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Thread: (C) Screening – Diagnosis – PSA – Imaging – Biopsies

  1. #101
    Cancer Core Length from Targeted Biopsy: An Index of Prostate Cancer Volume and Pathologic Stage



    To study the relationship of maximum cancer core length, on targeted biopsy of MRI‐visible index lesions, to volume of that tumor found at prostatectomy.

    Patients and Methods
    205 men undergoing fusion biopsy and radical prostatectomy were divided into two groups: 136 in whom the maximum cancer core length came from an index MRI‐visible lesion (targeted) and 69 in whom maximum cancer core length came from a non‐targeted lesion. MRI was 3T multi‐parametric and biopsy was via MRI‐US fusion.

    In the targeted biopsy group, maximum cancer core length correlated with volume of clinically‐significant index tumors (ρ=0.44‐0.60, p<0.01). The correlation was similar for first and repeat biopsy and for transition and peripheral zone lesions (ρ=0.42‐0.49, p<0.01). No correlations were found in the non‐targeted group. Targeted maximum cancer core length (6‐10 mm and >10 mm) and MRI lesion diameter (>20 mm) were independently associated with tumor volume. Targeted maximum cancer core lengths >10 mm and Gleason scores >7 were each associated with pathological T3 disease (OR, 5.73 and 5.04, respectively), but MRI lesion diameter lesion was not.

    Maximum cancer core length on a targeted biopsy from an MRI‐visible lesion is an independent predictor of both cancer volume and pathologic stage. This relationship does not exist for MCCL from a non‐targeted biopsy core. Quantifying cancer core length on MRI‐targeted biopsies may have a value, not previously described, to risk‐stratify patients with prostate cancer before treatment.
    [Emphasis mine]

  2. #102
    MRI-targeted biopsies: What’s next?
    [2019, Editorial]


    The two last years have witnessed the confirmed advent of MRI and MRI-targeted biopsies in routine prostate cancer management thanks to the publication of a high level of evidence trials. MRI does better than TRUS biopsies in ruling out clinically significant disease (PROMIS trial), and MRI followed by targeted biopsies alone improves its detection (PRECISION trial) as compared with systematic biopsies [1, 2]. The question is no longer whether we should use MRI before biopsy and target the lesion if positive, but how this new information that implements our reflection on daily practice influences our treatment decision-making process.

    Should we trust only targeted biopsies and definitively abandon systematic biopsies?

    Should we doubt the negativity of MRI and targeted biopsies and go for an extra-target set of biopsies? Should we all rely on MRI regardless of the radiological expertise of a given centre?

    Should we re-build our nomograms and prediction models by incorporating the targeted biopsies’ pathological features, especially in active surveillance or focal therapy protocols?

    Should we push for more precise targeted biopsies using dedicated softwares, using new biopsy approaches to improve the risk stratification and individualize the treatment strategy?

    Unfortunately, not all these questions have been answered yet. In the present Topic of the World Journal of Urology entitled “MRI-targeted biopsies for prostate cancer diagnosis and management”, the authors managed to deal with these clinical uncertainties by sharing their centre’s experience or by assessing the current literature.

    In the comprehensive review written by the European Association of Urology Young Academic Urologists Prostate Cancer Working Party, the importance of systematic biopsies has been highlighted [3]. The combination of both targeted and systematic biopsies improved the overall and significant (about 10%) prostate cancer detection rates as compared with a pure targeted strategy. The MRI-FIRST trial recently confirmed that a pure targeted biopsy strategy led to a not negligible risk of missing significant cancer symptoms, due to limitations of multiparametric MRI performance/reading and of precision during lesion targeting [4]. The physician facing a patient with a positive MRI should use the most accurate strategy to rule out/detect significant foci. So, systematic biopsies are not over, but till when? Technical issues as well as operator errors still exist in the targeted biopsy strategy leading to concerns of missing the disease, especially in case of negative targeted biopsies with MRI-visible lesions. Gold et al. [5] have reviewed all potential sources of error which can arise from each step of the process: false positive lesions in MRI, acquisition errors, fusion pitfalls, anatomic limits of needle placement, etc. New advances in technology will probably correct these sources of mistargeting, however, their widespread use will depend on the costs. To date, the vast majority of urologists do not use a dedicated fusion system when performing targeted cores, but cognitively target the lesion. Does it really matter? Marra et al. [6] emphasized that the strategy should be tailored to local expertise and resources availability. Software-based fusion biopsies probably improve the precision of targeting, in terms of millimeters but not in terms of detection rate [7, 8]. Another way of improvement might be the biopsy route. Indeed, especially for anterior and apical lesions, transperineal biopsies can lead to a not negligible rate of re-stratification by providing more cancer material for pathology [9]. This refinement of risk stratification (towards higher risk groups) meaningfully influences the treatment choice with more curative intent strategies due to a re-evaluation of cancer grade.

