More articles by this author Rachel Rodell More articles by this author Barbara Villarini More articles by this author Ester Bonmati More articles by this author Paul Martin More articles by this author David Hawkes More articles by this author Neil McCartan More articles by this author Ingrid Potyka More articles by this author Norman Williams More articles by this author Chris Brew-Graves More articles by this author Caroline Moore More articles by this author Mark Emberton More articles by this author Hashim Ahmed More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PD40-08 COMBINING 4KSCORE AND MRI FOR PROSTATE BIOPSY DECISION MAKING

You have accessJournal of UrologyProstate Cancer: Detection & Screening V1 Apr 2017PD40-08 COMBINING 4KSCORE AND MRI FOR PROSTATE BIOPSY DECISION MAKING Karim Marzouk, Behfar Ehdaie, Stephen Zappala, and Andrew Vickers Karim MarzoukKarim Marzouk More articles by this author , Behfar EhdaieBehfar Ehdaie More articles by this author , Stephen ZappalaStephen Zappala More articles by this author , and Andrew VickersAndrew Vickers More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1748AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Multiparametric Magnetic Resonance Imaging (mp-MRI) and the 4Kscore blood test (OPKO: Miami FL) have both been shown to identify significant prostate cancer in men with elevated PSA. In comparison to a blood test, mp-MRI is resource intensive, thus is difficult to apply at a population level. Moreover, results from the PROMIS MRI trial show that 11% of men with normal MRI harbor high-grade disease. One possibility is selective application of mp-MRI to men at intermediate risk as defined by the 4Kscore: this would reduce the number of MRIs and lower the chance of missed high-grade disease. The aim of this study was to evaluate mp-MRI as a follow-up test to the 4Kscore in prostate cancer early detection. METHODS The 4Kscore results from the US prospective validation study were combined with mp-MRI data available from the PROMIS study. Using the likelihood ratios for MRI detecting high grade disease and applying them to probabilities of 4Kscores, four different populations were identified based on a threshold for biopsy of 7.5% risk of high grade disease: 1. men with very low 4Kscore for whom risk would not be ≥7.5% even with positive MRI; 2. men with 4Kscores < 7.5% whose risk would be ≥7.5% if MRI were positive; 3. men with 4Kscores ≥7.5% whose risk would be <7.5% if MRI were negative; 4. men with high 4Kscores whose risk would remain ≥7.5% even if MRI were negative. In this strategy, group 1 would not be biopsied; groups 2 and 3 would receive MRI and then biopsy if MRI was positive; group 4 would be biopsied without MRI. Net benefit was calculated for each strategy using a threshold of 7.5%. RESULTS In the 4Kscore validation study, 1012 men underwent prostate biopsy with 231 (23%) diagnosed with ≥Gleason 7 disease. PROMIS gave a positive and negative likelihood ratio of 1.58 and 0.17 for MRI. The range of 4Kscores that could be influenced by the results of MRI was 5-32%, i.e. group 1: 26% of the population with risk <5%; group 2: 10% with risk 5-7.4%; group 3: 45% with risk 7.5-32%; group 4: 21% with risk > 32%. Net benefit of using 4Kscores alone was 17.7%, mp-MRI 17.6%, and combined strategy 18.2%. A difference of 0.5% between the combined strategy and 4Kscore alone is equivalent to 62 fewer biopsies per 1000 for the same number of high grade cancers detected or about 9 MRI per biopsy avoided. Results were similar using a 10% threshold. CONCLUSIONS Using mp-MRI in the setting of low-intermediate 4Kscores results in a biopsy strategy with higher net benefit compared to using either modality alone. The proposed risk stratification minimizes the utilization of resources and reduces the excessive rate of missed high-grade disease associated with use of mp-MRI. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e753 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Karim Marzouk More articles by this author Behfar Ehdaie More articles by this author Stephen Zappala More articles by this author Andrew Vickers More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PD40-02 RE-EXAMINING PSA DENSITY: DEFINING THE OPTIMAL PSA RANGE AND PATIENTS FOR USING PSA DENSITY TO PREDICT PROSTATE CANCER USING EXTENDED TEMPLATE BIOPSY

