Negative Digital Rectal Examination Research Articles

Filamin A Is a Prognostic Serum Biomarker for Differentiating Benign Prostatic Hyperplasia from Prostate Cancer in Caucasian and African American Men.

Prostate cancer represents a significant health risk to aging men, in which diagnostic challenges to the identification of aggressive cancers remain unmet. Prostate cancer screening is driven by the prostate-specific antigen (PSA); however, in men with benign prostatic hyperplasia (BPH) due to an enlarged prostate and elevated PSA, PSA's screening utility is diminished, resulting in many unnecessary biopsies. To address this issue, we previously identified a cleaved fragment of Filamin A (FLNA) protein (as measured with IP-MRM mass spectrometry assessment as a prognostic biomarker for stratifying BPH from prostate cancer and subsequently evaluated its expanded utility in Caucasian (CA) and African American (AA) men. All men had a negative digital rectal examination (DRE) and PSA between 4 and 10 ng/mL and underwent prostate biopsy. In AA men, FLNA serum levels exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.71 AUC and 12.2 OR in 48 men with BPH and 60 men with PCa) and outperformed PSA (0.50 AUC, 2.2 OR). In CA men, FLNA serum levels also exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.74 AUC and 19.4 OR in 191 men with BPH and 109 men with PCa) and outperformed PSA (0.46 AUC, 0.32 OR). Herein, we established FLNA alone as a serum biomarker for stratifying men with BPH vs. those with high Gleason (7-10) prostate cancers compared to the current diagnostic paradigm of using PSA. This approach demonstrates clinical actionability of FLNA alone without the requirement of prostate volume measurement as a test with utility in AA and CA men and represents a significant opportunity to decrease the number of unnecessary biopsies in aggressive prostate cancer diagnoses.

Interim analyses from the PROSPET-BX trial: [G8Ga]PSMA PET/CT vs. mpMRI in patients with suspicion of prostate cancer and previous negative biopsy.

282 Background: Herein we present the results of the interim analyses of our prospective trial (Identifier: NCT05297162), designed to compare [68Ga]PSMA PET/CT with mpMRI in men with a high suspicion of prostate cancer (PCa) after at least one previous negative biopsy. Methods: From April 2022 until September 2023, overall, 94 patients were screened, 78 were enrolled and 64 completed all study investigations. Inclusion criteria: PSA>4.0ng/ml; free-to-total PSA ratio <20%; progressive rise of PSA levels in two consecutive samples; at least one previous negative biopsy; negative digital rectal examination. [68Ga]PSMA PET/CT and 3T mpMRI were performed within one month, followed by TRUS-fusion prostate biopsy. Target lesions were defined based on PI-RADS v2.1 for mpMRI and Primary Score, SUVmax and SUVratio for [68Ga]PSMA PET/CT, then correlated to pathology findings. Results: Median age was 64 years (range 51-83) and median PSA 10.4 ng/ml (range 4.3-25,9). Most patients (76.6%) had one previous negative biopsy. According to re-biopsy results, 10 patients presented with clinically significant PCa (csPCa), 4 with GS 6, while the majority had a negative biopsy (78%). mpMRI results were: 40 patients with PI-RADS 2 (62.5%), 3 with PI-RADS 3 (4.7%), 15 with PI-RADS 4 (23.4%), and 6 with PI-RADS 5 (9.4%). Primary scores were: 45 score 1-2 (70%), and 19 score 3-5. PI-RADS and Primary scores were significantly correlated (P=0.0006). Median SUVmax and SUVratio were 3.7 and 1.35 for benign versus 8.9 and 3 for malignancy, respectively (P<0.001). ROC analyses identified optimal cut-off points for csPCA, with SUVmax>7.48 (AUC 0.756; 95%CI 0.633-0.855) and SUVratio>2.79 (AUC 0.748; 95%CI 0.624-0.848). PI-RADS, Primary score, SUVmax and SUVratio proved significantly associated to biopsy results. When combining [68Ga]PSMA PET/CT with mpMRI data, the detection rate was 90% for csPCa, and the combination of both modalities could spare 87.5% of unnecessary re-biopsies. Conclusions: In these interim results, [68Ga]PSMA PET/CT parameters predict biopsy results as mpMRI in patients who are candidates to re-biopsy; the combination of both modalities can spare most unnecessary re-biopsies, by granting a 90% detection rate for csPCa. Clinical trial information: NCT05297162 .

Triad of serum PSA, DRE and biopsy in diagnosing prostatic diseases- How useful it is?

Prostate specific antigen (PSA) is a glycoprotein produced by prostatic acini and prostatic tissue. Its concentration increases in prostatic diseases. Concentration above 4 ng/ml is considered abnormal but there is no clear-cut point between normal and abnormal PSA levels. PSA is considered as serum marker for prostatic cancer but it is organ specific, not cancer specific. Digital rectal examination (DRE) is a routine part of prostate cancer screening. Biopsies are performed when PSA test and DRE are abnormal. The study is an attempt for comparative analysis among serum PSA, age, DRE, and biopsy results for the institution of specific treatment at an early stage. Study was performed on 200 patients with different prostatic lesions in the Department of Pathology, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh. Clinical, DRE, PSA and histopathological biopsy were performed and analyzed by correlating the data. In our study 77.5% had normal (0-4 ng/ml) PSA level and 13.5% had >10 ng/ml PSA levels. BPH was the most common diagnosis (54.0%), followed by prostatitis (20.0%), BPH with prostatitis in 16.0% and carcinoma (10.0%). Serum PSA with positive DRE ranged from 1.2 ng/ml to 56 ng/ml while in negative DRE ranged from 0.18 ng/ml to 9.6 ng/ml. PSA is specific for prostate but not for prostatic diseases. With increasing age serum PSA also increases. Conjunction of serum PSA with other variables like age, DRE and biopsy makes a better diagnosis of prostatic diseases.

