Hypogonadism, frailty, and postoperative outcomes among men undergoing radical nephrectomy.

BACKGROUND AND OBJECTIVE: Hypogonadism and frailty may impact postoperative outcomes for men undergoing radical nephrectomy (RN). We aimed to determine the prevalence of hypogonadism in men undergoing RN and whether hypogonadism and frailty are associated with adverse postoperative outcomes. METHODS: We identified men undergoing RN between 2012 and 2021 using the IBM Marketscan database. Frailty was determined using the Hospital Frailty Risk Score (HFRS). Patients were considered to have hypogonadism if diagnosed <5 years before RN. Length of stay (LOS), complications, emergency department (ED) visits, and readmissions were evaluated between men with and without hypogonadism at the time of surgery. Subgroup analysis of men with hypogonadism was performed to determine the effect of testosterone replacement therapy (TRT) on clinical outcomes. RESULTS: Among 13 598 men who underwent RN, 972 (7.1%) had hypogonadism. Men with hypogonadism were more frail compared to men without hypogonadism (HFRS: median: 8.2, interquartile range [IQR]: 5.2-11.7 vs. median: 7.0, IQR: 4.3-10.7, p < 0.001) and had increased incidence of postoperative ileus (13.0% vs. 10.8%, p = 0.045), acute kidney injury (25.5% vs. 21.6% p = 0.005), and cardiac arrest (1.2% vs. 0.6%, p = 0.034). Hypogonadism was not associated with LOS, 90-day ED visit or readmission. However, high-risk frailty was associated with increased risk of 90-day ED visit (hazard ratio [HR]: 2.1, 95% confidence interval [95% CI]: 1.9-2.4, p < 0.001) and 90-day inpatient readmission (HR: 2.6, 95% CI: 2.2-3.1, p < 0.001), compared to low-risk frailty patients. Among men with hypogonadism, TRT was not associated with any postoperative outcomes. CONCLUSIONS: Hypogonadism and frailty should be considered in the preoperative evaluation for men undergoing RN as risk factors for adverse postoperative outcomes.

The association between frailty, hypogonadism, and postoperative outcomes among men undergoing radical cystectomy.

INTRODUCTION: Hypogonadism is associated with frailty, lower health-related quality of life, decreased muscle mass, and premature mortality, which may predispose patients to poor postoperative outcomes. We aimed to determine the prevalence of hypogonadism in men undergoing radical cystectomy (RC) and whether hypogonadism and frailty are associated with adverse postoperative outcomes. MATERIALS AND METHODS: The IBM MarketScan database was used to identify men who underwent RC between 2012 and 2021. Frailty was determined using published Hospital Frailty Risk Score ranges. Patients were considered to have hypogonadism if diagnosed within 5 years prior to RC. Length of stay (LOS), complications, emergency department (ED) visits and inpatient readmissions were compared. Sub-group analysis of men with hypogonadism was performed to determine the effect of testosterone replacement therapy (TRT) on clinical outcomes. RESULTS: Among 3,727 men who underwent RC, 226 (6.1%) had a diagnosis of hypogonadism. Overall, 565 (15.2%) men were low-risk frailty, 2,214 (59.4%) intermediate-risk frailty, and 948 (25.4%) were high-risk frailty, and men with hypogonadism were significantly more frail compared to men without hypogonadism (P = 0.027). There was no significant difference in LOS, complications, or rate of ED visits and inpatient readmissions between cohorts (P > 0.05). However, high-risk frailty was associated with an increased risk of 90-day ED visit (HR 1.19, 95%CI 1.00-1.41, P = 0.049) and 90-day readmission (HR 1.60, 95%CI 1.29-1.97, P < 0.001) after RC. Among men with hypogonadism, 58 (25.7%) were on TRT. There was no significant difference in frailty, LOS, complications, or 90-day ED visits or 90-day inpatient readmissions between patient with hypogonadism prescribed TRT and those without TRT. CONCLUSIONS: These findings suggest that hypogonadism and preoperative frailty may be important to evaluate prior to undergoing RC.

Prosteria - National Trends and Outcomes of More Frequent Than Guideline Recommended Prostate Specific Antigen Screening.

