Evaluation of Real-World Tumor Response Derived From Electronic Health Record Data Sources: A Feasibility Analysis in Patients With Metastatic Non-Small Cell Lung Cancer Treated With Chemotherapy.

PURPOSE: Real-world data (RWD) holds promise for ascribing a real-world (rw) outcome to a drug intervention; however, ascertaining rw-response to treatment from RWD can be challenging. Friends of Cancer Research formed a collaboration to assess available data attributes related to rw-response across RWD sources to inform methods for capturing, defining, and evaluating rw-response. MATERIALS AND METHODS: This retrospective noninterventional (observational) study included seven electronic health record data companies (data providers) providing summary-level deidentified data from 200 patients diagnosed with metastatic non-small cell lung cancer (mNSCLC) and treated with first-line platinum doublet chemotherapy following a common protocol. Data providers reviewed the availability and frequency of data components to assess rw-response (ie, images, radiology imaging reports, and clinician response assessments). A common protocol was used to assess and report rw-response end points, including rw-response rate (rwRR), rw-duration of response (rwDOR), and the association of rw-response with rw-overall survival (rwOS), rw-time to treatment discontinuation (rwTTD), and rw-time to next treatment (rwTTNT). RESULTS: The availability and timing of clinician assessments was relatively consistent across data sets in contrast to images and image reports. Real-world response was analyzed using clinician response assessments (median proportion of patients evaluable, 77.5%), which had the highest consistency in the timing of assessments. Relative consistency was observed across data sets for rwRR (median 46.5%), as well as the median and directionality of rwOS, rwTTD, and rwTTNT. There was variability in rwDOR across data sets. CONCLUSION: This collaborative effort demonstrated the feasibility of aligning disparate data sources to evaluate rw-response end points using clinician-documented responses in patients with mNSCLC. Heterogeneity exists in the availability of data components to assess response and related rw-end points, and further work is needed to inform drug effectiveness evaluation within RWD sources.

Established and emerging liquid biomarkers for prostate cancer detection: A review.

Prostate cancer remains one of the most frequently diagnosed cancers among men in the world today. Since its introduction in 1987 and FDA approval in 1994, prostate specific antigen (PSA) has reduced prostate cancer specific mortality considerably. However, the positive and negative predictive value of PSA is less than ideal and can lead to the over-detection of clinically insignificant prostate cancer. In the search for better screening measures to identify this cohort, liquid biomarkers for prostate cancer have emerged. In this review we will explore the commonly used urine and blood based prostate cancer liquid biomarkers. We detail the mechanism of each test and the validation studies that underscore their efficacy. Additionally, we will examine each test's effect on shared decision making as well as their cost efficacy in clinical practice.

The Association of a Peritoneal Interposition Flap With Lymphocele Formation After Pelvic Lymph Node Dissection During Robotic-assisted Laparoscopic Radical Prostatectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate the association of a peritoneal interposition flap (PIF) with lymphocele formation following robotic-assisted laparoscopic radical prostatectomy (RALP) with pelvic lymph node dissection. METHODS: We conducted a systematic search of MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials through August 30, 2023, to identify randomized and nonrandomized studies comparing RALP with pelvic lymph node dissection with and without PIF. A random effects meta-analysis was then performed to evaluate the associations of PIF with 90-day postoperative outcomes. RESULTS: Five randomized controlled trials (RCTs) and four observational studies, including a total of 2941 patients, were included. The use of PIF was associated with a reduced risk of 90-day symptomatic lymphocele formation after RALP when examining only RCTs (pooled odds ratios [OR] 0.44, 95% CI 0.28-0.69; I2 =3%) and both RCTs and observational studies (OR 0.35, 95% CI 0.22-0.56; I2 =17%). Similarly, use of PIF was associated with a reduced risk of 90-day any lymphocele formation (OR 0.40, 95% CI 0.28-0.56, I2 =39%). There were no statistically significant differences in postoperative complications between the two groups (OR 0.89; 95% CI 0.69-1.14; I2 =20%). CONCLUSION: Use of the PIF is associated with an approximately 50% reduced risk of symptomatic and any lymphocele formation within 90-days of surgery, and it is not associated with an increase in postoperative complications.

