Detection Of Prostate Carcinoma Research Articles

A novel rapid detection method for a single-nucleotide substitution mutation derived from canine urothelial and prostatic carcinoma cells present in small amounts in urine sediments.

For early detection of canine urothelial and prostatic carcinoma, we intend to develop and commercialize a simple and rapid detection method for the BRAF V595E mutation, a known mutation in this cancer. Detection of the single-nucleotide substitution in cancer cells contained in urine sediments is effective for early cancer diagnosis. However, urine sediment also contains many normal cells, and when there is a small relative composition of cancer cells, the mutation is difficult to detect by conventional methods other than next-generation sequencing. Our new detection method enables reliable discrimination with the same labor and cost as the PCR method. We compared the results of our new method with the results of the conventional Sanger method for 38 canine urine sediment samples, and the results of 34 samples were consistent between both methods. The remaining four results were all determined to be negative by the Sanger method and positive by our new method. For these four samples, the ratio of the mutated gene to the wild-type gene was estimated using a third-generation sequencer, and the ratio of the mutated gene was 0.1%-1.4%. We postulate that the Sanger method gave a negative result because of the low abundance of the mutated gene in these samples, proving the high sensitivity of our new method.

Study of Core Biopsies of the Prostate with Emphasis on Prostate Carcinoma Detection Rate, Its Quantification and Relation to Serum PSA Level

Study of Core Biopsies of the Prostate with Emphasis on Prostate Carcinoma Detection Rate, Its Quantification and Relation to Serum PSA Level

P024 - Prostate cancer diagnosis composite probability index (pPCacomp): A novel multi-parametric mathematical model for predicting detection and ISUP grading of prostatic carcinoma on TRUS biopsy

P024 - Prostate cancer diagnosis composite probability index (pPCacomp): A novel multi-parametric mathematical model for predicting detection and ISUP grading of prostatic carcinoma on TRUS biopsy

The significance of the extent of tissue embedding for the detection of incidental prostate carcinoma on transurethral prostate resection material: the more, the better?

The aim of this study is to investigate the incidental prostate cancer (iPCa) detection rates of different embedding methods in a large, contemporary cohort of patients with bladder outlet obstruction (BOO) treated with transurethral surgery. We relied on an institutional tertiary-care database to identify BOO patients who underwent either transurethral loop resection or laser (Holmium:yttrium–aluminium garnet) enucleation of the prostate (HoLEP) between 01/2012 and 12/2019. Embedding methods differed with regard to the extent of the additional prostate tissue submitted following the first ten cassettes of primary embedding (cohort A: one [additional] cassette/10 g residual tissue vs. cohort B: complete embedding of the residual tissue). Detection rates of iPCa among the different embedding methods were compared. Subsequently, subgroup analyses by embedding protocol were repeated in HoLEP-treated patients only. In the overall cohort, the iPCa detection rate was 11% (46/420). In cohort A (n = 299), tissue embedding resulted in a median of 8 cassettes/patient (range 1–38) vs. a median of 15 (range 2–74) in cohort B (n = 121) (p < .001). The iPCa detection rate was 8% (23/299) and 19% (23/121) in cohort A vs. cohort B, respectively (p < .001). Virtual reduction of the number of tissue cassettes to ten cassettes resulted in a iPCa detection rate of 96% in both cohorts, missing one stage T1a/ISUP grade 1 carcinoma. Increasing the number of cassettes by two and eight cassettes, respectively, resulted in a detection rate of 100% in both cohorts without revealing high-grade carcinomas. Subgroup analyses in HoLEP patients confirmed these findings, demonstrated by a 100 vs. 96% iPCa detection rate following examination of the first ten cassettes, missing one case of T1a/ISUP 1. Examination of 8 additional cassettes resulted in a 100% detection rate. The extent of embedding of material obtained from transurethral prostate resection correlates with the iPCa detection rate. However, the submission of 10 cassettes appears to be a reasonable threshold to reduce resource utilization while maintaining secure cancer detection.