    The management of presumed low-risk prostate cancer has also evolved from radical to focal therapy and active surveillance due to the visualization of significant lesions in MRI and the predictive value of imaging in the negative part of the gland. Through a single-centre report of patients treated by high-intensity focused ultrasound hemiablation, Dr Villers and his team showed that pathologically insignificant, MRI-negative, extra-target disease did not influence the follow-up course and did not have an impact on the radical treatment-free survival [10]. In active surveillance protocols, the strong negative value of MRI could also avoid the use of confirmatory biopsies in case of negative MRI at entry, and thereby improve patient’s heath-related quality of life while avoiding biopsy complications [11].

    The other benefit from targeted biopsies that has not yet been thoroughly evaluated is the improvement of the prognosis assessment. To date, the vast majority of prognostic tools used in clinical practice for treatment decision-making are based on systematic biopsies, in addition with clinico-biological parameters combined or not with imaging. An emerging literature tends to demonstrate that the incorporation of targeted biopsy features in this assessment clearly improves it [12]. The perfect proof is the recent update of the Briganti nomogram for predicting lymph node invasion and planning lymph node dissection during radical prostatectomy in which the incorporation of grade group on targeted biopsy has improved the overall performance of the statistical model [13].

    The MRI-targeted biopsies have now invaded our clinical practice. We must now ask ourselves how to use them optimally, to improve diagnosis, reduce the risks of misclassification, more accurately assess prognosis, and individualize patient care strategies.

  3. #103
    Defining Prostate Cancer at Favorable Intermediate Risk: the Potential Utility Of Magnetic Resonance Imaging And Genomic Tests



    To determine whether prostate multi parametric MRI (mpMRI) and genomic biomarkers might help further defining patients with favorable intermediate risk patients (FIR) prostate cancer which could safely considered suitable for active surveillance (AS).

    From our institutional database, we identified 509 patients who underwent radical prostatectomy with a preoperative MRI and a postoperative Decipher test (GenomeDx Biosciences, Vancouver, BC). According to NCCN risk stratification, 125 had FIR and 171 had Unfavorable Intermediate Risk (UIR) disease.Univariable and multivariable binary logistic regression analyses was used to test the utility of different variables in predicting AP, defined as Gleason Grade Group >2, pT3b or pN1.

    On univariable analysis, FIR, mpMRI and Decipher significantly predicted AP; on multivariable analysis, FIR and Decipher maintained their independent predictive value whereas mpMRI did not meet statistical significance (p=0.059). The 19 FIR patients with high genomic risk had an AP rate slightly higher than UIR patients (42.1% vs. 39.8%, respectively, p=0.56), whereas those with low genomic risk had an AP rate slightly lower than VLR-LR patients (7.5% vs. 10.2%, respectively, p=0.84). The 31 FIR patients with high mpMRI and genomic risk had an AP rate slightly lower than UIR patients (25.8% vs. 39.8%, respectively, p=0.14), whereas those at low mpMRI and genomic risk had an AP rate slightly lower than VLR-LR patients (8.5% vs. 10.2%, respectively, p=0.89).

    MpMRI and Decipher allowed to better define the risk of AP in FIR patients being diagnosed with PCa.
    (They forgot to define AP in the Abstract. I believe it is Adverse Pathology.)

