Self-reported quality of life as a predictor of mortality in renal cell carcinoma.

BACKGROUND: This study evaluated the utility of self-reported quality of life (QOL) metrics in predicting mortality among all-comers with renal cell carcinoma (RCC) and externally tested the findings in a registry of patients with small renal masses. METHODS: The Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) captured QOL metrics composed of mental component summary (MCS) and physical component summary (PCS) scores. Regression models assessed associations of MCS and PCS with all-cause, RCC-specific, and non-RCC-specific mortality. Harrell's concordance statistic (the C-index) and the Akaike information criterion (AIC) determined predictive accuracy and parsimony, respectively. Findings were tested in the prospective Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry. RESULTS: In SEER-MHOS, 1494 patients had a median age of 73.4 years and a median follow-up time of 5.6 years. Each additional MCS and PCS point reduced the hazard of all-cause mortality by 1.3% (95% CI, 0.981-0.993; P < .001) and 2.3% (95% CI, 0.971-0.984; P < .001), respectively. Models with QOL metrics demonstrated higher predictive accuracy (C-index, 72.3% vs 70.1%) and parsimony (AIC, 9376.5 vs 9454.5) than models without QOL metrics. QOL metrics exerted a greater effect on non-RCC-specific mortality than RCC-specific mortality. External testing in the DISSRM registry confirmed these findings with similar results for all-cause mortality. CONCLUSIONS: Models with self-reported QOL metrics predicted all-cause mortality in patients with RCC with higher accuracy and parsimony than those without QOL metrics. Physical health was a stronger predictor of mortality than mental health. The findings support the incorporation of QOL metrics into prognostic models and patient counseling for RCC.

Active Surveillance versus Immediate Intervention for Small Renal Masses: A Cost-Effectiveness and Clinical Decision Analysis.

PURPOSE: Active surveillance (AS) with the possibility of delayed intervention (DI) is emerging as a safe alternative to immediate intervention for many patients with small renal masses (SRMs). However, limited comparative data exist to inform the most appropriate management strategy for SRMs. MATERIALS AND METHODS: Decision analytic Markov modeling was performed to estimate the health outcomes and costs of 4 management strategies for 65-year-old patients with an incidental SRM: AS (with possible DI), immediate partial nephrectomy, radical nephrectomy, and thermal ablation. Mortality, direct medical costs, quality-adjusted life-years, and incremental cost-effectiveness ratios were evaluated over 10 years. RESULTS: The 10-year all-cause mortality was 22.6% for AS, 21.9% for immediate partial nephrectomy, 22.4% for immediate radical nephrectomy, and 23.7% for immediate thermal ablation. At a willingness-to-pay threshold of $100,000/quality-adjusted life-year, AS was the most cost-effective management strategy. The results were robust in univariate, multivariate, and probabilistic sensitivity analyses. Clinical decision analysis demonstrated that the tumor's metastatic potential, patient age, individual preferences, and health status were important factors influencing the optimal management strategy. Notably, if the annual probability of metastatic progression from AS was sufficiently low (under 0.35%-0.45% for most ages at baseline), consistent with the typical metastatic potential of SRMs <2 cm, AS would achieve higher health utilities than the other strategies. CONCLUSIONS: Compared to immediate intervention, AS with timely DI offers a safe and cost-effective approach to managing patients with SRMs. For patients harboring tumors of very low metastatic potential, AS may lead to better patient outcomes than immediate intervention.

Oncologic outcomes among Black and White men with grade group 4 or 5 (Gleason score 8-10) prostate cancer treated primarily by radical prostatectomy.