OBJECTIVE: To characterize national trends in and associated outcomes of more often than annual prostate-specific antigen (PSA) screening, which we term "prosteria." METHODS: Men in the Optum Clinformatics Data Mart with ≥2 years from first PSA test to censoring at the end of insurance or available data (January 2003 to June 2019) or following exclusionary diagnoses or procedures, such as PCa treatment, were included. PSAs within 90 days were treated as one PSA. Prosteria was defined as having ≥3 PSA testing intervals of ≤270 days. RESULTS: A total of 9,734,077 PSAs on 2,958,923 men were included. The average inter-PSA testing interval was 1.5 years, and 4.5% of men had prosteria, which increased by 0.53% per year. Educated, wealthy, non-White patients were more likely to have prosteria. Men within the recommended screening age (ie 55-69) had lower rates of prosteria. Prosteria patients had higher average PSA values (2.5 vs 1.4 ng/mL), but lower values at PCa diagnosis. Prosteria was associated with biopsy and PCa diagnosis; however, there were comparable rates of treatment within 2 years of diagnosis. CONCLUSION: In this large cohort study, prosteria was common, increased over time, and was associated with demographic characteristics. Importantly, there were no clinically meaningful differences in PSA values at diagnosis or rates of early treatment, suggesting prosteria leads to both overdiagnosis and overtreatment. These results support current AUA and USPTF guidelines and can be used to counsel men seeking more frequent PSA screening.

Sociodemographic factors associated with Wilms tumor treatment and survival: a population-based study.

INTRODUCTION: Though Wilms tumor (WT) is one of the most common malignancies in children, there is a paucity of epidemiologic studies exploring sociodemographic disparities in treatment and survival. Here, we leveraged a national cancer registry to examine sociodemographic factors associated with receipt of adjuvant therapy, either chemotherapy or radiation, as well as overall survival among pediatric patients with WT. MATERIALS AND METHODS: Within the Surveillance Epidemiology and End Results database (2000-2016), we identified 2043 patients (≤ 20 years of age) with unilateral WT. Multivariable logistic regression and Cox proportional hazard models were constructed to examine the association of sociodemographic factors with, respectively, adjuvant chemotherapy/radiotherapy and overall survival (OS). RESULTS: Patients in the lowest SES quintile (OR 0.56, 95% CI 0.33-0.93, p = 0.03) were less likely to receive chemotherapy as compared to those in the highest SES quintile, though this association did not persist in sensitivity analyses including only patients at least 2 years of age and patients with regional/distant disease. In addition, female patients were more likely to receive chemotherapy (OR 1.46, 95% CI 1.08-1.97, p = 0.02) than male patients. Age, race, year of diagnosis, insurance status, and tumor laterality were not associated with receipt of chemotherapy. No sociodemographic variables were associated with receipt of radiotherapy. Lastly, as compared to Non-Hispanic-White patients, Hispanic patients had worse OS (HR 1.59, 95% CI 1.08-2.35, p = 0.02); no other sociodemographic variables were associated with OS. CONCLUSIONS: This study suggests multilevel sociodemographic disparities involving ethnicity and SES in WT treatment and survival.

Biliary cancer brain metastases: a multi-institution case series with case reports.

Background: Biliary cancers are rare, and few reported cases of brain metastases from primary biliary cancers exist, especially describing patients in the United States. This report assesses the proportion and incidence of brain metastases arising from primary biliary cancers [cholangiocarcinoma (CCA) and gallbladder cancer] at Stanford University and the University of California, San Francisco, describes clinical characteristics, and provides a case series. Methods: We queried 3 clinical databases at Stanford and the University of California, San Francisco to retrospectively identify and review the charts of 15 patients with brain metastases from primary biliary cancers occurring between 1990 to 2020. Results: Among patients with brain metastases analyzed at Stanford (3,585), 6 had a primary biliary cancer, representing 0.17% of all brain metastases. Among biliary cancer patients at the University of California, San Francisco (1,055), 9 had brain metastases, representing an incidence in biliary cancer of 0.85%. A total of 15 biliary cancer patients with brain metastases were identified at the two institutions. Thirteen out of 15 patients (86.7%, 95% CI: 59.5-98.3) were female. The median overall survival from primary biliary cancer diagnosis was 214 days (95% CI: 71.69-336.82 days) and subsequent OS from the time of brain metastasis diagnosis was 57 days (95% CI: 13.43-120.64 days). Death within 90 days of brain metastasis diagnosis occurred in 66.67% of patients (95% CI: 38.38-88.17). Conclusions: Brain metastases from primary biliary cancers are rare, with limited survival once diagnosed. This report can aid health care providers in caring for patients with brain metastases from primary biliary cancers.

ALDH2 Expression, Alcohol Intake and Semen Parameters among East Asian Men.

