Real-world clinical outcomes among patients with metastatic castration-sensitive prostate cancer initiating apalutamide.

Aim: To describe overall survival, time to castration resistance and castration resistance-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) initiating apalutamide in a US oncology network. Patients & methods: Patients with mCSPC initiating apalutamide on or after 17 September 2019 from an electronic health record-derived deidentified database were included. Patients were followed from apalutamide initiation and were censored at the earlier of end of clinical activity or data availability (31 October 2022). Results: At 12 and 24 months, overall survival rates were 91.0 and 88.3%, rates of castration sensitivity were 85.7 and 72.1%, and castration resistance-free survival rates were 80.2 and 65.9%, respectively. Conclusion: Real-world clinical outcomes of patients with mCSPC treated with apalutamide were comparable to results from the phase III TITAN trial.

This study looked at health outcomes among 176 patients receiving a prostate cancer medication, apalutamide. The average age of patients was 72 years, and approximately two-thirds of patients were White. Two years after starting apalutamide, most patients remained alive and their cancer did not progress.

Evaluating relugolix for the treatment of prostate cancer in real-world settings of care: the OPTYX study protocol.

OPTYX is a multi-center, prospective, observational study designed to further understand the actual experience of patients with advanced prostate cancer treated with relugolix (ORGOVYX®), an oral androgen deprivation therapy (ADT), by collecting clinical and patient-reported outcomes from routine care settings. The study aims to enroll 1000 consented patients with advanced prostate cancer from community, academic and government operated clinical practices across the USA. At planned timepoints, real-world data analysis on treatment patterns, adherence and safety as well as health outcomes and health-related quality-of-life (HRQOL) after treatment discontinuation will be published in scientific peer-reviewed journals and presented at relevant conferences. This study will provide real-world data for practitioners and researchers in their understanding of the safety and effectiveness of relugolix. Clinical Trial Registration: NCT05467176 (ClinicalTrials.gov).

What is this summary about? This is a protocol summary for a research study named OPTYX. Who can participate in this research? Men 18 or older with advanced prostate cancer initiating treatment with relugolix, an oral androgen deprivation therapy (ADT), at the time of enrollment or within the 1 month before enrollment (remaining on treatment at enrollment) and are willing and able to complete patient assessments during the study. What institutions are performing this research? Community practices, academic institutions and Veterans Health Administration facilities across the USA. What are the research assessments to obtain the results? Data will be collected from the routine medical visits twice yearly including patient demographics, medical history (co-morbidities and cardiac risk factors), prostate cancer history and treatments and test results (routine lab testosterone, PSA levels and imaging). Relugolix response and all serious adverse events (SAEs) and any nonserious adverse events (AE) leading to relugolix treatment discontinuation will be assessed. Patients will be asked to respond to evaluations about their health-related quality of life and adherence to relugolix treatment. How long would the study last? Up to 5 years from enrollment date and/or up to 2 years after relugolix discontinuation. Follow-up will end with consent withdrawal, loss to follow-up, death, or study termination, whichever comes first. What do the results of the study mean? Real-world understanding of the experience and clinical outcomes in patients with advanced prostate cancer in routine clinical care and their clinical trajectory following cessation of relugolix therapy.

Incidence of Cardiovascular Events in Patients With Prostate Cancer and Treated With Androgen Deprivation Therapy.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death among prostate cancer (PC) patients. Androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone receptor (GnRH) agonist or antagonist is the standard treatment for advanced PC. Since 2010, the Food and Drug Administration has required labeling for GnRH agonists to include warnings about increased risk for diabetes and some CVDs. METHODS: In this observational, retrospective, real-world study, we evaluated time to a first cardiovascular (CV) event within 3 years postinitiation of ADT in PC patients while controlling for CVD history and risk factors. Data from a large administrative US claims dataset (2010-2019) were analyzed using Kaplan-Meier survival analysis to calculate the HR for time to first CV event and Cox regressions to identify factors associated with time to first CV event. RESULTS: Of 10,530 patients, 92% had no history of CVD, 8% had history of CVD, and 95% were exposed to a GnRH agonist during follow-up. Kaplan-Meier analysis indicated that patients with a baseline history of CVD had increased risk of CV events within 3 years of ADT initiation vs those without such history (HR, 3.20; 95% CI, 2.58-3.96; P < .0001). Among covariates associated with higher likelihood of CV event, baseline history of CVD yielded the highest HR (2.83; 95% CI, 2.40-3.32, P < .0001). CONCLUSIONS: PC patients with a history of CVD are at increased risk of a CV event within 3 years of ADT initiation compared with those with no history of CVD.

