Non-invasive Urine Test for Molecular Classification of Clinical Significance in Newly Diagnosed Prostate Cancer Patients

Objective: To avoid over-treatment of low-risk prostate cancer patients, it is important to identify clinically significant and insignificant cancer for treatment decision-making. However, no accurate test is currently available.Methods: To address this unmet medical need, we developed a novel gene classifier to distinguish clinically significant and insignificant cancer, which were classified based on the National Comprehensive Cancer Network risk stratification guidelines. A non-invasive urine test was developed using quantitative mRNA expression data of 24 genes in the classifier with an algorithm to stratify the clinical significance of the cancer. Two independent, multicenter, retrospective and prospective studies were conducted to assess the diagnostic performance of the 24-Gene Classifier and the current clinicopathological measures by univariate and multivariate logistic regression and discriminant analysis. In addition, assessments were performed in various Gleason grades/ISUP Grade Groups.Results: The results showed high diagnostic accuracy of the 24-Gene Classifier with an AUC of 0.917 (95% CI 0.892–0.942) in the retrospective cohort (n = 520), AUC of 0.959 (95% CI 0.935–0.983) in the prospective cohort (n = 207), and AUC of 0.930 (95% 0.912-CI 0.947) in the combination cohort (n = 727). Univariate and multivariate analysis showed that the 24-Gene Classifier was more accurate than cancer stage, Gleason score, and PSA, especially in the low/intermediate-grade/ISUP Grade Group 1–3 cancer subgroups.Conclusions: The 24-Gene Classifier urine test is an accurate and non-invasive liquid biopsy method for identifying clinically significant prostate cancer in newly diagnosed cancer patients. It has the potential to improve prostate cancer treatment decisions and active surveillance.

Transrectal ultrasound features and biopsy outcomes of transition PI-RADS 5

Background Transition Prostate Imaging and Reporting and Data System (PI-RADS) 5 is easily detected owing to typical magnetic resonance imaging features. However, it is unclear as to how transition PI-RADS 5 appears on transrectal ultrasound (TRUS). Purpose To assess TRUS features of transition PI-RADS 5 and outcomes of TRUS-guided target biopsy. Material and Methods Between March 2014 and November 2018, 186 male patients underwent TRUS-guided biopsy of PI-RADS 5. Of them, 82 and 104were transition and peripheral PI-RADS 5, respectively. Transition and peripheral PI-RADS 5 were compared according to echogenicity (hyperechoic or hypoechoic) and hypoechoic rim (present or absent). Each tumor was targeted with TRUS based on TRUS features. Significant (Gleason score ≥7) and insignificant (Gleason score 6) cancer detection rates (CDRs) were compared between transition and peripheral PI-RADS 5. Standard reference was biopsy examination. Fisher’s exact test was used for statistical analysis. Results Transition PI-RADS 5 was hyperechoic in 89.0% (73/82) and had a hypoechoic rim in 97.6% (80/82), whereas peripheral PI-RADS 5 was hypoechoic in 99.0% (103/104) and had a hypoechoic rim in 26.9% (28/104) (both, P<0.0001). The significant CDRs of transition and peripheral PI-RADS 5 were 56.1% (46/82) and 65.4% (68/104), respectively ( P=0.2263). However, the insignificant CDRs of these categories were 22.0% (18/82) and 8.7% (9/104), respectively ( P=0.0123). Conclusion Transition PI-RADS 5 tends to have hyperechoic echogenicity and a hypoechoic rim. These findings help to target the transition PI-RADS 5 using TRUS. However, transition PI-RADS 5 is confirmed more frequently as insignificant cancer than peripheral PI-RADS 5.

Fine Particulate Matter and Gaseous Compounds in Kitchens and Outdoor Air of Different Dwellings

Passive diffusion tubes for volatile organic compounds (VOCs) and carbonyls and low volume particulate matter (PM2.5) samplers were used simultaneously in kitchens and outdoor air of four dwellings. PM2.5 filters were analysed for their carbonaceous content (organic and elemental carbon, OC and EC) by a thermo-optical technique and for polycyclic aromatic hydrocarbon (PAHs) and plasticisers by GC-MS. The morphology and chemical composition of selected PM2.5 samples were characterised by SEM-EDS. The mean indoor PM2.5 concentrations ranged from 14 µg m−3 to 30 µg m−3, while the outdoor levels varied from 18 µg m−3 to 30 µg m−3. Total carbon represented up to 40% of the PM2.5 mass. In general, the indoor OC/EC ratios were higher than the outdoor values. Indoor-to-outdoor ratios higher than 1 were observed for VOCs, carbonyls and plasticisers. PAH levels were much higher in the outdoor air. The particulate material was mainly composed of soot aggregates, fly ashes and mineral particles. The hazard quotients associated with VOC inhalation suggested a low probability of non-cancer effects, while the cancer risk was found to be low, but not negligible. Residential exposure to PAHs was dominated by benzo[a]pyrene and has shown to pose an insignificant cancer risk.