You have accessJournal of UrologyProstate Cancer: Detection & Screening V1 Apr 2017PD40-02 RE-EXAMINING PSA DENSITY: DEFINING THE OPTIMAL PSA RANGE AND PATIENTS FOR USING PSA DENSITY TO PREDICT PROSTATE CANCER USING EXTENDED TEMPLATE BIOPSY Joshua Jue, Marcelo Panizzutti, Nachiketh Prakash, Vivek Venkatramani, Varsha Sinha, Nicola Pavan, Bruno Nahar, Pratik Kanabur, Michael Ahdoot, Ramgopal Satyanarayana, Dipen Parekh, and Sanoj Punnen Joshua JueJoshua Jue More articles by this author , Marcelo PanizzuttiMarcelo Panizzutti More articles by this author , Nachiketh PrakashNachiketh Prakash More articles by this author , Vivek VenkatramaniVivek Venkatramani More articles by this author , Varsha SinhaVarsha Sinha More articles by this author , Nicola PavanNicola Pavan More articles by this author , Bruno NaharBruno Nahar More articles by this author , Pratik KanaburPratik Kanabur More articles by this author , Michael AhdootMichael Ahdoot More articles by this author , Ramgopal SatyanarayanaRamgopal Satyanarayana More articles by this author , Dipen ParekhDipen Parekh More articles by this author , and Sanoj PunnenSanoj Punnen More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1742AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous guidelines to screen for prostate cancer (PCa) using serum PSA levels led to millions of unnecessary prostate biopsies that revealed no PCa or low-risk PCa that was unlikely to affect survival. PSA density has shown promise as a better marker to indicate prostate biopsy and has been well investigated in the past using sextant or octant biopsies. While most prior studies only showed that PSA density could distinguish between BPH and PCa, we compared the sensitivity and specificity of PSA density versus PSA to detect any and significant PCa across different PSA ranges using the current standard of extended template prostate biopsies. METHODS Participants were a prospective cohort of men referred for prostate biopsy using an extended template biopsy scheme to evaluate PCa at 26 sites throughout the US. We analyzed the area under the receiver operating characteristic curve to assess the predictive accuracy of PSA density versus PSA across three PSA ranges (<4, 4-10, >10 ng/mL) and in men with or without a prior negative biopsy. We assessed the detection of any and significant (Gleason score ≥ 7) PCa. RESULTS Among 1,290 patients with available data, 585 (45%) and 284 (22%) men had any PCa and significant PCa, respectively. PSA density was significantly more predictive than PSA for detecting any and significant PCa in the PSA ranges of 4-10 and >10 ng/mL. AUC for significant prostate cancer was 0.72 (0.68, 0.77), p<0.0001 for PSA 4-10 ng/mL and 0.82 (0.75, 0.89), p<0.0001 for PSA >10 ng/mL. PSA density was significantly more predictive than PSA in detecting any and significant PCa in men with and without a prior negative biopsy. However, the incremental AUC value was larger for significant PCA than any PCA in men who had a prior negative prostate biopsy (AUC 0.81 vs 0.70, p = 0.0042), and those who did not (AUC 0.77 vs 0.73, p = 0.0026). CONCLUSIONS In contrast to previous studies, we found that PSA density outperformed PSA most within the PSA range >10 ng/mL, suggesting that PSA density will save large volume prostate patients from the costs associated with the over-diagnosis of PCa. Additionally, PSA density performed best among men with a prior negative biopsy, saving these men from the burden of repeated biopsies that are likely to be negative in this population. With the current need for better markers to indicate prostate biopsy, PSA density may have significant value as a more sensitive and specific test than PSA to detect PCa when used with an extended template biopsy scheme. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e750-e751 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Joshua Jue More articles by this author Marcelo Panizzutti More articles by this author Nachiketh Prakash More articles by this author Vivek Venkatramani More articles by this author Varsha Sinha More articles by this author Nicola Pavan More articles by this author Bruno Nahar More articles by this author Pratik Kanabur More articles by this author Michael Ahdoot More articles by this author Ramgopal Satyanarayana More articles by this author Dipen Parekh More articles by this author Sanoj Punnen More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PD43-05 ABSENCE OF EVIDENCE IS NOT EVIDENCE OF ABSENCE: NORMAL AREAS ON MRI COULD HARBOUR SIGNIFICANT TUMOUR

