Factors affecting the non-publication of clinical trials of prevalent urological cancer.

OBJECTIVES: Clinical trials (CTs) are critical in understanding and managing cancer. However, despite being completed, CT results are often unpublished, compromising the ability to glean useful information from them. This study aimed to evaluate factors influencing the non-publication of urological oncology clinical trials. METHODOLOGY: We conducted a comprehensive search of ClinicalTrials.gov to identify CTs focused on urological cancers completed between 2000 and 2020. We used the National Clinical Trial (NCT) identifier number to check whether the trial was published. RESULTS: 9,145 oncology CTs were conducted between 2000 and 2020, of which 8.39% (n = 767) focused on urological cancers, and 47.2% (n = 362) of these trials remained unpublished. Univariable analysis revealed that trials with a sample size of less than 50 and phase 4 were significantly associated with non-publication p < 0.001. In contrast, trials involving triple masking, a higher number of agents, and those conducted in High-Income Countries were associated with a higher likelihood of publication p < 0.05. Multivariable analysis demonstrated that trials enrolling more than 50 patients and employing three or more agents, along with triple and quadruple masking, had higher odds of being published (OR = 1.62; 95%CI (1.22-2.16), 1.89; 95%CI (1.10-3.27), 3.04; 95%CI (1.44-6.44), 5.62; 95%CI (1.72-18.37), and 5.41; 95%CI (1.76-16.67), p < 0.05, respectively). However, trials conducted in low-middle-income Countries had lower odds of publication (OR = 0.26; 95%CI (0.08-0.87), p = 0.02). CONCLUSION: We found that almost one-half (47.2%) of all completed urologic oncology clinical trials are not published in a PubMed-indexed journal. This non-publication rate represents a significant loss of scientific knowledge and progress. We identified several key variables including sample size.

Racial and Ethnic Variation in Receipt and Intensity of Active Surveillance for Older Patients With Localized Prostate Cancer.

INTRODUCTION: The use of active surveillance (AS) for prostate cancer is increasing, and racial disparities have been identified in its implementation. We investigated differences by race and ethnicity in the utilization and intensity of AS by race and ethnicity among older men with low- and favorable intermediate-risk prostate cancer, with particular focus on the integration of multiparametric MRI (mpMRI) into AS protocols. METHODS: Using the Surveillance, Epidemiology, and End Results and Medicare fee-for-service linked database, we identified a cohort of men diagnosed between 2010 and 2017 with low- or favorable intermediate-risk prostate cancer. The odds of receiving AS were compared by patient race and ethnicity using multivariable logistic regression models, while the rates of usage of PSA tests, biopsy, and mpMRI within 2 years of diagnosis among men on AS were assessed using multivariable Poisson regression models. RESULTS: Our cohort included 33,542 men. The proportion of men with low-risk disease who underwent AS increased from 29.5% in 2010 to 51.7% in 2017, while the proportion among men with favorable intermediate disease grew from 11.4% to 17.2%. Hispanic (odds ratio [OR] = 0.68, 95% CI 0.58-0.79) and non-Hispanic Black men (OR = 0.78, 95% CI 0.68-0.89) were less likely to receive AS than non-Hispanic White men for low-risk disease, while non-Hispanic Black men were more likely to receive AS for favorable intermediate disease (OR = 1.21, 95% CI 1.04-1.39). Non-Hispanic Black men receiving AS underwent prostate MRI at a lower rate compared to non-Hispanic White men, regardless of whether they had low-risk (incidence rate ratio = 0.77, 95% CI 0.61-0.97) or favorable intermediate-risk (incidence rate ratio = 0.61, 95% CI 0.44-0.83) disease, respectively. CONCLUSIONS: The overall adoption of AS for low-risk prostate cancer increased among Medicare fee-for-service beneficiaries. However, a significant disparity exists for non-Hispanic Black men, as they exhibit lower rates of AS utilization. Moreover, non-Hispanic Black men are less likely to have access to novel technologies, such as mpMRI, as part of their AS protocols.

Gender inequality in genitourinary malignancies clinical trials leadership.