Impact of Peritoneal Interposition Flap on Patients Undergoing Robot-assisted Radical Prostatectomy and Pelvic Lymph Node Dissection: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

CONTEXT: Symptomatic lymphocele (sLC) occurs at a frequency of 2-10% after robot-assisted radical prostatectomy (RARP) with pelvic lymph node dissection (PLND). Construction of bilateral peritoneal interposition flaps (PIFs) subsequent to completion of RARP + PLND has been introduced to reduce the risk of lymphocele, and was initially evaluated on the basis of retrospective studies. OBJECTIVE: To conduct a systematic review and meta-analysis of only randomized controlled trials (RCTs) evaluating the impact of PIF on the rate of sLC (primary endpoint) and of overall lymphocele (oLC) and Clavien-Dindo grade ≥3 complications (secondary endpoints) to provide the best available evidence. EVIDENCE ACQUISITION: In accordance with the Preferred Reporting Items for Meta-Analyses statement for observational studies in epidemiology, a systematic literature search using the MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE databases up to February 3, 2023 was performed to identify RCTs. The risk of bias (RoB) was assessed using the revised Cochrane RoB tool for randomized trials. Meta-analysis used random-effect models to examine the impact of PIF on the primary and secondary endpoints. EVIDENCE SYNTHESIS: Four RCTs comparing outcomes for patients undergoing RARP + PLND with or without PIF were identified: PIANOFORTE, PerFix, ProLy, and PLUS. PIF was associated with odds ratios of 0.46 (95% confidence interval [CI] 0.23-0.93) for sLC, 0.51 (95% CI 0.38-0.68) for oLC, and 0.41 (95% CI 0.21-0.83) for Clavien-Dindo grade ≥3 complications. Functional impairment resulting from PIF construction was not observed. Heterogeneity was low to moderate, and RoB was low. CONCLUSIONS: PIF should be performed in patients undergoing RARP and simultaneous PLND to prevent or reduce postoperative sLC. PATIENT SUMMARY: A significant proportion of patients undergoing prostate cancer surgery have regional lymph nodes removed. This part of the surgery is associated with a risk of postoperative lymph collections (lymphocele). The risk of lymphocele can be halved via a complication-free surgical modification called a peritoneal interposition flap.

Prostate Cancer Detection and Complications of Transperineal Versus Transrectal Magnetic Resonance Imaging-fusion Guided Prostate Biopsies.

OBJECTIVE: To assess the rates of detection of clinically significant prostate cancer (csPCa) and complications associated with transperineal (TP) and transrectal (TR) biopsy approaches to magnetic resonance imaging (MRI)-fusion targeted biopsy. MATERIALS AND METHODS: We retrospectively identified men who underwent TP or TR MRI-targeted biopsy with concurrent systematic random biopsy from August 2020 to August 2021. Primary outcomes were detection rates of csPCa and 30-day complication rates between the 2 MRI-biopsy groups. Data were additionally stratified by prior biopsy status. RESULTS: A total of 361 patients were included in the analysis. No demographic differences were observed. No significant differences were observed between TP and TR approaches on any of the outcomes of interest. TR MRI-targeted biopsies identified csPCa in 47.2% of patients, and TP MRI-targeted biopsies identified csPCa in 48.6% of patients (P = .78). No significant differences were observed in csPCa detection between the 2 approaches for patients on active surveillance (P = .59), patients with prior negative biopsy (P = .34), and patients who were biopsy naïve (P = .19). Complication rates did not vary by approach (P = .45). CONCLUSION: Neither the identification of csPCa by MRI-targeted biopsy nor rates of complications differed significantly based on a TR or TP approach. No differences were seen between MRI-targeted approaches based on prior biopsy or active surveillance status.

Outcomes over 20 years performing robot-assisted laparoscopic prostatectomy: a single-surgeon experience.