BACKGROUND: The aim of this study was to describe pathologic and short-term oncologic outcomes among Black and White men with grade group 4 or 5 prostate cancer managed primarily by radical prostatectomy. METHODS: This was a multi-institutional, observational study (2005-2015) evaluating radical prostatectomy outcomes by self-identified race. Descriptive analysis was performed via nonparametric statistical testing to compare baseline clinicopathologic data. Univariable and multivariable time-to-event analyses were performed to assess biochemical recurrence (BCR), metastasis, cancer-specific mortality (CSM), and overall survival between Black and White men. RESULTS: In total, 1662 men were identified with grade group 4 or 5 prostate cancer initially managed by radical prostatectomy. Black men represented 11.3% of the cohort (n = 188). Black men were younger, demonstrated a longer time from diagnosis to surgery, and were at a lower clinical stage (all P < .05). Black men had lower rates of pT3/4 disease (49.5% vs 63.5%; P < .05) but higher rates of positive surgical margins (31.6% vs 26.5%; P = .14) on pathologic evaluation. There was no difference in BCR, CSM, or overall survival over a median follow-up of 40.7 months. Black men had a lower 5-year cumulative incidence of metastasis-free survival (93.6%; 95% confidence interval [CI], 86.5%-97.0%) in comparison with White men (85.8%; 95% CI, 83.1%-88.0%), which did not persist in an age-adjusted analysis. CONCLUSIONS: Black and White men with high-grade prostate cancer at diagnosis demonstrated similar oncologic outcomes when they were managed by primary radical prostatectomy. Our findings suggest that racial disparities in prostate cancer mortality are not related to differences in the efficacy of extirpative therapy.

Contemporary considerations in the management and treatment of lower pole stones.

The presence of lower pole stones poses a unique challenge due to the anatomical considerations involved in their management and treatment. Considerable research has been performed to determine the optimal strategy when faced with this highly relevant clinical scenario. Standard options for management include observation, shock wave lithotripsy, retrograde intrarenal surgery, or percutaneous nephrolithotomy. Indeed, each approach confers a distinct set of risks and benefits, which must be placed into the context of patient preference and expected outcomes. The current state of practice reflects a combination of lessons learned from managing calculi not only in the lower pole, but also from other locations within the kidney as well.

Downgrading from Biopsy Grade Group 4 Prostate Cancer in Patients Undergoing Radical Prostatectomy for High or Very High Risk Prostate Cancer.

PURPOSE: We examined rates of Grade Group 4 downgrading at radical prostatectomy among men diagnosed with high and very high risk prostate cancer at biopsy. MATERIALS AND METHODS: A pooled cohort of 1,776 patients from 3 tertiary referral centers who underwent radical prostatectomy for National Comprehensive Cancer Network® high risk (prostate specific antigen greater than 20 ng/ml, or Grade Group 4-5, or clinical stage T3 or greater) or very high risk (primary Gleason pattern 5, or more than 4 biopsy cores with Grade Group 4-5, or 2 or more high risk features) disease from 2005 to 2015 were reviewed. Overall 893 patients with Grade Group 4 disease at biopsy were identified and 726 patients were available for analysis. Multivariable logistic regression models were fit to determine factors associated with downgrading to Grade Group 3 or less at radical prostatectomy. RESULTS: Overall 333 (45%) cases were downgraded to Grade Group 3 or less at radical prostatectomy. Of these cases 198 (27%) had concordant Grade Group 4 biopsy and radical prostatectomy pathology and 195 (27%) were upgraded at radical prostatectomy to Grade Group 5. Of high risk cases with biopsy Grade Group 4 disease 49% had any downgrading vs 29% of very high risk cases (p <0.0001). Downgrading to Grade Group 2 or less occurred in 16% (98 of 604) of high risk and 7% (8 of 122) of very high risk cases (p <0.01). Downgraded cases had a lower prostate specific antigen, fewer positive biopsy cores and lower clinical stage (p <0.01). On multivariable analysis fewer positive biopsy cores were significantly associated with downgrading at radical prostatectomy (p <0.01). CONCLUSIONS: In this cohort of patients with high risk/very high risk prostate cancer, downgrading from biopsy Grade Group 4 at radical prostatectomy occurred less frequently than in other published reports. Any downgrading was significantly less common in very high risk compared to high risk patients, and downgrading to Grade Group 2 or less occurred in a minority of cases in high risk and very high risk patients.

Outcomes of very high-risk prostate cancer after radical prostatectomy: Validation study from 3 centers.

