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

  1. #131
    [#123]
    Comparison of Magnetic Resonance Imaging-stratified Clinical Pathways and Systematic Transrectal Ultrasound-guided Biopsy Pathway for the Detection of Clinically Significant Prostate Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials
    [2019, Review, Full Text]

    Abstract

    Context
    Recent studies suggested that magnetic resonance imaging (MRI) followed by targeted biopsy (“MRI-stratified pathway”) detects more clinically significant prostate cancers (csPCa) than the systematic transrectal ultrasound-guided prostate biopsy (TRUS-Bx) pathway, but controversy persists. Several randomized clinical trials (RCTs) were recently published, enabling generation of higher-level evidence to evaluate this hypothesis.

    Objective
    To perform a systematic review and meta-analysis of RCTs comparing the detection rates of csPCa in the MRI-stratified pathway and the systematic TRUS-Bx pathway in patients with a suspicion of prostate cancer (PCa).

    Evidence acquisition
    PubMed, EMBASE, and Cochrane databases were searched up to March 18, 2019. RCTs reporting csPCa detection rates of both pathways in patients with a clinical suspicion of prostate cancer were included. Relative csPCa detection rates of the MRI-stratified pathway were pooled using random-effect model. Study quality was assessed using the Cochrane risk of bias tool for randomized trials. A comparison of detection rates of clinically insignificant PCa (cisPCa) and any PCa was also performed.

    Evidence synthesis
    Nine RCTs (2908 patients) were included. The MRI-stratified pathway detected more csPCa than the TRUS-Bx pathway (relative detection rate 1.45 [95% confidence interval {CI} 1.09–1.92] for all patients, and 1.42 [95% CI 1.02–1.97] and 1.60 [95% CI 1.01–2.54] for biopsy-naοve and prior negative biopsy patients, respectively). Detection rates were not significantly different between pathways for cisPCa (0.89 [95% CI 0.49–1.62]), but higher in the MRI-stratified pathway for the detection of any PCa (1.39 [95% CI 1.05–1.84]).

    Conclusions
    The MRI-stratified pathway detected more csPCa than the systematic TRUS-guided biopsy pathway in men with a clinical suspicion of PCa, for both biopsy-naοve patients and those with prior negative biopsy. The detection rate of any PCa was higher in the MRI-stratified pathway, but not significantly different from that of cisPCa.

    Patient summary
    Our meta-analysis of clinical trials shows that the magnetic resonance imaging-stratified pathway detects more clinically significant prostate cancers than the transrectal ultrasound-guided prostate biopsy pathway in men with a suspicion of prostate cancer.

  2. #132
    [#124]
    68Ga-PSMA PET/CT: Does it predict adverse pathology findings at radical prostatectomy?
    [2019]

    https://www.sciencedirect.com/scienc...78143919302017

    Highlights

    • The role of 68Ga-PSMA PET/CT in assessing the extent of local prostate cancer has not been fully elaborated.
    • In our cohort of patients with intermediate/high-risk prostate cancer, 68Ga-PSMA PET/CT provided information regarding intraprostatic tumor location, SVI and LNI.
    • Our data suggest that 68Ga-PSMA PET/CT studies cannot be used reliably to assess EPE.

    Abstract

    Introduction
    Data on the accuracy of 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) in patients with intermediate/high-risk prostate cancer are being accumulated. Its role in assessing the extent of local disease has not been fully elaborated.

    Aim
    To determine the performance characteristics of 68Ga-PSMA PET/CT in identifying local disease extension in patients with intermediate/high risk prostate cancer.

    Methods
    68Ga-PSMA PET/CT studies of 61 consecutive patients with intermediate/high-risk prostate cancer who underwent radical prostatectomy were reviewed by nuclear medicine specialists. Tumor location, extraprostatic extension (EPE), seminal vesicle invasion (SVI), and lymph nodes involvement (LNI) were compared to pathological findings. The incremental value of 68Ga-PSMA PET/CT to established nomograms was determined.

