Predictive Value of Multiparametric Magnetic Resonance Imaging in Risk Group Stratification of Prostate Adenocarcinoma.

Purpose: The aim of this study was to further assess the clinical utility of multiparametric magnetic resonance imaging (MP-MRI) in prostate cancer (PC) staging following 2023 clinical guideline changes, both as an independent predictor of high-stage (>T3a) or high-risk PC and when combined with patient characteristics. Methods and Materials: The present study was a retrospective review of 171 patients from 2008 to 2018 who underwent MP-MRI before radical prostatectomy at a single institution. The accuracy of clinical staging was compared between conventional staging and MP-MRI-based clinical staging. Sensitivity, specificity, positive predictive value, and negative predictive value were compared, and receiver operating characteristic curves were generated. Linear regression analyses were used to calculate concordance (C-statistic). Results: Of the 171 patients, final pathology revealed 95 (55.6%) with T2 disease, 62 (36.3%) with T3a disease, and 14 (8.2%) with T3b disease. Compared with conventional staging, MP-MRI-based staging demonstrated significantly increased accuracy in identifying T3a disease, intermediate risk, and high/very-high-risk PC. When combined with clinical characteristics, MP-MRI-based staging improved the area under the curve from 0.753 to 0.808 (P = .0175), compared with conventional staging. Conclusions: MP-MRI improved the identification of T3a PC, intermediate-risk PC, and high- or very-high-risk PC. Further, when combined with clinical characteristics, MP-MRI-based staging significantly improved risk stratification, compared with conventional staging. These findings represent further evidence to support the integration of MP-MRI into prostate adenocarcinoma clinical staging guidelines.

Utility of noninvasive biomarker testing and MRI to predict a prostate cancer diagnosis.

PURPOSE: To assess the diagnostic performance and utility of the ExoDx IntelliScore and an OPKO4K score to predict prostate cancer in men presenting with elevated PSA-both as independent predictors and in combination with clinical/MRI characteristics. METHODS: Patients with elevated PSA were retrospectively reviewed. Abnormal tests were defined as an OPKO4K score ≥ 7.5% and an ExoDx IntelliScore ≥ 15.6. Four regression models and ROC curves were generated based on: (1) age, PSA, and DRE, (2) model 1 + OPKO4K 4Kscore ≥ 7.5%, (3) model 2 + ExoDx IntelliScore ≥ 15.6, and (4) model 3 + MRI PIRADS 4-5. RESULTS: 359 men received an OPKO4K test, 307 had MRI and 113 had ExoDx tests. 163 men proceeded to prostate biopsy and 196 (55%) were saved from biopsy. Mean age was 65.0 ± 8.7 years and mean PSA was 7.1 ± 6.1 ng/mL. Positive biopsies were found in 84 (51.5%) men. The sensitivity and negative predictive value of an OPKO4K score were 86.7% and 72.3%; values for an ExoDx test were 76.5% and 77.1%, respectively. On regression analysis, clinical markers (Age, PSA, DRE) generated an AUC of 0.559. The addition of an OPKO4K score raised the AUC to 0.653. The stepwise addition of an ExoDx score raised the AUC to 0.766. The combined use of both biomarkers, patient characteristics, and MRI yielded an AUC of 0.825. CONCLUSION: This analysis demonstrates the high negative predictive value of both the OPKO4K score and ExoDX IntelliScore independently while demonstrating that the combination of an OPKO4K score, an ExoDX IntelliScore, and MRI increases predictive capability for biopsy confirmed prostate cancer.

Multi-Institutional Development and Validation of a Radiomic Model to Predict Prostate Cancer Recurrence Following Radical Prostatectomy.