BACKGROUND: Among men with localized high-risk prostate cancer (PCa), patients who meet very high-risk (VHR) criteria have been shown to experience worse outcomes after radical prostatectomy (RP) in a previous study. Variations of VHR criteria have been suggested to be prognostic in other single-center cohorts, but multicenter outcomes validating VHR criteria have not been described. This study was designed to validate VHR criteria for identifying which PCa patients are at greatest risk for cancer progression. METHODS: Patients with high-risk PCa undergoing RP (2005-2015) at 3 tertiary centers were pooled. The outcomes of men with VHR PCa were compared with the outcomes of those who did not meet VHR criteria. The high-risk criteria were a clinical stage of T3 to T4, a prostate-specific antigen level > 20 ng/mL, or a biopsy Gleason grade sum of 8 to 10. The VHR criteria were multiple high-risk features, >4 biopsy cores with a Gleason grade sum of 8 to 10, or primary Gleason grade pattern 5. Biochemical recurrence, metastasis (METS), and cancer-specific mortality (CSM) were assessed with competing risks regressions. Overall mortality was assessed with Cox survival models. RESULTS: Among 1981 patients with high-risk PCa, men with VHR PCa (n = 602) had adverse pathologic outcomes: 37% versus 25% for positive margins and 37% versus 15% for positive lymph nodes (P < .001 for both comparisons). Patients with VHR PCa also had higher adjusted hazard ratios for METS (2.78; 95% confidence interval [CI], 2.08-3.72), CSM (6.77; 95% CI, 2.91-15.7), and overall mortality (2.44; 95% CI, 1.56-3.80; P < .001 for all comparisons). CONCLUSIONS: In a validation study of patients who underwent treatment for high-risk PCa, VHR criteria were strongly associated with adverse pathologic and oncologic outcomes.

Selecting Patients with Small Renal Masses for Active Surveillance: A Domain Based Score from a Prospective Cohort Study.

PURPOSE: We sought to identify predictors of active surveillance in a prospective cohort study of patients with a small renal mass demonstrating favorable outcomes. We generated a summary score to discriminate patients selected for active surveillance or primary intervention. MATERIALS AND METHODS: We analyzed the records of 751 patients from 2009 to 2018 who were enrolled in the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry to compare active surveillance and primary intervention in the domains of demographics, tumor characteristics, comorbidity and patient reported quality of life. Regression models were created to assess univariable and multivariable model discrimination by the AUC and quality by the AIC (Akaike information criterion). The DISSRM score was based on the most predictive combination of variables and validated for its association with overall survival by Kaplan-Meier survival curves and a Cox proportional hazards regression model. RESULTS: Of the patients 410 (55%) elected active surveillance and 341 (45%) elected primary intervention. Of the domains patient age, the Charlson comorbidity index, tumor diameter and the SF-12® Physical Component Score had the greatest discrimination for clinical selection into active surveillance. These domains made up the DISSRM score (AUC 0.801). The maximum DISSRM score was 7. The average score for active surveillance was 4.19 (median 4, IQR 2-6) and 72% of scores were 4 or greater. The average score for primary intervention was 3.03 (median 3, IQR 1-5) and 63% of scores were 3 or less. A higher DISSRM score was associated with worse overall survival, for example a score of 6-7 had a HR of 10.45 (95% CI 1.25-87.49, p = 0.03). CONCLUSIONS: The DISSRM score represents a measure of oncologic and competing risks of death in various important domains in patients with a small renal mass. It could be used to guide the management selection. Patients with intermediate scores that express illness uncertainty may require additional workup, such as confirmatory biopsy, to reach a treatment decision.

Comparative effectiveness of management options for patients with small renal masses: a prospective cohort study.

OBJECTIVES: To explore the comparative effectiveness of partial nephrectomy (PN), radical nephrectomy (RN), ablative therapies (ablation) and active surveillance (AS) for small renal masses (SRMs; tumour diameter ≤4.0 cm) in the domains of survival, renal function and quality of life (QoL) using the prospectively maintained Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry. PATIENTS AND METHODS: Estimated glomerular filtration rate (eGFR) was calculated from creatinine values to determine renal function. QoL was measured using the Short Form 12 (SF-12) questionnaire. The Kaplan-Meier method and Cox proportional hazards regression were used for survival analysis. The mixed-effects model was used for renal function and QoL analysis. RESULTS: Of 638 patients, 231 (36.2%) chose PN, 41 (6.4%) RN, 27 (4.2%) ablation and 339 (53.1%) AS. Cancer-specific survival at 7 years was 98.8% in PN patients and 100% in all other groups. Overall survival (OS) at 7 years was 87.9%, 90.2%, 83.5% and 66.1% in PN, RN, ablation and AS patients, respectively. The OS rate was significantly worse in the AS group than other groups and likely attributable to older age and increased comorbidities. The eGFR was lowest in RN patients but comparable in all other groups. QoL was lowest in AS patients due to lower physical health scores, but mental health scores were similar in all groups. CONCLUSIONS: With excellent oncological outcomes in all groups, nephron-sparing approaches, like PN and ablation, are preferred over RN when intervention is indicated for SRMs. AS is a reasonable option for select patients, given the comparable oncological and mental health outcomes.

