North American Fetal Therapy Network: Maternal Outcomes in Fetal Aqueductal Stenosis.

INTRODUCTION: Fetal aqueductal stenosis (AS) affects approximately 1:1,000 pregnancies. Obstruction of cerebral spinal fluid circulation occurs at the aqueduct of Sylvius, leading to progressive hydrocephalus and macrocephaly, which often necessitates cesarean section (CS). The purpose of this study was to describe maternal outcomes associated with fetal AS. METHODS: This study is conducted through the North American Fetal Therapy Network (NAFTNet). Subjects with a prenatal diagnosis of severe fetal central nervous system ventriculomegaly were recruited and followed longitudinally. Maternal events around the delivery of fetuses with AS were recorded and analyzed. RESULTS: Thirty-seven subjects with fetal AS confirmed by neonatal neuroimaging were analyzed. The average gestational age at delivery was 36.7 weeks. Overall, 86% were delivered by CS, and 62% of these were elective. Ninety-one percent of CSs were performed through a Pfannenstiel abdominal incision. A classical uterine incision was required in 13% of cesarean deliveries. The peripartum complication rate was 27%. CONCLUSION: Women carrying a fetus with AS were at risk for preterm birth, cesarean delivery, a classical uterine incision, and peripartum complications. These data highlight the maternal morbidity associated with fetal AS and the potential benefit of in utero therapy not only for neonatal outcomes but also for maternal outcomes.

Inflammatory, Metabolic and Endothelial Biomarkers Before and After Pregnancy Complications.

Women with gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth (PTB) have excess cardiovascular disease compared to those with uncomplicated births, perhaps related to pre-pregnancy inflammation, dysmetabolism or endothelial dysfunction. We included 1238 women in the Coronary Artery Risk Development in Young Adults Study (1985-2011) with 2215 births classified according to outcomes (term, uncomplicated births were the referent). Repeated measures ANOVA estimated pre-pregnancy, post-pregnancy and biomarker change according to pregnancy outcomes, adjusted for confounders. GDM and HDP groups had higher pre-pregnancy hsCRP (+0.37 [0.08, 0.65]; +0.29 [0.04, 0.55] log mg/L), leptin (+0.29 [0.09, 0.50]; +0.37 [0.17, 0.56] log ng/ml), and lower adiponectin (-0.25 [-0.36, -0.13); -0.11 [-0.22, -0.01] log ng/ml) than those with uncomplicated births and these profiles persisted in magnitude post-pregnancy. Controlling for BMI attenuated most profiles, except lower pre-pregnancy adiponectin remained associated with GDM. PTB without HDP or GDM was related to lower pre-pregnancy hsCRP and sICAM-1 (-0.31 [-0.56, -0.06] log mg/L; -0.05 [-0.09, - 0.01] log ng/ml) and a larger leptin increase from pre- to post-pregnancy, (+0.20 [0.02, 0.37] log ng/ml). Pre-pregnancy inflammation and metabolic dysfunction contributed to GDM and HDP, perhaps due to higher BMI. PTB may be related to adverse metabolic changes post-pregnancy, though the unexpected endothelial biomarker profile warrants further study.

Glycoprotein non-metastatic melanoma protein B promotes tumor growth and is a biomarker for lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease affecting almost exclusively female-sexed individuals. The cysts represent regions of lung destruction caused by smooth muscle tumors containing mutations in one of the two tuberous sclerosis (TSC) genes. mTORC1 inhibition slows but does not stop LAM advancement. Furthermore, monitoring disease progression is hindered by insufficient biomarkers. Therefore, new treatment options and biomarkers are needed. LAM cells express melanocytic markers, including glycoprotein non-metastatic melanoma protein B (GPNMB). The function of GPNMB in LAM is currently unknown; however, GPNMB's unique cell surface expression on tumor versus benign cells makes GPNMB a potential therapeutic target, and persistent release of its extracellular ectodomain suggests potential as a serum biomarker. Here, we establish that GPNMB expression is dependent on mTORC1 signaling, and that GPNMB regulates TSC2-null tumor cell invasion in vitro. Further, we demonstrate that GPNMB enhances TSC2-null xenograft tumor growth in vivo, and that ectodomain release is required for this xenograft growth. We also show that GPNMB's ectodomain is released from the cell surface of TSC2-null cells by proteases ADAM10 and 17, and we identify the protease target sequence on GPNMB. Finally, we demonstrate that GPNMB's ectodomain is present at higher levels in LAM patient serum compared to healthy controls and that ectodomain levels decrease with mTORC1 inhibition, making it a potential LAM biomarker.

