Trends in Industry-Sponsored Research Payments to Physician Principal Investigators.

This cohort study investigates trends in total and per-physician industry-sponsored research payments to physician principal investigators from 2015 to 2022.

Environmental impact of single-use and reusable flexible cystoscopes.

OBJECTIVES: To compare the carbon footprint and environmental impact of single-use and reusable flexible cystoscopes. MATERIALS AND METHODS: We analysed the expected clinical lifecycle of single-use (Ambu aScope™ 4 Cysto) and reusable (Olympus CYF-V2) flexible cystoscopes, from manufacture to disposal. Performance data on cumulative procedures between repairs and before decommissioning were derived from a high-volume multispecialty practice. We estimated carbon expenditures per-case using published data on endoscope manufacturing, energy consumption during transportation and reprocessing, and solid waste disposal. RESULTS: A fleet of 16 reusable cystoscopes in service for up to 135 months averaged 207 cases between repairs and 3920 cases per lifecycle. Based on a manufacturing carbon footprint of 11.49 kg CO2 /kg device for reusable flexible endoscopes and 8.54 kg CO2 /kg device for single-use endoscopes, the per-case manufacturing cost was 1.37 kg CO2 for single-use devices and 0.0017 kg CO2 for reusable devices. The solid mass of single-use and reusable devices was 0.16 and 0.57 kg, respectively. For reusable devices, the energy consumption of reusable device reprocessing using an automated endoscope reprocessor was 0.20 kg CO2 , and per-case costs of device repackaging and repair were 0.005 and 0.02 kg CO2 , respectively. The total estimated per-case carbon footprint of single-use and reusable devices was 2.40 and 0.53 kg CO2 , respectively, favouring reusable devices. CONCLUSION: In this lifecycle analysis, the environmental impact of reusable flexible cystoscopes is markedly less than single-use cystoscopes. The primary contributor to the per-case carbon cost of reusable devices is energy consumption of reprocessing.

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.

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.

Using Competing Risk of Mortality to Inform the Transition from Prostate Cancer Active Surveillance to Watchful Waiting.

BACKGROUND: For men on active surveillance (AS) for prostate cancer (PCa), disease progression and age-related changes in health may influence decisions about pursuing curative treatment. OBJECTIVE: To evaluate the predicted PCa and non-PCa mortality at the time of reclassification among men on AS, to identify clinical criteria for considering a transition from AS to watchful waiting (WW). DESIGN, SETTING, AND PARTICIPANTS: Patients enrolled in a large AS program who experienced biopsy grade reclassification (Gleason grade increase) were retrospectively examined. All patients who had complete documentation of medical comorbidities at reclassification were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A validated model was used to assess 10- and 15-yr untreated PCa and non-PCa mortalities based on patient comorbidities and PCa clinical characteristics. We compared the ratio of predicted PCa mortality with predicted non-PCa mortality ("predicted mortality ratio") and divided patients into four risk tiers based on this ratio: (1) tier 1 (ratio: >0.33), (2) tier 2 (ratio 0.33-0.20), (3) tier 3 (ratio 0.20-0.10), and (4) tier 4 (ratio <0.10). RESULTS AND LIMITATIONS: Of the 344 men who were reclassified, 98 (28%) were in risk tier 1, 85 (25%) in tier 2, 93 (27%) in tier 3, and 68 (20%) in tier 4 for 10-yr mortality. Fifteen-year risk tiers were distributed similarly. The 23 (6.7%) men who met the "transition triad" (age >75 yr, Charlson Comorbidity Index >3, and grade group ≤2) had a 14-fold higher non-PCa mortality risk and a lower predicted mortality ratio than those who did not (0.07 vs 0.23, p < 0.001). The primary limitations of our study included its retrospective nature and the use of predicted mortalities. CONCLUSIONS: At reclassification, nearly half of patients had a more than five-fold and one in five patients had a more than ten-fold higher risk of non-PCa death than patients having a risk of untreated PCa death. Despite a more significant cancer diagnosis, a transition to WW for older men with multiple comorbidities and grade group <3 PCa should be considered. PATIENT SUMMARY: Men with favorable-risk prostate cancer and life expectancy of >10 yr are often enrolled in active surveillance, which entails delay of curative treatment until there is evidence of more aggressive disease. We examined a group of men on active surveillance who developed more aggressive disease, and found, nevertheless, that the majority of these men continued to have a dramatically higher risk of death from non-prostate cancer causes than from prostate cancer based on a risk prediction tool. For men older than 75 yr, who have multiple medical conditions and who do not have higher-grade cancer, it may be reasonable to reconsider the need for curative treatment given the low risk of death from prostate cancer compared with the risk of death from other causes.