Usefulness of prostate specific antigen density in detecting prostate carcinoma: A hospital-based study in patients with prostate biopsies

Background: Prostate-specific antigen density has been suggested to enhance the diagnostic efficacy of serum prostate-specific antigen alone in detecting prostate cancer, thereby reducing unnecessary biopsies and associated morbidities. This study aimed to assess the diagnostic performance of prostate-specific antigen density in detecting prostate cancer. Materials and methods: A retrospective analysis of histologically proven benign and malignant prostate diseases, submitted in the histopathology department was performed from April 2019 to March 2020. The diagnostic performance of prostate-specific antigen density was assessed and its optimum cut-off value was determined using the receiver operating characteristic curves. The diagnostic efficacy of prostate-specific antigen density was also compared with prostate-specific antigen in detecting prostate cancer. Results: The AUC to predict prostate cancer was 0.89 (95% CI 0.79-0.98. p &lt;0.001) for prostate-specific antigen density. The diagnostic performance of prostate-specific antigen density at cut-off 0.18 ng/ml/cc was better than prostate-specific antigen alone (AUC, 0.838 vs 0.662). Sensitivity was 80% for both prostate-specific antigen density at cut-off 0.18 ng/ml/cc and prostate-specific antigen. But, prostate-specific antigen density had a higher specificity of 87.7 % than prostate-specific antigen (52.3%)and thus it could better distinguish benign diseases from prostate cancer. It would have reduced unnecessary biopsy by 35%. Conclusions: The diagnostic efficacy of prostate-specific antigen density was good and it was found to be a better predictor of prostate cancer at the cut-off value of 0.18ng/ml/cc when compared to prostate-specific antigen alone.

What’s behind 68Ga-PSMA-11 uptake in primary prostate cancer PET? Investigation of histopathological parameters and immunohistochemical PSMA expression patterns

PurposeProstate-specific membrane antigen (PSMA-) PET has become a promising tool in staging and restaging of prostate carcinoma (PCa). However, specific primary tumour features might impact accuracy of PSMA-PET for PCa detection. We investigated histopathological parameters and immunohistochemical PSMA expression patterns on radical prostatectomy (RPE) specimens and correlated them to the corresponding 68Ga-PSMA-11-PET examinations.MethodsRPE specimens of 62 patients with preoperative 68Ga-PSMA-11-PET between 2016 and 2018 were analysed. WHO/ISUP grade groups, growth pattern (expansive vs. infiltrative), tumour area and diameter as well as immunohistochemical PSMA heterogeneity, intensity and negative tumour area (PSMA%neg) were correlated with spatially corresponding SUVmax on 68Ga-PSMA-11-PET in a multidisciplinary analysis.ResultsAll tumours showed medium to strong membranous (2–3 +) and weak to strong cytoplasmic (1–3 +) PSMA expression. Heterogeneously expressed PSMA was found in 38 cases (61%). Twenty-five cases (40%) showed at least 5% and up to 80% PSMA%neg. PSMA%neg, infiltrative growth pattern, smaller tumour area and diameter and WHO/ISUP grade group 2 significantly correlated with lower SUVmax values. A ROC curve analysis revealed 20% PSMA%neg as an optimal cutoff with the highest sensitivity and specificity (89% and 86%, AUC 0.923) for a negative PSMA-PET scan. A multiple logistic regression model revealed tumoural PSMA%neg (p < 0.01, OR = 9.629) and growth pattern (p = 0.0497, OR = 306.537) as significant predictors for a negative PSMA-PET scan.ConclusionsWe describe PSMA%neg, infiltrative growth pattern, smaller tumour size and WHO/ISUP grade group 2 as parameters associated with a lower 68Ga-PSMA-11 uptake in prostate cancer. These findings can serve as fundament for future biopsy-based biomarker development to enable an individualized, tumour-adapted imaging approach.

Frequency of detection of carcinoma of prostate by TRUS guided core biopsy in patients with PSA level of 4 to 10 ng/ml: A comparison of eight verses fourteen core biopsies.