Comparison of prostate-specific antigen response in patients with metastatic castration-sensitive prostate cancer initiated on apalutamide or abiraterone acetate: A retrospective cohort study.

BACKGROUND: Deep prostate-specific antigen (PSA) response (≥90% reduction in PSA [PSA90]) is an important early response indicator of radiographic progression-free survival and overall survival in patients with metastatic castration-sensitive prostate cancer (mCSPC). This study compared PSA90 responses by 6 months between patients with mCSPC at first use of apalutamide or abiraterone acetate, both androgen receptor signaling inhibitors. METHODS: Clinical data from 77 community urology practices in the United States were analyzed. Patients with mCSPC were classified into treatment cohorts based on their first filled prescription (index date) for apalutamide or abiraterone acetate on or after September 17, 2019 (approval date of apalutamide for mCSPC). Patients were followed from the index date until the earliest of index treatment discontinuation, treatment switch, end of clinical activity, or end of data availability (September 17, 2021). Inverse probability of treatment weighting (IPTW) was used to ensure similarity in distribution of baseline characteristics between cohorts. PSA90 was defined as the earliest attainment of ≥90% reduction in PSA relative to baseline (most recent value within 13 weeks pre-index). Time to PSA90 between cohorts was compared by weighted Kaplan-Meier analysis and with Cox proportional hazards models. RESULTS: A total of 364 patients treated with apalutamide and 147 treated with abiraterone acetate met the study criteria. Patient characteristics were well balanced after IPTW. By 6 months post-index, patients initiated on apalutamide were 53% more likely to achieve PSA90 than those initiated on abiraterone acetate (P = 0.016). Similar results were observed by 9 and 12 months post-index (both P ≤ 0.019). The median time to PSA90 was 3.5 months for the apalutamide cohort and not reached for the abiraterone acetate cohort. CONCLUSIONS: In real-world patients with mCSPC, significantly more patients achieved PSA90 with apalutamide than with abiraterone acetate, and this response was achieved earlier with apalutamide.

Attainment of early, deep prostate-specific antigen response in metastatic castration-sensitive prostate cancer: A comparison of patients initiated on apalutamide or enzalutamide.

BACKGROUND: Deep prostate-specific antigen (PSA) response, defined as a ≥90% decline in PSA (PSA90), is an important early response indicator for achieving radiographic progression-free and overall survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with a next-generation androgen signaling inhibitor (ASI), such as apalutamide or enzalutamide. The objective of this study was to compare deep PSA response among patients with mCSPC newly initiated on apalutamide or enzalutamide. METHODS: Clinical data from 69 community urology practices in the United States were evaluated. Patients with mCSPC were classified into cohorts based on their first dispensation (index date) for apalutamide or enzalutamide and were followed until the earliest of treatment discontinuation, initiation of a new next-generation androgen receptor signaling inhibitor, end of clinical activity (including death), or end of data availability (03/05/2021). Inverse probability of treatment weights (IPTW) were used to reduce baseline confounding. PSA90 was defined as the earliest ≥90% PSA decline relative to baseline PSA. The proportion of patients achieving PSA90 and time to PSA90 were reported using weighted Kaplan-Meier analysis and weighted Cox proportional hazards models, respectively. RESULTS: The apalutamide and enzalutamide cohorts comprised 186 and 165 patients, respectively. Patient characteristics were generally well balanced after IPTW. By 6 months, patients initiated on apalutamide had a 56% greater likelihood of attaining PSA90 than those initiated on enzalutamide (P = 0.014). This result remained significant through the end of the observation period. The median time to achieving PSA90 was 3.1 months with apalutamide and 5.2 months with enzalutamide. CONCLUSIONS: This real-world study demonstrated that apalutamide initiation is associated with a significantly higher likelihood of achieving ≥90% reduction in PSA as compared to initiation of enzalutamide. Moreover, this deep PSA response was observed to occur earlier with apalutamide treatment than with enzalutamide.

Real-World Prostate-Specific Antigen Response and Treatment Adherence of Apalutamide in Patients With Non-Metastatic Castration-Resistant Prostate Cancer.