  4. #104
    Comparison of Prostate Biopsy with or without Prebiopsy Multiparametric Magnetic Resonance Imaging for Prostate Cancer Detection: An Observational Cohort Study



    We hypothesized that 1) introducing prebiopsy multiparametric magnetic resonance imaging would increase the diagnostic yield of transrectal prostate biopsy and 2) this would inform recommendations regarding systematic transrectal prostate biopsy in the setting of negative prebiopsy multiparametric magnetic resonance imaging.

    A total of 997 biopsy naοve patients underwent transrectal prostate biopsy alone to June 2016 (cohort 1) and thereafter 792 underwent transrectal prostate biopsy following prebiopsy multiparametric magnetic resonance imaging (cohort 2). Patients with lesions on prebiopsy multiparametric magnetic resonance imaging underwent cognitive targeted plus systematic transrectal prostate biopsy. Patients without lesions underwent systematic transrectal prostate biopsy.

    Cohort 2 comprised younger men (age 68 vs 69 years, p = 0.01) with lower prostate specific antigen (7.6 vs 7.9 ng/ml, p = 0.024) and smaller prostate volume (56.1 vs 62 cc, p = 0.006). In cohort 2 vs cohort 1 there was no increase in overall prostate cancer detection (57.6% vs 56.7%, p = 0.701), the Gleason Grade Group or the number of positive cores (each p >0.05). Increased multifocal prostatic intraepithelial neoplasia, maximum prostate cancer core length (5 mm or greater vs less than 5 mm) and radical surgery/high intensity focused ultrasound (each p <0.05) were observed in cohort 2. For Gleason Grade Group 2-5 prostate cancer negative prebiopsy multiparametric magnetic resonance imaging had 88.1% sensitivity, 59.8% specificity, 67.8% positive predictive value and 84% negative predictive value. For negative prebiopsy multiparametric magnetic resonance images a prostate specific antigen density cutoff of 0.15 ng/ml or greater increased clinically significant prostate cancer detection only if the latter was defined as Gleason Grade Group 3-5 disease and/or tumor length 6 mm or greater.

    Introducing prebiopsy multiparametric magnetic resonance imaging in our clinical setting increased the diagnostic yield of prostate cancer per biopsy core. Not performing a systematic transrectal prostate biopsy when prebiopsy multiparametric magnetic resonance imaging was negative would have led to under detection of 15.1% of Gleason Grade Group 2 or greater prostate cancer cases (approximately 1 in 6).

  5. #105
    Long-term Outcomes for Men in a Prostate Screening Trial with an Initial Benign Prostate Biopsy: A Population-based Cohort
    [2019, Full Text]


    A Swedish study.


    The optimal follow-up regimen for men after a benign prostate biopsy remains unknown.

    To investigate long-term outcomes for men after an initial benign prostate biopsy.

    Design, setting, and participants
    All men with a benign biopsy in the first screening round of the Gφteborg prostate cancer (PC) screening trial were included. The follow-up period was January 1, 1995–May 15, 2017.

    Prostate-specific antigen (PSA) tests were performed every second year (upper median age limit 69 yr). Men with PSA ≥3 ng/ml underwent prostate biopsy (sextant biopsy up to 2009).

    Outcome measurements and statistical analysis
    The 20-yr cumulative PC incidence and PC mortality were calculated using the 1 minus Kaplan-Meier method.

    Results and limitations
    Of 452 men with a benign biopsy and followed for a median of 21.1 yr, 169 were diagnosed with PC and five died from PC. The 20-yr cumulative PC incidence and PC mortality were 40.0% and 1.4%, respectively. The corresponding figures were 38.8% and 0.6% for men with initial PSA ≤10 ng/ml, and 64.4% and 21.4% for PSA >10 ng/ml. The proportion of men untreated at final follow-up was similar in the two PSA groups (22% vs 23%). The use of sextant biopsy for many years of the trial is a limitation.