Objective: To compare the frequency of detection of prostatic carcinoma in patients with prostatic specific antigen level of 4 to 10ng/ml by TRUS guided eight versus fourteen core biopsies in a tertiary care hospital. Study Design: Interventional Comparative study (Randomized Control Trial). Setting: Department of Urology, Jinnah Hospital, and Lahore. Period: January, 2014 to February, 2019. Material &amp; Methods: 340 patients included in the study, according to inclusion criteria, were divided in two groups of 170 patients each. Eight core biopsies were taken in one group and 14 core biopsies were taken in other group by single radiologist to diagnose carcinoma of prostate. Prostatic carcinoma was labeled when pathologist find atypical cells or anaplasia in the biopsy tissues under microscope. Results: Carcinoma of prostate was detected in 123 (36%) patients while rest 217 (64%) showed negative result on histopathology examination. Age of patients in both groups ranged from 40 to 62 years with mean 49.32+5.464 years. The CoP was detected in 55 out of 179 patients younger than 50 years and 68 out of 161 patients older than 50 years. Amongst the 123 patients having been detected CoP, 82 (67%) patients has PSA values ranging 6 to 10 ng/ml while just 41 (33%) has value of 4 to 5 ng/ml. The frequency of detection of CoP among patients having PSA values ranging from 4 to 10ng/ml. by TRUS guided eight core biopsy and fourteen core biopsy group is 17.35% and 18.82% respectively. Conclusion: There is no difference in the frequency of detection of CoP by TRUS guided fourteen core biopsy and eight core biopsy techniques.

Probability of Prostate Cancer Diagnosis following Negative Systematic and Targeted MRI: Transrectal Ultrasound Fusion Biopsy: A Real-Life Observational Study

Introduction: The risk of occult prostate carcinoma (PCa) after negative multiparametric MRI (mpMRI)-transrectal fusion biopsy (F-Bx) is unknown. To determine the false-negative predictive value, we examined PCa detection after prior negative F-Bx. Methods: Between December 2012 and November 2016, 491 patients with suspected PCa and suspicious mpMRI findings underwent transrectal F-Bx. Patients with benign pathology (n = 191) were eligible for our follow-up (FU) survey. Patient characteristics and clinical parameters were correlated to subsequent findings of newly detected PCa. Results: Complete FU with a median of 31 (interquartile range: 17–39) months was available for 176/191 (92.2%) patients. Of those, 54 men had either surgical interventions on the prostate or re-Bxs. Newly detected PCa was evident in 14/176 (7.95%) patients stratified to ISUP ≤2 in 10 and ≥3 in 4 cases. The comparison of patients with newly detected PCa to those without cancerous findings in FU showed significant differences in prostate-specific antigen (PSA) density (0.16 vs. 0.13 ng/mL²) and prostate volume (45 vs. 67 mL, both p < 0.05). Both factors are significant predictors for newly detected cancer after initial negative F-Bx. Conclusion: Only PSA density (>0.13 ng/mL²) and small prostate volume are significant predictors for newly detected PCa after initial negative F-Bx. Despite negative mpMRI/TRUS F-Bx results, patients should be further monitored due to a risk of developing PCa over time. Notwithstanding the limitation of our study that not all patients underwent another Bx, we assume that the false-negative rate is low but existing. Our data represent a real-world scenario.

Predicting Significance of Blood Parameters in Diagnosis of Prostate Carcinoma in a Tertiary Center in Udaipur, Rajasthan

Introduction: In development of cancer chronic inflammation plays a major role. Most established determinants of Prostate Carcinoma (PCa) are modern life style genetics, and age. In the first prostate biopsy, approximately 1 out 5 men i.e., 20% with PCa may be misdiagnosed. Therefore, there is clear requirement of novel markers, which can detect both clinically significant PCa, and prevent unnecessary biopsy. Some solid tumours found to have association of Neutrophil to Lymphocyte Ratio (NLR), Platelate to Lymphocyte Ratio (PLR) and Red-cell Distribution Width (RDW).Aim: Aim of this study was to scrutinise the significance of association of Prostate Specific Antigen (PSA), PLR, NLR and RDW with PCa. Materials and Methods: This study was conducted using the cross-sectional method in the Department of Pathology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan between Jan 2018 to Nov 2020. In this cross-sectional study 84 patients who underwent Tran Rectal Ultrasound (TRUS) guided were included. Complete Blood Count (CBC) was used to determine PLR, NLR and RDW and biochemical test for PSA. Patients were divided into two groups; having benign and malignant pathology. Unpaired t-test, Mann-whitney U test, logistic regression analysis and correlation were performed for statistical analysis. Results: With the use of univariate logistic regression, association between PSA, NLR, PLR, RDW values and PCa detection was determined. We found that serum PSA was significantly more in the PCa group (as BPH and prostatitis are both benign conditions so are kept in nonPCa group) compared to other two groups (p&lt;0.001). There was no statistically significant difference in NLR, PLR and RDW values (p=0.150, p=0.070. p=0.441, respectively was found in nonPCa and PCa group). Conclusion: PSA has statistically significant association with PCa group but PLR, NLR and RDW was not considered to be the significant predictor in benign as well as malignant group.