Prenatal Diagnosis of Fetal Aqueductal Stenosis: A Multicenter Prospective Observational Study through the North American Fetal Therapy Network.

INTRODUCTION: A critical component of an evidence-based reassessment of in-utero intervention for fetal aqueductal stenosis (fetal AS) is determining if the prenatal diagnosis can be accurately made at a gestational age amenable to in-utero intervention. METHODS: A multicenter, prospective, observational study was conducted through the North American Fetal Therapy Network (NAFTNet). Pregnancies complicated by severe central nervous system (CNS) ventriculomegaly (lateral ventricle diameter >15 mm) not secondary to a primary diagnosis (myelomeningocele, encephalocele, etc.) were recruited at diagnosis. Imaging and laboratory findings were recorded in an online REDCap database. After evaluation, investigators were asked to render their degree of confidence in the diagnosis of fetal AS. The prenatal diagnosis was compared to the postnatal diagnosis obtained through neonatal neuroimaging. Performance characteristics of ultrasound and magnetic resonance imaging (MRI) were calculated, as was the mean gestational age at diagnosis. RESULTS: Between April 2015 and October 2022, eleven NAFTNet centers contributed 64 subjects with severe fetal CNS ventriculomegaly. Of these, 56 had both prenatal and postnatal diagnoses recorded. Ultrasound revealed 32 fetal AS true positives, 4 false positives, 7 false negatives, and 13 true negatives, rendering a sensitivity of 0.82, a specificity of 0.76, a positive predictive value of 0.89, and a negative predictive value of 0.65. The mean gestational age at diagnosis by ultrasound was 25.5 weeks (std +/- 4.7 weeks). The proportion of agreement (true positive + true negative/n) was highest at 24 weeks gestation. For fetal MRI (n = 35), the sensitivity for fetal AS was 0.95, specificity was 0.69, positive predictive value was 0.84, and negative predictive value was 0.90. MRI was performed at 25 weeks on average. CONCLUSION: The prenatal diagnosis of fetal AS can be made with accuracy at a gestational age potentially amenable to in-utero intervention. Only 7% of subjects were incorrectly diagnosed prenatally with fetal AS by ultrasound and 11% by MRI. Diagnostic accuracy of fetal AS will likely improve with increased experience.

Postnatal oogenesis leads to an exceptionally large ovarian reserve in naked mole-rats.

In the long-lived naked mole-rat (NMR), the entire process of oogenesis occurs postnatally. Germ cell numbers increase significantly in NMRs between postnatal days 5 (P5) and P8, and germs cells positive for proliferation markers (Ki-67, pHH3) are present at least until P90. Using pluripotency markers (SOX2 and OCT4) and the primordial germ cell (PGC) marker BLIMP1, we show that PGCs persist up to P90 alongside germ cells in all stages of female differentiation and undergo mitosis both in vivo and in vitro. We identified VASA+ SOX2+ cells at 6 months and at 3-years in subordinate and reproductively activated females. Reproductive activation was associated with proliferation of VASA+ SOX2+ cells. Collectively, our results suggest that highly desynchronized germ cell development and the maintenance of a small population of PGCs that can expand upon reproductive activation are unique strategies that could help to maintain the NMR's ovarian reserve for its 30-year reproductive lifespan.

Perceptions and knowledge of COVID-19 vaccine safety and efficacy among vaccinated and non-vaccinated obstetric healthcare workers.