OBJECTIVE: To describe prostate-specific antigen (PSA) response and treatment adherence, overall and stratified by race, for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) treated with apalutamide. METHODS: Electronic medical records representing 63 urology practices from the United States were used to conduct this study. Patients with ≥2 apalutamide prescription fills and ≥12 months of prior prostate cancer management were identified. Patients were followed from apalutamide initiation until a switch to another antineoplastic treatment, death, or end of data availability (October 4, 2019). PSA response (≥50% decline from baseline PSA) and apalutamide adherence rates are described for the overall nmCRPC population treated and also stratified by race (Black and non-Black cohorts). RESULTS: Overall, 193 patients with nmCRPC were initiated on apalutamide. Thirty-three patients were Black (17.1%), 138 were non-Black (71.5%), and the remaining had an unknown racial background. The mean baseline PSA level for the overall, Black, and non-Black cohorts, was 7.0 ng/mL, 10.5 ng/mL, and 5.6 ng/mL, respectively. At 12 months of follow-up, PSA response was 86.0%, 93.1%, and 85.9% for the overall, Black, and non-Black cohorts, respectively. During a mean follow-up period of 333 days, 352 days, and 326 days, adherence was 93.6%, 90.1%, and 94.5% for the overall, Black and non-Black cohorts, respectively. CONCLUSION: This real-world study of patients with nmCRPC initiated on apalutamide showed that PSA response was robust and consistent with clinical trial data. Moreover, both Black and non-Black patients demonstrated high treatment adherence.

Understanding and Improving 18F-Fluciclovine PET/CT Reports: A Guide for Physicians Treating Patients with Biochemical Recurrence of Prostate Cancer.

The positron emission tomography (PET) tracer 18F-fluciclovine has seen increasing use to localize disease in men with biochemical recurrence of prostate cancer, i.e., elevated prostate-specific antigen (PSA) levels post-treatment. 18F-Fluciclovine PET/computed tomography (CT) imaging reports now play central roles in many physician-patient discussions. However, because no standardized grading system or templates yet exist for 18F-fluciclovine image assessment, reports vary in format, comprehensiveness, and terminology and may be challenging to fully understand. To better utilize these documents, referring physicians should be aware of six key features of 18F-fluciclovine PET/CT. First, 18F-fluciclovine is a radiolabeled synthetic amino acid targeting the amino acid transporters ASCT2 and LAT1, which are ubiquitous throughout the body, but overexpressed in prostate cancer. Second, 18F-fluciclovine image interpretation is predominantly visual/qualitative: radiotracer uptake in suspicious lesions is compared with uptake in bone marrow or blood pool. Location of 18F-fluciclovine-avid lesions relative to typical recurrence sites and findings elsewhere in the patient are considered when evaluating lesions' probability of malignancy, as is visibility on maximum intensity projection images when assessing bone lesions. Third, 18F-fluciclovine PET/CT detection rates increase as PSA levels rise. Fourth, detection rates may differ among centers, possibly due to equipment and reader experience. Fifth, since no diagnostic test is 100% accurate, scan data should not be used in isolation. Lastly, 18F-fluciclovine PET/CT findings frequently induce changes in disease management plans. In the prospective multicenter LOCATE and FALCON studies, scans altered management plans in 59% (126/213) and 64% (66/104) of patients, respectively; 78% (98/126) and 65% (43/66) of changes, respectively, involved modality switches. Referring physicians and imagers should collaborate to improve scan reports. Referrers should clearly convey critical information, including prescan PSA levels, and open clinical questions. Imagers should produce reports that read like consultations, avoid leaving open questions, and if needed, provide thoughts on next diagnostic steps.

Optimizing the role of androgen deprivation therapy in advanced prostate cancer: Challenges beyond the guidelines.