You have accessJournal of UrologyProstate Cancer: Detection & Screening VI1 Apr 2017PD43-05 ABSENCE OF EVIDENCE IS NOT EVIDENCE OF ABSENCE: NORMAL AREAS ON MRI COULD HARBOUR SIGNIFICANT TUMOUR Ashwin Sridhar, Ben Lamb, Gerald Busuttil, Mohammed Zahran, Keren Zaccai, Maria Davari, Imran Ahmad, Anna Mohammed, Greg Shaw, Prabhakar Rajan, Senthil Nathan, Timothy Briggs, Navin Ramachandran, Clare Allen, and John Kelly Ashwin SridharAshwin Sridhar More articles by this author , Ben LambBen Lamb More articles by this author , Gerald BusuttilGerald Busuttil More articles by this author , Mohammed ZahranMohammed Zahran More articles by this author , Keren ZaccaiKeren Zaccai More articles by this author , Maria DavariMaria Davari More articles by this author , Imran AhmadImran Ahmad More articles by this author , Anna MohammedAnna Mohammed More articles by this author , Greg ShawGreg Shaw More articles by this author , Prabhakar RajanPrabhakar Rajan More articles by this author , Senthil NathanSenthil Nathan More articles by this author , Timothy BriggsTimothy Briggs More articles by this author , Navin RamachandranNavin Ramachandran More articles by this author , Clare AllenClare Allen More articles by this author , and John KellyJohn Kelly More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1910AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Accurate prostate cancer risk stratification is essential to guide decision making on active surveillance and interventional therapy. The aim of this study was to determine if a targeted biopsy strategy to sample only MRI detected lesions could replace standard practice of systematic prostate biopsies. METHODS Prostate MRI scans of all patients undergoing RARP for prostate cancer between 2013 and 2016 were prospectively analysed with a uro-radiologist as part of an established quality assurance program. MRI scans were graded as optimal or suboptimal by the radiologist. Localisation of MRI detected prostate cancer (represented in a diagram) was compared to histopathological mapping of cancer following RALP. Significant out of MRI field cancer was defined as Gleason ≥3+4. Location was analysed according to 5 different zones: Anterior, left posterolateral, right posterolateral, apex and base. RESULTS The median Age, PSA and Gleason score were 62.9 (4576), 10.67 (156) and 7 (610) respectively. 778 (89.7%) of patients had = pT2c. Significant prostate cancer was found in 2418/4335 zones (55.8%) on final postoperative pathology. MRI was able to pick up 1797/2418 (74.3%) of the significant lesions and missed 25.7%. Of these significant lesions, 34.7% were ≥4+3. Optimal MRI scans picked up more significant lesions than suboptimal scans (79.6% vs 71.4%). The overall sensitivity of MRI to detect significant prostate cancer was 71.2%, specificity 84.9%, PPV 85.6% and NPV 63.4%. Cohen's Kappa coefficient varied from 0.12 (poor) to 0.44 (moderate); Area under the ROC curve ranged from 0.572 to 0.722 with apical and anterior lesions having lower values. Individual zonal accuracy data is as per table 1. CONCLUSIONS Our results show that in a population of men with significant prostate cancer, MRI can reliably detect significant prostate cancer in in 85.6% of the time. A targeted strategy using MRI will have a 36.6% chance of non detection of significant invisible cancer. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e819 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Ashwin Sridhar More articles by this author Ben Lamb More articles by this author Gerald Busuttil More articles by this author Mohammed Zahran More articles by this author Keren Zaccai More articles by this author Maria Davari More articles by this author Imran Ahmad More articles by this author Anna Mohammed More articles by this author Greg Shaw More articles by this author Prabhakar Rajan More articles by this author Senthil Nathan More articles by this author Timothy Briggs More articles by this author Navin Ramachandran More articles by this author Clare Allen More articles by this author John Kelly More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Sa1280 - Optimal Biopsy Strategies for the Diagnosis of Celiac Disease May be Underutilized

Sa1280 - Optimal Biopsy Strategies for the Diagnosis of Celiac Disease May be Underutilized

Impact of extended prostate biopsy including apical anterior region for cancer detection and prediction of surgical margin status for radical prostatectomy.