PURPOSE: Inactivating mutations in mitochondrial aldehyde dehydrogenase 2 (ALDH2) are highly prevalent. The most common variant allele, ALDH2*2, is present in 40%-50% of East Asians, and causes acetaldehyde accumulation, flushing and tachycardia after alcohol intake. The relationship between alcohol intake and ALDH2 genotype on semen parameters remains unknown. MATERIALS AND METHODS: We conducted a cross-sectional study to determine the association between ALDH2 genotype, alcohol consumption and semen parameters among East Asian men. Volunteers completed a survey and submitted a semen sample for analysis. Participants were genotyped to determine ALDH2 status (ALDH2*1/*1, ALDH2*1/*2, ALDH2*2/*2), and immunohistochemical staining was used to determine protein expression of ALDH2 in spermatozoa. RESULTS: Of 112 men 45 (40.2%) were ALDH2*2 carriers. Among ALDH2*2 carriers, alcohol consumption was associated with significantly lower total sperm motility (median 20% [interquartile range 11%-42%] vs 43% [IQR 31%-57%], p=0.005) and progressive sperm motility (19% [IQR 11%-37%] vs 36% [IQR 25%-53%], p=0.008). Among alcohol consumers, ALDH2*2 carriers had significantly lower total sperm motility (20% [IQR 11%--42%] vs 41% [IQR 19%-57%], p=0.02), progressive sperm motility (19% [IQR 11%-37%] vs 37% [IQR 17%-50%], p=0.02) and total motile sperm count (28 million [M; IQR 9-79M] vs 71M [IQR 23-150M], p=0.05) compared to ALDH2*1/*1 individuals. Secondly, ALDH2 expression in human spermatozoa was significantly lower in ALDH2*2 carriers (ALDH2*1/*1 vs ALDH2*1/*2, p=0.01; ALDH2*1/*1 vs ALDH2*2/*2, p <0.001). CONCLUSIONS: Our findings suggest genotyping ALDH2, coupled with alcohol cessation counseling, may improve semen parameters among men.

Delayed Ejaculation After Lumbar Spine Surgery: A Claims Database Analysis.

STUDY DESIGN: Retrospective cohort. OBJECTIVES: Delayed ejaculation (DE) is a distressing condition characterized by a notable delay in ejaculation or complete inability to achieve ejaculation, and there are no existing reports of DE following lumbar spine surgery. Inspired by our institutional experience, we sought to assess national rates of DE following surgery of the lumbar spine. METHODS: We queried the Optum De-identified Clinformatics Database for adult men undergoing surgery of the lumbar spine between 2003 and 2017. The primary outcome was the development of DE within 2 years of surgery. Multivariable logistic regression was performed to identify factors associated with the development of DE. RESULTS: We identified 117 918 men who underwent 162 646 lumbar spine surgeries, including anterior lumbar interbody fusion (ALIF), posterior lumbar fusion (PLF), and more. The overall incidence of DE was 0.09%, with the highest rate among ALIF surgeries at 0.13%. In multivariable analysis, the odds of developing DE did not vary between anterior/lateral lumbar interbody fusion, PLF, and other spine surgeries. A history of tobacco smoking (OR = 1.47, 95% CI 1.00-2.16, P = .05) and obesity (OR = 1.56, 95% CI 1.00-2.44, P = .05) were associated with development of DE. CONCLUSIONS: DE is a rare but distressing complication of thoracolumbar spine surgery, and patients should be queried for relevant symptoms at postoperative visits when indicated.

Partial versus total adrenalectomy for pheochromocytoma: a population-based comparison of outcomes.

PURPOSE: The literature assessing outcomes of partial adrenalectomy (PA) among patients with pheochromocytoma patients is largely limited to isolated, single-institution series. We aimed to perform a population-level comparison of outcomes between patients undergoing PA versus those undergoing total adrenalectomy (TA). METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) was queried to identify adults with pheochromocytoma who underwent either PA or TA. Survival was assessed using multivariable Cox proportional hazards regression, Fine and Gray competing-risks regression, propensity score matching, Kaplan-Meier analysis, and cumulative incidence plots. RESULTS: 286 patients (PA: 101, TA: 185) were included in this study. As compared to those undergoing TA, patients undergoing PA had fewer tumors ≥ 8 cm in size (28.7% versus 42.7%, p = 0.048) and were more likely to have localized disease (61.4% versus 44.3%, p = 0.01). In multivariable analysis, patients undergoing PA demonstrated similar all-cause mortality (HR = 0.71, 95% CI 0.44-1.14, p = 0.16) and cancer-specific mortality (HR = 0.64, 95% CI 0.35-1.17, p = 0.15) compared to those who underwent TA. Following 1:1 propensity score matching, Kaplan-Meier analysis revealed no difference in overall survival between PA and TA groups (p = 0.26) nor was there a difference in the cumulative incidence of cancer-specific mortality (p = 0.29). CONCLUSIONS: In this first population-level comparison of outcomes among patients with pheochromocytoma undergoing PA and those undergoing TA, we found no long-term differences in any survival metric between groups. PA circumvents the need for lifelong corticoid replacement therapy and remains a promising option for patients with bilateral or recurrent pheochromocytoma.