Targeted prostate biopsy: 68Ga-PSMA PET/CT vs. mpMRI in the diagnosis of prostate cancer.

To evaluate the diagnostic accuracy of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomog-raphy (PET/CT) vs. multiparametric magnetic resonance imaging (mpMRI) targeted biopsy (TPBx) in the diagnosis of clinical-ly significant prostate cancer (csPCa: Grade Group ≥ 2). From January 2021 to June 2022, 100 patients (median age: 66 years) with negative digital rectal examination underwent transperineal prostate biopsy for abnor-mal PSA values (median 7.5 ng/ml). Before prostate biopsy, all patients underwent mpMRI and 68Ga-PET/CT examinations and mpMRI (PI-RADS version 2 ≥ 3) or 68Ga-PET/CT index lesions suspicious for cancer (SUVmax > 5 g/ml) underwent cognitive targeted cores (mpMRI-TPBx and PSMA-TPBx: four cores) combined with extended systematic prostate biopsy (eSPBx: median 18 cores). The procedure was performed transperineally using a tru-cut 18-gauge needle under sedation and antibiotic prophylaxis. PCa was found in 58/100 (58.0%) men; in detail, 44/58 (75.9%) were csPCa; mpMRI and 68Ga-PSMA showed 66/100 (66%) and 62/100 (60%) lesions suspicious for PCa, respectively. 68Ga-PSMA-TPBx vs. mpMRI-TPBx vs. eSPBx diagnosed 42 (95.4%) vs. 36 (81.8%) vs. 30 (68.2%) csPCa, respectively; mpMRI-TPBx vs. 68Ga-PSMA-TPBx showed a diagnostic accuracy of 76.9% vs. 84.9% in diagnosing csPCa. 68GaPSMA PET/CT TPBx demonstrated good accuracy in the diagnosis of csPCa, which was not inferior to mpMRI TPBx (84.9% vs. 76.9%) improving the detection rate for cancer of systematic biopsy.

Digital Rectal Examination in Stockholm3 Biomarker-based Prostate Cancer Screening

BackgroundPathological digital rectal examination (DRE) is suggestive of prostate cancer but has low sensitivity and specificity. DRE is incorporated in many clinical risk calculators, but there is less evidence on how DRE performs in the setting of blood biomarkers and polygenic risk prediction models other than prostate-specific antigen (PSA) associated with prostate cancer. The Stockholm3 test combines a blood test and clinical variables including DRE. ObjectiveTo assess the predictive performance of DRE for finding clinically significant prostate cancer in systematic biopsy and evaluate its added value to the multivariable diagnostic test Stockholm3. Design, setting, and participantsThis population-based study in the screening by invitation setting included 5543 men aged 50–69 yr with PSA ≥3 ng/ml who were referred for systematic prostate biopsy between 2012 and 2015. The STHLM3 study is registered with ISRCTN.com as ISRCTN84445406. Outcome measurements and statistical analysisPredictive performance was assessed via estimates of sensitivity and specificity and in logistic regression. Clinically significant cancer was defined as International Society of Urological Pathology grade group ≥2 (GG ≥2) cancer on systematic biopsy. Results and limitationsWe found that 11% of men with PSA ≥3 ng/ml had a suspicious DRE. A suspicious DRE was associated with a 3.16-fold higher risk (95% confidence interval [CI] 2.83–3.52) of GG ≥2 cancer and greater length of cancer on biopsy. The risk of nonsignificant cancer was similar regardless of the DRE finding. The risk of GG ≥2 cancer was 46.2% (95% CI 42.2–50.3%) for men with a suspicious DRE versus 14.6% (95% CI 13.7–15.7%) for men with a negative DRE. The elevated risk of GG ≥2 cancer persisted after adjusting for the other Stockholm3 test parameters (odds ratio 2.88, 95% CI 2.32–3.57). For detection of GG ≥2 cancer among men with PSA ≥3 ng/ml, DRE had sensitivity of 27.8% (95% CI 25.1–30.7%) and specificity of 92.8% (95% CI 92.1–93.6%). ConclusionsIn this screening-by-invitation setting we found that for men with PSA ≥3 ng/ml, a suspicious DRE indicates more than threefold higher risk of harboring significant prostate cancer. DRE as a variable adds significant precision to the Stockholm3 prediction model. Men with a suspicious DRE should be referred for further diagnostic workup, including biopsy. Patient summaryWe investigated the ability of digital rectal examination to predict if a patient has clinically significant prostate cancer. We found that digital rectal examination provides valuable information and can help doctors in making an informed decision on whether to recommend prostate biopsy.

Association between obesity and frequency of high-grade prostate cancer on biopsy in men: A single-center retrospective study.