The use of multiparametric magnetic resonance imaging (mpMRI)-derived radiomics has the potential to offer noninvasive, imaging-based biomarkers for the identification of subvisual characteristics indicative of a poor oncologic outcome. The present study, therefore, seeks to develop, validate, and assess the performance of an MRI-derived radiomic model for the prediction of prostate cancer (PC) recurrence following radical prostatectomy (RP) with curative intent. mpMRI imaging was obtained from 251 patients who had undergone an RP for the treatment of localized prostate cancer across two institutions and three surgeons. All patients had a minimum of 2 years follow-up via prostate-specific antigen serum testing. Each prostate mpMRI was individually reviewed, and the prostate was delineated as a single slice (ROI) on axial T2 high-resolution image sets. A total of 924 radiomic features were extracted and tested for stability via intraclass correlation coefficient (ICC) following image normalization via histogram matching. Fourteen important and nonredundant features were found to be predictors of PC recurrence at a mean ± SD of 3.2 ± 2.2 years post-RP. Five-fold, ten-run cross-validation of the model containing these fourteen features yielded an area under the curve (AUC) of 0.89 ± 0.04 in the training set (n = 225). In comparison, the University of California San Fransisco Cancer of the Prostate Risk Assessment score (UCSF-CAPRA) and Memorial Sloan Kettering Cancer Center (MSKCC) Pre-Radical prostatectomy nomograms yielded AUC of 0.66 ± 0.05 and 0.67 ± 0.05, respectively (p < 0.01). When the radiomic model was applied to the test set (n = 26), AUC was 0.78; sensitivity, specificity, positive predictive value, and negative predictive value were 60%, 86%, 52%, and 89%, respectively. Accuracy in predicting PC recurrence was 81%.

New Artificial Intelligence ChatGPT Performs Poorly on the 2022 Self-assessment Study Program for Urology.

INTRODUCTION: Large language models have demonstrated impressive capabilities, but application to medicine remains unclear. We seek to evaluate the use of ChatGPT on the American Urological Association Self-assessment Study Program as an educational adjunct for urology trainees and practicing physicians. METHODS: One hundred fifty questions from the 2022 Self-assessment Study Program exam were screened, and those containing visual assets (n=15) were removed. The remaining items were encoded as open ended or multiple choice. ChatGPT's output was coded as correct, incorrect, or indeterminate; if indeterminate, responses were regenerated up to 2 times. Concordance, quality, and accuracy were ascertained by 3 independent researchers and reviewed by 2 physician adjudicators. A new session was started for each entry to avoid crossover learning. RESULTS: ChatGPT was correct on 36/135 (26.7%) open-ended and 38/135 (28.2%) multiple-choice questions. Indeterminate responses were generated in 40 (29.6%) and 4 (3.0%), respectively. Of the correct responses, 24/36 (66.7%) and 36/38 (94.7%) were on initial output, 8 (22.2%) and 1 (2.6%) on second output, and 4 (11.1%) and 1 (2.6%) on final output, respectively. Although regeneration decreased indeterminate responses, proportion of correct responses did not increase. For open-ended and multiple-choice questions, ChatGPT provided consistent justifications for incorrect answers and remained concordant between correct and incorrect answers. CONCLUSIONS: ChatGPT previously demonstrated promise on medical licensing exams; however, application to the 2022 Self-assessment Study Program was not demonstrated. Performance improved with multiple-choice over open-ended questions. More importantly were the persistent justifications for incorrect responses-left unchecked, utilization of ChatGPT in medicine may facilitate medical misinformation.

Climacturia and Penile Length Shortening: Adverse Outcomes following Robot-Assisted Radical Prostatectomy.

Purpose: While erectile dysfunction and urinary incontinence are commonly cited side effects following radical prostatectomy (RP), climacturia and penile length shortening are less explored. The present study seeks to explore the incidence, risk factors, and predictors of recovery associated with climacturia and penile length shortening following robot-assisted radical prostatectomy (RARP). Patients and Methods: From September 2018 to January 2020, 800 patients underwent RARP for primary treatment of localized prostate cancer. A survey was sent to patients following 1-year follow-up assessing outcomes of continence, erectile dysfunction, climacturia, and penile length shortening. Descriptive statistics were utilized to describe incidence and risk factors and logistic regression modeling was used to identify predictors associated with recovery. Results: Of the 800 patients surveyed, 339 (42%) and 369 (46%) patients responded, with 127/339 (37.5%) and 216/369 (58.5%) endorsing climacturia and penile length shortening. In univariate analysis, a lack of bilateral nerve sparing was associated with climacturia; high body mass index (BMI), high prostate weight, lack of nerve-sparing, and high pathologic stage was associated with penile length shortening. In logistic regression modeling, BMI, prostate weight, and p-stage were all significantly correlated with penile length shortening. Recovery from climacturia was associated with a preoperative International Index of Erectile Function-5 score >21. When patients were asked to rank the importance of these outcomes compared to erectile dysfunction and incontinence, <5% of patients ranked either climacturia or penile length shortening as a high priority following RP. Conclusion: While incidence of climacturia and penile length shortening following RP is significant, impact on patient- and partner-related quality of life are low in comparison to risks of erectile dysfunction and urinary incontinence.