Female Sexual Function During the COVID-19 Pandemic in the United States.

INTRODUCTION: International studies have demonstrated increasing rates of sexual dysfunction amidst the coronavirus disease 2019 (COVID-19) pandemic; however, the impact of the pandemic on female sexual function in the United States is unknown. AIM: To assess the impact of the COVID-19 pandemic on female sexual function and frequency in the United States. METHODS: A pre-pandemic survey containing the Female Sexual Function Index (FSFI) and demographic questions was completed by adult women in the United States from October 20, 2019 and March 1, 2020. The same women were sent a follow-up survey also containing the FSFI, as well as the Patient Health Questionnaire for Depression and Anxiety with 4 items (PHQ-4), and questions pertaining to mask wearing habits, job loss, and relationship changes. Risk for female sexual dysfunction (RFSD) was defined as FSFI < 26.55. MAIN OUTCOME MEASURE: Differences in pre-pandemic and intra-pandemic female sexual function, measured by the FSFI, and sexual frequency. RESULTS: Ninety-one women were included in this study. Overall FSFI significantly decreased during the pandemic (27.2 vs 28.8, P = .002), with domain-specific decreases in arousal (4.41 vs 4.86, P = .0002), lubrication (4.90 vs 5.22, P = .004), and satisfaction (4.40 vs 4.70, P = .04). There was no change in sexual frequency. Contingency table analysis of RFSD prior to and during the pandemic revealed significantly increased RFSD during the pandemic (P = .002). Women who developed RFSD during the pandemic had higher PHQ-4 anxiety subscale scores (3.74 vs 2.53, P = .01) and depression subscale scores (2.74 vs 1.43, P = .001) than those who did not. Development of FSD was not associated with age, home region, relationship status, mask wearing habits, knowing someone who tested positive for COVID-19, relationship change, or job loss and/or reduction during the pandemic. CONCLUSION: In this population of female cannabis users, risk for sexual dysfunction increased amidst the COVID-19 pandemic and is associated with depression and anxiety symptoms. Bhambhvani HP, Chen T, Wilson-King AM, et al. Female Sexual Function During the COVID-19 Pandemic in the United States. Sex Med 2021;9:100355.

Risk of secondary neoplasms after external-beam radiation therapy treatment of pediatric low-grade gliomas: a SEER analysis, 1973-2015.

OBJECTIVE: Although past studies have associated external-beam radiation therapy (EBRT) with higher incidences of secondary neoplasms (SNs), its effect on SN development from pediatric low-grade gliomas (LGGs), defined as WHO grade I and II gliomas of astrocytic or oligodendrocytic origin, is not well understood. Utilizing a national cancer registry, the authors sought to characterize the risk of SN development after EBRT treatment of pediatric LGG. METHODS: A total of 1245 pediatric patient (aged 0-17 years) records from 1973 to 2015 were assembled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable subdistribution hazard regression models were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Cumulative incidence analyses measured the time to, and rate of, SN development, stratified by receipt of EBRT and controlled for competing mortality risk. The Fine and Gray semiparametric model was used to estimate future SN risk in EBRT- and non-EBRT-treated pediatric patients. RESULTS: In this study, 366 patients received EBRT and 879 did not. Forty-six patients developed SNs after an LGG diagnosis, and 27 of these patients received EBRT (OR 3.61, 95% CI 1.90-6.95; p < 0.001). For patients alive 30 years from the initial LGG diagnosis, the absolute risk of SN development in the EBRT-treated cohort was 12.61% (95% CI 8.31-13.00) compared with 4.99% (95% CI 4.38-12.23) in the non-EBRT-treated cohort (p = 0.013). Cumulative incidence curves that were adjusted for competing events still demonstrated higher rates of SN development in the EBRT-treated patients with LGGs. After matching across available covariates and again adjusting for the competing risk of mortality, a clear association between EBRT and SN development remained (subhazard ratio 2.26, 95% CI 1.21-4.20; p = 0.010). CONCLUSIONS: Radiation therapy was associated with an increased risk of future SNs for pediatric patients surviving LGGs. These data suggest that the long-term implications of EBRT should be considered when making treatment decisions for this patient population.