Does time from diagnosis to treatment of high- or very-high-risk prostate cancer affect outcome?

OBJECTIVE: To determine whether time from diagnosis to treatment impacted outcomes in a multicentre cohort of high- and very-high-risk (VHR) patients with prostate cancer undergoing radical prostatectomy (RP). PATIENTS AND METHODS: In all, 1392 patients from three tertiary centres who underwent RP for either high-risk or VHR disease, from 2005 to 2015, were identified. The cohort was divided into tertiles based on time from diagnostic biopsy to RP. Cumulative incidence of biochemical recurrence (BCR), metastasis, and prostate cancer-specific mortality (PCSM) were calculated for each tertile. The Kaplan-Meier method was used to evaluate for differences in all-cause mortality (ACM) amongst tertiles. Competing risks regression models, as well as Cox proportional hazards regression models, were fitted to assess the association between time-to-event outcomes and patient characteristics. RESULTS: The median (interquartile range [IQR]) time from biopsy to RP was 68 (50-94) days. The median (IQR) follow-up was 31 (12.1-55.7) months. The cumulative incidence of BCR (P = 0.14), metastasis (P = 0.15), and PCSM (P = 0.69) did not differ amongst time-to-treatment tertiles of VHR patients. Also, Kaplan-Meier estimates of ACM (P = 0.53) did not differ amongst time-to-treatment tertiles. Similarly, BCR, metastasis, PCSM, and ACM did not significantly differ amongst time-to-treatment tertiles in multivariable modelling. CONCLUSION: In this pooled meta-dataset of patients with high-risk or VHR prostate cancer, time from diagnosis to RP did not appear to significantly contribute to differences in clinical outcomes. This finding supports the safety of enrollment of such patients into neoadjuvant clinical trials.

Tumor Volume on Biopsy of Low Risk Prostate Cancer Managed with Active Surveillance.

PURPOSE: Contemporary clinical guidelines recommend active surveillance of men with low risk prostate cancer. Low risk disease spans any potential volume of Gleason score 6 cancer without sufficient attention to tumor volume in the past. Therefore, we compared tumor characteristics in men at low risk on active surveillance to men treated with radical prostatectomy. MATERIALS AND METHODS: We evaluated an institutional cohort of 1,633 men with very low risk disease (clinical stage T1c, prostate specific antigen density less than 0.15 ng/ml/cm3, 2 or more positive cores and 50% or greater core involvement) and low risk disease (clinical stage T2a or less, prostate specific antigen less than 10 ng/ml and Gleason score 6 or less). Among patients at low risk we calculated the proportion who failed to meet very low risk volume criteria (greater than 2 positive cores or greater than 50% core involvement). Clinical and pathological metrics in the active surveillance cohort were compared to those in a cohort of men at low risk who underwent radical prostatectomy in the current era of 2011 to 2016. RESULTS: In the active surveillance cohort 1,119 men (69%) met very low risk criteria and 514 (31%) had low risk disease. In the low risk population only 138 men (27%) harbored higher volume cancer exceeding very low risk criteria compared to 815 (82%) at low risk who underwent radical prostatectomy (p <0.001). Overall the low risk active surveillance population had fewer positive biopsy cores (median 1 vs 3, p <0.001) and a lower maximum percent of core involvement (median 10% vs 40%, p <0.001) compared to patients at low risk who underwent radical prostatectomy. CONCLUSIONS: Data supporting the safety of active surveillance in men at low risk at our institution were derived from a distinct subgroup harboring a limited cancer volume. Until acceptable outcomes are confirmed for higher volume tumors it is important to remain mindful of these limitations before broadly recommending active surveillance to all low risk men.