Patient and in-hospital predictors of post-discharge opioid utilization: Individualizing prescribing after radical prostatectomy based on the ORIOLES initiative.

OBJECTIVE: Judicious opioid stewardship would match each patient's prescription to their true medical necessity. However, most prescribing paradigms apply preset quantities and clinical judgment without objective data to predict individual use. We evaluated individual patient and in-hospital parameters as predictors of post-discharge opioid utilization after radical prostatectomy (RP) to provide evidence-based guidance for individualized prescribing. METHODS: A prospective cohort of patients who underwent open or robotic RP were followed in the Opioid Reduction Intervention for Open, Laparoscopic, and Endoscopic Surgery (ORIOLES) initiative. Baseline demographics, in-hospital parameters, and inpatient and post-discharge pain medication utilization were tabulated. Opioid medications were converted to oral morphine equivalents (OMEQ). Predictive factors for post-discharge opioid utilization were analyzed by univariable and multivariable linear regression, adjusting for opioid reduction interventions performed in ORIOLES. RESULTS: Of 443 patients, 102 underwent open and 341 underwent robotic RP. The factors most strongly associated with post-discharge opioid utilization included inpatient opioid utilization in the final 12 hours before discharge (+39.6 post-discharge OMEQ if inpatient OMEQ was >15 vs. 0), maximum patient-reported pain score (range 0-10) in the 12 hours before discharge (+27.6 OMEQ for pain score ≥6 vs. ≤1), preoperative opioid use (+76.2 OMEQ), and body mass index (BMI; +1.4 OMEQ per 1 kg/m2). A final predictive calculator to guide post-discharge opioid prescribing was constructed. CONCLUSIONS: Following RP, inpatient opioid use, patient-reported pain scores, prior opioid use, and BMI are correlated with post-discharge opioid utilization. These data can help guide individualized opioid prescribing to reduce risks of both overprescribing and underprescribing.

A micro-costing analysis of outpatient flexible cystoscopy: implications for adoption of single-use flexible cystoscopes.

PURPOSE: To evaluate the total cost of outpatient flexible cystoscopy associated with reusable device purchase, maintenance, and reprocessing, and to assess potential cost benefits of single-use flexible cystoscopes. METHODS: Cost data regarding the purchasing, maintaining, and reprocessing of reusable flexible cystoscopes were collected using a micro-costing approach at a high-volume outpatient urology clinic. We estimated the costs to facilities with a range of annual procedure volumes (1000-3000) performed with a fleet of cystoscopes ranging from 10 to 25. We also compared the total cost per double-J ureteral stent removal procedure performed using single-use flexible cystoscopes versus reusable devices. RESULTS: The cost associated with reusable flexible cystoscopes ranged from $105 to $224 per procedure depending on the annual procedure volume and cystoscopes available. As a practice became more efficient by increasing the ratio of procedures performed to cystoscopes in the fleet, the proportion of the total cost due to cystoscope reprocessing increased from 22 to 46%. For ureteral stent removal procedures, the total cost per procedure using reusable cystoscopes (range $165-$1469) was higher than that using single-use devices ($244-$420), unless the annual procedure volume was sufficiently high relative to the number of reusable cystoscopes in the fleet (≥ 350 for a practice with ten reusable cystoscopes, ≥ 700 for one with 20 devices). CONCLUSION: The cost of reprocessing reusable cystoscopes represents a large fraction of the total cost per procedure, especially for high-volume facilities. It may be economical to adopt single-use cystoscopes specifically for stent removal procedures, especially for lower-volume facilities.