    Results
    Two patients without pathologic uptake of 68Ga-PSMA were excluded. Seventeen patients were diagnosed with EPE (29%), 12(20%) had SVI and 3(5%) LNI. The concordance between tumor location and 68Ga-PSMA PET/CT findings was 48%, and EPE was not indicated by PET in any of the patients. The sensitivity, specificity, positive, and negative predictive value for SVI were 58%, 96%, 78%, 90%, respectively (area under the receiver operating characteristic curve = 0.77) and for LNI 67%, 98%, 67%, 98%, respectively (area under the receiver operating characteristic curve = 0.82). Incorporating imaging findings into the MSKCC-SVI nomogram enhanced the diagnostic accuracy from 0.84 to 0.95 (Integrated Discrimination Increment 0.24, P = 0.004).

    Conclusion
    In patients with intermediate/high-risk prostate cancer, 68Ga-PSMA PET/CT provides information regarding intraprostatic tumor location, SVI and LNI but has no role in assessment for EPE. This information might be useful for pretreatment counseling, decision-making and possibly preoperative planning.
    [Emphasis mine]

  3. #133
    [#125]
    Current status of liquid biopsies for the detection and management of prostate cancer
    [2019, Full Text]

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559244/

    Abstract

    In recent years, new therapeutic options have become available for prostate cancer (PC) patients, generating an urgent need for better biomarkers to guide the choice of therapy and monitor treatment response. Liquid biopsies, including circulating tumor cells (CTCs), circulating nucleic acids, and exosomes, have been developed as minimally invasive assays allowing oncologists to monitor PC patients with real-time cellular or molecular information. While CTC counts remain the most extensively validated prognostic biomarker to monitor treatment response, recent advances demonstrate that CTC morphology and androgen receptor characterization can provide additional information to guide the choice of treatment. Characterization of cell-free DNA (cfDNA) is another rapidly emerging field with novel technologies capable of monitoring the evolution of treatment relevant alterations such as those in DNA damage repair genes for poly (ADP-ribose) polymerase (PARP) inhibition. In addition, several new liquid biopsy fields are emerging, including the characterization of heterogeneity, CTC RNA sequencing, the culture and xenografting of CTCs, and the characterization of extracellular vesicles (EVs) and circulating microRNAs. This review describes the clinical utilization of liquid biopsies in the management of PC patients and emerging liquid biopsy technologies with the potential to advance personalized cancer therapy.
    From the Full Text:

    ...
    In this review, we discuss the recent advances and key technologies (Tables 1 and ​and2)2) in the field of liquid biopsy, focusing on their use as candidate clinical biomarkers in PC. Additionally, significant breakthrough discoveries and studies are summarized (Figure 2), as well as more recent emerging liquid biopsy fields and their potential impact on PC management.
    ...

    Conclusion

    The liquid biopsy field continues to offer tantalizing opportunities to apply new technologies towards real-time tumor profiling. These assays have great potential to transform the clinical practice of PC by providing access to real-time molecular information and by reducing the need for costly and invasive biopsies. To be sure, it is a multidisciplinary field where physicians, scientists, and engineers with different expertise work closely to develop better assays, design clinical trials, and validate the clinical utility of these liquid biopsy assays. We are hopeful that liquid biopsies will continue to advance our understanding of cancer biology and ultimately improve patient outcomes in PC.
    An in-depth review.

  4. #134
    [#126]
    Prostate Imaging Reporting and Data System 3 Category Cases at Multiparametric Magnetic Resonance for Prostate Cancer: A Systematic Review and Meta-analysis
    [2019, Review]

    https://www.ncbi.nlm.nih.gov/pubmed/31279677

    (A review paper on PIRADS 3 lesions)

    Abstract

    CONTEXT:
    The Prostate Imaging Reporting and Data System (PI-RADS) 3 score represents a "grey zone" that need to be further investigated to solve the issue of whether to biopsy these equivocal cases or not.

