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

  1. #71
    PSMA Imaging and Theranostics: Future Impact to Patient Management [2018, 30 min video presentation]


    (Excellent introductory lecture/presentation on PSMA Imaging in prostate cancer)

    Flagged by Forum Brother Michael F.
    69 yr at Dx, BPH x 20 yr, 9 (!) neg. biopsies, PCA3 -
    2013 TURP (90→30 g) then PSA 2x/yr, DRE yearly
    6-06-17 DRE: nodule R, PSA rise, on finasteride: 3.6→4.3
    6-28-17 Biopsy #10: 2/14 cores: G10 (5+5) 50% RB, G9 (4+5) 5% RLM
    Bone scan, CTs, X-rays: negative
    8-7-17 Open RP, neg. frozen sections, Duke Regional
    SM EPE LVI SVI LN(16): negative, PNI+, nerves spared
    pT2c pN0 bilat. acinar adenocarcinoma G9 (4+5) 5% of prostate (4.5 x 5 x 4 cm, 64 g)
    11-10-17 Decipher 0.37=Low Risk: 5-yr met risk 2.4%; 10-yr PCa-specific mortality 3.3%
    Dry; ED OK with sildenafil
    9-16-17 (5 weeks) PSA <0.1; Pomi-T (2/day)
    LabCorp uPSA (Roche ECLIA):
    11-28-17 (3 mo. ) 0.010
    02-26-18 (6 mo. ) 0.009
    05-30-18 (9 mo. ) 0.007
    08-27-18 (1 year) 0.018
    09-26-18 (13 mo) 0.013 (checking rise)
    11-26-18 (15 mo) 0.012
    02-25-19 (18 mo) 0.015

  2. #72
    Radiologist as a Leader in the Diagnostic Process in Patients with Prostate Cancer


    Multiparametric MRI of the prostate gland is a relatively new diagnostic modality which is gathering a growing interest among urologists and radiologists. The second version of the PI-RADS guidelines enabled standardized imaging, evaluation and reporting of prostatic lesions. Nonetheless, since 2015 - when the PI-RADS v.2 was published, numerous questions regarding imaging of the prostate gland have appeared.
    Full Text:
    In January 2017, I had a pleasure to visit Radboud University Medical Centre (RUNMC) in Nijmegen, Holland which is a world-leading center for prostate imaging and research. I met professor Jelle Barentsz, who is the main author of PI-RADS [1], a professor of radiology, and Chair of a research department at RUNMC. Professor Barentsz heads also a worldwide network of MRI providers accredited by the Prostate Centres of Excellence (COE), which was also developed at RUNMC. It is an imaging team of radiologists and technicians trained in Holland by Prof. Barentsz and his team in the application of the RUNMC imaging protocol. Apart from that, during the course, participants are trained to produce structured reports that include key images and multiparametric data which are integrated with the written assessment of the radiologist.

    Although the general principles of imaging used in Nijmegen are similar to those applied in Poland, there are also significant differences which drew my attention. The patients are examined on a 3T scanner without an endorectal coil. The minimal protocol (including T2W images in three planes, DWI and ADC maps, k-trans contrast enhancement) is applied for diagnostic purposes. On the other hand spectroscopy is used primarily for scientific purposes. Strong confidence is put on ADC values, although the reporting team bears in mind that the values may differ between scanners. Such a short protocol enables performing the imaging within 30 minutes. However, if there is a suspicion of prostate cancer based on diagnostic prostate

    MRI, the patient undergoes MRI-guided biopsy within a couple of days. If there is a need to exclude distal metastases, PET-CT or whole-body MRI with a special contrast agent that is highly specific for prostate cancer [2] is performed without delay. In general, the whole diagnostic evaluation with establishment of further treatment can be performed within a week.

    Clinical meetings with urologists, radiologists, radiotherapists, oncologists, and pathologists take place weekly. Each participant is encouraged to share his or her opinion regardless of specialty. Apart from that, there are separate meetings for radiologists and technicians who perform MRI-guided biopsies. Such a close cooperation between team members significantly improves confidence of their diagnostic and therapeutic decisions. It also has a positive impact on patients’ quality of life.