We investigated diagnostic yield of initial biopsy and repeated biopsy including apical cores. We investigated 573 consecutive men with PSA of ≤20 ng/ml who underwent prostate biopsy between 2004 and 2013. The initial 14-core biopsy consisted of the sextant type, lateral sites at the base and middle, lateral apices (la) at anterior horn sites, and apical anterior sites (aa). The repeated 18-core biopsy consisted of the initial 14-core biopsy with four transition zone (TZ) sites at the base (tzb) and middle (tzm). Prostate cancer was diagnosed in 178 (38.9%) of 458 men with the initial 14-core biopsy, and 44 (38.3%) of 115 men with the repeated 18-core biopsy. In the initial biopsy setting, the unique cancer detection rate was high in apical sites (apex, la, and aa: 6.2%, 6.2% and 5.1%, respectively). In the repeated setting, it was high in the TZ site in addition to the apical site (apex, la, aa, tzm, and tzb: 6.8%, 6.8%, 11.4%, 9.1% and 11.4%, respectively). The positive SM rate at the apex was higher in patients whose cancer was detected only in sites other than the sextant region than for those in the sextant region (36.4% vs. 14.8%, P = 0.037). The initial 14-core and the repeated 18-core biopsy scheme including apical anterior cores are feasible for prostate cancer detection. We propose that apical biopsy cores can be used to predict not only the existence of cancer but also surgical margin status at the apex.

501 - Value of magnetic resonance imaging in population-based prostate cancer screening: Comparison of 3 biopsy strategies in the 5th screening round of the ERSPC Rotterdam

501 - Value of magnetic resonance imaging in population-based prostate cancer screening: Comparison of 3 biopsy strategies in the 5th screening round of the ERSPC Rotterdam

506 - Does the inclusion of non-index lesions at biopsy improve our ability to predict adverse pathologic outcomes at radical prostatectomy? Implications for targeted plus systematic biopsy schemes

506 - Does the inclusion of non-index lesions at biopsy improve our ability to predict adverse pathologic outcomes at radical prostatectomy? Implications for targeted plus systematic biopsy schemes

Can frequency of prostate biopsy on active surveillance be reduced without significantly increasing risk?

e546 Background: The goal of this investigation is to use longitudinal Active Surveillance (AS) data to identify whether biopsies could be eliminated from a 10-year AS plan calling for annual biopsy without substantially prolonging the time to detection of prostate cancer (CaP) grade progression. Methods: With data from 1,500 men with very-low or low-risk CaP enrolled in AS at Johns Hopkins, we developed a hidden Markov model to estimate probabilities of progression to Gleason 7 or higher. We then simulated all potential AS biopsy strategies where it was assumed biopsy would be performed no more often than annually and either would or would not be performed each year after diagnosis. For every strategy the model was used to predict the average time from occurrence to the detection of grade progression. Potential alternatives to annual biopsy were identified. Results: The estimated 10 year probability of grade progression was 40.0% and the annual probability was 4.0%. Simulation of an annual biopsy strategy estimated that for men who experience grade progression the mean time from occurrence to detection would be 14.1 months. Alternative strategies that reduced the number of biopsies received over 10 years increased the time to detecting grade progression; however several strategies eliminated biopsies with only small increases in the time to detecting grade progression (Table). For instance, a strategy calling for 6 biopsies over 10 years (biopsies in years 1-3,5,7, and 8) would only increase the average time to detecting grade progression by 4.6 months while eliminating 4 biopsies. Conclusions: While annual biopsy was associated with the shortest interval to detecting grade progression, several alternative strategies may allow for less frequent biopsy without sizable increases in time to detecting grade progression. [Table: see text]

Cost-effectiveness analysis of magnetic resonance imaging-ultrasound fusion biopsy versus systematic transrectal ultrasound-guided biopsy in diagnosing prostate cancer.