    OBJECTIVE:
    To critically analyze the current evidence on PI-RADS 3 cases. We evaluated the prevalence of PI-RADS 3 cases in the literature and detection rate of prostate cancer (PC) and clinically significant PC (csPC) at biopsy with regard to factors determining these rates.

    EVIDENCE ACQUISITION:
    We searched in the Medline and Cochrane Library database from the literature from January 2009 to January 2019, following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines.

    EVIDENCE SYNTHESIS:
    A total of 28 studies were included in our analysis (total number of PI-RADS 3 cases: 1759, range 20-187). The prevalence of PI-RADS 3 cases reported in available studies was 17.3% (range 6.4-45.7%). The PC detection rate was 36% (95% confidence interval [CI] 33.8-37.4; range 10.3-55.8%), whereas that of csPC was 18.5% (95% CI 16.6-20.3; range 3.4-46.5%). Detection rates of PC and csPC were found to be similar in men who underwent a target biopsy versus those with a systematic biopsy (23.5% vs 23.9% and 11.4% vs 12.3%, respectively) and lower than the rates achieved with the combined strategy (36.9% and 19.6%, respectively). A prostate-specific antigen density (PSAD) of ≥0.15ng/ml/ml may represent an index to decide whether to submit a PI-RADS 3 case to biopsy.

    CONCLUSIONS:
    In most investigations, PI-RADS 3 cases were not evaluated separately. A PI-RADS 3 lesion remains an equivocal lesion. Evaluation of clinical predictive factors in terms of csPC risk is a main aspect of helping clinicians in the biopsy decision process.

    PATIENT SUMMARY:
    Management of Prostate Imaging Reporting and Data System 3 cases remains an unmet need, and the detection rate of clinically significant prostate cancer (csPC) among this population varies widely. Performing a combined target plus a systematic biopsy yields the highest detection of csPC. A prostate-specific antigen density of lower than 0.15ng/ml/ml may select patients for a follow-up strategy.

  5. #135
    [#127]
    Comparison between "In-bore" MRI guided prostate biopsy and standard ultrasound guided biopsy in the patient with suspicious prostate cancer: Preliminary results
    [2019]

    https://www.ncbi.nlm.nih.gov/pubmed/31266272

    Abstract

    OBJECTIVES:
    To evaluate the detection rate of prostate cancer (PCa) in patients who underwent to "in bore" Magnetic Resonance Imaging -guided prostate (MRI-GB) biopsy compared to the standard transrectal ultrasound guided prostate biopsy (TRUS-GB).

    MATERIALS AND METHODS:
    Between January 2017 and March 2015 a cohort of 39 consecutive patients was prospectively enrolled. All the patients underwent an "in-bore" guided MRI prostatic biopsy and subsequently ultrasound-guided standard prostate biopsy.

    RESULTS:
    Median age of patients was 65.5 years (SD ± 6.6), median total PSA serum level was 6.6 ng/ml (SD ± 4.1), median prostate total volume was 51.1 cc (SD ± 26.7). Thirty of 39 (76.9%) were biopsy-naοve patients while 7/39 (17.9%) had at least one previous negative random TRUS-GB; 2/39 (5.1%) patients were already diagnosed as PCa and were on active surveillance. In 18/39 (53.8%) men Pca was diagnosed; as regards the MRI-GB results related to the PI-RADS score, biopsies of PIRADS 3 lesions were positive in 5/18 cases (27.8%), while the number of positive cases of PI-RADS 4 and 5 lesions was 7/11 (63.6%) and 6/10 (60%)respectively. At the histological examination, 4/39 (10.3%) had a PCa ISUP grade group 1, 11/39 (28.2%) had a ISUP 2, 6/39(15.4%) had a ISUP grade group 3 and 2/39 (5.1%) had a ISUP 4-5.

    CONCLUSIONS:
    MRI-GB represents a promising technique that may offer some of advantages compared to standard systematic TRUSGB. Our preliminary experience in MRI-GB resulted safe and feasible and represents a viable procedure for the diagnosis and characterization of PCa.