    Men with an initial benign prostate biopsy run a very low risk of dying from PC when participating in a screening program. However, if followed for a long period, many men will be diagnosed and treated for PC. Low-intensity follow-up, as in the Gφteborg trial, appears sufficient for men with PSA ≤10 ng/ml after a benign biopsy.

    Patient summary
    This study shows that men who participate in a prostate cancer screening trial have a low risk of dying from prostate cancer if the first biopsy does not show cancer.
    [Emphasis mine]

    From the Full Text:


    It is well known that the use of standard 10- and 12-core prostate biopsies to detect prostate cancer (PC) results in undersampling and undergrading [1]. The recently published PROMIS study highlighted the limitations of transrectal ultrasound-guided (TRUS) systematic biopsies; almost half of all clinically significant tumours were missed using this strategy [2]. Most guidelines therefore recommend that at least one set of repeat biopsies is taken if the first biopsy is benign and there are persistent indications for PC such as an elevated prostate-specific antigen (PSA) level [3, 4, 5]. However, with each biopsy there is a risk of sampling insignificant tumours with limited malignancy capacity, leading to overdiagnosis and overtreatment. In addition, prostate biopsies are associated with complications such as bleeding and infections [6]. It remains largely unknown which tumours are truly clinically significant, and the long-term clinical consequences of a delayed diagnosis due to undersampling have yet to be determined.

    Two recent publications report a low risk of PC-related death after a negative biopsy and therefore questioned whether new diagnostic interventions such as imaging and biomarkers would add value to PC management or whether they would unnecessarily increase the need for further follow-up for these men [7, 8]. Accurate identification of men who need further investigation and follow-up after a benign biopsy and definition of the optimal method for such follow-up are therefore of great interest. The aim of our study was to investigate long-term outcomes for men participating in a PSA screening trial who had an initial benign prostate biopsy.
    Last edited by DjinTonic; 02-20-2019 at 03:22 PM.

  6. #106
    Ga-PSMA PET/CT Staging of Newly Diagnosed Intermediate- and High-Risk Prostate Cancer
    [2019, Full Text]



    Ga-prostate-specific membrane antigen positron emission tomography/computerized tomography (Ga-PSMA PET/CT) is part of the initial workup of patients with intermediate and high-risk prostate cancer provided by the Israeli national health services.

    To assess the incidence of metastatic spread in consecutive patients with newly diagnosed cancer, and the potential added value of Ga-PSMA PET/CT to the staging imaging algorithm.

    Patients with newly diagnosed intermediate- and high-risk prostate cancer were referred for initial staging by Ga-PSMA PET/CT between May 2016 and April 2017. Blood prostate-specific antigen (PSA) levels, clinical history, imaging reports and histopathological reports (including Gleason scores) were obtained. Maximal standardized uptake values (SUVmax) were determined for the primary lesions detected within the prostate.

    The study included 137 consecutive patients with intermediate- and high-risk disease who underwent Ga-PSMA PET/CT staging. Of these, 75 had Ga-PSMA uptake in both prostate lobes, 57 had unilateral uptake, and 5 patients had no uptake. SUVmax in the primary tumor correlated significantly with PSA levels. Thirty-five patients had increased uptake compatible with metastatic disease involving lymph nodes, bone, and viscera. Twenty-seven patients had available bone scintigraphy results: 18 (69%) of their 26 bone metastases detected by Ga-PSMA PET/CT were missed on bone scintigraphy.

    Ga-PSMA PET/CT shows promise as a sole whole-body imaging modality for assessing the presence of soft tissue and bone metastases in the setting of prostate cancer.