The present study aimed to investigate the relationship between BMI and the prostate cancer (PCa) risk at biopsy in Italian men. Retrospective analyses of the clinical data of 2,372 consecutive men undergoing ultrasound-guided multicore (≥10) prostate biopsy transrectally between May 2010 and December 2018 were performed. BMIs were categorized, according to Western countries' classification of obesity, as follows: <18.5 kg/m2 (underweight), 18.5-24.99 kg/m2 (normal weight), 25-30 kg/m2 (overweight) and >30 kg/m2 (obese). The distribution of patients undergoing biopsy was compared with a model population from the official survey data. Patient characteristics and the relationships between characteristics were investigated using correlation analysis, ANOVA, Kruskal-Wallis and Dunn's tests. The present study estimated the influence on cancer incidence not only of BMI but also of other patient characteristics using multi-variable logistic modelling and compared, using the models, the expected outcomes for patients who differed only in BMI. From a sample of 2,372 men, the present study enrolled 1,079 men due to a lack of clinical data [such as prostate specific antigen (PSA) and BMI data] in the other patients undergoing prostate biopsy. Their distribution was significantly different from the model distribution with the probability of undergoing biopsy increasing with increasing BMI. The median age was 69.4 years. The median BMI was 26.4 kg/m2, while the median PSA level was 7.60 ng/ml. In total, the biopsies detected PCa in 320 men (29.7%) and high-grade PCa (HGPCa) in 218 men (20.2%). Upon applying the aforementioned Western countries' criteria for BMI categories, there were 4 (0.4%) underweight, 318 (29.5%) of normal weight, 546 (50.6%) overweight, and 211 (19.6%) obese patients. ANOVA/Kruskal-Wallis tests revealed that overweight and obese men were younger than the normal-weight men, while there was no statistical difference in their PSA values. Furthermore, 29.3% of normal-weight men, 29.5% of overweight men and 29.9% of obese men were diagnosed with PCa, while 19.5% of normal-weight men, 20.1% of overweight men and 21.8% of obese men were affected by severe cancer. BMI was found to be positively correlated with PCa risk and negatively correlated with both age and PSA level. Age and PSA level were both positively correlated with PCa risk, while digital rectal examination (DRE) outcome was strongly indicative of PCa discovery if the test outcome was positive. Logistics models attributed a positive coefficient to BMI when evaluated against both PCa risk and HGPCa risk. In patients having a negative DRE outcome who differed only in BMI, logistic regression showed a 60% increased risk of PCa diagnosis in obese patients compared with in normal-weight patients. This risk difference increased when other characteristics were less indicative of PCa (younger age/lower PSA), while it decreased when patient characteristics were more indicative (older age/higher PSA, positive DRE). In conclusion, the present study demonstrated that, in men with higher BMIs, the risk of PCa is higher. The relative difference in risk between low and high BMI is most pronounced in younger patients having a lower PSA level and a negative DRE outcome.

Detection Rate of 68Ga-PSMA PET/CT vs. mpMRI Targeted Biopsy for Clinically Significant Prostate Cancer.

To evaluate the diagnostic accuracy of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) vs. multiparametric magnetic resonance imaging (mpMRI) targeted biopsy (TPBx) in the diagnosis of clinically significant prostate cancer (csPCa: Grade Group ≥2). From January 2021 to January 2022, 45 patients (median age: 67 years) with negative digital rectal examination underwent transperineal prostate biopsy for abnormal PSA values (median 7.3 ng/ml). Before prostate biopsy, all patients underwent mpMRI and 68Ga-PET/CT examinations, which included mpMRI (PI-RADS version 2 ≥3), and 68Ga-PET/CT index lesions suspicious for cancer (SUVmax ≥5 g/ml) underwent cognitive targeted cores (mpMRI-TPBx and PSMA-TPBx: four cores) combined with extended systematic prostate biopsy (eSPBx: median 18 cores). The procedure was performed transperineally using a tru-cut 18-gauge needle under sedation and antibiotic prophylaxis. PCa was found in 29/45 (64.4%) men; in detail, 22/45 (48.9%) were csPCa. 68Ga-PSMA-TPBx vs. mpMRI-TPBx vs. eSPBx missed one (4.5%) vs. four (18.1%) vs. seven (31.8%) csPCa, respectively; mpMRI-TPBx vs. 68Ga-PSMA-TPBx for csPCa showed a diagnostic accuracy of 73.7 vs. 77.5%. 68Ga-PSMA PET/CT TPBx demonstrated good accuracy in the diagnosis of csPCa, which was not inferior to mpMRI-TPBx (77.5 vs. 73.7%), improving the detection rate for cancer in systematic biopsy.