Serum total prostate-specific antigen (tPSA): correlation with diagnosis and grading of prostate cancer in core needle biopsy.

Aim To investigate the impact of pre-treatment serum total prostate-specific antigen (PSA) level on prevalence of prostate carcinoma detection in prostate core needle biopsy, and its correlation with established prognostic factors. Methods Prostate needle biopsy samples of 115 patients with available pre-treatment serum total PSA (tPSA) level were analysed. For all cases where morphology alone was insufficient, immunohistochemistry was performed using p63, CKHMW and AMACR antibody panel in order to confirm or exclude the existence of prostate carcinoma. Results Statistically significant positive correlation between serum total PSA values and prevalence of finding prostate carcinoma in needle biopsy specimens was found (p=0.011), as well as in the case when the patients were classified into groups according to tPSA levels (p=0.028). Serum total PSA values and levels (level groups) showed significant positive correlation with Gleason score (p=0.029 and p=0.036, respectively) and Grade Group of prostate carcinomas (p=0.044 and p=0.046, respectively). Sensitivity of the screening test by using 4 ng/mL as cut off value for tPSA was 94.12% (CI: 80.32-99.28%), specificity 8.64% (CI: 3.55-17.00%), positive predictive value 30.19% (CI: 21.65-39.87%) and negative predictive value 77.78% (CI: 39.99-97.19%). Conclusion The increase of serum tPSA value increases the likelihood of finding prostate cancer on needle biopsy specimens. Due to such findings and its positive correlation with a grade of prostate cancer, our study indicates that tPSA can still be considered as a useful tool both in detecting and predicting aggressiveness of prostate cancer.

Feasibility of multi-parametric magnetic resonance imaging in detection and local staging of prostatic carcinoma

BackgroundThe objective of this study was to assess the feasibility of multi-parametric magnetic resonance imaging (mpMRI) in detection, localization and local staging of prostate cancer (Pca).MethodsThe study included 58 patients with Pca who underwent mpMRI before radical prostatectomy (RP) at two university hospitals, during the period June 2014 to April 2018. All prostatectomies were performed on the basis of preoperative transrectal ultrasound-guided prostatic biopsies. For tumor localization, the prostate in each patient was divided into six segmental regions. Biopsy specimens, for each segmental region, were evaluated for the presence of cancer. The diagnostic performance of mpMRI in tumor localization as well as extracapsular extension (ECE) and seminal vesicle (SV) invasion of the tumor was evaluated, by using the histopathological findings of RP specimens as reference standard.ResultsThe mean age of patients was 63.45 ± 7.45 years. Of the total number of 348 segmental regions, tumor was detected in 143. From them, cancer was detected in 142 regions by mpMRI. The sensitivity and specificity of mpMRI for cancer localization were 99.30% and 97.56%. On RP specimen, nine cases had ECE and five had SV invasion. All of them were detected preoperatively by mpMRI. The sensitivity and specificity of mpMRI for detection of ECE were 100% and 97.96%. For detection of SV invasion, the sensitivity and specificity were 100% and 98.11%.ConclusionsmpMRI enables localization and staging of cancer prostate with reasonable accuracy. Its combination with ultrasound should be counted on for improvement in efficacy of the prostatic biopsy procedure.

Diagnostic Performance of 68Ga-PSMA-11 Positron-emission-tomography/Computed-tomography in a Large Cohort of Patients with Biochemical Recurrence of Prostate Carcinoma.

