Prostate-based biofluids for the detection of prostate cancer: A comparative study of the diagnostic performance of cell-sourced RNA biomarkers

Background Prostate cancer (PCa) diagnosis requires improvement with the aid of more accurate biomarkers. Postejaculate urethral washings (PEUW) could be a physiological equivalent to urine obtained following rectal prostatic massage, the current basis for the prostate cancer antigen 3 (PCA3) test. The aim of this study was to investigate if PEUW contained prostate-based material, evidenced by the presence of prostate specific antigen (PSA), and to evaluate the diagnostic performance of PEUW-based biomarkers. Methods Male patients referred for elevated serum PSA or abnormal digital rectal examination provided ejaculate and PEUW samples. PSA, PCA3, and β2-microglobulin (β2M) were quantified in ejaculate and PEUW and compared with absolute and clinically significant (according to D\u27Amico criteria) PCa presence, as determined by biopsies. Diagnostic performance was determined and compared with serum PSA using receiver operating characteristic analysis. Results From 83 patients who provided PEUW samples, paired analysis with ejaculate samples was possible for 38 patients, while analysis in an unpaired, extended cohort was possible for 62 patients. PSA and PCA3 were detected in PEUW, normalized to β2M, and PCA3:PSA was calculated. In predicting absolute PCa status, PCA3:β2M in ejaculate [area under the curve (AUC) 0.717] and PEUW (AUC 0.569) were insignificantly better than PCA3:PSA (AUC 0.668 and 0.431, respectively) and comparable with serum PSA (AUC 0.617) with similar trends observed for the extended cohort. When considering clinically significant PCa presence, serum PSA in the comparison (AUC 0.640) and extended cohorts (AUC 0.665) was comparable with PCA3: β2M (AUC 0.667) and PCA3:PSA (AUC 0.605) in ejaculate, with lower estimates for PEUW in the comparison (PCA3: β2M AUC 0.496; PCA3:PSA AUC 0.342) and extended (PCA3: β2M AUC 0.497; PCA3:PSA AUC 0.469) cohorts. The statistical analysis was limited by sample size. Conclusion PEUW contains prostatic material, but has limited diagnostic accuracy when considering cell-derived DNA analysis. PCA3-based markers in ejaculate are comparable to serum PSA and digital rectal examination–urine markers

Measurement of SARS-CoV-2 in air and on surfaces in Scottish hospitals

BackgroundThere are still uncertainties in our knowledge of the amount of SARS-CoV-2 virus present in the environment; where it can be found, and potential exposure determinants, limiting our ability to effectively model and compare interventions for risk management.AimThis study measured SARS-CoV-2 in three hospitals in Scotland on surfaces and air, alongside ventilation and patient care activities.MethodsAir sampling at 200 L/min for 20 minutes and surface sampling were performed in two wards designated to treat COVID-19 -positive patients and two non-COVID-19 wards across three hospitals in November and December 2020. FindingsDetectable samples of SARS-CoV-2 were found in COVID-19 treatment wards but not in non-COVID-19 wards. Most samples were below assay detection limits, but maximum concentrations reached 1.7x10 3 genomic copies/m3 in air and 1.9x10 4 copies per surface swab (3.2x10 2 copies/cm2 for surface loading). The estimated geometric mean air concentration (geometric standard deviation) across all hospitals was 0.41 (71) genomic copies/m3 and the corresponding values for surface contamination were 2.9 (29) copies/swab. SARS-CoV-2 RNA was found in non-patient areas (patient/visitor waiting rooms and personal protective equipment (PPE) changing areas) associated with COVID-19 treatment wards.ConclusionsNon-patient areas of the hospital may pose risks for infection transmission and further attention should be paid to these areas. Standardization of sampling methods will improve understanding of levels of environmental contamination. The pandemic has demonstrated a need to review and act upon the challenges of older hospital buildings meeting current ventilation guidance