BACKGROUND: Over the past 2 decades, there has been a growing interest in the significance of gender roles in healthcare and several efforts and initiatives have focused on increasing female representation in the medical field. Clinical trials play a very important role in shaping medical practice; moreover, the leaders of clinical trials often represent the upper echelon of researchers in any designated field. Presently, there is no data regarding women's representation in urological oncology clinical trials leadership. Therefore, the aim of this study is to examine the extent of female representation in leading urological clinical trials. METHODOLOGY: To thoroughly examine the representation of females as principal investigators (PIs) in urological cancer clinical trials between 2000 and 2020, we conducted a comprehensive search of completed trials focused on kidney, prostate, and bladder cancer on ClinicalTrials.gov. We extracted relevant information regarding the PIs and analyzed the data using univariate analyses to identify any significant differences between male and female PIs. RESULTS: A total of 9145 cancer clinical trials were conducted over the last 2 decades, and 11.3% (n = 1033) of them were urological cancer clinical trials. We were able to obtain detailed information about the principal investigators (PI) in 79.0% (n = 816) of the clinical trials, and we found that 16.8% (n = 137) of them were led by female investigators. Upon evaluating the characteristics of the PIs, female PIs had a significantly lower median age and median total citations as compared to male PIs (55.0 vs 59.0 and 5333 vs 7902; p-value < 0.001 and 0.006, respectively). However, there was no statistically significant difference between the termination rate, publication rate, funding source, cancer type, and the subject of conducting the clinical trials between male and female PIs. CONCLUSION: Between 2000 and 2020, only 16.8% of urological cancer clinical trials were led by a female PI, perhaps reflective of a low percentage of senior female researchers in the fields of urology, oncology and radiation oncology. Universities, research institutes and funding agencies should work to improve mentorship, representation and opportunities for female investigators to encourage more involvement for female researchers in these clinical trials.

Functional Outcomes After Localized Prostate Cancer Treatment.

Importance: Adverse outcomes associated with treatments for localized prostate cancer remain unclear. Objective: To compare rates of adverse functional outcomes between specific treatments for localized prostate cancer. Design, Setting, and Participants: An observational cohort study using data from 5 US Surveillance, Epidemiology, and End Results Program registries. Participants were treated for localized prostate cancer between 2011 and 2012. At baseline, 1877 had favorable-prognosis prostate cancer (defined as cT1-cT2bN0M0, prostate-specific antigen level <20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. Exposures: Radical prostatectomy (n = 1043), external beam radiotherapy (n = 359), brachytherapy (n = 96), or active surveillance (n = 379) for favorable-prognosis disease and radical prostatectomy (n = 362) or external beam radiotherapy with androgen deprivation therapy (n = 206) for unfavorable-prognosis disease. Main Outcomes and Measures: Outcomes were patient-reported sexual, urinary, bowel, and hormone function measured using the 26-item Expanded Prostate Cancer Index Composite (range, 0-100; 100 = best). Associations of specific therapies with each outcome were estimated and compared at 10 years after treatment, adjusting for corresponding baseline scores, and patient and tumor characteristics. Minimum clinically important differences were 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritation, and 4 to 6 for bowel and hormone function. Results: A total of 2445 patients with localized prostate cancer (median age, 64 years; 14% Black, 8% Hispanic) were included and followed up for a median of 9.5 years. Among 1877 patients with favorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -12.1 [95% CI, -16.2 to -8.0]), but not worse sexual function (adjusted mean difference, -7.2 [95% CI, -12.3 to -2.0]), compared with active surveillance. Among 568 patients with unfavorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -26.6 [95% CI, -35.0 to -18.2]), but not worse sexual function (adjusted mean difference, -1.4 [95% CI, -11.1 to 8.3), compared with external beam radiotherapy with androgen deprivation therapy. Among patients with unfavorable prognosis, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel (adjusted mean difference, -4.9 [95% CI, -9.2 to -0.7]) and hormone (adjusted mean difference, -4.9 [95% CI, -9.5 to -0.3]) function compared with radical prostatectomy. Conclusions and Relevance: Among patients treated for localized prostate cancer, radical prostatectomy was associated with worse urinary incontinence but not worse sexual function at 10-year follow-up compared with radiotherapy or surveillance among people with more favorable prognosis and compared with radiotherapy for those with unfavorable prognosis. Among men with unfavorable-prognosis disease, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel and hormone function at 10-year follow-up compared with radical prostatectomy.