The Use of MRI-Derived Radiomic Models in Prostate Cancer Risk Stratification: A Critical Review of Contemporary Literature.

The development of precise medical imaging has facilitated the establishment of radiomics, a computer-based method of quantitatively analyzing subvisual imaging characteristics. The present review summarizes the current literature on the use of diagnostic magnetic resonance imaging (MRI)-derived radiomics in prostate cancer (PCa) risk stratification. A stepwise literature search of publications from 2017 to 2022 was performed. Of 218 articles on MRI-derived prostate radiomics, 33 (15.1%) generated models for PCa risk stratification. Prediction of Gleason score (GS), adverse pathology, postsurgical recurrence, and postradiation failure were the primary endpoints in 15 (45.5%), 11 (33.3%), 4 (12.1%), and 3 (9.1%) studies. In predicting GS and adverse pathology, radiomic models differentiated well, with receiver operator characteristic area under the curve (ROC-AUC) values of 0.50-0.92 and 0.60-0.92, respectively. For studies predicting post-treatment recurrence or failure, ROC-AUC for radiomic models ranged from 0.73 to 0.99 in postsurgical and radiation cohorts. Finally, of the 33 studies, 7 (21.2%) included external validation. Overall, most investigations showed good to excellent prediction of GS and adverse pathology with MRI-derived radiomic features. Direct prediction of treatment outcomes, however, is an ongoing investigation. As these studies mature and reach potential for clinical integration, concerted effort to validate these radiomic models must be undertaken.

Comprehensive evaluation of mitochondrial redox profile, calcium dynamics, membrane integrity and apoptosis markers in a preclinical model of severe penetrating traumatic brain injury.

Traumatic Brain Injury (TBI) is caused by the external physical assaults damages the brain. It is a heterogeneous disorder that remains a leading cause of death and disability in the military and civilian population of the United States. Preclinical investigations of mitochondrial responses in TBI have ascertained that mitochondrial dysfunction is an acute indicator of cellular damage and plays a pivotal role in long-term injury progression through cellular excitotoxicity. The current study was designed to provide an in-depth evaluation of mitochondrial endpoints with respect to redox and calcium homeostasis, and cell death responses following penetrating TBI (PTBI). To evaluate these pathological cascades, anesthetized adult male rats (N = 6/group) were subjected to either 10% unilateral PTBI or Sham craniectomy. Animals were euthanized at 24 h post-PTBI, and purified mitochondrial fractions were isolated from the brain injury core and perilesional areas. Overall, increased reactive oxygen and nitrogen species (ROS/RNS) production, and elevated oxidative stress markers such as 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT), and protein carbonyls (PC) were observed in the PTBI group compared to Sham. Mitochondrial antioxidants such as glutathione, peroxiredoxin (PRX-3), thioredoxin (TRX), nicotinamide adenine dinucleotide phosphate (NADPH), superoxide dismutase (SOD), and catalase (CAT) levels were significantly decreased after PTBI. Likewise, PTBI mitochondria displayed significant loss of Ca2+ homeostasis, early opening of mitochondrial permeability transition pore (mPTP), and increased mitochondrial swelling. Both, outer and inner mitochondrial membrane integrity markers, such as voltage-dependent anion channels (VDAC) and cytochrome c (Cyt C) expression were significantly decreased following PTBI. The apoptotic cell death was evidenced by significantly decreased B-cell lymphoma-2 (Bcl-2) and increased glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression after PTBI. Collectively, current results highlight the comprehensive picture of mitochondria-centric acute pathophysiological responses following PTBI, which may be utilized as novel prognostic indicators of disease progression and theragnostic indicators for evaluating neuroprotection therapeutics following TBI.