PD65-07 LIFESTYLE MODIFICATIONS AND THEIR EFFECT ON SERUM PROSTATE SPECIFIC ANTIGEN LEVELS

You have accessJournal of UrologyProstate Cancer: Detection & Screening VII (PD65)1 Sep 2021PD65-07 LIFESTYLE MODIFICATIONS AND THEIR EFFECT ON SERUM PROSTATE SPECIFIC ANTIGEN LEVELS Alexandre R. Zlotta, Jimmy Misurka, Katherine Lajkosz, Andrea Mari, Serena Marzario, Cynthia Kuk, Sophie O’Halloran, Alex Zisman, Annette Erlich, Michael Nesbitt, Dhiral Kot, Rob Hamilton, Girish Kulkarni, Nathan Perlis, Anto Finelli, Sigrid Carlsson, and Neil Fleshner Alexandre R. ZlottaAlexandre R. Zlotta More articles by this author , Jimmy MisurkaJimmy Misurka More articles by this author , Katherine LajkoszKatherine Lajkosz More articles by this author , Andrea MariAndrea Mari More articles by this author , Serena MarzarioSerena Marzario More articles by this author , Cynthia KukCynthia Kuk More articles by this author , Sophie O’HalloranSophie O’Halloran More articles by this author , Alex ZismanAlex Zisman More articles by this author , Annette ErlichAnnette Erlich More articles by this author , Michael NesbittMichael Nesbitt More articles by this author , Dhiral KotDhiral Kot More articles by this author , Rob HamiltonRob Hamilton More articles by this author , Girish KulkarniGirish Kulkarni More articles by this author , Nathan PerlisNathan Perlis More articles by this author , Anto FinelliAnto Finelli More articles by this author , Sigrid CarlssonSigrid Carlsson More articles by this author , and Neil FleshnerNeil Fleshner More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002109.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Guidelines recommend to repeat serum Prostate Specific Antigen (PSA) measurement to confirm an elevated value before proceeding with further testing. The effect of diet and lifestyle on repeat PSA levels to minimize false positives has rarely been examined. We aimed here to explore the effects of dietary and lifestyle changes on serum PSA values in men with intermediate PSA levels and normal digital rectal examination (DRE). METHODS: We used a case-control design including 204 men with PSA levels between 2-10ng/ml. 82 men who followed lifestyle changes (intervention group) were matched with 122 men (control group), who did not undergo any lifestyle modifications (avoiding spicy foods, alcohol, caffeine consumption and biking) before repeat PSA. PSA changes between baseline and repeat measurement were compared between the intervention group and controls using the Mann-Whitney U test. Multivariable logistic regression models were used to assess differences in PSA changes below different pre-determined thresholds. Linear mixed models implemented for changes in PSA as a continuous covariate helped visualize the predicted change in PSA from baseline. RESULTS: Age (61.0 vs 60.3 years), prostate volume (52.3 vs 49.0 cc) and PSA levels at baseline (5.83 vs 5.75 ng/ml) in the control and intervention arm, respectively, were not different. Compared to controls, at a median 2.81 months interval (IQR: 1.69-4.61), men in the intervention arm had a significantly lower total PSA on repeat PSA testing (4.14 vs 5.32ng/ml, p<0.001). Lifestyle changes resulted in PSA levels dropping below 4ng/ml in 40% of men with initial PSA 4-10 ng/ml in the intervention group vs 22% in controls (p=0.02). In the 2-4ng/ml range, 45% of men in the intervention group vs 14% in controls had their repeat PSA <2ng/ml (p=0.02). Intervention was an independent predictor of repeat PSA dropping <3ng/ml for men with baseline PSA of 3-10ng/ml (OR 5.39, 95% CI 1.96, 14.8, p=0.001). Limitations include the retrospective design of the study, absence of use of metrics to measure adherence to recommendations and lack of cycling information. CONCLUSIONS: In men with intermediate PSA levels and negative DRE, dietary and lifestyle modifications decrease serum PSA values more, and in a larger proportion than simply repeating the test. Source of Funding: N/A © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1154-e1154 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexandre R. Zlotta More articles by this author Jimmy Misurka More articles by this author Katherine Lajkosz More articles by this author Andrea Mari More articles by this author Serena Marzario More articles by this author Cynthia Kuk More articles by this author Sophie O’Halloran More articles by this author Alex Zisman More articles by this author Annette Erlich More articles by this author Michael Nesbitt More articles by this author Dhiral Kot More articles by this author Rob Hamilton More articles by this author Girish Kulkarni More articles by this author Nathan Perlis More articles by this author Anto Finelli More articles by this author Sigrid Carlsson More articles by this author Neil Fleshner More articles by this author Expand All Advertisement Loading ...

Diagnostic Accuracy of Single-plane Biparametric and Multiparametric Magnetic Resonance Imaging in Prostate Cancer: A Randomized Noninferiority Trial in Biopsy-naïve Men

BackgroundUrological guidelines recommend multiparametric magnetic resonance imaging (mpMRI) in men with a suspicion of prostate cancer (PCa). The resulting increase in MRI demand might place health care systems under substantial stress. ObjectiveTo determine whether single-plane biparametric MRI (fast MRI) workup could represent an alternative to mpMRI in the detection of clinically significant (cs) PCa. Design, setting, and participantsBetween April 2018 and February 2020, 311 biopsy-naïve men aged ≤75 yr with PSA ≤15 ng/ml and negative digital rectal examination were randomly assigned to 1.5-T fast MRI (n = 213) or mpMRI (n = 98). InterventionAll MRI examinations were classified according to Prostate Imaging-Reporting and Data System (PI-RADS) version 2. Men scored PI-RADS 1–2 underwent 12-core standard biopsy (SBx) and those with PI-RADS 4-5 on fast MRI or PI-RADS 3–5 on mpMRI underwent targeted biopsy in combination with SBx. Equivocal cases on fast MRI (PI-RADS 3) underwent mpMRI and then biopsy according to the findings. Outcome measurements and statistical analysisThe primary outcome was to compare the detection rate of csPCa in both study arms, setting a 10% difference for noninferiority. The secondary outcome was to assess the role of prostate-specific antigen density (PSAD) in ruling out men who could avoid biopsy among those with equivocal findings on fast MRI. Results and limitationsThe overall MRI detection rate for csPCa was 23.5% (50/213; 95% confidence interval [CI] 18.0–29.8%) with fast MRI and 32.7% (32/98; 95% CI 23.6–42.9%) with mpMRI (difference 9.2%; p = 0.09). The reproducibility of the study could have been affected by its single-center nature. ConclusionsFast MRI followed by mpMRI in equivocal cases is not inferior to mpMRI in the detection of csPCa among biopsy-naïve men aged ≤75 yr with PSA ≤15 ng/ml and negative digital rectal examination. These findings could pave the way to broader use of MRI for PCa diagnosis. Patient summaryA faster MRI (magnetic resonance imaging) protocol with no contrast agent and fewer scan sequences for examination of the prostate is not inferior to the typical MRI approach in the detection of clinically significant prostate cancer. If our findings are confirmed in other studies, fast MRI could represent a time-saving and less invasive examination for men with suspicion of prostate cancer.This trial is registered at ClinicalTrials.gov as NCT03693703.