Understanding the Termination of Urologic Cancer Clinical Trials: Insights and Challenges.

PURPOSE: Clinical trials are valuable evidence for managing urologic malignancies. Early termination of clinical trials is associated with a waste of resources and may substantially affect patient care. We sought to study the termination rate of urologic cancer clinical trials and identify factors associated with trial termination. METHODS: A cross-sectional search of ClinicalTrials.gov identified completed and terminated kidney, prostate, and bladder cancer clinical trials started. Trials were assessed for reasons for termination. Multivariable analyses were conducted to determine the significant factors associated with the termination. RESULTS: Between 2000 and 2020, 9,145 oncology clinical trials were conducted, of which 11.30% (n = 1,033) were urologic cancer clinical trials. Of the urologic cancer clinical trials, 25.38% (n = 265) were terminated, with low patient accrual being the most common reason for termination, 52.9% (n = 127). Multivariable analysis showed that only the university funding source odds ratio (OR) of 2.20 (95% CI, 1.45 to 3.32), single-center studies OR of 2.11 (95% CI, 1.59 to 2.81), and sample size of <50 were significant predictors of clinical trial termination OR of 5.26 (95% CI, 3.85 to 7.69); all P values are <.001. CONCLUSION: The termination rate of urologic cancer clinical trials was 25%, with low accrual being the most frequently reported reason. Trials funded by a university, single-center trials, and small trials (sample size <50) were associated with early termination. A better understanding of these factors might help researchers, funding agencies, and other stakeholders prioritize resource allocations for multicenter trials that aim to recruit a sufficient number of patients.

Estimating the Impact of the Inflation Reduction Act on the Out-of-Pocket Costs for Medicare Beneficiaries With Advanced Prostate Cancer.

INTRODUCTION: Combination systemic therapy for advanced prostate cancer has reduced mortality, but high out-of-pocket costs impose financial barriers for patients. The Inflation Reduction Act's $2,000 out-of-pocket spending cap for Medicare's prescription drug benefit (Part D) can potentially lower out-of-pocket spending for beneficiaries starting in 2025. This study aims to compare out-of-pocket spending for commonly prescribed regimens for advanced prostate cancer before and after implementation of the Inflation Reduction Act. METHODS: Medication regimens constructed to treat metastatic, hormone-sensitive prostate cancer consisted of baseline androgen deprivation therapy with traditional chemotherapy, androgen receptor inhibitors, and androgen biosynthesis inhibitors. Using 2023 Medicare Part B prices and the Medicare Part D plan finder, we estimated annual out-of-pocket costs under current law and under the Inflation Reduction Act's redesigned standard Part D benefit. RESULTS: Under current law, out-of-pocket costs for Part D drugs ranged from $464 to $11,336 per year. Under the Inflation Reduction Act, annual out-of-pocket costs for 2 regimens remained unchanged: androgen deprivation therapy with docetaxel and androgen deprivation therapy with abiraterone and prednisone. However, out-of-pocket costs for regimens using branded novel hormonal therapy were significantly lower under the 2025 law with potential savings estimated to be $9,336 (79.2%) for apalutamide, $9,036 (78.7%) for enzalutamide, and $8,480 (76.5%) for docetaxel and darolutamide. CONCLUSIONS: The $2,000 spending cap introduced by the Inflation Reduction Act may significantly decrease out-of-pocket costs and reduce financial toxicity associated with advanced prostate cancer treatment, impacting an estimated 25,000 Medicare beneficiaries.

Trends, Cost, and Predictors of Local Hemostatics Use in Major Urological Surgery.