Growth Kinetics of Small Renal Masses on Active Surveillance: Variability and Results from the DISSRM Registry.

PURPOSE: Active surveillance is emerging as a safe and effective strategy for the management of small renal masses (4 cm or less). We characterized the growth rate and its pertinence to clinical outcomes in a prospective multi-institutional study of patients with small renal masses. MATERIALS AND METHODS: Since 2009, the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) prospective, multi-institutional registry of patients with small renal masses has enrolled patients who elect primary intervention or active surveillance. Patients who elect active surveillance received regularly scheduled imaging and those with 3 or more followup images were included in the current study to evaluate growth rates. RESULTS: We evaluated 318 patients who elected active surveillance, of whom 271 (85.2%) had 3 or more followup images available with a median imaging followup of 1.83 years. The overall mean ± SD small renal mass growth rate was 0.09 ± 1.51 cm per year (median 0.09) with no variables demonstrating statistically significant associations. The growth rate and variability decreased with longer followup (0.54 and 0.07 cm per year at less than 6 months and greater than 1 year, respectively). No patients had metastatic disease or died of kidney cancer. No statistically significant difference was noted in the growth rate in patients with biopsy demonstrated renal cell carcinoma or in those who died. CONCLUSIONS: Small renal mass growth kinetics are highly variable early on active surveillance with growth rates and variability decreasing with time. Early in active surveillance, especially during the initial 6 to 12 months, the growth rate is variable and does not reliably predict death or adverse pathological features in the patient subset with available pathology findings. An elevated growth rate may indicate the need for further assessment with imaging or consideration of biopsy prior to progressing to treatment. Additional followup will inform the best clinical pathway for elevated growth rates.

Retroperitoneal lymph node dissection for testicular seminomas: population-based practice and survival outcomes.

PURPOSE: While retroperitoneal lymph node dissection (RPLND) is traditionally reserved for nonseminomatous germ cell tumors, recent efforts to reduce long-term toxicities of radiation and chemotherapy have turned attention to its application for testicular seminomas. Currently, RPLND is reserved for the post-chemotherapy for stage II testicular seminomas; we aimed to describe current utilization of RPNLD for testicular seminomas by stage and implications for survival. METHODS: A national sample of men diagnosed with stage IA/IB/IS/IIA/IIB/IIC testicular seminoma (1988-2013) was evaluated from SEER Program registries. Stage-specific utilization of RPLND was determined. Cox proportional hazards models, adjusted for age, race, and radiotherapy, evaluated overall (OS) and cancer-specific survival (CSS) for the RPLND cohort. Adjusted models assessed predictors of RPLND. RESULTS: A total of 17,681 men (mean age 38.1 years) with testicular seminoma were included with low utilization of RPLND for stage I disease (1.3% overall) and higher rates for stage II disease (10.6% overall). There were no appreciable trends over time. Patients receiving RPLND did not appear to have worse OS or CSS on adjusted stage-by-stage analysis. Higher stage disease (IIA-IIC) was associated with greater need for RPLND while radiotherapy was associated with decreased use [OR 0.40 (0.32-0.51), p < 0.001]. CONCLUSIONS: Utilization of RPLND for testicular seminomas in the post-chemotherapy setting has remained stable over a 25-year period. Patients undergoing RPLND are a higher risk cohort but stage-by-stage survival outcomes appeared comparable to men not undergoing RPLND. Upcoming trials implementing RPLND as a first-line modality for testicular seminoma or isolated retroperitoneal relapse will help better quantify relative recurrence and survival.

Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer.

Importance: The optimal treatment for Gleason score 9-10 prostate cancer is unknown. Objective: To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Design, Setting, and Participants: Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. Main Outcomes and Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. Results: Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer-specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]). Conclusions and Relevance: Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer-specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.

Technical aspects of branched graft aortic reconstruction in patients with connective tissue disorders.

Connective tissue disorders (CTDs) predispose patients to dilation of the entire aorta, resulting in the development of extensive aneurysms. Aortic reconstruction in CTD patients can be challenging and demands specific approaches to ensure initial success and lasting stability of aortic repair. Herein, we describe technical approaches to aortic reconstruction in patients with CTDs and briefly report our outcomes on the use of branched grafts for reconstruction in this unique population of patients. We conclude that aortic reconstruction in CTD patients with branched grafts can be performed safely, with a low morbidity and mortality and excellent branch patency. Branched surgical grafts should be used preferentially over the inclusion patch technique during open repair to minimize the late development of patch aneurysms.