The COVID-19 vaccines are highly effective in preventing COVID-19 illness; however, pregnant people were not included in the original COVID-19 vaccine trials, with resultant conflicting recommendations from health organizations regarding vaccinations for this high-risk population. Pregnant and lactating healthcare workers (HCWs), along with people planning a pregnancy, identified as "obstetric HCWs" in our study, were among the first to make decisions regarding vaccinating themselves against COVID-19. Given that HCWs are key sources of information and access to vaccinations, this study was conducted to understand the perceptions and knowledge of obstetric HCWs regarding the COVID-19 vaccine. An electronic survey to HCWs at a tertiary care institution in Pittsburgh, PA identified 83 obstetric HCWs, of which 65 (78.3%) received at least one dose of the either the Pfizer or Moderna COVID-19 vaccine, and 18 (21.7%) had not received any doses of vaccine. Pregnancy status influenced more people not to receive than to receive the vaccine. We found that both vaccinated and non-vaccinated obstetric HCWs had accurate knowledge regarding the COVID-19 vaccine. However, compared to non-vaccinated obstetric HCWs, vaccinated obstetric HCWs tended to endorse beliefs regarding herd immunity, believed they had a higher chance of acquiring COVID-19, and felt that the COVID-19 vaccine was safe for fetuses and people who were pregnant, lactating, breastfeeding, or planning a pregnancy. This study offers insight into obstetric individuals' perceptions and knowledge of the COVID-19 vaccine, and highlights areas where additional education and outreach may help obstetric individuals make informed decisions on receiving the COVID-19 vaccine.

Postoperative delirium in older patients after undergoing pelvic organ prolapse surgery.

INTRODUCTION AND HYPOTHESIS: To determine the 7-day incidence and risk factors of postoperative delirium (POD) occurring after prolapse surgery in women aged ≥60 years. METHODS: A prospective study of women ≥60 years undergoing prolapse surgery at a large academic center. The primary outcome is positive Confusion Assessment Method delirium screen administered in person or by telephone at the time of hospital discharge and postoperative days 1, 3, 5, and 7. RESULTS: This analysis included 165 patients, mean ± SD age of 72.5 ± 6.1 years, with median (IQR) years of education of 13 (12-16), and baseline Modified Mini-Mental Status (3MS) Exam score of 95 (92-98). Prolapse repair type was vaginal for 70% (n=115) and laparoscopic for 30% (n=50) of patients; most under general anesthesia, 151 (92.1%). The incidence of positive delirium screen during the first week after surgery was 12.1% (n=20). Most of these participants screened positive on postoperative day 0, 8.4% (n=14). In univariate analyses, a positive screen was associated with older age and fewer education years, lower 3MS exam score, greater baseline geriatric depression scale score, and greater frailty score. Lower 3MS score was the only variable that remained significant in the final model (adjusted odds ratio 0.84, 95% CI 0.75-0.95). CONCLUSIONS: One in 12 women ≥60 years deemed eligible for discharge on the day of prolapse surgery screens positive for delirium. The 7-day POD incidence is comparable to other elective non-cardiac surgery cohorts. Given the increasing trend toward same day discharge after major prolapse surgery, more research is needed to determine the impact of universal delirium screening as part of discharge assessments.

Endometrial cancer risk factors in Singapore Chinese: a prospective cohort study.

PURPOSE: The incidence of Endometrial cancer (EC) has grown substantially in Asia over the past decade. However, few studies have addressed risk factors associated with EC incidence in Asian populations. We explored the association between reproductive and dietary risk factors and EC in the Singapore Chinese Health Study (SCHS), one of the largest prospective cohort studies in Asia. METHODS: Data were collected from 34,028 ethnically Chinese women aged 45-74 residing in Singapore, enrolled between 1993 and 1998. Baseline demographic, dietary, and reproductive factors were collected via structured questionnaires. EC cases were identified from the Singapore Cancer Registry (n = 126) up to 2010. Cox proportional hazard models were used to analyze association between EC and personal, reproductive, and dietary factors. RESULTS: The incidence of EC in this population was 28.8 per 100,000 person-years. Regardless of menopausal status, obesity (BMI ≥ 27) was associated with increased EC risk (HR = 2.22, 95% CI 1.26-3.92), while later age at menarche was associated with decreased EC risk (HR = 0.14, 95% CI 0.04-0.46). In postmenopausal women, later age at menopause was associated with increased EC risk (HR = 2.82, 95% CI 1.24-6.43). Lifestyle and nutritional factors were not associated with risk of EC in this cohort. CONCLUSIONS: This study is one of the largest cohort studies exploring EC risk factors in Asian populations. Our study identified similarities in EC risk factors for European and Asian populations, which potentially suggests that strategies developed for EC prevention in Western populations can be potentially appropriate for the Singapore Chinese population due to risk factor similarities.