The Association of the COVID-19 Pandemic on Male Sexual Function in the United States: A Survey Study of Male Cannabis Users.

INTRODUCTION: International studies have suggested that social disruptions caused by the COVID-19 pandemic have led to sexual dysfunction, but the impact on males in the United States is less defined. AIM: To examine changes in male sexual function during the COVID-19 pandemic and to evaluate associated demographic variables. METHODS: Prepandemic survey data was collected between October 20, 2019 and March 1, 2020 on adult males in the United States. Follow-up survey data collected for comparison during the COVID-19 pandemic between August 1, 2020 and October 10, 2020 included International Index of Erectile Function (IIEF) scores, Patient Health Questionnaire for Depression and Anxiety with 4 items (PHQ-4) scores, and questions regarding sexual frequency. Questions were also asked about mask-wearing habits, job loss, relationship changes, and proximity to individuals who tested positive for COVID-19. MAIN OUTCOME MEASURES: Differences in prepandemic and pandemic male sexual function assessed by self-reported IIEF domain scores and sexual frequency RESULTS: Seventy six men completed both prepandemic and pandemic surveys with a mean age of 48.3 years. Overall, there were no differences in either overall IIEF score or any subdomain score when comparing men's pre-pandemic and pandemic survey data. There was an increase in sexual frequency during the pandemic with 45% of men reporting sex ten or more times per month during the pandemic compared to only 25% of men prior to the pandemic (P = .03). Among the subgroup of 36 men who reported a decrease in IIEF, the decrease was an average of 3.97, and significantly associated with higher PHQ-4 depression subscale scores (1.78 vs 1.03, P = .02). CONCLUSION: The COVID-19 pandemic is associated with increased sexual frequency and no change in overall sexual function in males in the United States. Interventions intended to promote male sexual health during the COVID-19 pandemic should include a focus on mental health. Chen T, Bhambhvani HP, Kasman AM, et al. The Association of the COVID-19 Pandemic on Male Sexual Function in the United States: A Survey Study of Male Cannabis Users. J Sex Med 2021;9:100340.

Primary malignancies of the epididymis: clinical characteristics and prognostic factors.

INTRODUCTION We sought to describe clinical characteristics and identify prognostic factors among patients with primary malignancies of the epididymis (PMEs). MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1975-2015) was queried to identify patients with PME. Descriptive statistics and multivariable Cox proportional hazards models were used. RESULTS: Eighty-nine patients with PME were identified. Median age was 57 years (5-85), and median overall survival (OS) was 16.8 years. The most commonly represented histologies were rhabdomyosarcoma (19.1%), B-cell lymphoma (16.9%), leiomyosarcoma (16.9%), and liposarcoma (12.4%). In multivariable analysis, tumor size ≥ 4 cm was associated with worse OS (HR = 4.46, p = 0.01) compared to tumors < 4 cm. Patients with nonsarcomatoid histology had OS similar to patients with sarcomatoid histology (HR = 0.95, p = 0.92). Disease with regional invasion (HR = 5.19, p = 0.007) and distant metastasis (HR = 29.80, p = 0.0002) had worse OS compared to localized disease. Receipt of radiotherapy was associated with enhanced OS (HR = 0.10, p = 0.006), whereas receipt of chemotherapy was not associated with OS. CONCLUSIONS: We describe the largest cohort of PMEs to date. Larger lesions and tumor stage were independently associated with poor overall survival, while receipt of radiotherapy was associated with enhanced overall survival.

The quality of systematic reviews and meta-analyses assessing the treatment and management of male infertility.