Gallium-68 (Ga) prostate-specific-membrane-antigen positron-emission-tomography/computed-tomography is a highly promising method for imaging primary and recurrent prostate cancer. These dual-modality imaging technologies enable whole-body functional and anatomical evaluation in a single session. This study investigated the performance of Ga-prostate-specific-membrane-antigen-11 positron-emission-tomography/computed-tomography for detecting prostate carcinoma in patients with rising prostate-specific-antigen after primary therapy. Six hundred sixty (660) patients with biochemical recurrence referred for positron-emission-tomography/computed-tomography with Ga-prostate-specific-membrane-antigen-11 were evaluated retrospectively. Prostate-specific-antigen-stratified cohorts of pathological scan results were analyzed, and relationships between prostate-specific-antigen kinetics and PSMA-positive tumor lesions were correlated. Gallium-68 prostate-specific-membrane-antigen-11 positron-emission-tomography/computed-tomography showed a pathological prostate-specific-membrane-antigen uptake in 76% (500 of 660 patients). Positive scans were positively associated with prostate-specific-antigen (p<0.001). For patients with prostate-specific-antigen <0.2 ng mL, the PSMA-positive tumor lesions rate was 41%. Patients with prostate-specific-antigen of 0.2-<0.5 ng mL, 0.5-<1.0 ng mL, 1.0-<2.0 ng mL, and 2.0-<5.0 ng mL showed rates of 44.7%, 61.7%, 72.3%, 85.2%, respectively, and for prostate-specific-antigen of ≥5.0 ng mL it increased to 94%. Prostate-specific-antigen velocity was also correlated with PSMA-positive tumor lesions (p<0.001). In contrast, no association was found for prostate-specific-antigen doubling time (p=0.74). PSMA-positive tumor lesions were significantly increased in patients with primary intermediate- (Gleason Score7) and high-risk (Gleason Score>7) vs. low-risk prostate cancer (Gleason Score<7) (p<0.001). Our data confirm the high performance of Ga-prostate-specific-membrane-antigen positron-emission-tomography/computed-tomography for the detection of recurrent prostate cancer. This may alter treatment planning and has been documented in other studies as well.

Diagnostic Accuracy of Prebiopsy Ga-68 PSMA PET/CT in Detecting Primary Prostate Carcinomas with Prostate-Specific Antigen

Background and Aim:Serum prostate-specific-antigen (PSA) guided systematic transrectal ultrasound (TRUS)-guided biopsies are known to have a low predictive value in detection of primary prostate carcinomas (PCa). Our aim was to evaluate the accuracy of gallium-68 (Ga-68) prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) for the detection of PCa with serum PSA <50 ng/ml.Patients and Methods:We retrospective analyzed prebiopsy Ga-68 PSMA PET/CT's of all patients with suspected PCa from October 2019 to March 2020. Several quantitative clinical and PET/CT variables were compared in benign and malignant groups and assessed for significance using an independent t-test. Diagnostic performance of PSMA PET/CT for detection of cancer was evaluated and compared with the diagnostic performance of cancer risk predicting calculator (European Randomized Study for Screening of Prostate Cancer [ERSPC3]). The standard of reference was 12-core TRUS-guided biopsies.Results:Sixty-four patients were included with mean age 70 years (range 48–94 years); mean PSA 15.67 ng/ml (range 1.74–44), mean PSA density 0.32 ng/ml2 (range 0.01–0.99) and mean prostate volume 54.55 cc (range 16.5–182). 64% (n = 41/64) patients had benign histology and 36% (n = 23/64) had carcinoma. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PSMA PET/CT for detecting PCa reported using the prostate cancer molecular imaging standardized evaluation (PROMISE) was 74%, 92%, 85%, 86%, and 86%, respectively. Mean prostate maximum standardized uptake value (SUVmax) was significantly higher in PCa versus Benign lesions (19.56 ± 18.11 vs. 4.21 ± 1.5, P = 0.00001), in patients with PSA >20 ng/ml versus PSA <20 ng/ml (19.1 ± 20.6 vs. 6.01 ± 5.4, P-0.0052), and in patients with Gleason's score (GS) score >7 versus GS ≤7 (28.1 ± 20.3 vs. 10.2 ± 8.9, P-0.010). SUVmax cutoff value of 5.6 on PSMA PET/CT showed a sensitivity of 95% and specificity of 90.9% (area under the curve 0.990, P < 0.0001).Conclusion:Ga-68 PSMA PET/CT can differentiate benign and malignant lesions of the prostate with very high accuracy and when used alongside with ERSPC3 calculator and magnetic resonance imaging, could potentially reduce painful and often unnecessary prostate biopsies.