Survival Outcomes After Radiotherapy for the Treatment of Synchronous Oligometastatic Prostate Cancer.

This cohort study assesses biochemical progression-free survival among patients receiving radiotherapy for the treatment of synchronous oligometastatic prostate cancer.

Active Observation of Biochemical Recurrence without Treatment following Radical Prostatectomy: Long-Term Analysis of Outcomes.

Biochemical recurrence (BCR) following radical prostatectomy (RP) is an unreliable predictor of prostate cancer (PC) progression. This study was a retrospective cohort analysis of prospectively collected data (407/1895) of men with BCR at a tertiary referral center. Patients were assessed for active observation (AO) compared with a treatment group (TG) utilizing doubling time (DT) kinetics. Risk assessment was based on the initial DT (>12 vs. <12 months), then based on the DT pattern (changed over time). Those with unstable, rapidly decreasing DTs received treatment. Those with increasing and slowly decreasing DTs prompted observation. The primary outcome was PC mortality, safety, and efficacy of observations based on DT kinetics. The secondary outcome was BCR patients managed with or without treatment. The median follow-up was 7.5 years (IQR 3.9−10.7). The PCSM in TG and AO was 10.7% and 0%, respectively (p < 0.001). The initial DT was >12 months in 73.6% of AO versus 22.6% of TG (p < 0.001). An increasing DT pattern was observed in 71.5% of AO versus 32.7% of TG (p < 0.001). Utilizing the Cleveland Clinic's PCSM nomogram, at 10 years, predicted and observed PCSM was 8.6% and 9.5% (p = 0.78), respectively. In conclusion, one-third of patients with BCR post-RP were managed without treatment using DT kinetics, avoiding treatment-related complications, quality-of-life issues, and expenses.

Prostate-Specific Antigen Doubling Time Kinetics following Radical Prostatectomy to Guide Need for Treatment Intervention: Validation of Low-Risk Recurrences.

Biochemical recurrence (BCR) following radical prostatectomy (RP) has a limited ability to predict prostate cancer (PC) progression, leading to overtreatment, decreased quality of life, and additional expenses. Previously, we established that one-third of men with BCR in our group experienced low-risk recurrences that were safely observed without treatment. Our retrospective cohort analysis of 407 BCR patients post RP validates the use of PSA doubling time (DT) kinetics to direct active observation (AO) versus treatment following RP. The primary outcome was no need for treatment according to the predictive value of models of ROC analysis. The secondary outcome was PC-specific mortality (PCSM) according to Kaplan−Meier analysis. A total of 1864 men underwent RP (June 2002−September 2019); 407 experienced BCR (PSA > 0.2 ng/dL, ×2), with a median follow-up of 7.6 years. In adjusted regression analysis, initial PSADT > 12 months and increasing DT were significant predictors for AO (p < 0.001). This model (initial PSADT and DT change) was an excellent predictor of AO in ROC analysis (AUC = 0.83). No patients with initial PSADT > 12 months and increasing DT experienced PCSM. In conclusion, the combination of PSADT > 12 months and increasing DT was an excellent predictor of AO. This is the first demonstration that one-third of BCRs are at low risk of PCSM and can be managed without treatment via DT kinetics.

Immunomodulatory Effects of Vitamin D and Prevention of Respiratory Tract Infections and COVID-19.

Little is known about potential protective factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), referred to as COVID-19. Suboptimal vitamin D status is a risk factor for immune dysfunction, respiratory tract infections (RTIs), and viral infections. Supplementation of vitamin D (2000-4000 IU) has decreased incidence and complications from RTIs, respiratory distress syndrome, and pneumonia and may be beneficial in high-risk populations. Given the possible link between low vitamin D status and RTIs, such as COVID-19, this review examined whether vitamin D supplementation can be supported as a nutritional strategy for reducing risk of infection, complications, and mortality from COVID-19 and found that the relationship between vitamin D and RTIs warrants further exploration.

Retrospective Concomitant Nonrandomized Comparison of "Touch" Cautery Versus Athermal Dissection of the Prostatic Vascular Pedicles and Neurovascular Bundles During Robot-assisted Radical Prostatectomy.