  7. #107
    The predictive value of DRE in the modern era of prostate cancer diagnostics



    Background: DRE (digital rectal examination) suspicious for prostate cancer is still used as a clinical tool to diagnose prostate cancer. We aim to analyse the predictive value of DRE to diagnose prostate cancer ISUP grade group ≥2 (GG≥2) prostate cancer including the setting of STHLM3 test as a variable. Methods: The previously described STHLM3 screening-cohort included men between 50 to 70 years with ≥10% risk of prostate cancer as assessed by PSA or the Stockholm3 test and invited for transrectal biopsy (TRUSbx). All 7415 biopsied men was included for analysis. DRE status was categorized as T1-T4. We analysed sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) for DRE status of T2-4 to predict GG≥2 and GG≥3 in biopsies. In a multivariate logistic regression analysis; we adjusted for PSA, age, PVol, earlier biopsy (EB) and adjusted STHLM3 model risk set to exclude DRE and prostate volume (PVol). We calculated adjusted odds ratio (OR) for different strata of adjusted STHLM3 risk. Results: Prevalence of ISUP≥2 was 16.8% (1,243/7415). 9.7% (716/7415) men had DRE suspicious for cancer (T2-4) with a Sn to detect GG≥2 of 25.2%. Sp, PPV and NPV was 93.5%, 43.7% and 86.1%, respectively. In univariate model the OR for DRE T2-4 vs. T1 to predict GG≥2 was 4.28 (95% CI 4.09–5.67). Logistic regression analysis including also age, PVol, PSA, earlier biopsies and adjusted STHLM3 risk (%) gave an OR for DRE T2-4 of 2.87 (95% CI 2.36–3.49). In the same analysis stratified PSA group 5-10 ng/ml with PSA < 3 ng/ml as baseline gave OR = 3.21. Using the same univariate model, OR for DRE T2-4 vs. T1 to predict GG≥3 was 6.68 (95% CI 5.44–8.21) and in the multivariate model OR was 3.25 (95% CI 2.54–4.17). Conclusions: As a diagnostic test DRE holds little merit on its own but in combination with other clinical factors and biomarkers in this study we could show that it contributes with value. Just under half of men with DRE suspicious for cancer has GG≥2 cancer. This study does not establish evidence to rule out DRE as a clinically valuable adjunct to PSA, other clinical parameters and new biomarkers like STHLM3.
    [Emphasis mine]

  8. #108
    Prostate cancer detection rate according to lesion visibility using ultrasound and MRI



    • Presence of TRUS-visible focal lesion increased cancer detection rate in patients without prebiopsy MRI.
    • TRUS-visibility was associated with detection of prostate cancer.
    • MRI-visibility was associated with detection of prostate cancer.

    To evaluate the difference in prostate cancer detection rates according to lesion visibility using transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) before biopsy.

    Patients who underwent TRUS-guided prostate biopsy in 2016 and 2017 (n=1,022) were divided into three groups: (1) patients who did not undergo a prebiopsy MRI (group 1, n=622); (2) patients without visible lesions on the prebiopsy MRI (group 2, n=77); and (3) patients with visible lesions on the prebiopsy MRI (group 3, n=323). Biopsy results were compared using chi-square tests or independent t-tests between patients with and without TRUS-visible lesions in each group. A logistic regression test was used to determine the variables independently associated with the detection of clinically significant cancer.

    Focal lesions were visible on TRUS in 710 patients. Clinically significant cancers were detected in 39.4% and 13.1% of patients with and without TRUS-visible lesions, respectively (p<0.001). The cancer detection rate was significantly higher in patients with TRUS-visible lesions in groups 1 and 3 (p<0.001). Within group 1, the Gleason scores, number of positive cores, and the cancer involvement ratios were significantly greater in patients with TRUS-visible lesions than in patients without TRUS-visible lesions. MRI- and TRUS visibility were positively associated with the detection of clinically significant prostate cancer (p=0.002 and p<0.001, respectively).

    TRUS- and MRI-visible focal lesions in the prostate were significantly associated with the detection of clinically significant cancer.
    Last edited by DjinTonic; 03-18-2019 at 04:19 PM.