BACKGROUND: Male factor infertility (MFI) is a common medical condition which requires high-quality research to guide clinical practice; however, systematic reviews (SRs) and meta-analyses (MAs) often vary in quality, raising concerns regarding the validity of their results. We sought to perform an objective analysis of SRs and MAs in MFI treatment and management and to report on the quality of published literature. METHODS: A comprehensive search in PubMed/MEDLINE and Embase was used to identify relevant publications. Primary search terms were male infertility, male sterility, and male subfertility. Two authors independently performed searches, screened citations for eligibility, extracted data for analysis, and graded methodological quality using the validated AMSTAR (A Measurement Tool to Assess Systematic Reviews) instrument, a validated tool used in the critical appraisal of SRs/MAs. RESULTS: Of 27 publications met inclusion criteria and were included in the analysis. Mean AMSTAR score (± SD) among all publications was 7.4 (1.9) out of 11, reflecting "fair to good" quality. Non-pharmacological medical treatment for MFI was the most commonly assessed intervention (n = 13, 48.1%). No publications met all AMSTAR criteria. While the number of SRs/MAs has increased over time (P = 0.037), the quality of publications has not significantly changed (P = 0.72). SRs/MAs of the Cochrane Library had higher AMSTAR score than non-Cochrane SRs/MAs (8.5 vs 6.3, P = 0.002). CONCLUSIONS: The methodological quality of SRs/MAs should be assessed to ensure high-quality evidence for clinical practice guidelines in MFI treatment and management. This review highlights a need for increased effort to publish high-quality studies in MFI treatment and management.

Racial and socioeconomic disparities in retroperitoneal lymph node dissection and survival in nonseminomatous germ cell tumor: A population-based study.

BACKGROUND: Though testicular cancer is the most common cancer in young men, there is a paucity of epidemiologic studies examining sociodemographic disparities in adjuvant therapy and outcomes. We examined the associations of sociodemographic factors with retroperitoneal lymph node dissection (RPLND) and survival among patients with nonseminomatous germ cell tumors (NSGCTs). METHODS: Within the Surveillance Epidemiology and End Results database (2005-2015), we identified 8,573 patients with nonseminomatous germ cell tumors. Multivariable logistic regression and Fine-Gray competing-risks regression models were constructed to examine the association of sociodemographic factors (neighborhood SES (nSES), race, and insurance) with, respectively, adjuvant RPLND within 1 year of diagnosis and cancer-specific mortality. RESULTS: Patients in the lowest nSES quintile (OR 0.59, 95% CI = 0.40-0.88, P = 0.01) and Black patients (OR 0.41, 95% CI = 0.15-1.00, P= 0.058) with stage II disease were less likely to receive RPLND compared to those in the highest quintile and White patients, respectively. Stage III patients with Medicaid (OR 0.64, 95% CI = 0.46-0.89, P= 0.009) or without insurance (OR 0.46, 95% CI = 0.27-0.76, P= 0.003) were less likely to receive RPLND compared to patients with private insurance. Lowest quintile nSES patients of all disease stages and Black patients with stage I disease (HR = 2.64, 95% CI = 1.12-6.20, P = 0.026) or stage II disease (HR=4.93, 95% CI = 1.48-16.44, P = 0.009) had higher risks of cancer-specific mortality compared to highest quintile nSES and White patients, respectively. CONCLUSIONS: This national study found multilevel, stage-specific sociodemographic disparities in receipt of RPLND and survival.

Brain Metastases from Endometrial Cancer: Clinical Characteristics, Outcomes, and Review of the Literature.

BACKGROUND: Brain metastases from endometrial cancer are rare and poorly described. We aimed to estimate the proportion of brain metastases at our institution that arose from endometrial cancer, and to detail clinicopathologic features and survival outcomes. METHODS: We retrospectively identified and reviewed the charts of 30 patients with brain metastases from endometrial cancer seen at Stanford Hospital from 2008 to 2018. RESULTS: Among all patients with brain metastases, the proportion arising from endometrial cancer was 0.84%. The median age at diagnosis was 62 years (range, 39-79 years), and the median overall survival from brain metastasis diagnosis was 6.8 months (range, 1.0-58.2 months). Most patients harbored endometrioid histology (53.3%), and some had concurrent metastases to lung (50.0%), bone (36.7%), and liver (20.0%). The median time from endometrial cancer diagnosis to brain metastasis development was 20.8 months (range, 1.4 months to 11.2 years), and the median number of brain metastases was 2 (range, 1-20). Patients with non-endometrioid histologies had more brain metastases than those with endometrioid histology (6.21 vs. 2.44, P = 0.029). There was no difference in overall survival by histology. CONCLUSIONS: We describe the largest cohort to date of patients with brain metastases originating from endometrial cancer. These patients represent a small fraction of all patients with brain metastases and have poor prognoses. These data enable providers caring for patients with brain metastases from endometrial cancer to appropriately counsel their patients.

A population-level analysis of nonsquamous penile cancer: The importance of histology.