OBJECTIVE: To evaluate a single surgeon's 20-year experience with robotic radical prostatectomy. METHODS: Patients who had undergone robot-assisted laparoscopic prostatectomy by a single surgeon were identified via an IRB approved prospectively maintained prostate cancer database. Patients were divided into 5-year cohorts (cohort A 2001-2005; cohort B 2006-2010; cohort C 2011-2015; cohort D 2016-2021) for analysis. Oncologic and quality of life outcomes were recorded at the time of follow-up visits. Continence was defined as 0-1 pad with occasional dribbling. Potency was defined as intercourse or an erection sufficient for intercourse within the last 4 weeks. RESULTS: Three thousand one hundred fifty-two patients met criteria for inclusion. Clavien ≥ 3 complication rates decreased from 5.9% to 3.2%, p = 0.021. There was considerable Gleason grade group (GG) and stage migration to more advanced disease between cohort A (6.4% GG4 or GG5, 16.2% pT3 or pT4, 1.2% N1) and cohort D (17% GG4 or GG5, 45.5% pT3 or pT4, 14.4% N1; p < 0.001). Consistent with this, an increasing proportion of patients required salvage treatments over time (14.6% of cohort A vs 22.5% of cohort D, p < 0.001). 1-year continence rates improved from 74.8% to greater than 92.4%, p < 0.001. While baseline potency and use of intraoperative nerve spare decreased, for patients potent at baseline, there were no significant differences for potency at one year (p = 0.065). CONCLUSIONS: In this 20-year review of our experience with robotic prostatectomy, complication rates and continence outcomes improved over time, and there was a migration to more advanced disease at the time of surgery.

The Effect of a Peritoneal Iliac Flap on Lymphocele Formation After Robotic Radical Prostatectomy: Results From the PLUS Trial.

OBJECTIVE: To assess the effectiveness of a peritoneal flap on the formation of lymphoceles after robotic assisted radical prostatectomy with bilateral extended pelvic lymph node dissection. METHODS: We conducted a single surgeon, assessor blinded prospective randomized controlled trial (the Prospective Lymphocele Ultrasound Study) in men undergoing robotic assisted radical prostatectomy with bilateral extended pelvic lymph node dissection. At the conclusion of the node dissection, patients were block randomized 1:1 to either standard of care (no bladder peritoneal flap) or to the creation of a bladder peritoneal flap. Lymphocele formation was assessed by pelvic ultrasound postoperatively. The primary outcome was lymphocele formation. Rates of lymphocele formation and complications were analyzed using chi-square. Other outcomes, including length of stay, number of lymph nodes removed, lymphocele volume, and quality of life measures, were analyzed by t-tests or Wilcoxon Ranked Sum Tests, as appropriate. An a priori power calculation was performed using O'Brien-Fleming alpha sharing for the interim analyses. Two preplanned interim analyses were performed when 45 and 90 patients per group had follow-up ultrasounds. RESULTS: A statistically significant difference in lymphocele formation was seen on the second interim analysis for 183 patients (4.3% vs. 15.6%, p = .011) stopping enrollment; this remained significant in the final analysis of 216 patients (3.6% vs 14.2%, p = .006). No other significant differences were observed. CONCLUSION: This prospective randomized trial supports the implementation of this simple modification for robotic assisted radical prostatectomy with bilateral extended pelvic lymph node dissection.

What is the most effective way to ensure that patients successfully undergo germline testing for prostate cancer?

INTRODUCTION: We sought to identify the most effective way to refer patients with prostate cancer to germline testing. METHODS: After IRB approval, we queried the electronic medical records (EMR) to identify patients (ages 18-89) with prostate cancer who were referred for or offered germline testing for prostate cancer from May 1, 2019 to February 24, 2021 through either telephone referral, EMR referral or in-office testing. The 3 cohorts were compared on receipt of testing and time to testing. Multivariate logistic regression and Cox regression evaluated the influence of referral cohort and reason for testing on receipt of testing and time to testing, respectively. RESULTS: A total of 184 patients met study inclusion criteria; 47 were referred for germline testing via telephone, 70 were referred through the EMR and 67 were offered testing in the office. No significant demographic or clinical differences were observed. Telephone referral yielded the lowest response (17%; P < 0.001) with the longest time interval between referral and testing (103 days; P < 0.001); in-office testing yielded the highest response (66%). More patients were referred because of both family history and high risk characteristics in the EMR and in-office testing cohorts (21.4% and 25.4% respectively). Referral method was significantly (P < 0.001) associated with receipt of test, while reason for testing was not. Referral method was also independently related to time to testing (P < 0.001) while reason for referral was not. CONCLUSIONS: Urologists should offer germline testing in the office for the most effective and expedient results.

Profiling gut microbiota and bile acid metabolism in critically ill children.