BACKGROUND: During robotic-assisted radical prostatectomy (RARP), the use of electrocautery near the neurovascular bundles (NVBs) frequently results in thermal injury to the cavernous nerves. The cut and "touch" monopolar cautery technique has been suggested to reduce desiccating thermal injury caused by bipolar energy when vessels are sealed. OBJECTIVE: To compare potency outcomes between an athermal technique (AT) and touch cautery (TC) to transect the prostatic vascular pedicles (PVPs) and dissect the NVBs. DESIGN, SETTING, AND PARTICIPANTS: A retrospective concomitant nonrandomized study of AT versus TC was performed in 733 men. A total of 323 undergoing AT had "thin" pedicles, easily suitable for suture ligation. TC was based on "thick" pedicles (n = 230) difficult to suture ligate. Men were excluded for an International Index of Erectile Function (IIEF-5) score of <15 or adjuvant therapies (n = 180). SURGICAL PROCEDURE: Single-surgeon RARP. MEASUREMENTS: Patient-reported outcomes with erectile function (EF) recovery defined as two affirmative answers to erections sufficient for intercourse (ESI; "are erections firm enough for penetration?" and "are the erections satisfactory?"), IIEF-5 scores 15-25, and a novel percent fullness score comparing pre- versus postoperative erection fullness. Logistic regression models assessed the correlation between cautery technique, covariates, and EF recovery. RESULTS AND LIMITATIONS: In an unadjusted analysis, preoperative IIEF-5, age, body mass index (BMI), and prostate weight were significant predictors of potency recovery. Follow-up was similar (AT 52.7 mo vs TC 54.6 mo, p = 0.534). In logistic regression, preoperative IIEF-5, age, and BMI were significant predictors of EF recovery, defined as IIEF-5 scores 15-25, ESI, and percent fullness >75%. Results were similar when IIEF-5 and percent fullness were assessed continuously. CONCLUSIONS: During transection of the PVPs and dissection of the NVBs, TC did not impact EF recovery significantly, compared with an AT. PATIENT SUMMARY: Electrocautery can be applied safely, with similar outcomes to those of an athermal technique.

Evidence for the integration of total and free testosterone levels in the management of prostate cancer.

OBJECTIVE: To comprehensively assess total and calculated free testosterone levels in a consecutive group of patients with prostate cancer (PCa) and any potential impact on disease aggressiveness and recurrence outcomes. PARTICIPANTS AND METHODS: The study included a single-centre prospective cohort of 882 patients presenting for radical prostatectomy from 2009 to 2018. Data on total testosterone (TT), sex hormone-binding globulin (SHBG), and calculated free testosterone (cFT) were prospectively collected. Stepwise logistic regression models were used to assess correlations of TT and cFT with pathological Gleason Grade Group (GGG), extraprostatic extension (EPE), seminal vesicle invasion (SVI) and biochemical recurrence (BCR). RESULTS: Total testosterone remained nearly constant across decades (40s-80s): 0.09 decrease/year (R = 0.02), while SHBG increased 0.87/year (R = 0.32) and cFT decreased 0.08/year (R = -0.02). Low cFT of <5.5 independently predicted: very-high-risk GGG (odds ratio [OR] 0.435, 95% confidence interval [CI] 0.846-0.994; P = 0.036), EPE (OR 0.557, 95% CI 0.810-0.987; P = 0.011), SVI (OR 0.396, 95% CI 0.798-1.038; P = 0.059), and BCR within 1 year after robot-assisted radical prostatectomy (OR 0.638, 95% CI 0.971-3.512, P = 0.046). TT was not a predictor. CONCLUSION: In contrast to popular belief, testosterone remained stable in men aged 40-80 years, whereas free testosterone decreased by 2-3%/year. Low cFT was an independent predictor of very-high-risk PCa and BCR.

Comparative assessment of outcomes and adverse effects using two different intramuscular testosterone therapy regimens: 100 mg IM weekly or 200 mg IM biweekly.