BACKGROUND: For specific clinical indications, androgen deprivation therapy (ADT) will induce disease prostate cancer (PC) regression, relieve symptoms and prolong survival; however, ADT has a well-described range of side effects, which may have a detrimental effect on the patient's quality of life, necessitating additional interventions or changes in PC treatment. The risk-benefit analysis for initiating ADT in PC patients throughout the PC disease continuum warrants review. METHODS: A 14-member panel comprised of urologic and medical oncologists were chosen for an expert review panel, to provide guidance on a more judicious use of ADT in advanced PC patients. Panel members were chosen based upon their academic and community experience and expertise in the management of PC patients. Four academic members of the panel served as group leaders; the remaining eight panel members were from Large Urology Group Practice Association practices with proven experience in leading their advanced PC clinics. The panel members were assigned to four separate working groups, and were tasked with addressing the role of ADT in specific PC settings. RESULTS: This article describes the practical recommendations of an expert panel for the use of ADT throughout the PC disease continuum, as well as an algorithm summarizing the key recommendations. The target for this publication is all providers (urologists, medical oncologists, radiation oncologists, or advanced practice providers) who evaluate and manage advanced PC patients, regardless of their practice setting. CONCLUSION: The panel has provided recommendations for monitoring PC patients while on ADT, recognizing that PC patients will progress despite testosterone suppression and, therefore, early identification of conversion from castrate-sensitive to castration resistance is critical. Also, the requirement to both identify and mitigate side effects of ADT as well as the importance of quality of life maintenance are essential to the optimization of patient care, especially as more combinatorial therapeutic strategies with ADT continue to emerge.

Adverse Events Associated with Cumulative Corticosteroid Use in Patients with Castration-Resistant Prostate Cancer: An Administrative Claims Analysis.

INTRODUCTION: Corticosteroids are a mainstay treatment for castration-resistant prostate cancer (CRPC). Although corticosteroids have been associated with adverse events, long-term outcomes related to their sustained use have not been assessed in men with CRPC. OBJECTIVE: This study evaluated the impact of cumulative corticosteroid exposure on the risk of developing specific adverse events in men with CRPC. METHODS: Data were obtained from administrative claims databases. Adult chemotherapy-naïve men who initiated CRPC treatment following surgical or medical castration were selected. Patients were grouped into four cohorts based on cumulative corticosteroid dose: no exposure, low exposure (< 0.5 g), medium exposure (0.5-2.0 g), and high exposure (> 2.0 g). Time to each adverse event was assessed using Kaplan-Meier analyses and time-dependent Cox proportional hazard models, adjusting for baseline characteristics. RESULTS: Overall, 9425 patients were included (no exposure, N = 6765; low exposure, N = 1660; medium exposure, N = 655; high exposure, N = 345). The mean age was 71-76 years across cohorts. During the study period, cumulative corticosteroid exposure was associated with a significantly higher risk of developing an infection [high vs. no exposure, adjusted hazard ratio (HR) 2.55; 95% confidence interval (CI) 2.27-2.85; p < 0.001 for trend], peptic ulcer (HR 1.91; 95% CI 1.39-2.64; p < 0.001), acute cardiovascular events (HR 1.62; 95% CI 1.43-1.83; p < 0.001), endocrine disorder (HR 1.61; 95% CI 1.34-1.94; p < 0.001), fracture (HR 1.59; 95% CI 1.37-1.86; p < 0.001), or mental health condition (HR 1.28; 95% CI 1.06-1.55; p = 0.014). Exposure to corticosteroids was associated with a more rapid onset of adverse events. CONCLUSION: Patients with CRPC receiving corticosteroids had a higher risk of developing a wide range of adverse events than those not receiving them. The increased adverse event risk was observed after accounting, to the extent possible, for patients' overall disease severity.

Health Care Resource Utilization and Costs Associated with Corticosteroid Use in Patients with Castration-Resistant Prostate Cancer: An Administrative Claims Analysis.