Broad-spectrum antimicrobial use during the treatment of critical illness influences gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary to secondary bile acids. We previously observed reduced fermentation capacity in the faecal microbiota of critically ill children upon hospital admission. Here, we further explore the timecourse of the relationship between the microbiome and bile acid profile in faecal samples collected from critically ill children. The microbiome was assayed by sequencing of the 16S rRNA gene, and faecal water bile acids were measured by liquid chromatography mass spectrometry. In comparison to admission faecal samples, members of the Lachnospiraceae recovered during the late-acute phase (days 8-10) of hospitalisation. Patients with infections had a lower proportion of Lachnospiraceae in their gut microbiota than controls and patients with primary admitting diagnoses. Keystone species linked to ecological recovery were observed to decline with the length of PICU admission. These species were further suppressed in patients with systemic infection, respiratory failure, and undergoing surgery. Bile acid composition recovers quickly after intervention for critical illness which may be aided by the compositional shift in Lachnospiraceae. Our findings suggest gut microbiota recovery can be readily assessed via measurement of faecal bile acids.

Outcomes of MRI fusion-guided versus systematic standard prostate biopsies.

INTRODUCTION: The current utility of MRI-fusion targeted biopsy as either an adjunct to or replacement for systematic template biopsy for the detection of clinically significant prostate cancer is disputed. The purpose of this study is to assess the current effectiveness of MRI-targeted versus systematic template prostate biopsies at two institutions and to consider possible underlying factors that could impact variability between detection rates in our patient population compared to others. MATERIALS AND METHODS: A retrospective review from our prospectively maintained prostate cancer databases was conducted. Patients with prostate MRI lesions (PI-RADSv2) receiving concurrent systematic 12-core and MRI-fusion targeted biopsies were reviewed. Clinically significant cancer was considered to be Grade Group ≥ 2. RESULTS: A total of 457 patients were included in the analysis; 255 patients received their biopsy at Institution A and 202 at Institution B. Overall cancer detection rate was 68%; the clinically significant cancer detection rate was 34%. Both MRI-targeted and systematic biopsies identified unique cases of clinically significant prostate cancer that the other modality missed. Out of 157 cases of clinically significant prostate cancer, MRI-targeted biopsy identified 29/157 cases (18%) missed by systematic biopsy, while systematic biopsy identified 37/157 cases (24%) missed by MRI-targeted biopsy (p = .39). Individual biopsy performance was similar when stratified by active surveillance or prior biopsy status, PI-RADSv2 score, and institution. CONCLUSIONS: MRI-fusion targeted and systematic biopsy each identified unique cases of clinically significant prostate cancer. Both biopsy modalities should be utilized in order to provide the greatest sensitivity for the detection of clinically significant prostate cancer.

Patterns of Care in Maintenance Therapy in US Patients Undergoing Definitive Chemoradiation for Stage 3 Non-Small Cell Lung Cancer (NSCLC).

OBJECTIVE: The recommended treatment for patients with unresectable stage 3 non-small cell lung cancer (NSCLC) is definitive chemoradiation followed by 1 year of maintenance durvalumab. Our objective was to assess the rate of maintenance durvalumab use after chemoradiation. METHODS: Analyses were conducted in both open claims (IQVIA pharmacy and medical claims data) and adjudicated closed claims (IQVIA PharMetrics Plus Health Plan Claims Database). Patients with a lung cancer diagnosis between November 2017 and November 2020 who received definitive chemoradiation were included. RESULTS: Of the 5802 NSCLC patients included in the open claims source, 1794 (31%) received durvalumab, 1403 (24%) received maintenance chemotherapy, and 2605 (45%) did not receive any maintenance therapy. Of the 239 NSCLC patients included in the closed claims source, 127 (53%) received durvalumab, 40 (17%) received maintenance chemotherapy, and 72 (30%) did not receive any maintenance therapy. The most common maintenance chemotherapy agents patients received were carboplatin, pemetrexed, and paclitaxel. CONCLUSIONS: The rate of durvalumab utilization was overall low in both the open and closed claims data sources (31% and 53%, respectively). It remains unknown what percent of eligible patients end up receiving durvalumab, as our analysis was unable to filter out patients who were unfit for durvalumab or if they had progression after chemoradiation. Future efforts are needed to increase maintenance durvalumab utilization and to determine how best to manage patients who are unfit for durvalumab.

Do commonly used prostate medications alter prostate MRI and fusion biopsy performance?