High-intensity end-of-life care among Medicare beneficiaries with bladder cancer.

OBJECTIVES: To quantify the proportion of patients receiving high-intensity end-of-life care, identify associated risk factors, and assess how receipt of palliative care impact end-of-life care; as the delivery of such care, and how it relates to palliative care, has not been reported in bladder cancer SUBJECTS AND METHODS: We conducted a retrospective cohort study of patients with bladder cancer who died within 1 year of diagnosis using Surveillance, Epidemiology, and End Results linked Medicare data. The primary outcome was a composite measure of high-intensity end-of-life care (>1 hospital admission, >1 ED visit, or ≥1 ICU admission within the last month of life; receipt of chemotherapy within the last 2 weeks of life; or acute care in-hospital death). Secondary outcomes included the use of such care over time and any association with the use of palliative care. A generalized linear mixed model assessed for independent determinants. RESULTS: Overall, 45% of patients received high-intensity end-of-life care. This proportion decreased over time. Patients receiving high-intensity care had higher rates of comorbidities, advanced bladder cancer, and nonbladder cancer cause of death. These patients more often received palliative care but, compared to those not receiving high-intensity care, this occurred farther removed from bladder cancer diagnosis and closer to death. CONCLUSIONS: Nearly half of Medicare beneficiaries with bladder cancer who die within 1 year of diagnosis receive high-intensity care at the end of life. Palliative care was seldom used and only very near the time of death.

Same-day discharge after minimal invasive hysterectomy: Applications for improved value of care.

OBJECTIVE: Hysterectomy is one of the most common surgical procedures. Same-day discharge (SDD) is increasingly utilized for minimally invasive hysterectomies, but its uptake varies across healthcare systems and surgical specialties. An evidence-based initiative was developed to aid in the incorporation of SDD into the practice of minimally invasive hysterectomy (MIH) in the UPMC Health System. The objective of this study was to identify trends of SDD utilization across various gynecologic specialties at UPMC, as well as evaluate the impact of SDD on length of stay (LOS) and complications after the implementation of SDD initiative. STUDY DESIGN: We retrospectively identified 5554 patients who underwent MIH between 2014 and 2017 and were eligible for SDD, as determined by physicians and authorized by patients' insurance plans. Multivariable logistic regression models evaluated the trend of SDD utilization among four specialty types (general gynecologists, urogynecologists, specialized minimally invasive surgeons, and oncologists) and trends in complications. Multivariable logistic and linear regression models were applied to compare complications and LOS between patients with SDD vs. those with overnight admissions. RESULTS: SDD utilization increased from 28.55% to 74.99% during the study period. SDD significantly increased over the study period for all specialty types, with urogynecologists having the highest uptake from 3.9% in 2014 to 95.8% in 2017 (p<.01). After adjusting for year, specialty types, MIH procedure type, and total case time, SDD utilization was associated with shorter mean LOS (p<.01); such that mean LOS was 764.43 min (95% CI: 735.46-793.40) for SDD patients and 2041.84 min (95% CI: 2015.99-2067.70) for patients with overnight admissions. SDD was also associated with 42% lower odds (95% CI: 0.37-0.93, p=.02) of complications compared with patients with overnight admissions. CONCLUSION: Same-day discharge uptake increased over years and was associated with lower odds of complications and decreased length of stay. More studies are needed to explore same-day discharge process to improve patient outcomes, patient satisfaction, and value of care.

Survival and recurrence after intraperitoneal chemotherapy use: Retrospective review of ovarian cancer hospital registry data.