BACKGROUND: Corticosteroids are used in the management of castration-resistant prostate cancer (CRPC) to reduce tumor-related symptoms because of CRPC therapies. Since corticosteroids have been associated with a range of toxicities, their use may increase the economic burden sustained by patients with CRPC. However, the economic impact of using corticosteroids in patients with CRPC has not been well characterized. OBJECTIVE: To assess the effect of previous corticosteroid use on health care resource utilization (HRU) and health care costs among men with CRPC. METHODS: Using administrative claims data (2007-2016), adult chemotherapy-naive patients who initiated CRPC treatment following surgical or medical castration were identified. Based on the cumulative corticosteroid dose during the 12 months before CRPC treatment initiation, patients were grouped into 4 cohorts: no corticosteroid (0 gm), low corticosteroid (< 0.5 gm), medium corticosteroid (0.5-2.0 gm), and high corticosteroid (> 2.0 gm). All-cause HRU and costs (2017 U.S. dollars) were compared between cohorts during the 1-year study period following CRPC treatment initiation using the no corticosteroid cohort as reference. Multivariable regression models were used to adjust for baseline covariates, including age, region, index year, Charlson Comorbidity Index score, presence of bone metastases, baseline all-cause HRU, and corticosteroid-related clinical events during baseline. RESULTS: 9,425 patients were included (no corticosteroid = 6,765, low corticosteroid = 1,660, medium corticosteroid = 655, and high corticosteroid = 345). On average, patients in the no corticosteroid cohort were older and had a lower baseline HRU and comorbidity burden than patients in the other 3 cohorts. During the study period, patients with corticosteroid exposure (across all corticosteroid cohorts) had significantly more inpatient admissions (high corticosteroid vs. no corticosteroid adjusted incidence rate ratio [IRR] = 1.56; P < 0.001), emergency department visits (high corticosteroid vs. no corticosteroid adjusted IRR = 1.30; P = 0.001), and outpatient visits (high corticosteroid vs. no corticosteroid adjusted IRR = 1.11; P < 0.001). In addition, compared with the no corticosteroid cohort, patients with corticosteroid exposure had significantly higher monthly total costs (high corticosteroid vs. no corticosteroid adjusted difference = $2,600; P < 0.001), including medical service costs (high corticosteroid vs. no corticosteroid adjusted difference = $1,564; P < 0.001) and pharmacy costs (high corticosteroid vs. no corticosteroid adjusted difference = $825; P < 0.001). CONCLUSIONS: Cumulative corticosteroid exposure before CRPC treatment initiation was associated with significantly higher HRU and costs. This increase in economic burden was more prominent among patients with annual cumulative corticosteroid doses of more than 2.0 gm. These results suggest that previous corticosteroid use may result in a higher economic burden among patients with CRPC. DISCLOSURES: This study was funded by Astellas Pharma (Northbrook, IL) and Medivation, a Pfizer Company (San Francisco, CA), the codevelopers of enzalutamide. The study sponsor was involved in the study design, data interpretation, and review. All authors contributed to the development of the manuscript and maintained control over the final content. Schultz and Wilson are employed by Astellas Pharma. Schultz owns stock in Gilead Sciences and Shire. Song and Yang are employed by Analysis Group, which received consultancy fees from Astellas Pharma. Ramaswamy is employed by Pfizer, and Lowentritt is employed by Chesapeake Urology and has served as a speaker and consultant for Astellas Pharma, Pfizer, Bayer, Dendreon, and Janssen. A synopsis of the current research was presented in poster format at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2019, which took place in San Diego, CA, on March 25-28, 2019.

Robot-assisted radical cystectomy in women: technique and initial experience.

BACKGROUND AND PURPOSE: Robot-assisted radical cystectomy (RARC) is a new management option for the treatment of bladder cancer. This study evaluates an initial experience with RARC with ileal conduit diversion in women. PATIENTS AND METHODS: Twenty patients underwent RARC with ileal conduit urinary diversion, including four women, and our surgical technique is described here. A retrospective chart review was performed to evaluate clinical stage, tumor grade, operative times, estimated blood loss (EBL), pathologic stage, lymph node pathology, and complications. RESULTS: Mean patient age was 69.5 years, median operative time was 350 minutes, and median EBL was 300 mL. Median length of stay was 5 days, with the two most recent patients leaving by postoperative day 3. The median number of lymph nodes removed was 12, with one patient revealing node-positive disease. Surgical margins were negative for disease in all patients. No patients required blood transfusion or had major complications. CONCLUSION: RARC is a new technique available for the treatment of high-risk or invasive bladder cancer in women. This surgery provides decreased morbidity while maintaining the oncologic goals of traditional radical cystectomy.

EGF and HB-EGF modulate inward potassium current in human bladder urothelial cells from normal and interstitial cystitis patients.