Untargeted Metabolomic Profile for the Detection of Prostate Carcinoma-Preliminary Results from PARAFAC2 and PLS-DA Models.

Prostate-specific antigen (PSA) is the main biomarker for the screening of prostate cancer (PCa), which has a high sensibility (higher than 80%) that is negatively offset by its poor specificity (only 30%, with the European cut-off of 4 ng/mL). This generates a large number of useless biopsies, involving both risks for the patients and costs for the national healthcare systems. Consequently, efforts were recently made to discover new biomarkers useful for PCa screening, including our proposal of interpreting a multi-parametric urinary steroidal profile with multivariate statistics. This approach has been expanded to investigate new alleged biomarkers by the application of untargeted urinary metabolomics. Urine samples from 91 patients (43 affected by PCa; 48 by benign hyperplasia) were deconjugated, extracted in both basic and acidic conditions, derivatized with different reagents, and analyzed with different gas chromatographic columns. Three-dimensional data were obtained from full-scan electron impact mass spectra. The PARADISe software, coupled with NIST libraries, was employed for the computation of PARAFAC2 models, the extraction of the significative components (alleged biomarkers), and the generation of a semiquantitative dataset. After variables selection, a partial least squares–discriminant analysis classification model was built, yielding promising performances. The selected biomarkers need further validation, possibly involving, yet again, a targeted approach.

Peripheral ganglia in healthy rats as target structures for the evaluation of PSMA imaging agents

BackgroundThe recent implementation of PET with prostate specific membrane antigen (PSMA)-specific radiotracers into the clinical practice has resulted in the significant improvement of accuracy in the detection of prostate carcinoma (PCa). PSMA-expression in ganglia has been regarded as an important pitfall in prostate carcinoma-PET diagnostics but has not found any practical use for diagnosis or therapy.MethodsWe explored this phenomenon and demonstrated the applicability of peripheral ganglia in healthy rats as surrogates for small PSMA positive lesions for the preclinical evaluation of diagnostic PCa PET probes. Healthy rats were measured with PET/CT using the tracers [18F]DCFPyL, [Al18F]PSMA-11 and [68Ga]PSMA-11. Sections of ganglia were stained with an anti-PSMA antibody. [18F]DCFPyL uptake in ganglia was compared to that in LNCaP tumor xenografts in mice.ResultsWhereas [18F]DCFPyL and [68Ga]PSMA-11 were stable in vivo and accumulated in peripheral ganglia, [Al18F]PSMA-11 suffered from fast in vivo deflourination resulting in high bone uptake. Ganglionic PSMA expression was confirmed by immunohistochemistry. [18F]DCFPyL uptake and signal-to-noise ratio in the superior cervical ganglion was not significantly different from LNCaP xenografts.ConclusionsOur results demonstrated the non-inferiority of the novel model compared to conventionally used tumor xenografts in immune compromised rodents with regard to reproducibility and stability of the PSMA signal. Furthermore, the model involves less expense and efforts while it is permanently available and avoids tumor-growth associated animal morbidity and distress. To the best of our knowledge, this is the first tumor-free model suitable for the in vivo evaluation of tumor imaging agents.

Utility of NKX3.1 Immunostaining in the Detection of Metastatic Prostatic Carcinoma on Fine-Needle Aspiration Smears.

NK3 homeobox 1 (NKX3.1) has been increasingly used to diagnose metastatic prostatic carcinoma in histologic samples. However, its utility and reliability in cytologic direct smears have not been studied. A total of 59 fine-needle aspiration (FNA) cases with a definitive diagnosis of metastatic carcinoma from the prostate were included. The cases were grouped based on different Gleason score in their corresponding primary tumors and morphologic variants. For each case, tumor cells were immunostained with NKX3.1, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP) on cell-transferred smears. NKX3.1 was strongly and diffusely positive in all 40 metastatic prostatic adenocarcinomas, including those with ductal features, but negative for the 19 small cell carcinoma (SmCC) cases. NKX3.1 had a better detection rate than PSA (13/50, 26%) and PAP (0/47, 0%). NKX3.1 immunostaining on FNA smears is highly reliable for detecting metastatic prostatic carcinomas of conventional and ductal types but not for SmCC.