Assessing quality of care in the diagnosis and treatment of early-stage testicular cancer: A critical review and summary.

OBJECTIVE: To review the current literature on quality of care in the diagnosis and management of early-stage testicular cancer. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies on quality of care in testicular cancer diagnosis and management from January 1980 to August 2018. Major overlapping themes related to quality of care in the diagnosis and management of TGCT were identified and evidence related to these themes were abstracted. EVIDENCE: 62 studies were included in the review. A number of themes were identified including (1) trends in survival and outcomes, (2) management patterns, (3) adherence to evidence-based clinical guidelines, (4) delays in care, (5) treatment complications and toxicities, (6) sociodemographic factors, (7) volume of patients treated, (8) gaps in provider knowledge and medical errors, and (9) multidisciplinary approaches to care. EVIDENCE SUMMARY: As survival for patients with testicular cancer improves, there has been a greater emphasis on other components of quality of care, such as reducing treatment toxicity and minimizing delays in diagnosis. Efforts to meet these goals include encouragement of adherence to evidence-based guidelines, greater utilization of surveillance, and promotion of multidisciplinary team-based care. Although outcomes have improved, social determinants of health, such as insurance status, race, and geographical residence all may influence survival and cancer-related outcomes. Additionally, qualitative review indicates patients who receive care at high-volume institutions appear to experience better outcomes than those treated at smaller centers. CONCLUSIONS: As outcomes and survival improve for patients with testicular cancer, quality of care has become an important consideration. Future avenues of research on this topic include identifying an appropriate balance between centralization of care and expanding access to underserved areas, minimizing delays in care, ensuring greater adherence to clinical guidelines, and addressing sociodemographic and racial disparities in outcomes.

Complications after open and robot-assisted radical prostatectomy and association with postoperative opioid use: an analysis of data from the PREVENTER trial.

OBJECTIVE: To evaluate perioperative complications for open radical prostatectomy (ORP) and robot-assisted RP (RARP) for patients enrolled in the PREvention of VENous ThromboEmbolism Following Radical Prostatectomy (PREVENTER; ClinicalTrials.gov Identifier: NCT03006562) trial, to determine predictors and impact on opioid consumption. PATIENTS AND METHODS: A prospective cohort of 500 patients undergoing ORP and RARP was followed to determine rates of complications and opioid use. Complications were classified 30 days after RP using the Clavien-Dindo system. Patient characteristics and outcomes were compared using appropriate statistical tests. Logistic and linear regressions were performed to identify predictors of complications and evaluate the relationship between complications and postoperative opioid use. RESULTS: A total of 124 (24.8%) men underwent ORP and 376 (75.2%) RARP, with 418 (83.6%) receiving pelvic lymph node dissection (PLND). While 83 patients (16.6%) had complications, only 19 (3.8%) were major (Clavien-Dindo Grade ≥III), with no differences by surgical approach. PLND (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.25-8.71; P = 0.03) and Stage pT3b (OR 2.76, 95% CI 1.23-6.00;P = 0.01) were the only predictors of complications after controlling for potential confounders. Patients who had complications had greater inpatient (P = 0.02) and outpatient (P = 0.005) opioid use, which persisted after controlling for patient-reported pain, attending surgeon variation, surgical approach, and undergoing PLND (inpatient ß:77.2, 95% CI 17.9-136.5,P = 0.03; and outpatient ß:21.9, 95% CI 4.7-39.1,P = 0.01). CONCLUSION: In an analysis of prospectively collected data, overall and major complications rates did not differ by surgical approach. Patients receiving PLND and with Stage pT3b disease had more complications. Complications were independently associated with higher inpatient and outpatient postoperative opioid use.

A prospective comparative study of routine versus deferred pelvic drain placement after radical prostatectomy: impact on complications and opioid use.