Conditional probability of reclassification in an active surveillance program for prostate cancer.

PURPOSE: We evaluated the risk of prostate cancer reclassification by time on active surveillance. MATERIALS AND METHODS: From 1995 to 2014 we evaluated 557 and 251 men at very low and at low risk, respectively, who were on active surveillance and compliant with prostate biopsies. Our primary study outcome was reclassification to higher risk disease by grade or extent. Freedom from reclassification was estimated using the Kaplan-Meier approach with adjustment for covariates using the Cox proportional hazards model. RESULTS: Within the first 2 years of surveillance patient survival free of reclassification by grade (p = 0.20) and by any biopsy criteria (p = 0.25) was similar in men with very low and low risk disease. After 2 years men with low risk disease were 2.4 times more likely to be diagnosed with a Gleason score of greater than 6 than men with very low risk disease (p = 0.002, HR 2.4, 95% CI 1.9-3.5). Additionally, beyond 2 years on surveillance the risk of lifetime reclassification by grade and by any criteria decreased by 30% and 35% (each p <0.0001, HR 0.70, 95% CI 0.60-0.76 and HR 0.65, 95% CI 0.57-0.72, respectively) with each biopsy that showed no reclassification. CONCLUSIONS: The reclassification rate during surveillance is not equally distributed across time or risk groups. Due to misclassification at diagnosis the reclassification rate in very low and low risk groups is similar in the first 2 years but differs significantly beyond 2 years. The risk of reclassification decreases with time for each nonreclassifying biopsy beyond 2 years.

Detecting QT prolongation from a single-lead ECG with deep learning.

For a number of antiarrhythmics, drug loading requires a 3-day hospitalization with continuous monitoring for QT-prolongation. Automated QT monitoring with wearable ECG monitors would enable out-of-hospital care. We therefore develop a deep learning model that infers QT intervals from ECG Lead-I-the lead that is often available in ambulatory ECG monitors-and use this model to detect clinically meaningful QT-prolongation episodes during Dofetilide drug loading. QTNet-a deep neural network that infers QT intervals from Lead-I ECG-was trained using over 3 million ECGs from 653 thousand patients at the Massachusetts General Hospital and tested on an internal-test set consisting of 633 thousand ECGs from 135 thousand patients. QTNet is further evaluated on an external-validation set containing 3.1 million ECGs from 667 thousand patients at another healthcare institution. On both evaluations, the model achieves mean absolute errors of 12.63ms (internal-test) and 12.30ms (external-validation) for estimating absolute QT intervals. The associated Pearson correlation coefficients are 0.91 (internal-test) and 0.92 (external-validation). Finally, QTNet was used to detect Dofetilide-induced QT prolongation in a publicly available database (ECGRDVQ-dataset) containing ECGs from subjects enrolled in a clinical trial evaluating the effects of antiarrhythmic drugs. QTNet detects Dofetilide-induced QTc prolongation with 87% sensitivity and 77% specificity. The negative predictive value of the model is greater than 95% when the pre-test probability of drug-induced QTc prolongation is below 25%. These results show that drug-induced QT prolongation risk can be tracked from ECG Lead-I using deep learning.

Clinical patterns and implications of prescription opioid use in a pediatric population for the management of urolithiasis in the emergency room.