A Multicenter Prospective Clinical Trial of 68Gallium PSMA HBED-CC PET-CT Restaging in Biochemically Relapsed Prostate Carcinoma: Oligometastatic Rate and Distribution Compared With Standard Imaging

The purpose of this study is to assess the utility of 68Gallium prostate-specific membrane antigen (PSMA) Division of Radiopharmaceutical Chemistry (DKFZ)-PSMA-11positron emission tomography (PET)-computed tomography (CT), compared with standard imaging, in the detection of recurrent prostate carcinoma in patients with biochemical relapse to determine the prevalence of oligometastatic disease recurrence and its distribution. This is a prospective, multicenter clinical trial of PSMA-HBED PET/CT imaging in patients with early biochemical relapse of prostate carcinoma (median prostate-specific antigen [PSA], 2.55ng/mL) after definitive prostatectomy (152 patients) or radiation therapy (86 patients) with either no lesions or oligometastatic disease on abdominopelvic CT and bone scan (BS). PSMA-HBED PET/CT scan was performed within 8weeks of restaging imaging, and all sites of abnormal PSMA-HBED binding determined as probable or definite for prostate carcinoma were included in the analysis. PSMA positivity was assessed for correlation with Gleason Score, PSA level, and PSA doubling time. Two hundred thirty-eight patients underwent PSMA-HBED PET/CT imaging. In 199 patients with no lesions on restaging CT and BS, 148 patients (74%) demonstrated PSMA-positive lesions, with 113 patients (57%) being oligometastatic. In 39 patients with oligometastatic lesions on restaging CT and BS, 19 patients (49%) were confirmed as oligometastatic on PSMA PET/CT and 16 patients (41%) were upstaged to polymetastatic. The 4 remaining patients (10%) with sites of possible metastatic disease were not confirmed as having prostate carcinoma. Combining the overall group, there were 183 patients (77%) with PSMA-HBED-positive lesions (682 lesions), suggesting prostate carcinoma, of whom 132 patients (55%) were oligometastatic. In the oligometastatic group, PSMA positivity was limited to the pelvis in 65% of patients, involving either the prostate or nodes (American Joint Committee on Cancer stage N1). This study found a positive correlation between PSMA-HBED positivity and PSA levels; no other factors were statistically significant. For patients with biochemical relapse with BS and CT demonstrating either no disease or low-volume disease, there is a high overall prevalence of PSMA PET/CT-positive disease. More than half of the patients were oligometastatic, and of those, disease was confined to the pelvis in nearly two-thirds of patients. This result confirms that PSMA PET/CT is significantly more sensitive than standard restaging imaging, and it may be useful in identifying patients for subsequent targeted therapy.

18F-Fluciclovine PET/CT Detection of Recurrent Prostate Carcinoma in Patients With Serum PSA ≤ 1 ng/mL After Definitive Primary Treatment.

The aims of this study were to report on our initial experience using F-fluciclovine PET/CT to detect recurrent prostate carcinoma in patients with low serum prostate-specific antigen (PSA) after definitive treatment of primary disease and to conduct a preliminary investigation for factors associated with positive scan findings. In this retrospective study, F-fluciclovine PET/CT scans from 28 men with suspected recurrence of prostate carcinoma and PSA values of 1 ng/mL or less were examined to identify the site(s) of disease recurrence. Differences in detection rate for Gleason scores of 7 and greater than 7, T2 and T3 disease, negative and positive surgical margins, and negative and positive seminal vesicle invasion were compared using the Fisher exact test. Mean PSA and mean PSA doubling time of patients with positive scans and negative scans were compared using the independent 2-group t test. At least one site of disease recurrence was identified in 13 (46.4%) of 28 patients. Disease detection rate was significantly higher in patients with history of Gleason score greater than 7 (Fisher exact test, P = 0.004). Mean PSA and PSA doubling time were not significantly different between patients with positive and negative F-fluciclovine PET/CT scans (P = 0.29 and 0.70, respectively). Detection of recurrent prostate cancer using F-fluciclovine PET/CT is possible in patients with low but rising PSA levels of 1 ng/mL or less. In such patients, local and nodal recurrences are more common than distant metastasis, and Gleason score greater than 7 is associated with positive scan results.

