Validation of a 2-gene mRNA urine test for the detection of ≥GG2 prostate cancer in an opportunistic screening population.

BACKGROUND: A 2-gene urine-based molecular test that targets messenger RNAs known to be overexpressed in aggressive prostate cancer (PCa) has been described as a helpful method for detecting clinically significant prostate cancer (grade group [GG] ≥2). We performed an external validation of this test in men undergoing initial prostate biopsy (Bx) within a Spanish opportunistic screening scenario. METHODS: We analyzed archived samples from 492 men who underwent prostate Bx in an opportunistic screening scenario, with prostate-specific antigen (PSA) 3 to 10 ng/mL and/or suspicious digital rectal exploration (DRE) and without previous multi-parametric magnetic resonance imaging (mpMRI). Urinary biomarker measurements were combined with clinical risk factors to determine a risk score, and accuracy for GG ≥ 2 PCa detection was compared with PCA3, European randomized screening in prostate cancer (ERSPC), and prostate biopsy collaborative group (PBCG) risk calculators in a validation workup that included calibration, discrimination, and clinical utility analysis. RESULTS: In our cohort, the detection rates for GG1 and GG ≥ 2 PCa were 20.3% and 14.0%, respectively. The median PSA level was 3.9 ng/mL and 13.4% of subjects had suspicious DRE findings. The median risk score for men with GG ≥ 2 PCa was 21 (interquartile range: 14-28), significantly higher than benign+GG1 PCa (10, 6-18), P < .001, achieving the highest area under the curve among the models tested, 0.749 (95% confidence interval: 0.690-0.807). The urine test was well-calibrated, while ERSPC showed a slight underestimation and PBCG a slight overestimation of risk. Assuming a GG2 non-detection rate of 11% without using mpMRI, use of the urinary biomarker-based clinical model could have helped avoid 37.2% of excess biopsies while delaying the diagnosis of eight patients (1.6% of the entire cohort) with GG ≥ 2 PCa. CONCLUSIONS: In this first evaluation in an opportunistic screening population, the urinary biomarker-based test improved the detection of clinically significant PCa. Facing men with elevated PSA and/or suspicious DRE, it could be a useful tool to help avoid excess initial Bx and to identify patients most likely to benefit from Bx.

Prostate cancer patients with lymphatic node involvement detected by immunohistochemistry. Is the effort worthwhile?

INTRODUCTION: Lymph node (LN) status is one of the main prognostic factors in localized prostate cancer (CaP) patients after surgery. Examining palpable lymph nodes with hematoxylin and eosin (HE) is the most common approach in clinical practice; however, immunohistochemistry (IHC) has been reported to increase the LN detection rate. We reviewed the oncological results of patients with LN metastasis detected by IHC. METHODS: Retrospective study of CaP patients who underwent lymphadenectomy at the time of the prostatectomy. Extended lymphadenectomy was performed with complementary indocyanine green (ICG) guidance. Three groups were considered according to LN status. Definition of the pN+ group was made if LNs were detected by HE, occulted lymph node-positive (OLN+) was considered when ≥ 1 LN was identified with IHC and occulted lymph node-negative (OLN-) if no metastatic nodes were found. Oncological outcomes were reported regarding PSA kinetics, biochemical recurrence (BCR), need for secondary treatments and metastasis-free survival (MFS). RESULTS: A total of 283 patients with a median follow-up of 69 months were included in the study. Immunohistochemical assessment revealed metastatic LNs in 8.9% of patients. The rate of locally advanced disease and positive surgical margins was higher in the OLN + and pN + groups vs the OLN - group (P < 0.05). At the end of follow-up, 19%, 44% and 52% of patients from the OLN -, OLN + and pN + groups experienced BCR (P < 0.001), respectively. Additionally, 2.6%, 17% and 22% of patients developed metastatic progression from the OLN -, OLN + and pN+ group (P < 0.001), respectively. In the multivariate analysis, the OLN + group had a higher risk HR: 12 (95% CI, 2.4-56; P = 0.002) of metastatic progression in comparison with OLN - patients. This difference was not observed in the risk of biochemical recurrence HR 1.8 (95% CI, 0.9-3.8; P = 0.09). CONCLUSION: Conventional HE histological analysis underdiagnosed nearly 10% of patients. IHC-detected patients were at higher risk of metastasis development than OLN - patients. This report highlights the importance of optimizing the anatomopathological analysis properly.

Evaluation of Fluorescent Confocal Microscopy for Intraoperative Analysis of Prostate Biopsy Cores.

BACKGROUND: Diagnosis of prostate cancer is based on histopathological evaluation, which is time-consuming. Fluorescent confocal microscopy (FCM) is a novel technique that allows rapid tissue analysis. OBJECTIVE: To determine if FCM could be used for real-time diagnosis of prostate cancer and evaluate concordance with traditional analysis. DESIGN, SETTING, AND PARTICIPANTS: From January 2019 to March 2020, 182 magnetic resonance imaging-targeted prostate biopsy cores from 57 consecutive biopsy-naïve men with suspected prostate cancer were taken. These were intraoperatively stained with acridine orange for analysis using FCM (VivaScope; MAVIG, Munich, Germany) and subsequently sent for traditional haematoxylin-eosin histopathological (HEH) examination. Two expert uropathologists analysed the FCM and HEH cores blinded to the counterpart results in a single institution. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Agreement between FCM and HEH analysis in terms of the presence of cancer was analysed at biopsy core and region of interest (ROI) levels, considering HEH as the reference test. RESULTS AND LIMITATIONS: FCM allowed intraoperative assessment of prostate biopsy cores with strong histopathological evaluation agreement: Cohen's κ for agreement was 0.81 at the biopsy core level and 0.69 for the ROI level. Positive predictive values (85% and 83.78%) and negative predictive values (95.1% and 85.71%) were high at the biopsy core and ROI levels. These initial results are encouraging, but given the single-centre and preliminary nature of the study, further confirmation is required. CONCLUSIONS: FCM allowed rapid evaluation of prostate biopsy cores. This technique is feasible and achieves rapid closure with a reliable diagnosis, parallel to the gold standard analysis. Initial results are promising but further studies are needed to validate and define the role of this technique. PATIENT SUMMARY: A novel microscopic technique reduces the time needed to obtain a prostate cancer diagnosis by speeding up biopsy processing. Although the initial results are promising; this development needs to be confirmed in further studies.

Ex-vivo confocal fluorescence microscopy for rapid evaluation of renal core biopsy.

Small renal mass incidentally diagnosed are common findings nowadays due to the widespread of imaging. Renal mass biopsy is still underutilized by urologists due to its non-diagnostic rates. Confocal microscopy allows for rapid imaging of fresh tissue samples. We report the feasibility of using confocal technology for determining the quality of the renal core at renal mass biopsy on 4 consecutive cases at our institution.