BACKGROUND: Nonsquamous penile cancers comprise 5% of penile malignancies, though their clinicopathologic features and prognostic significance remain unknown. We used a national cancer registry to detail clinical characteristics and compare cancer-specific mortality (CSM) of nonsquamous cancers with squamous cell carcinoma (SCC). METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) was queried to identify adults with nonsquamous penile cancer and penile SCC. Multivariable Fine and Gray competing-risks regression, propensity score matching, and cumulative incidence plots were used. RESULTS: 666 men with nonsquamous penile cancer and 5,894 men with penile SCC were identified. The most commonly represented nonsquamous histological subtypes were Kaposi sarcoma (n = 183, 27.5%), melanoma (n = 74, 11.1%), basal cell carcinoma (n = 65, 9.8%), and extramammary Paget disease (n = 42, 6.3%). Cumulative incidence plots revealed a 10-year CSM rate of 32.6% in the nonsquamous penile cancer group and 25.6% in the matched penile SCC group (P < 0.0001). Among Kaposi sarcoma patients and matched SCC patients, we found a 10-year CSM rate of 29.6% in the Kaposi sarcoma group and 15.3% in the penile SCC group (P = 0.002). Similarly, a comparison of penile melanoma patients with matched SCC patients revealed a 10-year CSM rate of 38.4% in the melanoma group and 16.6% in the SCC group (P = 0.002). There was no difference in CSM between patients with basal cell carcinoma and SCC. In a sensitivity analysis limiting year of diagnosis to 2000 and onward, we found no difference in CSM between the general nonsquamous cohort or the Kaposi sarcoma cohort and matched SCC patients, but contemporary melanoma patients maintained worse CSM with a 10-year rate of 38.4% vs. 15.8% in matched SCC patients (P = 0.045). CONCLUSIONS: The most common nonsquamous penile cancers are Kaposi sarcoma, melanoma, and basal cell carcinoma. Overall, CSM is higher in nonsquamous penile cancers as compared to stage-matched SCC. Outcomes are similar in modern patients, likely due to improved control of systemic HIV in patients with Kaposi sarcoma. However, men with penile melanoma continue to experience a higher rate of CSM.

Clinicopathologic features, outcomes, and prognostic factors of testicular sarcoma: a population-based study.

PURPOSE: To describe clinical characteristics and identify prognostic factors among men with testicular sarcoma, and to compare survival with other testicular cancers. METHODS: The surveillance, epidemiology, and end results (SEER) database (1975-2016) was queried to identify adults with testicular sarcoma. Multivariable Cox proportional hazards, Fine and Gray competing-risks regression, propensity score matching, and Kaplan-Meier analyses were used. RESULTS: 230 men were included in this study. Median age at diagnosis was 58 years (range 18-94), and median OS was 10.3 years. Patients with tumors larger than 8 cm in size had worse OS (HR 1.88, p = 0.016) compared to patients with tumors < 8 cm. Disease with distant metastasis was associated with worse OS (HR 4.70, p < 0.0001) and worse CSS (HR 11.41, p < 0.0001) as compared to disease localized to the testis. Men with rhabdomyosarcoma had worse CSS (HR 3.25, p = 0.03) as compared to men with liposarcoma. Testicular sarcoma patients had worse OS than matched patients with either seminomatous germ cell tumors (GCTs, p < 0.0001) or nonseminomatous GCTs (p = 0.0019), and similar survival to matched patients with sex cord stromal tumors, testicular lymphoma, or sarcomas of the lower limb-the most common anatomic site of origin of soft tissue sarcomas. CONCLUSIONS: In the largest cohort of men with testicular sarcoma to date, we identified tumor size, disease extent, and rhabdomyosarcoma histology as independent predictors of worse survival. Stage-adjusted survival was worse as compared to men with GCTs, and similar to men with sex cord stromal tumors, testicular lymphoma, and sarcomas of other primary sites.

Evaluation of Patient Treatment Preferences for 15 to 20 mm Kidney Stones: A Conjoint Analysis.