PURPOSE: To evaluate the association of post-RP drain placement with post-operative complications and opioid use at a high-volume institution. METHODS: A prospective, comparative cohort study of patients undergoing robot-assisted or open RP was conducted. Patients for two surgeons did not routinely receive pelvic drains ("No Drain" arm), while the remainder routinely placed drains ("Drain" arm). Outcomes were evaluated at 30 days including Clavien-Dindo complications and opioid use. Intention-to-treat primary analysis and additional secondary analyses were performed using appropriate statistical tests and logistic regression. RESULTS: Of 498 total patients, 144 (28.9%) were in the No Drain arm (all robot-assisted) and 354 (71.1%) in the Drain arm. In the No Drain arm, 19 (13.2%) intraoperatively were chosen to receive drains. There was no difference in overall or major (Clavien ≥ 3) complications between groups (p = 0.2 and 0.4, respectively). Drain deferral did not predict complications on multivariable analysis adjusted for age, BMI, comorbidities, clinical risk, surgical approach, operating time, lymphadenectomy, and number of nodes removed [OR 0.61, 95% CI 0.34-1.11, p = 0.10]; nor did it predict symptomatic fluid collection, adjusting for lymphadenectomy and nodes removed [OR 1.14, 95% CI 0.43-3.60, p = 0.8]. Drain deferral did not decrease opioid use (p = 0.5). Per protocol analysis and restriction to robot-assisted cases demonstrated similar results. CONCLUSION: There was no difference in adverse events, complications, symptomatic collections, or opioid use with deferral of routine drain placement after RP. Experienced surgeons may safely defer drain placement in the majority of robot-assisted RP cases.

Cost-effectiveness Analysis of 99mTc-sestamibi SPECT/CT to Guide Management of Small Renal Masses.

BACKGROUND: Incidentally detected small renal masses (SRMs) may be one of several benign or malignant tumor histologies, and are heterogeneous in oncologic potential. Renal mass biopsy can be used to determine the histology of SRMs. However, this invasive approach has significant limitations. Technetium-99m sestamibi single photon emission computed tomography/computed tomography (99mTc-sestamibi SPECT/CT) is a promising imaging tool that can aid in identifying benign renal oncocytomas and hybrid oncocytic/chromophobe tumors. OBJECTIVE: To evaluate the clinical and economic value of 99mTc-sestamibi SPECT/CT in guiding the management of SRMs. DESIGN, SETTING, AND PARTICIPANTS: We developed a decision analysis model to estimate the costs and health outcomes of competing management strategies for a healthy 65-yr-old patient with an asymptomatic SRM. INTERVENTION: Empiric surgery (reference); real-world clinical practice (RWCP) consisting of empiric surgery, thermal ablation, and active surveillance (alternative reference); renal mass biopsy (option 1); 99mTc-sestamibi SPECT/CT (option 2); and 99mTc-sestamibi SPECT/CT followed by biopsy to confirm benign SRMs (option 3). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed lifetime health utilities, measured in quality-adjusted life years (QALYs), and direct medical costs from a health payer perspective. We calculated the incremental cost-effectiveness ratio (ICER) for options 1-3 versus the reference and alternative reference arms, with a willingness-to-pay threshold of $50 000/QALY. Univariate, multivariate, and probabilistic sensitivity analyses were performed. RESULTS AND LIMITATIONS: Option 3 had a very low risk of untreated malignant tumors (0.2%, vs 2.1% for option 1, 4.2% for option 2, and 0% for empiric surgery) and the highest probability of leaving benign tumors untreated (84.4%, vs 53.9% for option 1, 51.7% for option 2, and 0% for empiric surgery). Option 3 dominated empiric surgery and options 1 and 2 (ie, lower costs and higher QALYs). Compared with RWCP, options 1-3 were all cost effective; option 3 had the lowest ICER of $18 821/QALY. These findings were robust to alternative input values. Study limitations included data uncertainties and a limited number of centers from which 99mTc-sestamibi SPECT/CT performance data were collected. CONCLUSIONS: 99mTc-sestamibi SPECT/CT followed by confirmatory biopsy helps avoid surgery for benign SRMs, minimizes untreated malignant SRMs, and is cost effective compared with existing strategies. PATIENT SUMMARY: Our research suggests that by using a noninvasive imaging test, known as technetium-99m sestamibi single photon emission computed tomography/computed tomography, to diagnose small renal masses, urologists may avoid unnecessary surgery for benign tumors and minimize the risk of leaving a malignant tumor untreated. Moreover, the use of this strategy to diagnose small renal masses is cost effective for the health care system.