BACKGROUND: Intraperitoneal/intravenous chemotherapy (IP/IV) was associated with improved survival for ovarian cancer (OC) patients in several randomized clinical trials. However, the uptake of IP/IV in clinical practice is varied due to conflicting evidence about its impact on survival and recurrence. The aim of this study was to explore the uptake of IP/IV treatment and to evaluate its impact on survival and recurrence in OC patients. METHODS: Demographic and clinical information on OC patients (N = 2916) who underwent treatment for OC between 2000 and 2017 was obtained from the large healthcare system cancer registry. Duplicate records, grade 1, rare (eg, gelatinous carcinoma), and non-epithelial (eg, granulosa cell carcinoma) tumors were excluded. Kaplan-Meier survival curves were constructed to compare 5- and 10-year survival based on the chemotherapy type, surgery type, and stage. Multivariable Gray's piecewise constant time-varying coefficient models were fitted to evaluate the effect of IP/IV on adjusted hazard ratio (AHR) of OC survival and recurrence adjusting for potential confounders. RESULTS: The final sample consisted of 1846 OC patients, 14% (250/1846) of which received IP/IV chemotherapy. IP/IV was significantly associated with improved 10-year survival (P < .001). Multivariable Gray's model demonstrated that IP/IV therapy significantly reduced the AHR of death (AHR = 0.39-1.07, P < .001) with the beneficial effect gradually declining over time. Use of IP/IV chemotherapy had no impact on OC recurrence. CONCLUSIONS: These findings demonstrated that only a small fraction of eligible patients underwent IP/IV chemotherapy. We report a significant 10-year survival, but not necessarily recurrence benefit is associated with IP/IV chemotherapy compared to IV only, suggesting the need for novel ways of identifying patients who may benefit from IP/IV chemotherapy.

Early Pregnancy Blood Pressure Elevations and Risk for Maternal and Neonatal Morbidity.

OBJECTIVE: To investigate whether women with early pregnancy elevated blood pressure (BP) or stage 1 hypertension exhibit increased risk of preeclampsia and maternal or neonatal morbidity. METHODS: We conducted a clinical cohort study of 18,162 women who delivered a singleton neonate from 2015 to 2018 and attended at least two prenatal appointments before 20 weeks of gestation. Data were collected within the Magee Obstetric Maternal and Infant database, an aggregate of prenatal and delivery health records. Early pregnancy BP was defined as average BP before 20 weeks of gestation, and women were classified with normal, elevated BP, stage 1 or 2 hypertension according to current guidelines. The primary outcome was preeclampsia. Secondary outcomes were severe maternal morbidity, placental abruption, gestational diabetes, and composite neonatal morbidity. RESULTS: Overall, 75.2% of the women were categorized with normal BP, 13.9% with elevated BP, 5.4% with stage 1 hypertension, and 5.5% with stage 2 hypertension. Risk of preeclampsia increased in a stepwise fashion with increasing BP category, adjusted for covariates (normal BP, 4.7%, referent; elevated BP, 7.3%, adjusted odds ratio [aOR] 1.29, 95% CI 1.07-1.56; stage 1, 12.3%, aOR 2.35, 95% CI 1.86-2.96), and stage 2, 30.2%, aOR 6.49, 95% CI 5.34-7.89). Results were similar among black and white women. Gestational diabetes was more prevalent among women with stage 1 (11.4%; aOR 1.50, 95% CI 1.18-1.91] and stage 2 hypertension (14.2%; aOR 1.65, 95% CI 1.30-2.10). Severe maternal morbidity and neonatal morbidity were increased only among women with stage 2 hypertension (aOR 2.99, 95% CI 2.26-3.99, and aOR 2.67, 95% CI 2.28-3.12, respectively). CONCLUSION: Women with elevated BP, and stage 1 and 2 hypertension in early pregnancy are at increased risk for preeclampsia. These findings emphasize the importance of applying the 2017 BP guidelines to reproductive-aged women. Strategies to incorporate these guidelines into obstetric care may also be warranted.

Prolapse Recurrence After Sacrocolpopexy Mesh Removal: A Retrospective Cohort Study.

