Search

Purpose: MiR-371a-3p represents a novel liquid biomarker that detects all histologies of germ-cell tumors (GCT) except teratoma. However, it is currently unclear whether miR-371a-3p results obtained directly from RT-PCR (raw Cq) or normalized for housekeeper genes and transformed into the relative quantity (RQ) value should be used and at what cut-off level. The purpose of this research was to evaluate, which values should be used, and a potential cut-off level for relapse-detection to inform subsequent studies., Materials and Methods: We applied a CE-certified qRT-PCR test to measure miR-371a-3p at each follow-up visit during active surveillance in 34 men with stage I testicular GCT. MiR-371a-3p levels were calculated by the ΔΔ method., Results: About 18 Patients had pure seminoma and 16 had mixed or nonseminomatous testicular GCT. Recurrences were detected in 10 patients and were correctly identified by both raw and housekeeper-normalized miR-371a-3p serum levels. The raw Cq, with a cut-off value of <28, resulted in only 1 false positive (3%), whereas RQ, with a cut-off value of >15, produced 6 false positive results (17%). Most of these false positive results normalized in subsequent measurements. The RQ approach detected recurrence in 1 patient 6 months earlier than the raw Cq approach., Conclusion: Our preliminary data suggest that this CE-certified assay, using previously suggested cut-off values, is a promising method for detecting disease recurrence, provided a confirmatory second test is conducted to identify false positive results. To avoid unnecessary scans or overtreatment, we are currently validating this assay and cut-offs in a prospective cohort study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: A second transurethral resection of the bladder tumor (TURBT) within 2 - 6 weeks after initial TURBT is thought to have diagnostic, therapeutic, and prognostic benefits in T1 bladder cancer (BC). However, little is known about the real-world uptake of this guideline-endorsed intervention. We aimed (1) to measure re-resection rates over time, (2) to investigate if a guideline revision (April 2008) explicitly endorsing re-resection within 2 - 6 weeks in all T1 BC patients led to an increase in re-resection rates, and (3) to investigate the uptake among different groups of surgeons., Methodology: Province-wide BC pathology reports (January 2001 to December 2015; Ontario, Canada) were linked with health administrative data to (1) identify primary cases of T1 BC and to (2) ascertain whether these patients received re-resection. The resulting patients were then aggregated into quarterly time series and investigated by descriptive analysis, interventional autoregressive moving average (ARIMA) modeling, and Poisson regression analysis., Results: A cohort of 7,373 patients was aggregated into a time series. We observed a linear increase in re-resection rates from 8.4% in 2001 to 28.3% in 2015. An actual effect of the guideline revision in April 2008 on re-resection rates could not be detected (P = 0.41). However, we observed a rather heterogeneous uptake behavior among different groups of surgeons. Specifically, female surgeons, more junior surgeons, high-volume surgeons, Canadian graduates, and surgeons without an academic affiliation were all independently more likely to re-resect their patients (all P-values < 0.05 in adjusted analysis)., Conclusions: Re-resection rates in primary T1 BC increased between 2001 and 2015 in the province of Ontario regardless of the guideline revision in April 2008. Our study demonstrates that the uptake of this guideline-endorsed intervention varies among different groups of surgeons and therefore warrants further research to identify barriers to change that can be addressed by tailored interventions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: With the current movement toward treating oligometastatic hormone sensitive prostate cancer (OMPC), we design a study with the objective of gathering opinions regarding what would be considered a clinically significant benefit from such treatments., Methods: Data was collected from physicians of the Society of Urologic Oncology using a self-administered questionnaire using SurveyMonkey. The questionnaire was designed to obtain characteristics on clinical practice of the respondents, definitions used for OMPC and also what would be considered a clinically significant benefit according to the respondents. We present a descriptive analysis of the responses obtained., Results: We obtained 119 responses (response rate of 12.6%) after sending the questionnaire twice with one month apart. Most of them being staff/faculty (89%) practicing in the United States of America (84.87%). Most of the responders referred that a significant proportion of their practice comes from PC patients. Most defined OMPC <3 bone/lymph node metastasis seen with conventional imaging, only 26.9% of the responders used positron emission tomography. Regarding the clinical benefit of metastasis-oriented treatment, a curing rate >10% or an increase in 1 year of androgen deprivation therapy-free survival would make the treatment worthwhile. We present examples of sample size calculations for future clinical trials using these parameters as an expected "clinically-significant" benefit., Conclusion: This study shows that most clinicians still support the use of conventional imaging to define OMPC. Our findings show that a curing rate of a minimum of 11% and an androgen deprivation therapy-free survival at 1 year are considered clinically significant and this should be used for estimating the sample size in future clinical trials., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Highly sensitive and specific urinary biomarkers for the early detection of bladder cancer (BC) to improve the performance of urinary cytology are needed., Objective: To investigate the usefulness of methylation markers in voided urine to identify BC presence and grade., Design, Settings, and Participants: Using genome-wide methylation strategies in Toronto, Canada and Liège, Belgium, we have identified differentially methylated genes (TWIST1, RUNX3, GATA4, NID2, and FOXE1) in low-grade vs. high-grade BC tissue and urine. We accrued urine samples from 313 patients using a 2:1 ratio in a case-control setting from Toronto, Canada, Halifax, Canada, and Zurich, Switzerland. We studied the usefulness of these 5 methylated genes to identify BC and discriminate cancer grade in voided urine specimens. Urinary cell sediment DNA was evaluated using qPCR-based MethyLight assay. Multivariable logistic regression prediction models were created., Results and Limitations: We included 211 BC patients (180 nonmuscle invasive) and 102 controls. In univariate analyses, all methylated genes significantly predicted BC vs. no BC, and high grade vs. low grade (all P < 0.05). In multivariable analysis, NID2, TWIST1, and age were independent predictors of BC (all P < 0.05). Sensitivity of NID2 and TWIST1 to predict BC and BC grade was 76.2% and 77.6%, respectively, whereas specificity was 83.3% and 61.1%, respectively. Multivariable models predicting BC overall and discriminating between high-grade and low-grade BC reached area under the receiver operating characteristics curves of 0.89 and 0.78, respectively., Conclusions: This multi-centric study in a real life scenario (different countries, techniques, and pathologists) supports the promise of epigenetic urinary markers in noninvasively detecting BC. With sensitivities and specificities in the range of 80%, the overall performance characteristics of this panel of methylated genes probably does not allow such signature to significantly alter clinical care at this stage but is worth further studying for instance in BC surveillance or screening in high-risk populations., (Copyright © 2020 Elsevier Inc. All rights reserved.)