  6. #136
    [#128]
    A Prospective Head-to-Head Comparison of 18F-Fluciclovine With 68Ga-PSMA-11 in Biochemical Recurrence of Prostate Cancer in PET/CT
    [2019]

    https://www.ncbi.nlm.nih.gov/pubmed/31283605

    Abstract

    PURPOSE:
    One of the major challenges for all imaging modalities is accurate detection of prostate cancer (PCa) recurrence. Beyond the established Ga-PSMA, a novel promising PET tracer in PCa imaging is F-fluciclovine. For evaluating the advantages and disadvantages and the comparability, we conducted a prospective head-to-head comparison on F-fluciclovine and Ga-PSMA-11 in patients with biochemical recurrence of PCa.

    METHODS:
    58 patients with biochemical recurrence of PCa after definitive primary therapy were included. Both scans were performed within a time window of mean 9.4 days. All scans were visually analyzed independently on a patient-, region- and lesion-based analysis. All the examinations were performed in the same medical department using identical scanners at any time.

    RESULTS:
    The overall detection rate for PCa recurrence was 79.3% in F-fluciclovine and 82.8% in Ga-PSMA-11 (P = 0.64). Local recurrence was detected in 37.9% on F-fluciclovine and in 27.6% on Ga-PSMA-11 (P = 0.03). Local pelvic lymph node recurrence was detected on F-fluciclovine versus Ga-PSMA-11 in 46.6% versus 50%, in extrapelvic lymph node metastases in 41.4% versus 51.7% and in bone metastases in 25.9% versus 36.2%. Lesion-based analysis showed identical findings in local pelvic lymph nodes in 39.7%, in extrapelvic lymph nodes in 22.4%, and in bone metastases in 13.8%.

    CONCLUSIONS:
    The advantage of F-fluciclovine is detecting curable localized disease in close anatomical relation to the urinary bladder, whereas Ga-PSMA-11 fails because of accumulation of activity in the urinary bladder. F-fluciclovine is almost equivalent to Ga-PSMA-11 in detecting distant metastases of PCa recurrence.
    [Emphasis mine]

  7. #137
    [#129]
    Digital Rectal Examination Remains a Key Prognostic Tool for Prostate Cancer: A National Cancer Database Review
    [2019, JNCCN, Review, Full Text]

    https://jnccn.org/view/journals/jncc...ticle-p829.xml

    Abstract

    Background: Prostate cancer clinical stage T2 (cT2) subclassifications, as determined by digital rectal examination (DRE), are a historic method of staging prostate cancer. However, given the potential discomfort associated with prostate examination and the wide availability of other prognostic tests, the necessity of DRE is uncertain. This study sought to determine the prognostic value of the prostate cancer cT2 subclassifications in a contemporary cohort of patients. Methods: The National Cancer Database was used to identify a cohort of men with high-risk clinical T2N0M0 prostate cancer treated with external-beam radiotherapy and androgen deprivation therapies ± surgery from 2004 to 2010. We assessed overall survival from a landmark time of 10 months using Kaplan-Meier and log-rank test analysis. A multivariate proportional hazards model was used to estimate the simultaneous effects of multiple factors, including cT2 subclassification and other well-established prognostic indicators of overall survival in prostate cancer. Results: A total of 5,291 men were included in the final analysis, with a median follow-up of 5.4 years. The cT2a, cT2b, and cT2c subclassifications demonstrated increasing hazard ratios of 1.00 (reference), 1.25 (95% CI, 1.07–1.45; P=.0046), and 1.43 (95% CI, 1.25–1.63; P<.0001), respectively, reflecting a higher probability of death with each incremental increase in cT2 subclassification. This finding was independent of other known prognostic variables on multivariate analysis. Conclusions: Results show that cT2 subclassifications had independent prognostic value in a large and contemporary cohort of men. cT2 classification remains an important, low-cost prognostic tool for men with prostatic adenocarcinoma. The clinical relevance of this test should be appreciated and accounted for by providers treating prostate adenocarcinoma.
    From the Full Text:

    Demonstration of the prognostic significance of the cT2 subclassifications has important clinical and cost-effectiveness implications. In an era in which physicians have come to rely on new and expensive diagnostic tests, such as multiparametric MRI and genomic prognostics assessments, it is critical to highlight that traditional DRE remains a simple and valuable clinical tool for predicting prostate cancer outcome. Literature on how MRI compares with DRE for T2 subclassification is sparse, but MRI has been shown to outperform DRE in localization of cancer within the gland.20 Data show that for clinical detection of T3 disease, subsequently confirmed on pathology, MRI has higher sensitivity than DRE; however, DRE has higher specificity.21 Given the inexpensive, efficient, and widely available nature of DRE, we feel this physical examination component remains critical for oncologists to consider in evaluation of patients with prostate cancer.

    Unfortunately, studies suggest that DRE is an underused component of the physical examination, and may not be emphasized as a critical skill in the training of future physicians.12–14 We believe that DRE should continue to be performed and documented as a key component of the physical examination for all patients with prostate cancer and should be recognized as a low-cost prognostic tool for men with adenocarcinoma of the prostate. DRE also continues to have an important role in screening for prostate cancer, because abnormal findings in conjunction with abnormal PSA levels have been shown to increase detection of clinically significant prostate cancer.22

  8. #138
    [#130]
    Accuracy of standard clinical 3T prostate MRI for pelvic lymph node staging: Comparison to 68Ga-PSMA PET-CT
    [2019, Full Text]

    https://www.nature.com/articles/s41598-019-46386-3

    Abstract

    The aim was to assess the performance of prostate 3T MRI for pelvic lymph node (LN) staging in prostate cancer (PCa), in comparison to 68Gallium-prostate specific membrane antigen PET-CT (68Ga-PSMA PET-CT) as reference standard for LN detection. 130 patients with PCa underwent non-contrast-enhanced multiparametric prostate 3T MRI and 68Ga-PSMA-PET-CT within 180 days at our institution. Overall, 187 LN metastases (n = 43 patients) detected by 68Ga-PSMA-PET-CT were characterized by calculating maximum standardized uptake value (SUVmax), area, diameter and anatomical location including iliac, obturator, presacral and inguinal region. MRI achieved an overall sensitivity, specificity, positive and negative predictive value of 81.6% (CI 71.1–88.9%), 98.6% (CI 97.6–99.2%), 73.5% (CI 52.1–87.6%) and 99.5% (CI 98.8–99.8%), respectively. On a region-based analysis, detection rates differed non-significantly (ps > 0.12) in the anatomical regions. On a size-dependent analysis, detection of LN > 10 mm did not differ significantly (ps > 0.09) from LN ≤ 10 mm. In comparison to single T1 sequence evaluation, additional use of the T2 weighted sequences did not improve the overall performance significantly (p > 0.05). 3T prostate MRI represented an accurate tool for the detection of LN compared to 68Ga-PSMA-PET-CT. Especially for LN metastases smaller than 10 mm, MRI was less accurate compared to 68Ga-PSMA-PET-CT.

  9. #139
    [#131]
    COULD A SPECIFIC PORTION OF D'AMICO INTERMEDIATE GROUP BE RECLASSIFIED AS A LOW RISK GROUP ACCORDING TO MULIPARAMETRIC MAGNETIC RESONANCE IMAGING?
    [2019]