INTRODUCTION: The national usage and cost trends associated with hemostatic agents in major urologic procedures remain unknown. This study aims to describe the trends, costs, and predictors of local hemostatic use in major urologic surgeries. METHODS: We utilized the Premier Healthcare Database to analyze 385,261 patient encounters between 2000 and 2020. Our primary objective was to describe the usage patterns of topical hemostatic agents in open and laparoscopic/robotic major urological surgeries. The data from the last 5 years (2015-2020) were used to characterize specific cost trends, and multivariable regression analysis was performed to identify predictors of hemostatic agent use in relation to surgical approach, patient, and hospital characteristics. RESULTS: By 2020, at least 1 topical hemostatic agent was used in 37.3% (95% CI: 35.5-39.1) of laparoscopic/robotic prostatectomies and 30.7% (95% CI: 24.2-37.1) of open prostatectomies; 60.8% (95% CI: 57.6-64.1) of laparoscopic/robotic partial nephrectomies and 55.9% (95% CI: 47.3-64.5) of open partial nephrectomies; 40.7% (95% CI: 36.9-44.3) of laparoscopic/robotic radical nephrectomies and 43.2% (95% CI: 38.8-47.6) of open radical nephrectomies; and 40.52% (95% CI: 35.02-46.02) of open radical cystectomies. For the 2015-2020 cohort, predictors for hemostatic agent use varied by surgery type and included gender, race, surgical approach, insurance coverage, geographical location, urbanicity, and attending volume. The cost of the hemostatic agent accounted for less than 1.6% of the total cost of hospitalization for each procedure. CONCLUSIONS: The use of hemostatic agents in major urologic surgeries has grown over the past 2 decades. For all procedures, the specific cost of using a hemostatic agent constitutes a small fraction of the total hospitalization cost and does not vary significantly between open and laparoscopic/robotic approaches. Some patient, surgeon, and hospital characteristics are highly correlated with their use.

Projected Savings for Generic Oncology Drugs Purchased via Mark Cuban Cost Plus Drug Company Versus in Medicare.

PURPOSE: Self-administered oncology drugs contribute disproportionately to Medicare Part D spending; prices often remain high even after generic entry. Outlets for low-cost drugs such as Mark Cuban Cost Plus Drug Company (MCCPDC) offer opportunities for decreased Medicare, Part D, and beneficiary spending. We estimate potential savings if Part D plans obtained prices such as those offered under the MCCPDC for seven generic oncology drugs. METHODS: Using the 2020 Medicare Part D Spending dashboard, Q3-2022 Part D formulary prices, and Q3-2022 MCCPDC prices for seven self-administered generic oncology drugs, we estimated Medicare savings by replacing Q3-2022 Part D unit costs with costs under the MCCPDC plan. RESULTS: We estimate potential savings of $661.8 million (M) US dollars (USD; 78.8%) for the seven oncology drugs studied. Total savings ranged from $228.1M USD (56.1%) to $2,154.5M USD (92.4%) compared with 25th and 75th percentiles of Part D plan unit prices. The median savings replacing Part D plan prices were abiraterone $338.0M USD, anastrozole $1.2M USD, imatinib 100 mg $15.6M USD, imatinib 400 mg $212.0M USD, letrozole $1.9M USD, methotrexate $26.7M USD, raloxifene $63.8M USD, and tamoxifen $2.6M USD. All 30-day prescription drug prices offered by MCCPDC generated cost savings except for three drugs offered at the 25th percentile Part D formulary pricing: anastrozole, letrozole, and tamoxifen. CONCLUSION: Replacing current Part D median formulary prices with MCCPDC pricing could yield significant savings for seven generic oncology drugs. Individual beneficiaries could save nearly $25,200 USD per year for abiraterone or between $17,500 USD and $20,500 USD for imatinib. Notably, Part D cash-pay prices for abiraterone and imatinib under the catastrophic phase of coverage were still more expensive than baseline MCCPDC prices.

Adoption and Outcomes of Holmium Laser Enucleation of the Prostate in the United States.