AIMS: To determine whether phosphodiesterase inhibitors (PDEi) or α-antagonists (AA) were associated with differences in region of interest (ROI) characteristics or prostate cancer detection on fusion biopsy (FB). MATERIALS AND METHODS: Records from 847 consecutive patients undergoing FB at three separate institutions over a period of 2 years were retrospectively reviewed. Associations between medication use, Prostate Imaging Reporting & Data System (PIRADS) scores, and ROI locations were assessed with ordinal logistic regression. Associations with lesion size and International Society of Urologic Pathology (ISUP) grade group (GG) on biopsy were tested using multivariate regression. RESULTS: Medication use included PDEi in 14.2% and AA in 23.0%. PDEi use was associated with 19.3% smaller lesion diameter (-2.8 mm; CI from -4.8 to -0.7; p < 0.01) and lower PIRADS scores on MRI (OR 0.60; CI 0.40 - 1.00; p = 0.05). AA use was associated with higher PIRADS scores (OR 1.43; CI 0.97 - 2.11; p = 0.06), fewer positive fusion-directed biopsy cores (-28.6%, CI from -57.9 to 0.01%, p = 0.05), and downgrading on final pathology (-19%; CI from -40 to 2%; p = 0.06). CONCLUSION: For PIRADS scores ≥ 3, PDEi use is associated with smaller ROI and lower PIRADS scores, while AA use is associated with higher PIRADS scores. Neither medication was associated with differences in biopsy GG. Prospective studies are needed to investigate the discordance between multi-parametric magnetic resonance imaging (mpMRI) results and oncologic outcomes associated with PDEi and AA use.

Real-world Overall Survival Using Oncology Electronic Health Record Data: Friends of Cancer Research Pilot.

In prior work, Friends of Cancer Research convened multiple data partners to establish standardized definitions for oncology real-world end points derived from electronic health records (EHRs) and claims data. Here, we assessed the performance of real-world overall survival (rwOS) from data sets sourced from EHRs by evaluating the ability of the end point to reflect expected differences from a previous randomized controlled trial across five data sources, after applying inclusion/exclusion criteria. The KEYNOTE-189 clinical trial protocol of platinum doublet chemotherapy (chemotherapy) vs. programmed cell death protein 1 (PD-1) in combination with platinum doublet chemotherapy (PD-1 combination) in first-line nonsquamous metastatic non-small cell lung cancer guided retrospective cohort selection. The Kaplan-Meier product limit estimator was used to calculate 12-month rwOS with 95% confidence intervals (CIs) in each data source. Cox proportional hazards models estimated hazard ratios (HRs) and associated 95% CIs, controlled for prognostic factors. Once the inclusion/exclusion criteria were applied, the five resulting data sets included 155 to 1,501 patients in the chemotherapy cohort and 36 to 405 patients in the PD-1 combination cohort. Twelve-month rwOS ranged from 45% to 58% in the chemotherapy cohort and 44% to 68% in the PD-1 combination cohort. The adjusted HR for death ranged from 0.80 (95% CI: 0.69, 0.93) to 1.15 (95% CI: 0.71, 1.85), controlling for age, gender, performance status, and smoking status. This study yielded insights regarding data capture, including ability of real-world data to precisely identify patient populations and the impact of criteria on end points. Sensitivity analyses could elucidate data set-specific factors that drive results.

The Friends of Cancer Research Real-World Data Collaboration Pilot 2.0: Methodological Recommendations from Oncology Case Studies.

The purpose of this study was to evaluate the potential collective opportunities and challenges of transforming real-world data (RWD) to real-world evidence for clinical effectiveness by focusing on aligning analytic definitions of oncology end points. Patients treated with a qualifying therapy for advanced non-small cell lung cancer in the frontline setting meeting broad eligibility criteria were included to reflect the real-world population. Although a trend toward improved outcomes in patients receiving PD-(L)1 therapy over standard chemotherapy was observed in RWD analyses, the magnitude and consistency of treatment effect was more heterogeneous than previously observed in controlled clinical trials. The study design and analysis process highlighted the identification of pertinent methodological issues and potential innovative approaches that could inform the development of high-quality RWD studies.

Identification of a five gene signature to predict time to biochemical recurrence after radical prostatectomy.