OBJECTIVES: There is limited literature regarding outcomes after sacrocolpopexy mesh removal. We sought to compare the proportion of prolapse recurrence in women after sacrocolpopexy mesh removal with women who underwent sacrocolpopexy without subsequent mesh removal. We hypothesize that more women will experience prolapse recurrence after mesh removal. METHODS: This is a retrospective cohort study of women who underwent sacrocolpopexy mesh removal between 2010 and 2019. These patients were time matched with women who had a sacrocolpopexy but did not undergo mesh removal. Prolapse recurrence was defined as the leading edge past the hymen or retreatment. Analysis was done using χ, Wilcoxon rank-sum, or t test with a Cox proportional hazard model to assess the association between mesh removal and time to recurrence. RESULTS: We identified 26 mesh removals, which were matched with 78 patients without mesh removal. The most common indications for mesh removal were exposure (69.2%) and pain (57.7%). Women who underwent mesh removal were more likely to have Mersilene mesh (19.2% vs 1.3%, P = 0.006). Recurrence occurred in 46% of women who had mesh removal compared with 7.7% in those without (P < 0.001). When adjusted for age, parity, menopause, smoking, and diabetes status, those who had mesh removal had a 15 times higher hazard of prolapse recurrence (adjusted hazard ratio = 15.4, 95% confidence interval = 4.3-54.8, P = <.0001). CONCLUSIONS: When compared with time-matched controls, women who underwent sacrocolpopexy mesh removal had a significantly higher proportion of prolapse recurrence. Prospective studies are needed to further explore the utility of concomitant prolapse repair at the time of mesh removal.

Impact of intrauterine transfusion on fetal coagulation physiology by thromboelastography.

OBJECTIVE: Thromboelastography (TEG) is a point-of-care device used to evaluate whole blood coagulation function. The TEG is unique as a test of coagulation function in that it measures the interaction of all components of clot formation, which is different than traditional laboratory-based tests that measure isolated components of coagulation. Little is known about fetal coagulation physiology. We sought to evaluate the impact of severe fetal anemia and intrauterine transfusion (IUT) on fetal coagulation physiology by use of the TEG and to compare fetal TEG values to those of healthy neonates and adults. METHOD: One milliliter of fetal blood was collected immediately before (pre) and after (post) IUT of packed red blood cells (PRBCs). Sampling and transfusion were performed for fetal anemia due to hemolytic disease of the fetus and newborn. Samples were run in duplicate. For descriptive summary, duplicate pre-IUT and post-IUT values were averaged. Values for R (initiation of clot in minutes), K (clot firmness in minutes), angle (kinetics of clot development in degrees), and MA (maximum strength in mm) were obtained for each sample and presented using mean ± SE. Pre-IUT values for R, K, angle, and MA were compared with post-IUT values using linear mixed-effect model to account for clustering due to repeated observation from the same fetus. Pre-IUT values are compared with normal healthy term neonates and healthy adults using Wald test. The study was approved by the University of Pittsburgh Institutional Review Board (PRO14050051). RESULTS: Four fetuses underwent nine IUTs rendering 17 pre-IUT and 17 post-IUT specimens. The mean gestational age at IUT was 31 weeks 2 days (25 weeks 4 days to 35 weeks 2 days). The mean IUT volume transfused was 69 mL (30-170 mL). The mean estimated percent intravascular volume transfused was 33.4% (19%-52%). Of the four variables analyzed, only R showed a significant difference, with the initiation of clot formation being modestly delayed after transfusion by an estimated 2.87 minutes (95% CI, 0.82-4.92, P = .0480). Pre-IUT values were compared with 100 normal term neonates and 118 healthy adults. Compared with pre-IUT, only R was affected (shorter) compared with term neonates (mean ± SE = 5.46 ± 0.16 minute, P < .001) and healthy adults (mean ± SE = 6.8 ± 0.13 minute, P < .001). CONCLUSION: OTHER THAN A MODEST PROLONGATION OF CLOT FORMATION TIME, IUT OF PRBCS OF UP TO 52% OF THE ESTIMATED INTRAVASCULAR VOLUME DID NOT AFFECT FETAL COAGULATION FUNCTION BY TEG. OTHER THAN A SHORTER CLOT FORMATION TIME (R), THERE IS NO DIFFERENCE IN TEG VALUES BETWEEN ANEMIC PRETERM FETUSES AND HEALTHY TERM NEONATES AND HEALTHY ADULTS. BEYOND GENERALIZABLE KNOWLEDGE, THIS INFORMATION COULD BE EXPLOITED FOR FUTURE FETAL INTERVENTION TECHNIQUES.