OBJECTIVE: To investigate the utilization of holmium laser enucleation of the prostate (HoLEP) using a large real-world cohort. We compare the safety, readmission, and retreatment rates of HoLEP to other widely used endoscopic surgical interventions for benign prostatic hyperplasia (BPH) including transurethral resection of the prostate (TURP), photoselective vaporization of the prostate, and prostatic urethral lift. METHODS: Men who underwent endoscopic treatments for BPH from 2000 to 2019 were identified in the Premier Healthcare Database (n = 218,793). We compared the relative proportion of each procedure performed and annual physician volume data to identify trends in adoption and utilization. Readmission and retreatment rates were determined at both 30- and 90-days postoperation. Multivariable logistic regression was used to assess the association between procedure type and outcomes. RESULTS: HoLEP accounted for 3.2% (n = 6967) of all the BPH procedures performed between 2000 and 2019 and increased from 1.1% of the procedures in 2008 to 4% in 2019. Patients undergoing HoLEP had lower odds of 90-days readmission compared to TURP (Odds ratio (OR) 0.87, p = 0.025). HoLEP had similar odds of retreatment compared to TURP at both 1-year (OR 0.96, p = 0.7) and 2-years (OR 0.98, p = 0.9), while patients undergoing photoselective vaporization of the prostate and prostatic urethral lift were more likely to retreat within 2-years (OR 1.20, P < 0.001; OR 1.87, P < 0.001). CONCLUSION: HoLEP is a safe therapy for BPH with lower readmission and comparable retreatment rates to the gold standard TURP. Despite this, the utilization of HoLEP has lagged behind other endoscopic procedures and remains low.

Impact of Magnetic Resonance Imaging Targeting on Pathologic Upgrading and Downgrading at Prostatectomy: A Systematic Review and Meta-analysis.

CONTEXT: The evidence supporting multiparametric magnetic resonance imaging (MRI) targeting for biopsy is nearly exclusively based on biopsy pathologic outcomes. This is problematic, as targeting likely allows preferential identification of small high-grade areas of questionable oncologic significance, raising the likelihood of overdiagnosis and overtreatment. OBJECTIVE: To estimate the impact of MRI-targeted, systematic, and combined biopsies on radical prostatectomy (RP) grade group concordance. EVIDENCE ACQUISITION: PubMed MEDLINE and Cochrane Library were searched from July 2018 to January 2022. Studies that conducted systematic and MRI-targeted prostate biopsies and compared biopsy results with pathology after RP were included. We performed a meta-analysis to assess whether pathologic upgrading and downgrading were influenced by biopsy type and a net-benefit analysis using pooled risk difference estimates. EVIDENCE SYNTHESIS: Both targeted only and combined biopsies were less likely to result in upgrading (odds ratio [OR] vs systematic of 0.70, 95% confidence interval [CI] 0.63-0.77, p < 0.001, and 0.50, 95% CI 0.45-0.55, p < 0.001), respectively). Targeted only and combined biopsies increased the odds of downgrading (1.24 (95% CI 1.05-1.46), p = 0.012, and 1.96 (95% CI 1.68-2.27, p < 0.001) compared with systematic biopsies, respectively. The net benefit of targeted and combined biopsies is 8 and 7 per 100 if harms of up- and downgrading are considered equal, but 7 and -1 per 100 if the harm of downgrading is considered twice that of upgrading. CONCLUSIONS: The addition of MRI-targeting results in lower rates of upgrading as compared to systematic biopsy at RP (27% vs 42%). However, combined MRI-targeted and systematic biopsies are associated with more downgrading at RP (19% v 11% for combined vs systematic). Strong heterogeneity suggests further research into factors that influence the rates of up- and downgrading and that distinguishes clinically relevant from irrelevant grade changes is needed. Until then, the benefits and harms of combined MRI-targeted and systematic biopsies cannot be fully assessed. PATIENT SUMMARY: We reviewed the ability of magnetic resonance imaging (MRI)-targeted biopsies to predict cancer grade at prostatectomy. We found that combined MRI-targeted and systematic biopsies result in more cancers being downgraded than systematic biopsies.

The lived experience of prostate cancer: 10-year survivor perspectives following contemporary treatment of localized prostate cancer.