The additive value of mpMRI on prostate cancer detection: Comparison between patients with and without a suspicious digital rectal examination (DRE)

PurposeDiagnosis of prostate cancer (CaP) is based on digital rectal examination (DRE) and/or elevated prostate specific antigen (PSA) level. This approach lacks sensitivity and specificity and is associated with many negative biopsies, high rate of diagnosing clinically insignificant disease and lacks accuracy to predict clinically significant (CS) cancer. The addition of multiparametric magnetic resonance imaging (mpMRI) before prostate biopsy reduces the detection of low-grade tumors while improving the detection of CS CaP. Most studies that evaluated mpMRI performance did not separate the DRE status of the examined patients. Therefore, the aim of our study is to investigate whether mpMRI provides similar advantages in detection of CaP according to the DRE findings. Materials and MethodsThis prospective study included patients with clinically suspected CaP that were referred to MRI-fusion biopsy from 2014 to 2019. All patients had mpMRI of the prostate with an index lesion of PIRADS ≥3. Analysis was done comparing systemic and targeted biopsy. Patients were divided into two groups according to the DRE findings (positive or negative DRE) and the primary outcomes were compared between the 2 study groups: detection rate of CaP and the detection rate of CS disease defined as Gleason score ≥ 7. ResultsThe final study cohort included 86 patients: 47 with negative DRE and 39 with positive DRE. Overall cancer detection rate was higher in patients with a positive DRE (70.3% vs 48.9%, P <0.05). In the region of interest a higher overall detection rate and of CS disease was found in those with abnormal DRE (51.3% vs. 40.4% and 48.6% vs. 34.0% respectively). The systematic biopsy analysis showed an overall lower detection rate in the negative DRE group (8.5% vs. 18.9 %). The targeted biopsies detected more cancer and significant tumors per core in patients with positive DRE (29.2% vs. 18.5% and 22.1% vs. 14.5% respectively). ConclusionsPatients submitted to fusion biopsy and have a positive DRE are diagnosed more often with CaP, have higher grade disease and larger tumors. In patients suspicious for CaP and having a significant lesion on mpMRI one should combine targeted and systematic biopsy regardless of the DRE status.

Solitary cerebral metastasis from undiagnosed prostate cancer. Potential role of multiparametric MRI prostate in pre-treatment diagnostic protocols

A 73-year-old man presented with a three-week history of weakness and loss of co-ordination of the left-hand side and weakness of left-hand grip. MRI brain revealed an enhancing lesion in the right parietal lobe, adjacent to the central sulcus, with surrounding oedema and a small satellite lesion in motor cortex. Body CT and FDGPET CT revealed no obvious primary neoplasm. The patient underwent craniotomy with resection of the lesion, subsequent histopathology confirmed a metastatic carcinoma of likely prostate cancer primary origin. The patient was on 5-ARI (Finasteride) for lower urinary tract symptoms that decrease serum PSA levels to half and had benign feeling prostate on digital rectal examination (DRE). Subsequent MRI prostate confirmed presence of a lesion with very high probability of prostate cancer. The patient’s serum Prostate Specific Antigen (PSA) level was 6.8 (13.6 corrected for Finastride) which is relatively low in the context of metastatic disease. Given the recent NICE guidelines of using pre-biopsy multiparametric MRI (mpMRI) for diagnosis of prostate cancer, we suggest that in patients with cerebral metastases of unknown primary, with negative body CT, FDG PET-CT, low PSA and negative DRE, mpMRI prostate should be included in diagnostic protocol in the selected group of men, to enable early diagnosis and performing more suitable and targeted treatment. Keywords: Brain metastasis; prostate cancer; multiparametric MRI; metastasis of unknown origin

Prospective Evaluation of 68Ga-labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography in Primary Prostate Cancer Diagnosis

BackgroundPositron emission tomography (PET)/computed tomography (CT) with 68Ga-labeled prostate-specific membrane antigen ligand (68Ga-PSMA) may represent the most promising alternative to multiparametric magnetic resonance imaging (mpMRI) for prostate cancer (PCa) diagnosis. ObjectiveTo test the diagnostic performance of 68Ga-PSMA PET/CT in this clinical context. Design, setting, and participantsFrom January 2017 to December 2018 we prospectively enrolled 97 patients with persistently elevated prostate-specific antigen and/or Prostate Health Index score, negative digital rectal examination, and previous negative biopsy. We also included patients with either negative mpMRI or contraindications to or positive mpMRI but previous negative biopsy. InterventionPatients underwent 68Ga-PSMA PET/CT with additional pelvic reconstruction. Outcome measurements and statistical analysisThe primary endpoint of the study was the diagnostic performance of 68Ga-PSMA PET/CT in detecting malignant lesions and clinically significant PCa (Gleason score [GS] ≥7). Results and limitations68Ga-PSMA PET/transrectal ultrasound fusion biopsy was performed in 64 of 97 patients (66%) for 114 regions of interest (ROIs). Forty patients (41%) had already undergone mpMRI with either a negative result for PCa (n = 15; 22 ROIs) or a positive mpMRI result but a previous negative biopsy. According to pathology, 23 patients (36%) had evidence of PCa: eight (16 ROIs) with GS 6, 13 (21 ROIs) with GS 7 (3 + 4 or 4 + 3), one (2 ROIs) with GS 8, and one (2 ROIs) with GS 10. Clinically significant PCa was identified in four patients with previous negative mpMRI (25%). PET/CT demonstrated PCa in seven patients (14 ROIs) with previous positive mpMRI and negative biopsy. The median maximum standardized uptake value (SUVmax) and median SUV ratio were significantly higher for PCa lesions than for benign lesions (p < 0.001). Optimal cutoff points obtained for SUVmax (>5.4) and SUV ratio (>2.2) could identify clinically significant PCa with accuracy of 81% and 90%, respectively. ConclusionsIn our cohort of patients with high suspicion of cancer,68Ga-PSMA PET/CT was capable of detecting malignancy and accurately identifying clinically relevant PCa. Patient summaryPositron emission tomography/computed tomography with a 68Ga-labeled ligand for prostate-specific membrane antigen is capable of detecting prostate cancer in patients with a high suspicion of cancer and a previous negative biopsy.