Extrapolations from the adult population have suggested that opioids should be avoided in the management of pediatric urolithiasis, but the literature is sparse with regards to actual practice patterns and the downstream implications. We sought to investigate the rate of oral opioid administration for children presenting to the emergency room (ER) with urolithiasis and to identify associations between opioid administration and return visits and persistent opioid use. The TriNetX Research and Diamond Networks were used for retrospective exploratory and validation analyses, respectively. Patients <18 years presenting to the emergency room with urolithiasis were stratified by the receipt of oral opioids. Propensity score matching was performed in a 1:1 fashion. Incident cases of opioid administration and risk ratios (RRs) for a return ER visit within 14 days and the presence of an opioid prescription at 6 to 12 months were calculated. Of the 4672 patients in the exploratory cohort, 11.9% were prescribed oral opioids. Matching yielded a total of 1084 patients. Opioids at the index visit were associated with an increased risk of return visits (RR 1.51, 95% CI 1.04-2.20, P = 0.03) and persistent opioid use (RR 4.00, 95% CI 2.20-7.26, P < 0.001). The validation cohort included 6524 patients, of whom 5.7% were prescribed oral opioids. Matching yielded a total of 722 patients and demonstrated that opioids were associated with an increased risk of return visits (RR 1.50, 95% CI 1.04-2.16, P = 0.03) but not persistent opioid use (RR 1.70, 95% CI 0.79-3.67, P = 0.17). We find that the opioid administration rate for pediatric urolithiasis appears reassuringly low and that opioids are associated with a greater risk of return visits and persistent use.

Urologist-level variation in the management of T1a renal cell carcinoma: A population-based cohort study.

OBJECTIVES: Lack of strict indications in current guidelines have led to significant variation in management patterns of small renal masses. The impact of the urologist on the management approach for patients with small renal masses has not been explored previously. MATERIALS AND METHODS: Using the linked Surveillance, Epidemiology, and End Results-Medicare database, patients aged ≥66 years diagnosed with small renal masses from January 1, 2004 to December 31, 2013 were identified and assigned to primary urologists. Mixed-effects logistic models were used to evaluate factors associated with different management approaches, estimate urologist-level probabilities of each approach, assess management variation, and determine urologist impact on choice of approach. RESULTS: A total of 12,402 patients with 2,794 corresponding primary urologists were included in the study. At the individual urologist level, the estimated case-adjusted probability of different approaches varied markedly: nonsurgical management (mean, 12.8%; range, 4.9%-36.1%); thermal ablation (mean, 10.8%; range, 2.4%-66.3%); partial nephrectomy (mean, 30.1%; range, 10.1%-66.6%); and radical nephrectomy (mean, 40.4%; range, 17.7%-71.6%). Compared to patient and tumor characteristics, the primary urologist was a more influential measured factor, accounting for 13.6% (vs. 12.9%), 33.8% (vs. 2.1%), 15.1% (vs. 8.4%), and 13.5% (vs. 4.0%) of the variation in management choice for nonsurgical management, thermal ablation, partial nephrectomy, and radical nephrectomy, respectively. CONCLUSIONS: Significant variation exists in the management of small renal masses and appears to be driven primarily by urologist preference and practice patterns. Our findings emphasize the need for unified guidance regarding management of these masses to reduce unwarranted variation in care.

QTNet: Deep Learning for Estimating QT Intervals Using a Single Lead ECG.

QT prolongation often leads to fatal arrhythmia and sudden cardiac death. Antiarrhythmic drugs can increase the risk of QT prolongation and therefore require strict post-administration monitoring and dosage control. Measurement of the QT interval from the 12-lead electrocardiogram (ECG) by a trained expert, in a clinical setting, is the accepted method for tracking QT prolongation. Recent advances in wearable ECG technology, however, raise the possibility of automated out-of-hospital QT tracking. Applications of Deep Learning (DL) - a subfield within Machine Learning - in ECG analysis holds the promise of automation for a variety of classification and regression tasks. In this work, we propose a residual neural network, QTNet, for the regression of QT intervals from a single lead (Lead-I) ECG. QTNet is trained in a supervised manner on a large ECG dataset from a U.S. hospital. We demonstrate the robustness and generalizability of QTNet on four test-sets; one from the same hospital, one from another U.S. hospital, and two public datasets. Over all four datasets, the mean absolute error (MAE) in the estimated QT interval ranges between 9ms and 15.8ms. Pearson correlation coefficients vary between 0.899 and 0.914. By contrast, QT interval estimation on these datasets with a standard method for automated ECG analysis (NeuroKit2) yields MAEs between 22.29ms and 90.79ms, and Pearson correlation coefficients 0.345 and 0.620. These results demonstrate the utility of QTNet across distinct datasets and patient populations, thereby highlighting the potential utility of DL models for ubiquitous QT tracking.Clinical Relevance- QTNet can be applied to inpatient or ambulatory Lead-I ECG signals to track QT intervals. The method facilitates ambulatory monitoring of patients at risk of QT prolongation.