Towards sarcosine determination in urine for prostatic carcinoma detection

Sarcosine, a potential biomarker for prostate cancer, can be detected in a solid state enzyme based biosensor using sarcosine oxidase, with particle immobilised reagents. A novel fusion protein of the fluorescent protein, mCherry, sarcosine oxidase (SOx), and the polypeptide R5 (R52-mCherry-SOx-R5-6 H), was explored, which allowed self-immobilization on silica microparticles and long-term (90 days +) retention of activity, even at room temperature. In contrast, commercial wildtype SOx lost activity in a few days. A silica-R52-mCherry-SOx-R5-6H microparticle sensor for determination of sarcosine in urine, linked the SOx coproduct, H2O2, to a measurement catalysed by horseradish peroxidase (HRP) immobilised on silica, in the presence of Amplex Ultrared (AR) to generate fluorescence at 582 nm. Silica microparticles carrying all the reagents (R52-mCherry-SOx-R5-6H, HRP and AR) were used to produce a silica-microparticle biosensor which responded to sarcosine at micromolar levels. Interference by amino acids and uric acid was examined and it was found that the silica-reagent carrying system could be calibrated in urine and responded across the clinically relevant concentration range. This contrasted with similar assays using commercial SOx, where interference inhibited the sarcosine signal measurement in urine. The microparticle biosensor was tested in urine from healthy volunteers and prostate cancer patients, showing higher concentrations of sarcosine in cancer patients consistent with previous reports of elevated sarcosine levels.

Multiparametric MRI and MR Spectroscopic Imaging of Prostate Lesions with Implementation of PI-RADS and Histopathological Correlation: A Prospective Analysis

Introduction Majority of the elderly male population suffers from prostatism due to enlargement of the prostate as a result of what is now regarded as male climacteric. For standardizing multiparametric magnetic resonance imaging (MRI) of the prostate, the European Society of Urogenital Radiology published Prostate Imaging Reporting and Data System (PI-RADS) in 2012. Magnetic resonance spectroscopic imaging (MRSI) uses a strong magnetic field to obtain metabolic information that identifies the relative concentrations of various metabolites in the cell cytoplasm and the extracellular space. Prostate carcinoma is associated with proportionately lower levels of citrate and higher levels of choline and creatine than are seen in benign prostatic hyperplasia (BPH) or in normal prostate. This difference can be detected by MRSI. Aim This study has been undertaken with the objective of finding how reliable MRI is in establishing the diagnosis of lesions of prostate and to correlate the histopathological (HPE) findings of transrectal ultrasound (TRUS)–guided targeted prostate biopsy with the PI-RADS scoring (Version 2) on MRI in patients. Also, the study evaluates the accuracy of MRSI in the detection of prostatic carcinoma in men with elevated prostate-specific antigen (PSA) levels. Materials and Methods A prospective study was undertaken at a tertiary care hospital during a period of 2 years from May 2017 to April 2019 on 50 patients with PSA &gt; 4 ng/dL and with palpable lesion on digital rectal examination. MRI and MRSI were performed with a 1.5-Tesla body MRI system. The pelvic phased-array coil was used for both excitation and signal reception. Imaging was done using standard protocols. Histological material was obtained from prostate chippings from transurethral resection of prostate. Results Fifty patients with elevated PSA levels underwent MRI, MRSI, TRUS-guided biopsy and documented PI-RADS scores. Eight patients had PI-RADS 1 score, 2 patients had PI-RADS 2 score, 8 patients had PI-RADS 3 score, 14 patients had PI-RAD 4 score, and 18 patients had PI-RADS 5 score. Thirty-two patients with PI-RADS 4 and PI-RADS 5 on imaging showed positive for malignancy on HPE, showing significant association on Chi-square test with X2 = 16.412 and p &lt; 0.001 (statistically significant). MRSI detected 36 patients on biopsy proven cases of carcinoma (sensitivity 89.5%, specificity 64%, and accuracy 88%). Conclusion This study showed a very good correlation between positivity of prostate carcinoma on HPE and higher PI-RADS (4 and 5, respectively). PI-RADS overall score had 94% sensitivity compared with components such as diffusion-weighted imaging (DWI, 78%) and T2 hypointensity (72%). MRSI is more sensitive and specific compared with T2-weighted images alone.