MP74-11 FEASIBILITY AND RELIABILITY OF TELEPHONE FOLLOW-UP AFTER RADICAL PROSTATECTOMY FOR PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy IV (MP74)1 Apr 2020MP74-11 FEASIBILITY AND RELIABILITY OF TELEPHONE FOLLOW-UP AFTER RADICAL PROSTATECTOMY FOR PROSTATE CANCER Matteo Balzarro*, Emanuele Rubilotta, Marilena Gubbiotti, Alberto Diminutto, Simone Francavilla, Chiara Lonati, Antonio Benito Porcaro, Mariaangela Cerruto, Michele Di Nauta, Ester Illiano, Vito Mancini, Luigi Cormio, Elisabetta Costantini, Giuseppe Carrieri, and Alessandro Antonelli Matteo Balzarro*Matteo Balzarro* More articles by this author , Emanuele RubilottaEmanuele Rubilotta More articles by this author , Marilena GubbiottiMarilena Gubbiotti More articles by this author , Alberto DiminuttoAlberto Diminutto More articles by this author , Simone FrancavillaSimone Francavilla More articles by this author , Chiara LonatiChiara Lonati More articles by this author , Antonio Benito PorcaroAntonio Benito Porcaro More articles by this author , Mariaangela CerrutoMariaangela Cerruto More articles by this author , Michele Di NautaMichele Di Nauta More articles by this author , Ester IllianoEster Illiano More articles by this author , Vito ManciniVito Mancini More articles by this author , Luigi CormioLuigi Cormio More articles by this author , Elisabetta CostantiniElisabetta Costantini More articles by this author , Giuseppe CarrieriGiuseppe Carrieri More articles by this author , and Alessandro AntonelliAlessandro Antonelli More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000960.011AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To evaluate the feasibility and reliability of telephone follow-up after radical prostatectomy (RP) for prostate cancer (PC). METHODS: This is a multicenter prospective observational study (January 2017- ongoing). Patients received telephone call 7-10 days before the office evaluation. During the telephone call clinical history and last available PSA were assessed. During office evaluation a urologist performed digital rectal examination (DRE) and was blind to PSA level, a second urologist assessed the PSA and the reported DRE. Correlation between PSA and DRE was performed. Patients were stratified according to PSA levels as follow: Group 1 PSA < 0.2 ng/ml. Group 2 PSA > 0.2 ng/ml. Patients were stratified also according to surgical margin specimen and pT stages. Agreement evaluation was performed. Telephone follow-up satisfaction was assessed by VAS scale. RESULTS: All patients with PSA < 0.2 ng/ml had negative DRE with agreement of 100%. Pts with PSA > 0.2 ng/ml had a positive DRE in 3/34, all pts with PSA <4 ng/ml. The concordance between DRE and PSA in non-biochemical recurrence patients was 100% (461/461), while the concordance between DRE and PSA in biochemical recurrence patients was 8.8% (3/34). Surgical margin specimen and pT stages did not influenced DRE results (Table 1). The patient management between telephone follow-up and in clinic evaluation did not change in all cases with PSA <0.2, while in case of biochemical recurrence could change in 8.8%. Satisfaction rate was high (82%). Stratification of patients according with DRE and PSA levels is reported in table 2. CONCLUSIONS: Telephone follow-up was feasible and reliable in the management of males without biochemical recurrence after RP. While, in case of biochemical recurrence an office evaluation is advisable. Telephone follow-up had high patients’ satisfaction rate. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1135-e1136 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matteo Balzarro* More articles by this author Emanuele Rubilotta More articles by this author Marilena Gubbiotti More articles by this author Alberto Diminutto More articles by this author Simone Francavilla More articles by this author Chiara Lonati More articles by this author Antonio Benito Porcaro More articles by this author Mariaangela Cerruto More articles by this author Michele Di Nauta More articles by this author Ester Illiano More articles by this author Vito Mancini More articles by this author Luigi Cormio More articles by this author Elisabetta Costantini More articles by this author Giuseppe Carrieri More articles by this author Alessandro Antonelli More articles by this author Expand All Advertisement PDF downloadLoading ...

Prostate Volume Index Is Able to Differentiate between Prostatic Chronic Inflammation and Prostate Cancer in Patients with Normal Digital Rectal Examination and Prostate-Specific Antigen Values

Introduction: To assess the association of prostate volume index (PVI), defined as the ratio of the central transition zone volume to the peripheral zone volume, and prostatic chronic inflammation (PCI) as predictors of prostate cancer (PCA) risk in patients presenting with normal digital rectal exam and prostate-specific antigen (PSA) ≤10 ng/mL at baseline random biopsies. Methods: We evaluated patients with a negative digital rectal examination (DRE) and a PSA ≤10 ng/mL who underwent initial baseline prostate biopsy from 2010 to 2017. Parameters evaluated included age, PSA, total prostate volume (TPV), PSA density (PSAD), PVI and PCI. All patients underwent 14 core trans-perineal standard biopsies. The association of factors with the risk of PCA was evaluated by logistic regression analysis, utilizing 2 multivariate models: model I included age, TPV, PVI and PCI; model II included age, PSAD, PVI and PC. Results: Overall, 564 Caucasian patients were included. PCA and PCI were detected in 242 (42.9%) and 129 (22.9%) cases respectively. In patients with PCA, the median PVI was 0.83 (interquartile range [IQR] 0.62–1.04). In patients with PCI, the median PVI was 1.12 (IQR 0.81–1.47). In model I, age (OR 1.080) TPV (OR 0.961), PVI (OR 0.517) and PCI (OR 0.249) were associated with PCA risk. In model II, the age (OR 1.074), PSAD (OR 3.080), PVI (OR 0.361) and PCI (OR 0.221) were associated with PCA risk. Conclusions: Higher PVI and PCI predicted decreased PCA risk in patients presenting with normal DRE, and a PSA ≤10ng/mL at baseline random biopsy. In this subset of patients, PVI is able to differentiate patients with PCI or PCA.