Comparison between target magnetic resonance imaging (MRI) in-gantry and cognitively directed transperineal or transrectal-guided prostate biopsies for Prostate Imaging–Reporting and Data System (PI-RADS) 3–5 MRI lesions

Objective: To compare the detection rates of prostate cancer (PCa) in men with Prostate Imaging–Reporting and Data System (PI-RADS) 3–5 abnormalities on 3-Tesla multiparametric (mp) magnetic resonance imaging (MRI) using in-bore MRI-guided biopsy compared with cognitively directed transperineal (cTP) biopsy and transrectal ultrasonography (cTRUS) biopsy. Methods: This was a retrospective single-centre study of consecutive men attending the private practice clinic of an experienced urologist performing MRI-guided biopsy and an experienced urologist performing cTP and cTRUS biopsy techniques for PI-RADS 3–5 lesions identified on 3-Tesla mpMRI. Results: There were 595 target mpMRI lesions from 482 men with PI-RADS 3–5 regions of interest during 483 episodes of biopsy. The abnormal mpMRI target lesion was biopsied using the MRI-guided method for 298 biopsies, the cTP method for 248 biopsies and the cTRUS method for 49 biopsies. There were no significant differences in PCa detection among the three biopsy methods in PI-RADS 3 (48.9%, 40.0% and 44.4%, respectively), PI-RADS 4 (73.2%, 81.0% and 85.0%, respectively) or PI-RADS 5 (95.2, 92.0% and 95.0%, respectively) lesions, and there was no significant difference in detection of significant PCa among the biopsy methods in PI-RADS 3 (42.2%, 30.0% and 33.3%, respectively), PI-RADS 4 (66.8%, 66.0% and 80.0%, respectively) or PI-RADS 5 (90.5%, 89.8% and 90.0%, respectively) lesions. There were also no differences in PCa or significant PCa detection based on lesion location or size among the methods. Conclusion: We found no significant difference in the ability to detect PCa or significant PCa using targeted MRI-guided, cTP or cTRUS biopsy methods. Identification of an abnormal area on mpMRI appears to be more important in increasing the detection of PCa than the technique used to biopsy an MRI abnormality

Long-term outcomes of high-dose-rate brachytherapy for intermediate- and high-risk prostate cancer with a median follow-up of 10 years

To evaluate the long-term outcomes of high-dose-rate (HDR) brachytherapy for patients with intermediate- and high-risk prostate cancer.We retrospectively analysed a prospective longitudinal cohort database including a single-surgeon series of 507 consecutive men treated with external beam radiotherapy and an HDR prostate brachytherapy boost between August 2000 and December 2009. The risk factors used were based on the D'Amico classification. We measured the incidence of no biochemical evidence of disease (bNED) based on the Phoenix definition of failure (nadir PSA + 2 ng/mL). We also reviewed the incidence of urethral stricture in this cohort.With minimum and median follow-ups of 6 and 10.3 years, respectively, the bNED rates for men with intermediate- and high risk disease were 93.3% and 74.2%, respectively, at 5 years and 86.9% and 56.1%, respectively, at 10 years. The 10-year bNED rate for men with only one intermediate-risk factor was 94%, whereas for patients with all three high-risk factors it was 39.5%. The overall urethral stricture rate was 13.6%. Before 2005, the urethral stricture rate was 28.9% and after January 2005 it was 4.2%. For the 271 men with a minimum follow-up of 10 years the actuarial 10-year prostate cancer-specific survival rate was 90.8% and the actuarial overall survival rate was 86.7%.For men with intermediate- or high-risk prostate cancer features, who are considered not suitable for, or wish to avoid a radical prostatectomy, HDR prostate brachytherapy remains an appropriate treatment option. From December 2004, prevention strategies decreased the risk of post-brachytherapy urethral strictures

Risk of metastatic disease on 68gallium-prostate-specific membrane antigen positron emission tomography/computed tomography scan for primary staging of 1253 men at the diagnosis of prostate cancer