    Another advantage of such a close cooperation is a possibility of implementation of multiparametric MRI of the prostate gland as a screening method, along with PSA evaluation. A new short protocol might possibly serve as a reliable tool to select men who may benefit from early detection and prostate biopsy. Such a protocol has a reduced duration of imaging (approximately 15 minutes), and it does not involve routine contrast administration. Doubtlessly, it would enable more accurate diagnosis in a much shorter time without the need of repetitive TRUS-biopsies.

    A growing interest in multiparametric imaging of the prostate gland is justified, since there is no better tool for imaging of prostate cancer [3, 4]. However, it must be kept in mind that new solutions are being constantly implemented in terms of diagnosis and treatment, and a close cooperation between specialties is essential to improve medical care.

  3. #73
    Prostate-specific antigen 10–20 ng/mL: A predictor of degree of upgrading to ≥8 among patients with biopsy Gleason score 6
    [2017, Full Text]



    This study aimed to identify the predictors of upgrading and degree of upgrading among patients who have initial Gleason score (GS) 6 treated with robot-assisted radical prostatectomy (RARP).

    Materials and Methods
    A retrospective review of the data of 359 men with an initial biopsy GS 6, localized prostate cancer who underwent RARP between July 2005 to June 2010 was performed. They were grouped into group 1 (nonupgrade) and group 2 (upgraded) based on their prostatectomy specimen GS. Logistic regression analysis of studied cases identified significant predictors of upgrading and the degree of upgrading after RARP.

    The mean age and prostate-specific antigen (PSA) was 63±7.5 years, 8.9±8.77 ng/mL, respectively. Median follow-up was 59 months (interquartile range, 47–70 months). On multivariable analysis, age, PSA, PSA density and ≥2 cores positive were predictors of upgrading with (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01–1.06; p=0.003; OR, 1.006; 95% CI, 1.01–1.11; p=0.018; OR, 0.65; 95% CI, 0.43–0.98, p=0.04), respectively. On subanalysis, only PSA level of 10–20 ng/mL is associated with upgrading into GS ≥8. They also had lower biochemical recurrence free survival, cancer specific survival, and overall survival (p≤0.001, p=0.003, and p=0.01, respectively).

    Gleason score 6 patients with PSA (10–20 ng/mL) have an increased risk of upgrading to pathologic GS (≥8 ), subsequently poorer oncological outcome thus require a stricter follow-up. These patients should be carefully counseled in making an optimal treatment decision.

  4. #74
    Can single positive core prostate cancer at biopsy be considered a low-risk disease?



    Prostate cancer (PCa) may be a multifocal or bilateral disease. A single positive biopsy core is usually associated with indolent PCa, and doctors may choose to perform active surveillance or focal therapy. We investigated the correlation between finding a single positive biopsy core and the pathological outcome after radical prostatectomy (RP).

    Data from the Michinoku Japan Urological Cancer Study Group database including pre- and post-operative information, on 1928 consecutive patients with PCa treated with RP alone at four institutions was used. Among them, 503 patients with a single positive core PCa were followed up, and the clinical and pathological parameters influencing prognosis were analyzed.

    Of the 503 patients, 258 (51.3%) had pathological findings ≥ pT2c and 160 (32%) had an undergraded Gleason Score (GS) based on their biopsy findings. A total of 112 patients (39.5%) with clinical T1c developed bilateral tumors (pT2c–T3). The rate of developing pT3 tumors in the single positive core group was significantly higher than that of the multiple positive core group. Moreover, there was no significant difference in the number of pT3b patients between the single and multiple positive core PCa groups.

    Based on analysis of radical prostatectomy specimens, positive core PCa can lead to clinically significant disease, with considerable rates of pT3. For patients with PCa and a positive prostate biopsy core, definitive therapy such as RP should be considered.

  5. #75
    Changes in the outcome of prostate biopsies after preventive task force recommendation against prostate-specific antigen screening
    [2018, Full Text]



    The benefits of PSA-based screening for prostate cancer (PCa) are controversial. The Canadian and American Task Forces on Preventive Health Care (CTFPHC & USPSTF) have released recommendations against the use of routine PSA-based screening for any men. We thought to assess the impact of these recommendations on the outcomes and trends of prostate needle biopsies.

    A complete chart review was conducted for all men who received prostate needle biopsies at McGill University Health Center between 2010 and 2016. Of those, we included 1425 patients diagnosed with PCa for analysis. We Compared 2 groups of patients (pre and post recommendations’ release date) using Welch’s t-tests and Chi-square test. A multivariate logistic regression model was used to analyze variables predicting worse pathological outcomes.