This study aimed to compare the change in levels of several laboratory values and the development of adverse events using two commonly used intramuscular testosterone therapy regimens. Men were included if they were 18 years or older and received one of the following testosterone therapy regimens: 100 mg intramuscular once weekly or 200 mg intramuscular once every other week. Primary outcomes were relative changes in total testosterone, free testosterone, estradiol, prostate-specific antigen, and hematocrit at 6 months after initiation of testosterone therapy. Secondary outcomes were any significant rises in estradiol, hematocrit, prostate-specific antigen, and any other treatment-related adverse events requiring cessation of testosterone therapy. A total of 263 men were enrolled. In a subanalysis of men who had a baseline hematocrit below 54% before intramuscular testosterone therapy initiation, we found the following: men who received 100 mg weekly injections were significantly less likely to have hematocrit levels rising above 54% (1/102 (1%) vs. 4/51 (8%); p = 0.023). No significant differences were recorded in the increase in total testosterone, free testosterone, prostate-specific antigen, and estradiol levels between both groups. A higher average serum testosterone over the dosing interval seen with the 200 mg regimen appears to be associated with a higher risk of erythrocytosis.

Development of bullous pemphigoid following radiation therapy combined with nivolumab for renal cell carcinoma: A case report of abscopal toxicities.

RATIONALE: Concern for immune-related adverse events from immunotherapy and radiation therapy are well-documented; however, side effects are mostly mild to moderate. However, high-grade, potentially life-threatening adverse events are increasing. While case reports regarding immunotherapy-related bullous pemphigoid (BP) have been rising, only 1 has described BP following concomitant use of both nivolumab and radiation therapy (RT). For that patient, nivolumab was used for 10 weeks prior to RT and development of PB followed 7 weeks later. This case presents a patient who tolerated nivolumab well for 38 months prior to developing BP less than 2 weeks after completing RT. PATIENT CONCERNS: We present the case of DH, a 67-year-old gentleman on nivolumab for metastatic renal cell carcinoma to the lung since May of 2017. Following progressing lung nodules, the patient had his nivolumab paused and completed a course of short-beam radiation therapy. After restarting nivolumab post-radiation, the patient presented with itchy rash and blisters on his arm, legs, and trunk. DIAGNOSIS: DH consulted dermatology following development of rash and was diagnosed with bullous dermatosis, likely bullous pemphigoid. Bullous pemphigoid following concomitant nivolumab (OPDIVO), despite prior tolerance and no history of autoimmune disease, was confirmed by biopsy a month later. INTERVENTIONS: Initial treatment was betamethasone 0.05% cream mixed 1:1 with powder to form paste applied twice daily. Given progressive symptoms and confirmatory biopsy of BP, nivolumab was held and 100 mg doxycycline and 80 mg prednisone daily was prescribed for a week, reduced to 60 mg during the second week. OUTCOMES: A week following discontinuation of nivolumab and beginning of doxycycline and prednisone, the blistering and rash was almost entirely resolved. Four months later, nivolumab was restarted and the patient continued low-dose tapering of prednisone until December. Since completing prednisone, the patient has shown no recurrence of bullous pemphigoid and has not developed any other immune-related adverse events to nivolumab upon rechallenge. Follow-up through October 2021 demonstrates the patient's sites of disease, both in- and out-field, have remained responsive to treatment. LESSONS: Treating physicians should be aware of off-target effects of radiotherapy for oligoprogressive disease, which may include abscopal toxicities and the development of new immune-related adverse effects.

Mesh for Hernia Repair as Cause of Bowel Obstruction.

Ventral hernia repairs are commonly treated by abdominal wall repair where a prosthetic mesh is placed over the hernia site, to prevent future hernia recurrences. Risks of a ventral hernia repair include urinary retention, seroma, recurrence, and in rare cases, bowel injury or obstruction. Our patient's clinical presentation and history, supported by an abdominal X-ray and CT findings, were consistent with the diagnosis of small bowel obstruction (SBO) due to adhesions between the patient's small bowel and the mesh used for abdominal wall hernia repair. Our patient underwent an exploratory laparotomy due to exquisite abdominal wall tenderness and evidence of SBO. Appropriate identification of the cause of our patient's SBO, careful and meticulous treatment, and appropriate inpatient monitoring all contributed to a successful outcome.