BACKGROUND: Identification of novel biomarkers associated with high-risk prostate cancer or biochemical recurrence can drive improvement in detection, prognosis, and treatment. However, studies can be limited by small sample sizes and sparse clinical follow-up data. We utilized a large sample of prostate specimens to identify a predictive model of biochemical recurrence following radical prostatectomy and we validated this model in two external data sets. METHODS: We analyzed prostate specimens from patients undergoing radical prostatectomy at Hartford Hospital between 2008 and 2011. RNA isolated from formalin-fixed paraffin-embedded prostates was hybridized to a custom Affymetrix microarray. Regularized (least absolute shrinkage and selection operator [Lasso]) Cox regression was performed with cross-validation to identify a model that incorporated gene expression and clinical factors to predict biochemical recurrence, defined as postoperative prostate-specific antigen (PSA) > 0.2 ng/ml or receipt of triggered salvage treatment. Model performance was assessed using time-dependent receiver operating curve (ROC) curves and survival plots. RESULTS: A total of 606 prostate specimens with gene expression and both pre- and postoperative PSA data were available for analysis. We identified a model that included Gleason grade and stage as well as five genes (CNRIP1, endoplasmic reticulum protein 44 [ERP44], metaxin-2 [MTX2], Ras homolog family member U [RHOU], and OXR1). Using the Lasso method, we determined that the five gene model independently predicted biochemical recurrence better than a model that included Gleason grade and tumor stage alone. The time-dependent ROCAUC for the five gene signature including Gleason grade and tumor stage was 0.868 compared to an AUC of 0.767 when Gleason grade and tumor stage were included alone. Low and high-risk groups displayed significant differences in their recurrence-free survival curves. The predictive model was subsequently validated on two independent data sets identified through the Gene Expression Omnibus. The model included genes (RHOU, MTX2, and ERP44) that have previously been implicated in prostate cancer biology. CONCLUSIONS: Expression of a small number of genes is associated with an increased risk of biochemical recurrence independent of classical pathological hallmarks.

Does post prostatectomy decipher score predict biochemical recurrence and impact care?

PURPOSE: To examine the ability of the Decipher test to predict early biochemical recurrence after radical prostatectomy and to impact clinical decisions in advance of metastasis and death. METHODS: We identified Decipher tests ordered after radical prostatectomy for adverse pathology in men treated for prostate cancer between 1/1/14 and 8/31/18. Biochemical recurrence was defined as prostate-specific antigen > 0.02 ng/mL. Decipher score is reported as lower risk (< 0.6) and higher risk ≥ 0.60). Kaplan-Meier analysis was used to examine the relationship between Decipher score and time to biochemical recurrence (months). Cox regression was used to analyze the relationship between Decipher score and time to biochemical recurrence while controlling for a number of clinical characteristics. Secondary analyses focused on a subset of men with prostate-specific antigen > 0.02 and < 0.20 ng/mL to determine if high-risk Decipher scores were associated with receipt of salvage treatment. RESULTS: A total of 203 cases were analyzed: 37.9% and 62.1% had lower and higher risk Decipher scores respectively, and 56.2% had a biochemical recurrence. Median (inter-quartile range) follow-up was 20 (13.5, 25.3) months. Decipher score was significantly associated with time to biochemical recurrence (p = 0.027) while in the secondary analyses, high-risk Decipher scores (≥ 0.60) were associated with salvage treatment (p = 0.018). Stage category and Decipher score were significant predictors of time from elevated PSA to salvage treatment in the secondary analyses. CONCLUSION: While it might not contribute statistically, Decipher score can be clinically useful in helping patients reach treatment decisions.

Use of EPIC 26 to identify men likely to benefit from surgical interventions for urinary incontinence after radical prostatectomy.

PURPOSE: To examine outcomes of surgical procedures for urinary incontinence after radical prostatectomy (post-RP UI) and to identify patients who may benefit from a surgical intervention to treat post-RP UI. METHODS: A retrospective chart review identified men who underwent radical prostatectomy (RP) from July 2004 through July 2016 at our institution. Cases underwent surgical interventions for UI following RP. Controls had RP during the study period but did not have an intervention for UI following RP. We used the UI scale of the Expanded Prostate Index Composite (EPIC) 26 to: (1) quantify post-RP UI before and after UI intervention overall and for specific surgical procedures; (2) evaluate the significance of improvement in post-RP UI before and after UI intervention and (3) identify controls with levels of post-RP UI that were comparable to the cases. RESULTS: Two thousand nine hundred and sixty-eight RPs were performed; 48 patients underwent further surgical intervention (39 slings, 9 artificial urinary sphincter, AUS). For 20 cases with complete EPIC UI data (15 slings, 5 AUS), the median (IQR) pre-UI intervention score was 27.00 (IQR 22.75-42.75). Improvement was significant overall (p < 0.001) and for slings (p = 0.001). 71/2085 controls had post-prostatectomy UI scores ≤ 27.0, suggesting that they may have benefited from a post-RP surgical intervention for UI. CONCLUSION: Data support the effectiveness of surgery to treat post-RP UI. A sizeable population of unidentified men may benefit from a surgical intervention to treat urinary incontinence after RP.