PURPOSE: Studies relying on standardized instruments to measure patient-centered harms and benefits of cancer treatment may fail to capture important elements of the lived experience of cancer patients. Further, qualitative studies on the survivorship experience of men with localized prostate cancer (PCa) are limited. We sought to explore the early experience, long-term experience, and advice provided for others among long-term survivors of localized PCa. METHODS: Semi-structured qualitative interviews with a subset (n = 66) of respondents to a survey of 10-year PCa survivors who underwent active surveillance, radical prostatectomy, or radiotherapy. Topics included early and long-term experiences and advice to other men and physicians. RESULTS: Immediately after treatment, men were mostly satisfied with radiation and active surveillance due to remaining whole and avoiding surgical removal of the prostate. Meanwhile, men treated with surgery felt relieved by the removal of cancer. Some early negative perception was related to short-term anxiety, particularly among men who underwent active surveillance. Long-term experiences included accepting the trade-offs of urinary and sexual side effects with survival. Most men fared well financially, some had strengthened relationships, and many reported greater appreciation and compassion. Men provided essential advice to other men and physicians on the importance of gathering detailed information on treatments and establishing a strong relationship with physicians. CONCLUSIONS: Long-term survivors of localized PCa generally do well by accepting the long-term effects of contemporary treatments, experiencing strengthened relationships, and developing a better overall life approach. IMPLICATIONS FOR CANCER SURVIVORS: We provide useful perspectives and insights for men opting to use current-day treatments for localized PCa.

Use of Active Surveillance vs Definitive Treatment Among Men With Low- and Favorable Intermediate-Risk Prostate Cancer in the US Between 2010 and 2018.

This cross-sectional study of data from the Surveillance, Epidemiology and End Results database assesses temporal trends in the use of active surveillance and watchful waiting vs definitive treatment in men with low- and favorable intermediate­risk prostate cancer in the US between 2010 and 2018.

Combined Use of Magnetic Resonance Imaging and Biomarker Testing to Detect Clinically Significant Prostate Cancer.

We performed a narrative review of studies that produced clinically applicable data by examining the combined use of at least one biomarker test and multiparametric MRI to predict GG ≥2 prostate cancer on biopsy and by reporting the resultant clinical outcomes (i.e, the proportion of biopsies avoided and GG ≥2 cancers missed) following the application of various testing strategies incorporating these diagnostic tests.

Novel Therapies for High-Risk Non-Muscle Invasive Bladder Cancer.

PURPOSE OF REVIEW: The treatment options for high-risk non-muscle invasive bladder cancer (NMIBC), particularly following BCG, remain limited. We highlight recent, promising therapies for high-risk NMIBC. RECENT FINDINGS: Several therapies utilizing different mechanisms of action have demonstrated favorable results in the BCG-naïve and BCG-unresponsive settings. These treatments include intravenous and intravesical immunotherapy, viral- and bacterial-based intravesical therapies, combination intravesical chemotherapy regimens, and novel intravesical chemotherapy administration. Overall, the efficacy and tolerability of emerging treatments for NMIBC appear promising and provide potential alternatives to radical cystectomy. As the landscape of managing BCG-unresponsive disease evolves, clinical trials will explore future options and determine effective alternatives.

Implementation of a comprehensive prehabilitation program for patients undergoing radical cystectomy.

BACKGROUND: Coordinated preoperative optimization programs for radical cystectomy (RC) are limited and non-comprehensive. We evaluated the feasibility and acceptability of a coordinated, multi-faceted prehabilitation program for RC patients at a high-volume bladder cancer referral center. METHODS: We performed a narrative literature review for prehabilitation in bladder cancer management as of December 1, 2020, with specific emphasis on examining higher-level evidence sources. We selected domains with the highest level of evidence and recruited a multidisciplinary team of experts to design our program. We implemented a comprehensive prehabilitation program with a pre-defined order set as standard of care for all patients undergoing RC beginning February 1, 2021. Demographic and clinicopathologic data were collected prospectively. Rates of adherence to the prehabilitation program services were analyzed using Stata version 13. RESULTS: A total of 82 patients were enrolled between February - December 2021, of which 67 (81%) had undergone RC at data cutoff. Mean age was 68 years (SD 11) and 63 (76%) identified as male. Neoadjuvant chemotherapy (NAC) was utilized in 48 (59%) patients. The mean Charlson Comorbidity Index was 3.8 (SD 2.3). 100% of patients were screened for malnutrition, with 82% consuming nutritional supplements. Fifty-two percent of patients attended physical therapy pre-op. The 30-day and 30- to 90-day rates of complications were 56% and 40%, respectively. Resource length of stay (RLOS) declined after implementation of prehabilitation. CONCLUSIONS: Implementation of a comprehensive prehabilitation program at a high-volume bladder cancer referral center is feasible and has a modest effect on resource consumption and complications in our early experience.