Comparison of Perioperative and Pathologic Outcomes Between Single-port and Standard Robot-assisted Radical Prostatectomy: An Analysis of a High-volume Center and the Pooled World Experience.

OBJECTIVE: To perform an early comparative study of outcomes between single-port and robot-assisted laparoscopic radical prostatectomy (SP-RALRP) and standard RALRP at our institution and pooled analysis of series to date. PATIENTS AND METHODS: Patients with organ-confined prostate cancer undergoing SP-RALRP at a high-volume institution were identified retrospectively along with reported SP-RALRP series to date. Data were compared to a contemporary prospective cohort of men undergoing standard RALRP. Patient demographics, perioperative and postoperative data, and complications categorized by the Clavien-Dindo system were compared for the institutional and pooled SP-RALRP cohorts to standard RALRP. RESULTS: A total of 208 SP-RALRP cases were identified (26 from our institution) and compared to 376 standard RALRP cases. In the institutional analysis, there was no difference in operative time, length of stay, overall complications (15.4% vs 17.3%, P= 1.0), major (Clavien ≥III) complications (3.8% vs 3.7%, P = .6), inpatient opioid use, or patient-reported pain scores; median estimated blood loss (100 mL vs 150 mL, P = .02) and number of lymph nodes removed (5.5 vs 9, P = .002) were lower for SP-RALRP. In the pooled analysis, 208 patients receiving SP-RALRP had similar estimated blood loss and complication rates but fewer lymph nodes removed (P = .02) and marginally longer operating time (+16 minutes, P = .01) compared to standard RALRP. The difference in rate of positive surgical margins was not statistically significant (31.3% vs 24.5%, P = .08). CONCLUSION: Based on an early experience with SP-RALRP at a high-volume center and a pooled analysis of SP series to date, perioperative and pathologic outcomes appear nearly equivalent compared to standard RALRP.

Cost-effectiveness Analysis of Non-risk-adapted Active Surveillance for Postorchiectomy Management of Clinical Stage I Seminoma.

BACKGROUND: Cancer-specific survival for men with clinical stage I (CSI) seminoma approaches 100%, regardless of the management approach chosen after orchiectomy. Given the young age and high survival rate of these patients, there has been a shift toward minimizing treatment-related morbidity and cost. In this context, non-risk-adapted active surveillance (NRAS) has emerged as a desirable management strategy. OBJECTIVE: To evaluate the clinical, quality of life, and economic values of postorchiectomy NRAS for CSI seminoma. DESIGN, SETTING, AND PARTICIPANTS: We developed a decision analytic Markov model to estimate the costs and health outcomes of competing postorchiectomy management strategies for otherwise healthy 30-yr-old men with CSI seminoma. INTERVENTION: Real-world current practice, comprising active surveillance and adjuvant therapies (reference arm), was compared with empiric adjuvant radiotherapy (option 1), empiric adjuvant chemotherapy (option 2), risk-adapted active surveillance (RAAS; option 3), and NRAS (option 4). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Quality-adjusted life-years (QALYs), medical costs, incremental cost-effectiveness ratio, mortality, and unnecessary treatment avoidance were estimated over a 10-yr period. Uncertainties in model input values were accounted for using univariate, scenario, and probabilistic sensitivity analyses. RESULTS AND LIMITATIONS: NRAS dominated all other management options, offering the lowest per-patient health care cost ($3839) and the highest QALYs gained (7.74) over 10 yr. On probabilistic sensitivity analysis, NRAS had the highest chance of being most cost effective. Although NRAS resulted in the highest rate of salvage chemotherapy (20% vs 6% radiotherapy, 6% chemotherapy, 15% current practice, and 16% RAAS), it had the same mortality rate compared to current practice (2.5%). NRAS also allowed 80% of patients to avoid unnecessary treatment compared with 46% for current practice and 52% for RAAS. Study limitations included model simplifications, model parameter assumptions, as well as the absence of patient preference as a decision factor. CONCLUSIONS: NRAS maintains high cure rates for CSI seminoma, minimizes unnecessary treatment, and is cost effective compared with other management strategies. PATIENT SUMMARY: Clinical stage I (CSI) seminoma is one of the most common forms of testicular cancer. Surgery is the first step in the treatment of men with this disease, and some men may receive additional treatment with radiation or chemotherapy afterward. As most men are cured with surgery alone, non-risk-adapted active surveillance (NRAS), which involves routine monitoring with imaging and blood tests for disease recurrence after surgery, has become a desirable treatment option. Our study shows that in addition to maintaining high survival rates and avoiding unnecessary radiation and chemotherapy, NRAS is cost effective for the health care system.