25 Background: We sought to determine if the reported improved performance of magnetic resonance imaging-ultrasound (MRI-US) fusion biopsy over systematic transrectal ultrasound-guided biopsy (TRUS) in the detection of prostate cancer justifies the added cost of the MR imaging. Methods: A decision-analytic Markov model with a lifetime horizon of 10 years was developed to evaluate diagnostic accuracy, long-term health outcomes, costs, and quality-of-life of two strategies (i.e., TRUS versus MRI-US fusion biopsy [prostate MRI followed potentially by MRI-US fusion biopsy]) as the initial diagnostic test in men with elevated prostate-specific antigen ( &gt; 4 ng/ml) without prior evaluation. Probabilities of clinical events were obtained from published literature. Direct medical costs, including diagnostic and treatment-related costs, were derived from the Premier Hospital Database. Costs were inflated to 2015 US dollars and discounted at an annual rate of 3%. Health outcomes were measured in quality-adjusted life years (QALYs), which were determined based on published literature and expert opinion. We calculated the incremental cost-effectiveness ratio and performed sensitivity analyses to assess uncertainty. Results: The MRI-US fusion biopsy strategy yielded a lower average discounted cost ($5,358 versus $6,372) and higher total QALYs-gained (7.21 versus 7.19) than TRUS. The reduced expenditures associated with MRI-US fusion biopsy was primarily due to avoiding intervention for clinically insignificant prostate cancer. The results were robust with the sensitivity analyses. Conclusions: For men in the United States with an elevated PSA, the use of MRI-US fusion biopsy in the evaluation for prostate cancer represents a greater value than TRUS, the standard of care option. Widespread adoption of MRI-US fusion biopsy may serve to reduce the economic burden of prostate cancer.

Abstract P1-01-11: Something from nothing? The case for quality control in liquid biopsy studies

Abstract Background: Circulating tumor cells (CTCs) as a liquid biopsy strategy are currently being studied as a surrogate biomarker that may reflect metastatic tumor biology. Given the rarity of CTCs, target enrichment is commonly used to profile the gene signatures of valuable clinical samples to evaluate for multiplexed gene panels of interest. The aim of our study was to evaluate if the NanoString PAM50 could be used for accurate gene expression profiling of CTCs and controls using the research-use-only probeset. Methods: We collected two 7.5mL EDTA tubes of blood from 12 healthy female volunteers. CTC assays were performed using the ANGLE Parsortix system as a microfluidics filter that separates cells based on size and deformability. The cell lines Hs578T (basal-like) and SK-BR-3 (HER2 amplified) were used to spike 20 cells into n=6 blood tubes per cell line (termed spiked samples). N=12 7.5mL tubes of blood (termed unspiked samples) and n=12 spiked samples were processed using Parsortix for CTC harvesting and lysis using a 10 micron cassette. From each lysate, 5uL was taken for cDNA amplification, multiple target enrichment for 14 cycles, followed by NanoString PAM50 assays. From each of the 12 peripheral blood (PB) samples, we extracted RNA and used 100ng for NanoString PAM50 assays. For cell line controls, 100ng of Hs578T or SK-BR-3 were subjected to NanoString Assays. Results: Low PAM50 gene expression was observed in all 12 PB samples. Unspiked PB harvested from the CTC assay showed a higher level of PAM50 gene expression compared to PB, suggesting that the target enrichment amplification produces false positive detection of expected breast cancer related transcripts. On ANOVA testing, 10/12 (83%) of unspiked, sorted, target enriched samples had significant differential expression (p&amp;lt;0.0001) of the mean log normalized counts for the PAM50 genes compared to PB. In spiked experiments using n=20 cells in 7.5mL of PB, sorted Hs578T were found to be triple negative in only 3/6 (50%) while sorted SK-BR-3 were found to be HER2 positive in only 3/6 (50%). On ANOVA testing, the spiked/sorted and bulk were found to have a difference among the mean log normalized counts for the PAM50 genes across all samples for both cell lines (p&amp;lt;0.0001). However, 3/6 (50%) samples had a difference in mean PAM50 gene expression when compared to bulk Hs578t on multiple comparison testing while 2/6 (33%) were statistically significantly different when comparing spiked, sorted SK-BR-3 versus bulk cell line. Conclusions: Unspiked blood processed via a CTC assay and subjected to target enrichment showed high expression of genes in the NanoString PAM50 assay, likely due to amplification bias. When working with enriched but not ultra-pure CTC samples, amplified gene expression of background leukocytes may influence read counts. This is important to consider in assays that enrich for CTCs but retain a leukocyte background. Further studies will address the effect of the CTC assay procedure and number of leukocytes on accuracy of gene expression of rare CTC mimics. This study emphasizes the importance of selecting genes that are not expressed in PB or performing background subtraction or normalization as strategies for accurate gene expression profiling of CTCs. Citation Format: Porras TB, Bains PK, Ring A, Carrasco S, Forte V, Punj V, Lang JE. Something from nothing? The case for quality control in liquid biopsy studies [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-01-11.