Objective: To determine the number of men with gallium-prostate-specific membrane antigen positron emission tomography/computed tomography (Ga-PSMA PET/CT) avid metastasis at diagnosis, as most data on Ga-PSMA PET/CT are for the evaluation of recurrent disease after primary treatment and to our knowledge this study is the largest series of primary prostate cancer staging with Ga-PSMA PET/CT. Patients and Methods: A retrospective review conducted on 1253 consecutive men referred by urologists or radiation oncologists to our tertiary referral centre for Ga-PSMA PET/CT scan for staging at the initial diagnosis of prostate cancer between July 2014 and June 2018. The primary outcome measure was to determine the risk of metastasis based on Ga-PSMA PET/CT. Patients were risk stratified based on histological biopsy International Society of Urological Pathology (ISUP) grade, prostate-specific antigen (PSA) level, and staging with pre-biopsy multiparametric magnetic resonance imaging (mpMRI). Univariate and multivariate logistic regression were used to analyse results. Results: The median PSA level was 6.5\ua0ng/mL and median ISUP grade was 3, with high-risk disease in 49.7%. The prostate primary was PSMA avid in 91.7% of men. Metastatic disease was identified in 12.1% of men, including 8.2% with a PSA level of 20\ua0ng/mL. Metastases were identified in 6.4% with ISUP grade 2–3 and 21% with ISUP grade 4–5. Pre-biopsy mpMRI identified metastasis in 8.1% of T2 disease, increasing to 42.4% of T3b. Lymph node metastases were suspected in 107 men, with 47.7% outside the boundaries of an extended pelvic lymph node dissection. Skeletal metastases were identified in 4.7%. In men with intermediate-risk prostate cancer, metastases were identified in 5.2%, compared to 19.9% with high-risk disease. Conclusions: These results support the use of Ga-PSMA PET/CT for primary staging of prostate cancer. Increasing PSA level, ISUP grade and radiological staging with mpMRI were all statistically significant prognostic factors for metastasis on both univariate and multivariate analysis

Outcomes of primary lymph node staging of intermediate and high risk prostate cancer with 68Ga-PSMA positron emission tomography/computerized tomography compared to histological correlation of pelvic lymph node pathology

PURPOSE: The majority of men who undergo pelvic lymph node dissection at radical prostatectomy have benign lymph node histology. The aim of this study was to assess the predictive value of preoperative 68Ga-PSMA (prostate specific membrane antigen) positron emission tomography/computerized tomography to predict histological metastasis on pelvic lymph node dissection performed during radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed the sensitivity, specificity, and positive and negative predictive values of preoperative staging 68Ga-PSMA positron emission tomography/computerized tomography to identify histological lymph node metastasis in 208 consecutive men who subsequently proceeded with pelvic lymph node dissection at radical prostatectomy. RESULTS: Median prostate specific antigen was 7.6 μg/l, the lymph node count was 13 and Gleason score was 4 + 5. On a per patient basis only 21 of the 55 men with metastasis on histological examination were identified on 68Ga-PSMA positron emission tomography/computerized tomography for 38.2% sensitivity. Of the 143 men with no lymph node metastasis on 68Ga-PSMA imaging 34 had metastasis on histology for 80.8% negative predictive value. Specificity was 93.5% and positive predictive value was 67.7%. For the 172 histologically identified malignant lymph node metastases the sensitivity per node was 24.4% and specificity was 99.5%. CONCLUSIONS: If negative 68Ga-PSMA positron emission tomography/computerized tomography is used as the basis of not performing pelvic lymph node dissection, 80% of men would avoid unnecessary pelvic lymph node dissection. However, 68Ga-PSMA positron emission tomography/computerized tomography has poor sensitivity per node to detect all histologically positive lymph node metastases. Thus, pelvic lymph node dissection remains the gold standard to stage pelvic lymph nodes despite its known limitations and complications