    When the release date of the USPSTF draft (October 2011) was used as a cut-off, we found an average annual decrease of 10.6% in the total number of biopsies. The median (IQR) baseline PSA levels were higher in post-recommendations group (n = 977) when compared to pre-recommendations group (n = 448 ) [8 ng/ml (5.7–12.9) versus 6.4 ng/ml (4.9–10.1), respectively. P = 0.0007]. Also, post-recommendations group’s patients had higher Gleason score (G7: 35.4% versus 28.4% and G8-G10: 31.2% versus 18.1%, respectively. P < 0.0001). Moreover, they had higher intermediate and high-risk PCa classification (36.4% versus 32.8% and 35.5% versus 22.1%, respectively. P < 0.0001). The recommendations release date was an independent variable associated with higher Gleason score in prostate biopsies (OR: 2.006, 95%CI: 1.477–2.725). Using the CTFPHC recommendations release date (October 2014) as a cut-off in further analysis, revealed similar results.

    Our results revealed a reduction in the number of prostate needle biopsies performed over time after the recommendations of the preventive task forces. Furthermore, it showed a significant relative increase in the higher risk PCa diagnosis. The oncological outcomes associated with this trend need to be examined in further studies.

  6. #76
    The Stockholm3 blood-test predicts clinically-significant cancer on biopsy: independent validation in a multi-center community cohort


    Several blood-based tests have been suggested to improve prostate cancer testing. The Stockholm3 test has been shown to reduce the number of prostate biopsies, to decrease detection of low-grade cancer and to maintain the detection rate of ISUP Gleason Group (GG) ≥ 2 cancer in a screening-by-invitation setting. We aimed to validate the performance of the Stockholm3 test in an independent, clinical practice cohort.

    The study-population consisted of 533 men in ages 45–75 without previous diagnosis of prostate cancer scheduled for prostate biopsy at any of three centers in Norway and Sweden. Blood samples for Stockholm3 analysis were drawn prior to systematic prostate biopsies. Clinically significant prostate cancer was defined as any finding of ISUP Grade Group (GG) 2 or higher. We calculated area under the curve (AUC) for predicting prostate cancer at biopsy and calculated. Models including PSA and PSA-density (PSA/prostate volume) were compared to a model including also clinical information, protein levels and single nucleotide polymorphisms (SNP).

    263 of 533 (49%) participants were diagnosed with prostate cancer. 162 men had prostate cancer with GG ≥ 2. The Stockholm3 test discriminated better for GG ≥ 2 prostate cancer than PSA in combination with PSA-density AUC 8.9 (95% CI 82.7–89.2) and AUC 74.8 (95% CI 70.3–79.3). Using a Stockholm3 cut-off of 10% risk of GG ≥ 2 cancer, 38% of the biopsy procedures were saved, however delaying diagnosis for 6% (n = 10) of men with GG ≥ 2 cancer. Using PSA-density 0.1 as cut-off for biopsy saved 35% of biopsies, delaying diagnosis for 16% (n = 26) of men with GG ≥ 2 cancer.

    A prediction model including clinical information, protein levels and SNPs was independently validated in a clinical practice cohort and reduces the number of un-necessary biopsies while delaying diagnosis for a limited number of men.

  7. #77
    How many cores are needed to detect clinically significant prostate cancer on targeted MRI-ultrasound fusion biopsy? [2018]


    See Table in the Abstract that shows how the detection rate increases with the number of cores.