  9. #109
    Multivariate risk prediction tools including MRI for individualized biopsy decision in prostate cancer diagnosis: current status and future directions
    [2019, Full Text]


    Transrectal ultrasound-guided systematic biopsy in the work-up of prostate cancer (PCa) diagnosis has shown a rising prevalence of antibiotic-resistant bacterial infections with biopsy-related septic complications [1]. Furthermore, systematic biopsy is associated with increased detection of indolent or low-grade PCa [2]. Reduction of systematic biopsies is pivotal in men who eventually prove to have no or low-grade PCa. Utility of validated multivariate risk prediction models to determine the risk of clinically significant PCa (csPCa) and to reduce (unnecessary) biopsy is nowadays recommended in guidelines [3].

    The individualized risk-adapted approach in prostate cancer diagnosis is about to change with the introduction of prostate multi-parametric magnetic resonance imaging (mpMRI) in daily practice. Despite the qualities of mpMRI in predicting the absence or presence of csPCa, today mpMRI is still utilized as a diagnostic test for improving the performance of the diagnostic work-up, and not reducing biopsy [3, 4]. In other words, mpMRI is indicated when systematic biopsy is indicated, and thus when the likelihood is high of having clinically significant disease in a subsequently systematic biopsy.

    mpMRI is especially indicated in men with prior negative biopsy who are still suspected of having significant disease. However, in biopsy-naοve men mpMRI is also suggested as an upfront or prebiopsy diagnostic test, to improve the diagnostic yield when combining targeted and systematic biopsy [5, 6, 7]. Moreover, mpMRI has also been introduced as a triage test to indicate performing or not performing a biopsy [5, 8, 9, 10]. As a result of its high negative predictive value, men with no suspected evidence for csPCa on MRI may defer systematic biopsy [11, 12].

    Utilizing mpMRI as a triage test shows resemblance with risk prediction, and may have overlap with current multivariate risk prediction models for prostate cancer [13, 14, 15, 16, 17, 18, 19]. Most of these current risk models have been externally validated several times, and all use prostate-specific antigen (PSA), and digital rectal examination (DRE) as individual predictive input variables. To improve their predictive value, some use extra input variables such as age, prostate volume, free PSA, family history, race, and prior negative biopsy.

    Due to the predictive value of mpMRI in PCa diagnosis, recently new multivariate risk prediction tools have been constructed, with the inclusion of the mpMRI suspicion score [20, 21, 22, 23, 24, 25, 26, 27, 28, 29]. The purpose of this review is to explore the performance of these new MRI risk models for indicating a biopsy for prostate cancer diagnosis.

  10. #110
    Transperineal Prostate Biopsies Using Local Anesthesia: Experience in 1,287 Patients. Prostate Cancer Detection Rate, Complications and Patient Tolerability



    We report our experience with transperineal prostate biopsy as well as the cancer diagnosis rate, complications and patient tolerability in 1,287 consecutive patients at risk for prostate cancer.

    Materials and Methods:
    Beginning in October 2016 transperineal prostate biopsy was performed using local anesthesia in all patients undergoing prostate biopsy. Data on prebiopsy characteristics and results, including the cancer detection rate, complications and patient tolerability scores, were collected retrospectively from patient records.

    The cancer detection rate of transperineal prostate biopsy was 49.8% (641 of 1,287 patients). Clinically significant prostate cancer was detected in 385 patients and 62 (9.7%) had exclusively anterior zone pathology findings. Urinary retention developed in 20 patients (1.6%) following transperineal prostate biopsy, requiring temporary catheterization. In 4 patients (0.3%) lower urinary tract symptoms were suggestive of infection but only 1 had a positive urine culture. The only hospital admission was for a patient with persistent hypotension after biopsy. Patients tolerated transperineal prostate biopsy reasonably well and generally reported only mild levels of discomfort on a pain visual analogue scale. Infiltration of the anesthesia was rated more painful than the biopsy.

    Transperineal prostate biopsy with the patient under local anesthesia is a feasible alternative to transrectal biopsy in the detection of prostate cancer. Transperineal prostate biopsy has an acceptable cancer detection rate with additional detection of anterior zone cancers. It is a safer alternative in patients due to the low risk of complications, in particular urosepsis and it is well tolerated. Transperineal prostate biopsy using local anesthesia could be considered a standard modality for the initial diagnosis of prostate cancer.


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