Comparison of Neoadjuvant and Adjuvant Chemotherapy in Muscle-invasive Bladder Cancer.

BACKGROUND: We use observational methods to compare impact of perioperative chemotherapy timing (ie, neoadjuvant and adjuvant) on overall survival (OS) in muscle-invasive bladder cancer because there is no head-to-head randomized trial, and patient factors may influence decision-making. PATIENTS AND METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified patients receiving cystectomy for muscle-invasive bladder cancer diagnosed between 2004 and 2013. Patients were classified as receiving neoadjuvant or adjuvant chemotherapy. Propensity of receiving neoadjuvant chemotherapy was determined using gradient boosted models. Inverse probability of treatment weighted survival curves were adjusted for 13 demographic, socioeconomic, temporal, and oncologic covariates. RESULTS: We identified 1342 patients who received neoadjuvant (n = 676) or adjuvant chemotherapy (n = 666) with a median follow-up of 23 months (interquartile range, 9-55 months). Inverse probability of treatment weighted adjustment allows comparison of the groups head-to-head as well as counterfactual scenarios (eg, effect if those getting one treatment were to receive the other). The average treatment effect (ie, "head-to-head" comparison) of adjuvant compared with neoadjuvant on OS was not significant (hazard ratio, 1.14; 95% confidence interval, 0.99-1.31). However, the average treatment effect of the treated (ie, the effect if the neoadjuvant patients were to receive adjuvant instead) was associated with a 33% increase in risk of mortality if they were given adjuvant therapy instead (hazard ratio, 1.33; 95% confidence interval, 1.12-1.57). CONCLUSION: Significant treatment selection bias was noted in peri-cystectomy timing, which limits the ability to discriminate differential efficacy of these 2 approaches with observational data. However, patients with higher propensity to receive neoadjuvant therapy were predicted to have increased OS with approach, in keeping with existing paradigms from trial data.

The Development and Validation of Prostate Cancer-specific Physician-Hospital Networks.

OBJECTIVE: To develop prostate cancer-specific physician-hospital networks to define hospital-based units that more accurately group hospitals, providers, and the patients they serve. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare, we identified men diagnosed with localized prostate cancer between 2007 and 2011. We created physician-hospital networks by assigning each patient to a physician and each physician to a hospital based on treatment patterns. We assessed content validity by examining characteristics of hospitals anchoring the physician-hospital networks and of the patients associated with these hospitals. RESULTS: We identified 42,963 patients associated with 344 physician-hospital networks. Networks anchored by a teaching hospital (compared to a nonteaching hospital) had higher median numbers of prostate cancer patients (117 [interquartile range {71-189} vs 82 {50-126}]) and treating physicians (7 [4-11] vs 4 [3-6]) (both P <0.001). On average, patients traveled farther to networks anchored by a teaching hospital (49 miles [standard deviation] [207] vs 41 [183]; P <.001). Hospitals known as high-volume centers for robotic prostatectomies, proton-beam therapy, and active surveillance had network rates for these procedures well above the mean. Hospitals known as safety net providers served higher proportions of minorities. CONCLUSION: We empirically developed prostate-cancer specific physician-hospital networks that exhibit content validity and are relevant from a clinical and policy perspective. They have the potential to become targets for policy interventions focused on improving the delivery of prostate cancer care.

The Influence of Stereotactic Body Radiation Therapy Adoption on Prostate Cancer Treatment Patterns.