Multiparametric MRI in men with clinical suspicion of prostate cancer undergoing repeat biopsy: a prospective comparison with clinical findings and histopathology

Background Multiparametric magnetic resonance imaging (mpMRI) can improve detection of clinically significant prostate cancer (csPCa). Purpose To compare mpMRI score subgroups to systematic transrectal ultrasound-guided biopsies (TRUSbx) and prostate-specific antigen (PSA)-based findings for detection of csPCa in men undergoing repeat biopsies. Material and Methods MpMRI was performed prior to re-biopsy in 289 prospectively enrolled patients. All underwent repeat TRUSbx followed by targeted biopsies (MRITB) of any mpMRI-identified lesion. MpMRI suspicion grade, PSA level, and density (PSAd) were compared with biopsy results and further matched to the radical prostatectomy (RP) specimen if available. Results PCa was detected in 128/289 (44%) patients with median age, PSA, and prior negative TRUSbx of 64 (interquartile range [IQR] = 59–67), 12.0 ng/mL (IQR = 8.3–19.1), and 2 (IQR = 1–3), respectively. TRUSbx detected PCa in 108/289 (37%) patients, of which 49 (45%) had insignificant cancer. MRITB was performed in 271/289 (94%) patients and detected PCa in 96 (35%) with 78 (81%) having csPCa. MpMRI scores showed a high association between suspicion level and biopsy results on both lesion and patient level ( P < 0.001). MpMRI was better than PSA and PSAd ( P < 0.001) to identify patients with missed csPCa. In total, 64/128 (50%) patients underwent RP; 60/64 had csPCa. MpMRI was significantly better in predicting csPCa on RP compared with TRUSbx ( P = 0.019) as MRITB and TRUSbx correctly identified 47/60 (78%) and 35/60 (58%) patients, respectively. Conclusion MpMRI improves detection of missed csPCa and suspicion scores correlate well with biopsy and RP results on both patient and lesion level.

Accuracy of 3 Tesla pelvic phased-array multiparametric MRI in diagnosing prostate cancer at repeat biopsy

Introduction. Multiparametric pelvic magnetic resonance imaging (mpMRI) accuracy in prostate cancer (PCa) diagnosis was evaluated. Materials and Methods. From June 2011 to December 2013, 168 patients (median 65 years) with negative digital rectal examination underwent repeat transperineal saturation biopsy (SPBx; median 28 cores) for persistently high or increasing PSA values, PSA &gt;10 ng/ml or PSA values between 4.1-10 o r 2.6-4 ng/ml with free/total PSA &lt; 25% and &lt; 20%, respectively. All patients underwent mpMRI using a 3.0 Tesla scanner equipped with surface 16 channels phased-array coil and lesions suspicious for PCa were submitted to additional targeted biopsies. Results. A T1c PCa was found in 66 (39%) cases; SPBx and mpMRI-suspicious targeted biopsy diagnosed 60 (91%) and 52 (78.8%) cancers missing 6 (all of the anterior zone) and 14 cancers (12 and 2 of the lateral margins and anterior zone), respectively; in detail, mpMRI missed 12 (18.1%) PCa charaterized by microfocal (1 positive core with greatest percentage of cancer and Gleason score equal to 5% and 6, respectively) disease at risk for insignificant cancer. The diameter of the suspicious mpMRI lesion was directly correlated to the diagnosis of PCa with poor Gleason score (p &lt; 0.05); detection rate of cancer for each suspicious mpMRI core was 35.3%. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive value of mpMRI in diagnosing PCa was 75.7%, 82.5%, 71.8%, 78.9%, 87.9%, respectively. Conclusion. Multiparametric pMRI improved SPBx accuracy in diagnosing significant anterior PCa; the diameter of mpMRI suspicious lesion resulted significantly predictive of aggressive cancers.