    https://insights.ovid.com/urology/ju...p/251/00076734

    Abstract

    INTRODUCTION AND OBJECTIVES:
    Various recent literature suggests that a negative multiparametric MRI (mpMRI) allows to rule out significant prostate cancer. The objective of our study was to investigate whether a specific portion of D'Amico intermediate risk group could be reclassified as low risk if the mpMRI is negative. We evaluated the histopathological results after radical prostatectomy (RP) in preoperative D'Amico intermediate risk patients that had a negative preoperative mpMRI.
    METHODS:
    We retrospectively identified 604 D'Amico intermediate risk patients and 355 low risk patients among 1,347 who underwent a preoperative mpMRI and radical prostatectomy in a single institution. Intermediate risk patients were sub-classified according to Gleason score, clinical stage and preoperative PSA level and the positivity of mpMRI. The final pathology from each RP specimen of each sub-classified group was compared with that of D'Amico low risk group. The MRIs were considered negative when no suspicious lesion was seen or when PI-RAD Version 2 grade≤2. Patients with advanced pathologic stage (pT3-T4 and/or pN1) and/or a pGS 4 + 3 were considered as “unfavorable disease” at RP. Pathologic stage pT3-4 or pN1 was classified as “non-organ-confined disease”.
    RESULTS:
    Among 604 intermediate risk group patients, 48 patients were PSA only elevated group (Gleason 6, cT1-cT2b and PSA 10 to 20 ng/dl) with negative MRI. The rate of unfavorable disease was 18.8% (9/48 ) and non-organ confined disease was 10.4% (5/48 ) among the subgroup. Pathological profile of this subgroup was comparable with D'Amico low risk group in terms of the risk of unfavorable disease and non-organ-confined disease. The comparability was still consistent even after 1:4 propensity score matching of clinical profiles exceptliterature preoperative PSA (Table). The rate of unfavorable disease or non-organ-confined disease among other subgroups were significantly worse than D'Amico low risk group regardless the findings of mpMRI.
    CONCLUSIONS:
    In case of negative mpMRI, If the only violation of D'Amico low risk criterion is moderate PSA elevation (≤20ng/ml), the pathological outcome was comparable with conventional literature group. Our results suggest that the oncological hazard of such specific portion of conventional D'Amico intermediate risk group could be considered as low risk in the era of mpMRI.

  10. #140
    [#132]
    Preoperative PI-RADS Version 2 scores helps improve accuracy of clinical nomograms for predicting pelvic lymph node metastasis at radical prostatectomy
    [2019]

    https://www.ncbi.nlm.nih.gov/pubmed/31383954

    Abstract

    BACKGROUND:
    Lymph node invasion (LNI) is a strong adverse prognostic factor in prostate cancer (PCa). The purpose of this study was to evaluate the role of Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) scores for estimating the risk of LN metastasis. The study also aimed to investigate the additional value of PI-RADSv2 scores when used in combination with clinical nomograms for the prediction of LNI in patients with PCa.

    METHODS:
    We retrospectively identified 308 patients who underwent multiparametric magnetic resonance imaging (mpMRI) and RP with pelvic lymph node dissection (PLND). Clinicopathological parameters and PI-RADSv2 scores were assessed. Univariate and multivariate logistic analyses were performed. The area under the receiver operating characteristic curves (AUCs) and decision curve analysis (DCA) were generated for assessing the incremental value of PI-RADSv2 scores combined with the Briganti and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms.

    RESULTS:
    Overall, 20 (6.5%) patients had LNI. At univariate analysis, all clinicopathological characteristics and PI-RADSv2 scores were significantly associated to LNI (p < 0.04). However, multivariate analysis revealed that only PI-RADSv2 scores and percentage of positive cores were independently significant (p ≤ 0.006). The PI-RADSv2 score was the most accurate predictor (AUC, 80.2%). The threshold of PI-RADSv2 score was 5, which provided high sensitivity (18/20, 90.0%) and negative predictive value (203/205, 99.0%). When PI-RADSv2 scores were combined with Briganti and MSKCC nomograms, the AUC value increased from 75.1 to 86.3% and from 79.2 to 87.9%, respectively (p ≤ 0.001). The DCA also demonstrated that the two nomograms plus PI-RADSv2 scores improved clinical risk prediction of LNI.

    CONCLUSIONS:
    The patients with a PI-RADSv2 score <5 were associated with a very low risk of LNI in PCa. Preoperative PI-RADSv2 scores could help improve the accuracy of clinical nomograms for predicting pelvic LN metastasis at radical prostatectomy.

    The day after I posted that I didn't know the usefulness of an overall PI_RADS score (as distinguished from PI-RADS evaluations of individual lesions), I came across this this study!

 

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