PURPOSE: To our knowledge it is unknown whether stereotactic body radiation therapy of prostate cancer is a substitute for other radiation treatments or surgery, or for expanding the pool of patients who undergo treatment instead of active surveillance. MATERIALS AND METHODS: Using SEER (Surveillance, Epidemiology, and End Results)-Medicare we identified men diagnosed with prostate cancer between 2007 and 2011. We developed physician-hospital networks by identifying the treating physician of each patient based on the primary treatment received and subsequently assigning each physician to a hospital. We examined the relative distribution of prostate cancer treatments stratified by whether stereotactic body radiation therapy was performed in a network by fitting logistic regression models with robust SEs to account for patient clustering in networks. RESULTS: We identified 344 physician-hospital networks, including 30 (8.7%) and 314 (91.3%) in which stereotactic body radiation therapy was and was not performed, respectively. Networks in which that therapy was and was not done did not differ with time in the performance of robotic and radical prostatectomy, and active surveillance (all p >0.05). The relationship with intensity modulated radiation therapy did not show any consistent temporal pattern. In networks in which it was performed less intensity modulated radiation therapy was initially done but there were similar rates in later years. Brachytherapy trends differed among networks in which stereotactic body radiation therapy was vs was not performed with a lower brachytherapy rate in networks in which stereotactic body radiation therapy was done (p=0.03). CONCLUSIONS: Surgery and active surveillance rates did not differ in networks in which stereotactic body radiation therapy was vs was not performed but when that therapy was done there was a lower brachytherapy rate. Stereotactic body radiation therapy may represent more of an alternative to brachytherapy than to active surveillance.

Patterns of stereotactic body radiation therapy: The influence of lung cancer treatment on prostate cancer treatment.

INTRODUCTION: Technology availability and prior experience with novel cancer treatments may partially drive their use. We sought to examine this issue in the context of stereotactic body radiation therapy (SBRT) by studying how its use for an established indication (lung cancer) impacts its use for an emerging indication (prostate cancer). METHODS: Using SEER-Medicare from 2007 to 2011, we developed prostate cancer-specific physician-hospital networks. Our primary dependent variable was SBRT use for prostate cancer and our primary independent variable was SBRT use for lung cancer, both at the network level. To assess the influence of SBRT availability and experiential use, we generated predicted probabilities of SBRT use for prostate cancer stratified by a network's use of lung cancer SBRT, adjusting for network characteristics. To assess intensity of use, we examined the correlation between the proportion of prostate cancer patients and lung cancer patients receiving SBRT within a network. RESULTS: We identified 316 networks that served 41,034 prostate cancer and 83,433 lung cancer patients. A network was significantly more likely to use SBRT for prostate cancer if that network used SBRT for lung cancer (e.g., in 2011, odds ratio [OR] 12.7; 95% confidence interval [CI] 3.9-41.8). The Pearson's correlation between the proportion of prostate cancer patients and lung cancer patients receiving SBRT in a network was 0.34, which was not statistically significant (P = 0.12). CONCLUSIONS: SBRT availability and experiential use for lung cancer influences its use for prostate cancer, but intensity of use for one does not relate to intensity of use for the other.

Change in Functional Status After Prostate Cancer Treatment Among Medicare Advantage Beneficiaries.

OBJECTIVE: To examine the relationship between treatment and subsequent functional status among prostate cancer patients. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data, we identified men 65 years or older diagnosed with prostate cancer between 1998 and 2009 (follow-up through 2010) who were treated with conservative management, surgery, or radiation. Our primary outcome was functional status as measured by activities of daily living. Secondary outcomes included physical component summary and mental component summary scores, which are both calculated from the Short Form 36 (SF-36) and the Veterans RAND 12-item health survey (VR-12) questionnaires. We included patients who completed 2 surveys and performed propensity score analyses to match patients 1:5 with noncancer controls. We used generalized linear mixed effects models, accounting for clustering due to insurance plan. RESULTS: We identified 408 patients of whom 143 (35%) underwent conservative management, 59 (14%) underwent surgery, and 206 (51%) underwent radiation. Among conservative management and radiation patients, changes in functional status mirrored that of their noncancer controls (all P > .05). Among surgery patients, changes in activities of daily living scores were not significant, but physical component summary (mean difference = 4.5, P < .001) and mental component summary (mean difference = 3.3, P = .01) scores declined slightly more than for their noncancer peers. CONCLUSION: Surgery patients had a slight decline in their general functional status whereas conservative management and radiation patients had no differences in functional status compared with their noncancer peers. Although the functional status of surgery patients declined more than that of their noncancer peers, this difference may not be clinically significant.