    Background: The optimal number of MRI-US fusion biopsy cores to adequately sample regions of interest (ROI) remains unknown. To better understand the optimal approach to lesion targeting, we aimed to examine the cancer detection rate based on sequential number of cores obtained. Methods: Of 744 patients undergoing MRI-US fusion biopsy between 2012 and 2016 at our institution, we identified 628 men with targets on multi-parametric MRI (mpMRI) who underwent targeted and systematic fusion biopsy using the Artemis platform for clinical suspicion (n=465) or known history of PCa (n=163). mpMRI studies were reviewed by genitourinary radiologists using a 3-tiered Likert scale and PI-RADS classification schema. Biopsy was performed by two urologists performing a high volume of fusion biopsies (PS and RD). Cores were taken sequentially from each ROI with an even distribution. The primary outcome was the proportion of high-grade (Gleason ≥3+4) cancers missed on a 2-core lesion biopsy. Results: We biopsied 1,233 ROI with a median of 5 cores (IQR 3-5) from each ROI. A total of 581 ROI (47%) were positive for any Gleason grade PCa, in 380 (61%) patients. On a per-lesion basis, 84% of any Gleason score cancers were detected with a two-core biopsy and 77% of Gleason ≥3+4 tumors. Cancer detection rates improved with increasing number of cores (Table 1). For any Gleason grade PCa, additional cores beyond 5 cores had no significance. For G≥3+4 cancer, there was no significance with additional sampling from 3 to 4 cores, but improved detection from 3 to 5 cores (P<0.05). For PI-RADs 4 and 5 lesions, additional sampling up to 4 cores significantly improves G≥3+4 detection, while for PI-RADs 1-3 lesions sampling up to 2 cores improves detection. Conclusions: On a per-lesion basis, sampling two cores of mpMRI-evident lesions at the time of fusion biopsy misses nearly one-quarter of clinically significant PCa that would be detected on additional sampling.

    MRI/US fusion-guided prostate biopsy allows for equivalent cancer detection with significantly fewer needle cores in biopsy-naive men [2018, Full Text]



    We aimed to investigate the efficiency and cancer detection of magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided prostate biopsy in a cohort of biopsy-naive men compared with standard-of-care systematic extended sextant transrectal ultrasonography (TRUS)-guided biopsy.

    From 2014 to 2016, 72 biopsy-naive men referred for initial prostate cancer evaluation who underwent MRI of the prostate were prospectively evaluated. Retrospective review was performed on 69 patients with lesions suspicious for malignancy who underwent MRI/US fusion-guided biopsy in addition to systematic extended sextant biopsy. Biometric, imaging, and pathology data from both the MRI-targeted biopsies and systematic biopsies were analyzed and compared.

    There were no significant differences in overall prostate cancer detection when comparing MRI-targeted biopsies to standard systematic biopsies (P = 0.39). Furthermore, there were no significant differences in the distribution of severity of cancers based on grade groups in cases with cancer detection (P = 0.68 ). However, significantly fewer needle cores were taken during the MRI/US fusion-guided biopsy compared with systematic biopsy (63% less cores sampled, P < 0.001)

    In biopsy-naive men, MRI/US fusion-guided prostate biopsy offers equal prostate cancer detection compared with systematic TRUS-guided biopsy with significantly fewer tissue cores using the targeted technique. This approach can potentially reduce morbidity in the future if used instead of systematic biopsy without sacrificing the ability to detect prostate cancer, particularly in cases with higher grade disease.
    Flagged by Forum Brother Info Gathering.

  8. #78
    Which Patients with Negative Magnetic Resonance Imaging Can Safely Avoid Biopsy for Prostate Cancer? [2018]



    To determine if there is a sub-set of men who can avoid prostate biopsy (PBx), based on multi-parametric MRI (mpMRI) and clinical characteristics.

    Materials and Methods
    Of 1,149 consecutive men undergoing PBx (10/2011–03/2017), 135 had a pre-biopsy negative mpMRI (Prostate Imaging-Reporting and Data System score<3). Detection rates of clinically-significant prostate cancer (CSPCa) were evaluated according to PSA density (PSAD) and prior biopsy history. CSPCa was defined as Grade Group ≥ 2. Multivariable logistic regression analysis was performed to identify predictors for non-CSPCa on biopsy.

    PCa and CSPCa detection rates were 38% and 18%, respectively. Men with biopsy-detected CSPCa had smaller prostates (p=0.004), higher PSAD (p=0.02) and no history of prior negative biopsy (p=0.01) compared to the non-CSPCa cohort. PSAD<0.15ng/mL/cc (p<0.001) and prior negative biopsy (p=0.005) were independent predictors of absence of CSPCa on biopsy. Negative predictive value of mpMRI for biopsy-detection of CSPCa improved with decreasing PSAD, primarily in men with prior negative biopsy (p=0.001), but not for biopsy-naοve men. Thirty-two percent of men had the combination of negative mpMRI, PSAD<0.15ng/mL/cc and negative prior biopsy; none had CSPCa on repeat biopsy. Incidence of biopsy-identified CSPCa in men with negative mpMRI only; men with negative mpMRI and PSAD<0.15ng/mL/cc; and men with negative mpMRI, PSAD <0.15ng/mL/cc and negative prior biopsy was 18%, 10% and 0%, respectively.