Downgrading of grade group 2 intermediate-risk prostate cancer from biopsy to radical prostatectomy: Comparison of outcomes and predictors to identify potential candidates for active surveillance.

BACKGROUND: A proportion of men with grade group (GG) 2 intermediate risk (IR) prostate cancer are downgraded to GG1 or harbor favorable pathology (FP, defined as GG1 or GG2 with <5% Gleason pattern 4) at radical prostatectomy (RP). Prediction of downgrading or FP may help identify potential active surveillance candidates within this group that have outcomes similar to biopsy low-risk (LR) disease. METHODS: We performed a comparative cohort study of biopsy LR and IR men who underwent RP at The Johns Hopkins Hospital and Bayview Medical Center between 2005 and 2018. We evaluated pathological outcomes at RP and recurrence-free survival (RFS). Multivariable logistic regression and Cox proportional hazards regression were applied and individual predicted probabilities were calculated. RESULTS: Among 2943 biopsy GG2 IR patients, 223 (7.6%) were downgraded to GG1, while 525 (17.8%) had FP; 730 of 1325 biopsy LR patients (55.1%) were upgraded (GG >1). Concordance statistics for final predictive regression models were 0.76 for downgrading and 0.70 for upgrading. Biopsy GG2 IR patients downgrading to GG1 or harboring FP had similar RFS to biopsy LR patients. A cutoff of >10% predicted probability of downgrading (24.7% of patients; hazard ratio [HR], 1.55; 95% CI, 0.89-2.68) or >20% predicted probability of FP (37.0% of patients; HR, 1.35; 95% CI, 0.81-2.24) led to similar RFS to biopsy LR patients. CONCLUSION: GG2 IR patients who experience downgrading or harbor FP had similar oncologic outcomes as LR patients. The developed models may serve as tools to inform patients about the risks of pathological downgrading/upgrading and help identify a segment of GG2 IR patients who would consider pursuing active surveillance based on predicted probability cutoffs.

The Use of Computer Simulation Modeling to Estimate Complications in Patients with Type 2 Diabetes Mellitus: Comparative Validation of the Cornerstone Diabetes Simulation Model.

OBJECTIVE: The objective of this study was to assess the validity of the Cornerstone Diabetes Simulation (CDS), a Microsoft Excel®-based patient-level simulation for type 2 diabetes mellitus based on risk equations from the revised United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS-OM2, also known as UKPDS 82). METHODS: Three levels of validation were conducted. Internal validation was assessed through independent review and model stress-testing. External validation was addressed by populating the CDS with baseline characteristics and treatment effects from three major diabetes clinical trials used in the Fifth Mount Hood Diabetes Challenge (MH5) for computer simulation models. Cross-validation of predicted outcomes was tested versus eight models that participated in the MH5. Simulated results were compared with observed clinical outcomes via the coefficient of determination (R2) for both the absolute risk of each clinical outcome and the difference in absolute risk between control and intervention arm in each trial. We ensured transparency of all model inputs and assumptions in reporting. RESULTS: The CDS could be used to predict 18 of 39 single and composite endpoints across the three trials. The model obtained an R2 of 0.637 for predicted versus observed absolute risks, and an R2 of 0.442 for predicted versus observed risk differences between control and intervention. Among the other eight models, only one obtained a higher R2 value under both definitions, albeit based on only four predicted endpoints. CONCLUSIONS: The CDS provides good predictions of diabetes-related complications when compared to observed trial outcomes and previously validated models. The model has value as a validated tool in cost-effectiveness evaluations.