Caprini score and surgical times linked to the risk for venous thromboembolism after robotic-assisted radical prostatectomy.

OBJECTIVE: To evaluate the Caprini score as an independent predictor of venous thromboembolism (VTE) in patients undergoing robotic-assisted radical prostatectomy (RARP) and to identify appropriate cut-points for clinical use. MATERIAL AND METHODS: We performed a retrospective review of patients who underwent RARP for prostate cancer between December 2003 and February 2016. VTE cases developed the condition within 90 days of discharge. The control group was comprised of patients whose RARP most closely preceded and followed each VTE case in time and who were matched on lymph node dissection and surgeon. The Caprini score was calculated for each patient, and the groups were compared on a number of clinical variables. Multiple logistic regression was used to evaluate whether the Caprini score was an independent predictor of VTE. Receiver operating characteristics (ROC) curves were used to establish appropriate clinical cutpoints. RESULTS: A total of 3719 patients underwent RARP during the study period. A total of 52 (1.4%) of patients met the criteria for cases. Data were available for 97 patients who met the criteria for controls. Multiple logistic regression indicated that the Caprini score and operative time were independently both significant predictors of VTE (p=0.005 and p=0.044, respectively). ROC indicated that the Caprini score showed a significant but moderate relationship to VTE (area under curve [AOC]=0.64; p=0.004). A Caprini score >6 was the best arithmetic balance for sensitivity (61.5; 95% confidence interval [CI]: 47.0-74.7) and specificity (59.8; 95% CI: 49.3-69.6). CONCLUSION: The Caprini score predicts postoperative VTE in patients undergoing RARP.

Immunoregulatory Potential of Exosomes Derived from Cancer Stem Cells.

Head and neck squamous cell carcinomas (HNSCCs) are malignancies that originate in the mucosal lining of the upper aerodigestive tract. Despite advances in therapeutic interventions, survival rates among HNSCC patients have remained static for years. Cancer stem cells (CSCs) are tumor-initiating cells that are highly resistant to treatment, and are hypothesized to contribute to a significant fraction of tumor recurrences. Consequently, further investigations of how CSCs mediate recurrence may provide insights into novel druggable targets. A key element of recurrence involves the tumor's ability to evade immunosurveillance. Recent published reports suggest that CSCs possess immunosuppressive properties, however, the underlying mechanism have yet to be fully elucidated. To date, most groups have focused on the role of CSC-derived secretory proteins, such as cytokines and growth factors. Here, we review the established immunoregulatory role of exosomes derived from mixed tumor cell populations, and propose further study of CSC-derived exosomes may be warranted. Such studies may yield novel insights into new druggable targets, or lay the foundation for future exosome-based diagnostics.

Prostate cancer genomics: comparing results from three molecular assays.

INTRODUCTION: OncotypeDx, Prolaris, and Decipher have each been validated to predict outcomes and guide treatment for patients with clinically localized prostate cancer, but they have yet to be compared to one another. Here we assess the correspondence between the results of each. MATERIALS AND METHODS: We performed a retrospective chart review to identify patients who underwent at least two of the three genomic tests at Hartford Hospital between 2014 and 2017. We used test-specific definitions of a favorable prediction for each to compare the percent agreement between each pair. Results were also compared to treatment recommendations based on current National Comprehensive Cancer Network (NCCN) guidelines. We compared pair-wise agreement using Cohen's kappa (K). RESULTS: Twenty-two patients received at least two different genomic tests. For 12 patients who received both the Decipher and Prolaris, % agreement and K were 66.7 and 0.31 (p = .276), respectively. For 8 patients who received both Prolaris and Oncotype DX, % agreement and K were 75 and 0.39 (p = .168), respectively. Two patients received both Decipher and Oncotype DX, yielding 50% agreement and an incalculable K. For Prolaris versus NCCN, % agreement and K were 75 and .21, respectively (p = .117; n = 20). For Decipher versus NCCN, % agreement and K were 60 and .15, respectively (p = .268; n = 15). For Oncotype DX versus NCCN (n = 10), agreement was 50%, K was incalculable. CONCLUSIONS: Notable differences exist in prognostic outcomes obtained from OncotypeDx, Prolaris, and Decipher.