    We propose a sub-set of men (with negative mpMRI, PSAD<0.15ng/mL/cc and prior negative biopsy) who may safely avoid re-biopsy. Conversely, PBx should be considered in biopsy-naοve men, regardless of negative mpMRI, particularly those with PSAD>0.15ng/mL/cc.
    [Emphasis mine]

    My take on this is this statement is that when a targeted first-time biopsy is done, it should be 12 cores plus and not just a few cores in the identified targets.

  9. #79
    Pain during Transrectal Ultrasound-Guided Prostate Biopsy and the Role of Periprostatic Nerve Block: What Radiologists Should Know
    [2014, Full Text]


    Early prostate cancers are best detected with transrectal ultrasound (TRUS)-guided core biopsy of the prostate. Due to increased longevity and improved prostate cancer screening, more men are now subjected to TRUS-guided biopsy. To improve the detection rate of early prostate cancer, the current trend is to increase the number of cores obtained. The significant pain associated with the biopsy procedure is usually neglected in clinical practice. Although it is currently underutilized, the periprostatic nerve block is an effective technique to mitigate pain associated with prostate biopsy. This article reviews contemporary issues pertaining to pain during prostate biopsy and discusses the practical aspects of periprostatic nerve block.
    From the Full Text:

    Current Recommendations

    Periprostatic nerve block provides effective anesthesia with unequivocal efficacy, and it is recommended as a routine adjunct to mitigate pain in patients undergoing TRUS-guided prostate biopsy (79). If the periprostatic nerve block is to be used selectively, identification of patients with high risk of exaggerated pain associated with prostate biopsy is essential. An optimal periprostatic nerve block is achieved by using a combination of bi-basal and apical injections, and if required, augmenting with lateral injections. The topical perianal-intrarectal anesthetic application combined with the periprostatic nerve block ensures optimal pain control during TRUS-guided prostate biopsy (43, 56).

  10. #80
    The U Shape of Prostate-specific Antigen and Prostate Cancer-specific Mortality in High-grade Metastatic Prostate Adenocarcinoma
    [2018, Full Text]



    Accumulated evidence suggests that metastatic prostate cancer (mPCa) with a low prostate-specific antigen (PSA) level may be a unique entity. However, its clinical features and prognosis have not been fully evaluated.

    To investigate the clinical features of low-PSA mPCa and the impact of low PSA level on overall survival (OS) and PCa-specific mortality (PCSM) of mPCa.

    Design, setting, and participants
    A total of 8479 mPCa patients were retrieved from the Surveillance, Epidemiology, and End Results program (2010–2015). The median follow-up was 18 mo.

    Outcome measurements and statistical analysis
    Cox regression and Fine-Gray competing risk were used to calculate the hazard ratio (HR) and subdistribution hazard ratio (sHR) for OS and PCSM, respectively.

    Results and limitations
    A higher rate of T4 stage disease (19.8%) and visceral metastasis (18.2%) and the shortest median OS (34 mo) were observed in mPCa patients with Gleason 8–10 and PSA ≤4 ng/ml. In the Cox regression model, PSA ≤4 ng/ml was a significant predictor of OS for Gleason 8–10 disease. The distribution of PCSM by PSA was U-shaped for Gleason score 8–10 (PSA 4.1–10 ng/ml as the referent), with an adjusted sHR of 1.52 for PSA ≤4.0 ng/ml (95% confidence interval: 1.17–1.96) versus 0.99 for PSA 10.1–20 ng/ml and 1.35 for PSA >20 ng/ml. In contrast, the distribution of PCSM by PSA was linear for Gleason 5–7. Sensitivity analyses showed similar results in Gleason 9–10 and Gleason 10 subgroup. The study is limited by its retrospective design.

    Low PSA, high-grade mPCa has a higher proportion of T4 stage disease, visceral metastasis, and PCSM.

    Patient summary
    We found that 2.8% of high-grade metastatic prostate cancer has a prostate-specific antigen level ≤4 ng/ml at diagnosis. This population has aggressive clinical features and a poor cancer-specific outcome. Our results highlighted this under-reported population, and the management of these patients warrants further research.
    [Emphasis mine]


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