Screening of BRCA2 mutated men for detection of prostate cancer: Preliminary results from a national high volume cancer center.

e16567 Background: Up to 10% of cases of Prostate Cancer (PCa) are hereditary. Germline pathogenic mutations in BRCA2 gene confer the highest risk (2.5 to 8.6 fold in men ≤ 65 yr). Beyond periodic Prostate Specific Antigen (PSA) dosage and digital rectal examination (DRE), a targeted screening for carriers is still undefined. Prostate Health Index (PHI), a combination of the tPSA, fPSA and proPSA tests, may be a more accurate biomarker than PSA only to detect PCa. We evaluated how to better screen BRCA2 mutated men for PCa. Methods: We reviewed the genealogical trees of all women tested positive for germline BRCA2 pathogenic mutation at our clinic. We offered targeted BRCA2 mutational analysis to all first/second degree relative men between 40 and 69 yr. A targeted screening program (annual PSA and PHI dosages and DRE) was proposed to all men tested positive. In case of PSA and/or PHI values out of range ( &gt; 4ng/ml and &gt; 20, respectively) we proceeded with a multiparametric Magnetic Resonance Imaging (mpMRI) and fusion biopsy of suspected lesions. Results: From June 2008 to October 2018 610 breast/ovarian cancer patients had BRCA test: 35 (5.7%) tested positive for BRCA1 pathogenic mutation, 32 (5.2%) for BRCA2 pathogenic mutation. From October 2017 90 relatives were checked for the familial mutation and 24 (27%) (12 women, 12 men) tested positive for BRCA2 mutation. All the 12 men (median age 48 yr, IQR 44 to 60) accepted to join our screening program. During the first year all men had negative DRE. Median PSA was 0.70 (IQR 0.43 to 1.02), median PHI was 17.56 (IQR 11.85 to 24.06). One patient with out of range PHI value already had mpMRI resulted negative. During the second year 4 men underwent screening so far: they had negative DRE. Median PSA was 0.57 (IQR 0.38-0.77), median PHI was 16.88 (IQR 11.87-21.90). Two men had PHI out of range and will undergo mpMRI. Conclusions: An accurate review of the genealogical trees of breast/ovarian cancer BRCA2 mutated patients allows to identify male relatives potentially carriers of the same mutation. These men have a high lifetime risk of PCa and require an appropriate screening, currently absent. Our approach may be leveraged as proof of concept of selection and screening program in carriers of BRCA2 mutations.

Thrombospondin 1 and cathepsin D improve prostate cancer diagnosis by avoiding potentially unnecessary prostate biopsies.

ObjectivesTo investigate and further validate if two novel cancer‐related glycoproteins, discovered by a genetic‐guided proteomics approach, can distinguish benign disease from prostate cancer (PCa) in men with enlarged prostates.Patients and MethodsA retrospective study was performed that included men with a total prostate‐specific antigen (PSA) concentration of 2.0–10 ng/mL, negative digital rectal examination and enlarged prostate (volume ≥35 mL). Serum samples were collected between 2011 and 2016 at a single centre from 474 men before they underwent prostate biopsy. Serum concentrations of thrombospondin 1 (THBS1) and cathepsin D (CTSD) glycoproteins were combined with the percentage of free PSA to total PSA ratio (%fPSA) to predict any or significant cancer at biopsy.ResultsThe multivariable logistic regression model including THBS1, CTSD and %fPSA discriminated among biopsy‐positive and biopsy‐negative patients in the validation set with an area under the curve (AUC) of 0.86 (P < 0.001, 95% confidence interval (CI) 0.82–0.91), while %fPSA alone showed an AUC of 0.64 (P < 0.001, 95% CI 0.57–0.71). At 90% sensitivity for PCa, the specificity of the model was 62%, while %fPSA had a specificity of 23%. For high grade (Gleason score ≥ 7 in prostatectomy specimen) PCa, the specificity was 48% at 90% sensitivity, with an AUC of 0.83, (P < 0.001, 95% CI 0.77 to 0.88). Limitations of the study include the retrospective set‐up and single‐centre cohort.ConclusionsA model combining two cancer‐related glycoproteins (THBS1 and CTSD) and %fPSA can improve PCa diagnosis and may reduce the number of unnecessary prostate biopsies because of its improved specificity for PCa when compared to %fPSA alone.

Prospective performance of the Prostate Health Index in prostate cancer detection in the first prostate biopsy of men with a total prostatic specific antigen of 4–10 ng/mL and negative digital rectal examination

BackgroundThe disadvantage of using total serum prostatic specific antigen (PSA) test for detection of prostate cancer is that it has a low specificity. The low specificity of total PSA (tPSA) test leads to unnecessary prostate biopsies. In this prospective study, we assessed the serum tPSA, free PSA, p2PSA, and the Prostate Health Index (PHI) in the detection of prostate cancer in men with a tPSA of 4–10 ng/mL and a negative digital rectal examination (DRE).Materials and methods101 male outpatients with a serum PSA of 4–10 ng/mL and nonsuspicious DRE for prostate cancer who underwent first transrectal ultrasound with a prostate biopsy were recruited. A blood sample to enable tPSA, free PSA, and p2PSA levels to be calculated was drawn before the prostate biopsy. The diagnosis and detection of high-grade cancer are correlated with the blood sample.ResultsSixteen patients were positive for prostate cancer. All had significantly higher serum 2pPSA and PHI levels than patients with no cancer. A PHI level at 90% sensitivity (cutoff of 34.14) demonstrated a higher area under the receiver operating characteristic curve and more specificity in diagnosis and detection of high-grade prostate cancer than other tests.ConclusionsThe PHI in men with a PSA level of 4–10 ng/mL with negative DRE increased specificity in the detection of prostate cancer. This test is useful in discriminating between patients with or without cancer and also enables the detection of high-grade cancer avoiding unnecessary biopsies.