Introduction and Objective: Ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) are standard treatments for intermediate-size (15-20 mm) kidney stones but differ in their postoperative recovery, stone-free rates, and complication risks. We aimed to evaluate what affects patient treatment preferences. Methods: Patients with urinary stone disease completed a choice-based conjoint analysis exercise assessing four treatment attributes associated with URS and PCNL. A sensitivity analysis using a market simulator was performed, and the relative importance of each attribute was calculated. Differences in treatment preferences by demographic subgroup were assessed. Results: A total of 58 patients completed the conjoint analysis exercise. Stone-free rate was the most important treatment attribute, while the length of hospital stay and cosmesis were less important. Overall, sensitivity analysis based on market simulation scenarios predicted an almost equal preference for URS (52.4%) compared with PCNL (47.6%) for treatment of an intermediate-size stone. Older patients (>65 years old) expressed their stronger preferences for lower infection rates and shorter hospital stays, and were more likely to prefer URS (67.2%, 95% confidence interval [CI]: 52% to 82.5%) compared with younger patients (20-34 years old) (20.3%, 95% CI: 0% to 41.5%) who preferred higher procedure success rates and fewer repeat procedures. Conclusion: Conjoint analysis predicts nearly equal patient preference for URS or PCNL for the treatment of intermediate-size kidney stones. Older patients prefer the lower urinary tract infection risk and shorter hospital stay associated with URS, while younger patients prefer higher stone-free rates associated with PCNL. These results can help guide urologists in counseling patients and improve the shared decision-making process.

The Association of Medicaid Insurance and Affordable Care Act Expansions with Survival among Patients with Testicular Cancer.

INTRODUCTION: Following passage of the Affordable Care Act, Medicaid access was expanded in several states beginning in 2014. We sought to determine the oncologic implications by comparing outcomes between testicular germ cell tumor patients with Medicaid and those without insurance, and by assessing for changes in outcomes after 2014. METHODS: A total of 18,506 men with seminomatous or nonseminomatous germ cell tumors were identified within the Surveillance, Epidemiology, and End Results database (2007-2016). Multivariable Cox proportional hazards, Fine and Gray competing-risks regression, propensity score matching, cumulative incidence plots and segmented Poisson regression models were used. RESULTS: Compared to no insurance, Medicaid insurance was not associated with differences in all-cause mortality or cancer-specific mortality among seminoma patients (all-cause mortality: HR=1.24, p=0.87; cancer-specific mortality: HR=0.92, p=0.75) or nonseminoma patients (all-cause mortality: HR=1.13, p=0.33; cancer-specific mortality: HR=1.10, p=0.51). Among matched Medicaid and uninsured patients, there was again no difference in cancer-specific mortality for those with seminoma (p=0.81) or nonseminoma (p=0.23). There was a 99% increase in Medicaid enrollment in expansion states in the post-Affordable Care Act era. There was no difference in post-expansion all-cause mortality between expansion states and nonexpansion states for men with seminoma (p=0.42) or nonseminoma (p=0.53). CONCLUSIONS: Medicaid enrollment increased in expansion states following the Affordable Care Act. However, there was no difference in survival between Medicaid patients and uninsured patients, or between patients in expansion states versus nonexpansion states, highlighting the need for population-level policy interventions to improve access and quality of care among testicular cancer patients with Medicaid.

Deep learning enabled prediction of 5-year survival in pediatric genitourinary rhabdomyosarcoma.

BACKGROUND: Genitourinary rhabdomyosarcoma (GU-RMS) is a rare, pediatric malignancy originating from embryonic mesenchyme. Current approaches to prognostication rely upon conventional statistical methods such as Cox proportional hazards (CPH) models and have suboptimal predictive ability. Given the success of deep learning approaches in other specialties, we sought to develop and compare deep learning models with CPH models for the prediction of 5-year survival in pediatric GU-RMS patients. METHODS: Patients less than 20 years of age with GU-RMS were identified within the Surveillance, Epidemiology, and End Results (SEER) database (1998-2011). Deep neural networks (DNN) were trained and tested on an 80/20 split of the dataset in a 5-fold cross-validated fashion. Multivariable CPH models were developed in parallel. The primary outcomes were 5-year overall survival (OS) and disease-specific survival (DSS). Variables used for prediction were age, sex, race, primary site, histology, degree of tumor extension, tumor size, receipt of surgery, and receipt of radiation. Receiver operating characteristic curve analysis was conducted, and DNN models were tested for calibration. RESULTS: 277 patients were included. The area under the curve (AUC) for the DNN models was 0.93 for OS and 0.91 for DSS. AUC for the CPH models was 0.82 for OS and 0.84 for DSS. The DNN models were well-calibrated: OS model (slope = 1.02, intercept = -0.06) and DSS model (slope = 0.79, intercept = 0.21). CONCLUSIONS: A deep learning-based model demonstrated excellent performance, superior to that of CPH models, in the prediction of pediatric GU-RMS survival. Deep learning approaches may enable improved prognostication for patients with rare cancers.