Can preoperative renal mass biopsy change clinical practice and reduce surgical intervention for small renal masses?

INTRODUCTION: The role of renal biopsy prior to surgical intervention for a renal mass remains controversial despite the fact that for all other urological organs except the testicle, biopsy inevitably precedes treatment as is true for all other specialties dealing with solid masses (e.g. thyroid, breast, colon, liver, etc.). Accordingly, we sought to determine the impact of a routine biopsy regimen on the course of patients with cT1a lesions in comparison with a contemporary series of cT1a individuals who went directly to treatment without a preoperative biopsy. METHODS: We analyzed a multi-institutional, prospectively maintained database of patients who underwent an office-based, ultrasound-guided, renal mass biopsy (RMB) for a cT1a renal mass (i.e. ≤4cm in largest dimension). Controls were selected from all patients in the database who had a cT1a renal lesion but did not undergo RMB. Both groups were analyzed for differences in treatment modality and surgical pathology results. RESULTS: A total of 72 RMB and 73 control patients were analyzed. The groups were similar in regards to their baseline characteristics. Overall RMB diagnostic rate was 75%. Surgical pathology revealed that excision of benign tumors was eight-fold less in the RMB cohort compared to the control group (3% vs. 23%; P < 0.001). Additionally, the rate of active surveillance in the RMB cohort was nearly three times higher at 35% vs. 14% for the controls (P < 0.001). Biopsy was concordant with surgical pathology in 97% of cases for primary histology (i.e. benign vs. malignant), 97% for histologic subtype, and 46% for low (I or II) vs. high (III or IV) grade. On multivariate analysis patients who underwent surgical intervention without preoperative RMB were 6.7 times more likely to have benign histopathology compared to patients who underwent preoperative RMB (OR 6.7, 95% CI = 0.714 - 63.626, P = 0.096). There were no procedural or post-procedural RMB complications. CONCLUSIONS: For patients with cT1a lesions, the implementation of routine office-based RMB led to a significant decrease in the rate of surgical intervention for benign tumors. This practice also resulted in a higher rate of active surveillance for the management of renal cortical neoplasms with benign histopathology compared to a control group.

Pragmatic applications of implementation science frameworks to regulatory science: an assessment of FDA Risk Evaluation and Mitigation Strategies (REMS) (2014-2018).

BACKGROUND: A Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program for certain medications with serious safety concerns required by the U.S. Food and Drug Administration (FDA) of manufacturers to implement to help ensure the benefits of the medication outweigh its risks. FDA is encouraging "the research community to develop novel methods for assessing REMS," conveying the unmet need for a standardized evaluation method of these regulatory-mandated healthcare programs. The objective of this research is to evaluate FDA REMS assessment plans using established implementation science frameworks and identify opportunities for strengthening REMS evaluation. METHODS: A content analysis was conducted of publicly available assessment plans for all REMS programs (N = 23) approved 1/1/2014-12/31/2018 for new drug applications (NDAs) and biologics license applications (BLAs) requiring FDA-mandated Elements to Assure Safe Use (ETASU). Blinded reviewers critically appraised REMS assessment measures (n = 674) using three established implementation science frameworks: RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance); PRECEDE-PROCEED (Predisposing, Reinforcing, and Enabling Constructs in Educational/Environmental Diagnosis and Evaluation - Policy, Regulatory, and Organizational Constructs in Educational and Environmental Development); and CFIR (Consolidated Framework for Implementation Research). Framework constructs were mapped to REMS Assessment categories as defined by FDA Guidance for Industry to evaluate congruence. RESULTS: REMS assessment measures demonstrated strong congruence (> 90% mapping rate) with the evaluative constructs of RE-AIM, PRECEDE-PROCEED, and CFIR. Application of the frameworks revealed that REMS assessment measures heavily emphasize implementation and operations, focus less on health outcomes, and do not evaluate program context and design assumptions. CONCLUSIONS: Implementation science frameworks have utility for evaluating FDA-mandated drug safety programs including the selection of primary measures to determine whether REMS goals are being met and of secondary measures to evaluate contextual factors affecting REMS effectiveness in varying organizational settings.