68Ga-PSMA Positron Emission Tomography/Computerized Tomography for Primary Diagnosis of Prostate Cancer in Men with Contraindications to or Negative Multiparametric Magnetic Resonance Imaging: A Prospective Observational Study

68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography may represent the most promising imaging modality to identify and risk stratify prostate cancer in patients with contraindications to or negative multiparametric magnetic resonance imaging. In this prospective observational study we analyzed 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography in a select group of patients with persistently elevated prostate specific antigen and/or Prostate Health Index suspicious for prostate cancer, negative digital rectal examination and at least 1 negative biopsy. The cohort comprised men with equivocal multiparametric magnetic resonance imaging (Prostate Imaging-Reporting and Data System, version 2 score of 2 or less), or an absolute or relative contraindication to multiparametric magnetic resonance imaging. Sensitivity, specificity and CIs were calculated compared to histopathology findings. ROC analysis was applied to determine the optimal cutoff values of 68Ga labeled prostate specific membrane antigen uptake to identify clinically significant prostate cancer (Gleason score 7 or greater). A total of 45 patients with a median age of 64 years were referred for 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography between January and August 2017. The 25 patients (55.5%) considered to have positive positron emission tomography results underwent software assisted fusion biopsy. We determined the uptake values of regions of interest, including a median maximum standardized uptake value of 5.34 (range 2.25 to 30.41) and a maximum-to-background standardized uptake value ratio of 1.99 (range 1.06 to 14.42). Mean and median uptake values on 68Galabeled prostate specific membrane antigen positron emission tomography/computerized tomography (ie the maximum standardized uptake value or the maximum-to-background standardized uptake value ratio) were significantly higher for Gleason score 7 lesions than for Gleason score 6 or benign lesions (p <0.001). On ROC analysis a maximum standardized uptake value of 5.4 and a maximum-to-background standardized uptake value ratio of 2 discriminated clinically relevant prostate cancer with 100% overall sensitivity in each case, and 76% and 88% specificity, respectively. Our findings support the use of 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography for primary detection of prostate cancer in a specific subset of men.

DIAGNOSTIC VALUE OF SERUM PROSTATE-SPECIFIC ANTIGEN IN PATIENTS WITH POTENTIALLY CURABLE PROSTATIC CARCINOMA

The aim of the paper was to analyze the age structure of patients in whom early diagnosis of prostatic carcinoma was performed. Diagnostic values of total PSA and age-specific PSA were compared. One hundred patients (mean age 67 years) with the negative digital rectal examination and serum PSA levels 4 ng/ml-10 ng/ml were analyzed. In all patients trans-rectal ultrasound guided biopsy (12 biopsy cores) was performed. Serum PSA was measured in the control group as well. Control group consisted of 100 age-matched males (mean age 66), with the good overall health state-human blood donors, with the negative digital rectal examination and PSA levels below 4 ng/ml. Age-specific PSA was analyzed in both groups. PSA was significantly different in patients with benign prostatic hyperplasia compared to the patients with prostatic carcinoma. There was no difference between the PSA and age-specific PSA. Sensitivity and specifity of the age-specific PSA referral range was 92.3% and 16.4%, respectively. Principles of early detection of the prostatic carcinoma were not necessary in 38% of patients. They were not the target population for the early diagnosis of the prostatic carcinoma. Unnecessary prostate biopsies could be reduced up to 16%, using the age-specific PSA. Prostatic carcinoma would be missed in 7.6% of patients. False positive biopsy rate in patients within the referral range of the age specific PSA was 83.8%, so the question remains how the number of unnecessary prostate biopsies could be reduced.

Prostate Health Index density improves detection of clinically significant prostate cancer.

To explore the utility of Prostate Health Index (PHI) density for the detection of clinically significant prostate cancer (PCa) in a contemporary cohort of men presenting for diagnostic evaluation of PCa. The study cohort included patients with elevated prostate-specific antigen (PSA; >2 ng/mL) and negative digital rectal examination who underwent PHI testing and prostate biopsy at our institution in 2015. Serum markers were prospectively measured per standard clinical pathway. PHI was calculated as ([{-2}proPSA/free PSA] × [PSA]½ ), and density calculations were performed using prostate volume as determined by transrectal ultrasonography. Logistic regression was used to assess the ability of serum markers to predict clinically significant PCa, defined as any Gleason score ≥7 cancer or Gleason score 6 cancer in >2 cores or >50% of any positive core. Of 118 men with PHI testing who underwent biopsy, 47 (39.8%) were found to have clinically significant PCa on biopsy. The median (interquartile range [IQR]) PHI density was 0.70 (0.43-1.21), and was 0.53 (0.36-0.75) in men with negative biopsy or clinically insignificant PCa and 1.21 (0.74-1.88) in men with clinically significant PCa (P < 0.001). Clinically significant PCa was detected in 3.6% of men in the first quartile of PHI density (<0.43), 36.7% of men in the IQR of PHI density (0.43-1.21), and 80.0% of men with PHI density >1.21 (P < 0.001). Using a threshold of 0.43, PHI density was 97.9% sensitive and 38.0% specific for clinically significant PCa, and 100% sensitive for Gleason score ≥7 disease. Compared with PSA (area under the curve [AUC] 0.52), PSA density (AUC 0.70), %free PSA (AUC 0.75), the product of %free PSA and prostate volume (AUC 0.79), and PHI (AUC 0.76), PHI density had the highest discriminative ability for clinically significant PCa (AUC 0.84). Based on the present prospective single-centre experience, PHI density could be used to avoid 38% of unnecessary biopsies, while failing to detect only 2% of clinically significant cancers.