Interstitial cystitis (IC) is an idiopathic condition characterized by bladder hyperalgesia. Studies have shown cytokine and purinergic signaling abnormalities in cultured bladder urothelial cells (BUC) from IC patients. We performed single-cell electrophysiological studies in both normal and IC BUC. A strongly inward rectifying potassium current with conductance of the Kir2.1 channel was identified in normal BUC. This current was significantly reduced in IC BUC. Kir2.1 protein and mRNA were detected in both IC and normal BUC. Epidermal growth factor (EGF) caused a dose-dependent decrease in the inward potassium current in normal BUC. EGF is secreted in higher amounts by IC BUC and is known to decrease Kir2.1 conductance by phosphorylation of Kir2.1. Genistein, a nonspecific phosphorylation inhibitor, increased the inward potassium current in IC BUC and blocked the effect of EGF on normal BUC. Treatment of IC BUC with heparin-binding epidermal growth factor-like growth factor (HB-EGF), previously shown to be secreted in lower amounts by IC BUC, significantly increased inward potassium current. These data show that the inward potassium current in BUC can be modulated by EGF and HB-EGF. Changes in BUC membrane potassium conductance caused by altered levels of EGF and HB-EGF may therefore play a role in the pathophysiology of IC.

Venacavoscopy during nephrectomy for renal cell carcinoma with inferior vena caval thrombus.

PURPOSE: Renal cell carcinoma with inferior vena caval thrombus remains a complex challenge for the urologist. Aggressive surgery to remove all tumor can result in long-term survival. Liver transplant techniques, assistance from cardiac surgeons and bypass techniques can yield optimal vascular control but there is still a blind element inside the inferior vena cava when the thrombus is evacuated. We present data on a technique using a flexible cystoscope to evaluate the lumen of the intrahepatic and suprahepatic inferior vena cava after nephrectomy and tumor thrombectomy. MATERIALS AND METHODS: Seven patients underwent radical nephrectomy and tumor thrombectomy for renal cell carcinoma with inferior vena caval thrombus. During surgery and after removal of the tumor thrombus a flexible cystoscope was inserted into the venacavotomy for direct inspection of the inferior vena caval lumen. Any residual tumor was manipulated out of the lumen and removed. Patient records were reviewed for data on the time of this procedure, estimated blood loss, residual tumor, postoperative complications and survival. RESULTS: Venacavoscopy required an average additional 5.6 minutes and residual tumor was found in 3 of 7 patients. Average estimated blood loss was 1,170 cc and it was not affected by venacavoscopy. One patient experienced acalculous cholecystitis, possibly as a result of this procedure. Mean followup was 17.6 months with 5 of 7 patients alive. CONCLUSIONS: Venacavoscopy is a safe, reliable method of intraoperative inspection of the inferior vena cava that uses equipment and techniques familiar to every urologist. This can help prevent incomplete thrombectomy and disastrous pulmonary embolus.

Variants of the exstrophy complex: a single institution experience.

PURPOSE: Variants of the bladder/cloacal exstrophy complex are rare. Different presentations and subsequent management and outcome are discussed. MATERIALS AND METHODS: We performed a retrospective review of our database of more than 815 patients with the exstrophy complex. Patients with variants of classic epispadias or bladder or cloacal exstrophy were identified. Anatomical presentation, surgical management, type of continence procedures and final outcome were evaluated. RESULTS: Of the 25 patients with variants 13 were treated primarily at our institution and 12 were referred. Time until primary bladder closure ranged from 1 day to 4 years. Followup after continence procedure ranged from 1 month to 39 years. Seven of the 25 patients are awaiting a continence procedure. Six patients are dry without a continence procedure, of whom 4 have superior vesical fistulas. A total of 11 patients underwent bladder neck reconstruction (BNR), of whom 3 are dry, 2 are dry during the day but are wet at night, 1 had a failed procedure and 5 are dry after continent diversion (CD). One additional patient underwent CD initially and is dry. Referred cases of epispadias with bladder prolapse were not recognized at birth and had delayed closure. Impaired bladder growth or failed BNR required CD in 4 patients, and 2 are awaiting a continence procedure. Skin covered and duplicate exstrophy had comparable outcomes to the classic presentations. Duplicated organs were used for reconstructive procedures. Of the 6 patients with cloacal variant 2 are continent of stool and 2 await a Pena procedure. One of these patients has an ileal stoma and 1 has a colostomy. CONCLUSIONS: The initial presentation of exstrophy variants can be confusing, often delaying initial treatment. Superior vesical fistulas permit continence without BNR due to an intact urinary sphincter. Variants such as epispadias with bladder prolapse and duplicate or skin covered exstrophy should be closed at birth with standardized techniques to promote bladder growth for later BNR. These cases are faced with the same long-term problems as the classic presentation. Cloacal variants can present with intact anal innervation, allowing a later Pena procedure.