Genetic and Epigenetic Intra-tumour Heterogeneity in Colorectal Cancer

IntroductionColorectal cancer (CRC) is a highly heterogeneous disease, with pathologically similar cancers having completely different responses to treatment and patient survival. Intra-tumour heterogeneity (defined as distinct morphological and phenotypic differences) has recently been demonstrated to be an important factor in the development and behaviour of cancer cells and can be used to determine response to anticancer therapy.MethodPatients with resected CRC had DNA extracted from eight defined tumour areas which were analysed for two genetic mutations (BRAF and KRAS) and one epigenetic trait (CpG island methylator phenotype/CIMP). Normal adjacent tissue was studied as control.ResultsTwelve patients with CRC were included. Intra-tumoural heterogeneity for KRAS mutation was seen in 2 patients (17%). There was no statistical evidence of CIMP status heterogeneity (p = 0.85), but 6 of the 12 patients (50%) demonstrated at least one heterogeneous area within the tumour.DiscussionIntra-tumoural heterogeneity for both genetic and epigenetic factors in CRC is more prevalent than previously thought in Stage II and Stage III CRC. This study provides new insight into epigenetic heterogeneity of CRC and supports the development of a more targeted biopsy strategy to support expansion of personalised treatment.

Frequency of Propionibacterium acnes Infection in Prostate Glands with Negative Biopsy Results Is an Independent Risk Factor for Prostate Cancer in Patients with Increased Serum PSA Titers.

BackgroundPropionibacterium acnes has recently been implicated as a cause of chronic prostatitis and this commensal bacterium may be linked to prostate carcinogenesis. The occurrence of intracellular P. acnes infection in prostate glands and the higher frequency of P. acnes-positive glands in radical prostatectomy specimens from patients with prostate cancer (PCa) than in those from patients without PCa led us to examine whether the P. acnes-positive gland frequency can be used to assess the risk for PCa in patients whose first prostate biopsy, performed due to an increased prostate-specific antigen (PSA) titer, was negative.MethodsWe retrospectively collected the first and last prostate biopsy samples from 44 patients that were diagnosed PCa within 4 years after the first negative biopsy and from 36 control patients with no PCa found in repeated biopsy for at least 3 years after the first biopsy. We evaluated P. acnes-positive gland frequency and P. acnes-positive macrophage number using enzyme-immunohistochemistry with a P. acnes-specific monoclonal antibody (PAL antibody).ResultsThe frequency of P. acnes-positive glands was higher in PCa samples than in control samples in both first biopsy samples and in combined first and last biopsy samples (P < 0.001). A frequency greater than the threshold (18.5 and 17.7, respectively) obtained by each receiver operating characteristic curve was an independent risk factor for PCa (P = 0.003 and 0.001, respectively) with odds ratios (14.8 and 13.9, respectively) higher than those of serum PSA titers of patients just before each biopsy (4.6 and 2.3, respectively). The number of P. acnes-positive macrophages did not differ significantly between PCa and control samples.ConclusionsThese results suggested that the frequency of P. acnes-positive glands in the first negative prostate biopsy performed due to increased PSA titers can be supportive information for urologists in planning repeated biopsy or follow-up strategies.