A Multicenter Evaluation of Treatment-associated Changes in Body Composition in Men With Germ Cell Tumors of the Testis: Implications for Adverse Events and Complications.

OBJECTIVE: To characterize changes in body composition following cytotoxic chemotherapy for germ cell carcinoma of the testis (GCT) and quantify associations between body composition metrics and chemotherapy-associated adverse events (AEs) and post-retroperitoneal lymph node dissection (RPLND) complications. MATERIALS AND METHODS: This retrospective multi-center study included 216 men with GCT treated with cytotoxic chemotherapy and/or RPLND (2005-2020). We measured body composition including skeletal muscle (SMI), visceral adipose (VAI,), subcutaneous adipose (SAI), and fat mass (FMI) indices on computed tomography. We quantified chemotherapy-associated changes in body composition and evaluated associations between body composition and incidence of grade 3 + AEs and post-RPLND complications on multivariable logistic regression analyses. RESULTS: One hundred and eighty-two men received a median of 3 cycles of cisplatin-based chemotherapy. Following chemotherapy, median change in SMI was -6% (P = <.0001), while VAI, SAI, and FMI increased by +13% (P = <.0001), +11% (P = <.0001), and +6% (P = <.0001), respectively. Seventy-nine patients (43%) experienced at least one grade 3 + AE. A decrease in SMI following chemotherapy was associated with increased risk of grade 3 + AEs (P = .047). One hundred and 3 men with a median age of 28.5 years (IQR 23-35.5) underwent RPLND of whom 22 (21.3%) experienced at least 1 grade 3 + post-RPLND complication. No baseline body composition metrics were associated with post-RPLND complications. CONCLUSION: In men with GCT of the testis, chemotherapy was associated with 6% loss of lean muscle mass and gains in adiposity. Lower skeletal muscle was associated with a higher incidence of chemotherapy-associated AEs. Body composition was not associated with the incidence of post-RPLND complications.

Patterns of chemotherapy use with primary radiotherapy for localized bladder cancer in patients 65 or older.

Introduction: Bladder preservation with concurrent chemoradiotherapy after maximum transurethral resection of bladder tumor is an alternative to radical cystectomy in select patients with muscle invasive bladder cancer (MIBC). Concurrent administration of radio-sensitizing chemotherapy and radiation therapy (RT) has been shown to have superior disease control compared with RT alone and can often be administered with modest added toxicity. We sought to describe national patterns of chemotherapy use. Methods: The linked surveillance, epidemiology, and end results (SEER)-Medicare database was used to identify patients with cT2-4, N0/X, M0/X BC who received radiation between 2004 and 2018. Data on demographics, clinicopathologic factors, therapy and outcomes were extracted. Concurrent utilization of chemotherapy with RT was also identified (CRT). Multivariate logistic regression (MVA) models were used to explore factors associated with receipt of chemotherapy and overall survival (OS). Results: 2190 patients met inclusion criteria. Of these, 850 (38.8%) received no chemotherapy. Among those receiving chemotherapy, the most frequent regimens were single agent carboplatin, cisplatin, or gemcitabine. Factors that were independently associated with decreased likelihood of chemotherapy use were increasing age (OR 0.93, CI 0.92 - 0.95), Hispanic race (compared with White, OR 0.62, CI 0.39 - 0.99), cT3 or T4 (compared with cT2, OR 0.70, CI 0.55 - 0.90), and lower National Cancer Institute comorbidity index (OR 0.60, CI 0.51 - 0.70) (p < 0.05). Variables independently associated with increased likelihood of receipt of chemotherapy were married status (OR 1.28, CI 1.06 - 1.54), higher socioeconomic status (OR 1.31, CI 1.06 - 1.64), and later year of diagnosis (OR 1.09, CI 1.06 - 1.12). Receipt of concurrent chemotherapy with RT was associated with superior OS compared with RT alone. Conclusion: Over a third of patients >/65 years old receiving curative-intent RT for MIBC do not receive concurrent chemotherapy. Considering the improvement in oncologic outcomes with CRT over RT alone and more options, such as low dose gemcitabine which can be administered with modest toxicity, efforts are needed to identify barriers to utilization and increase the use of radio-sensitizing chemotherapy.

Phase 1/2 Randomized Clinical Trial of In-clinic acupuncture Prior to Bacillus Calmette-Guérin in Patients with High-risk Non-muscle-invasive Bladder Cancer.

BACKGROUND: Treatment-related dose-limiting dysuria and irritative bladder symptoms are common in patients receiving intravesical bacillus Calmette-Guérin (BCG) to treat non-muscle-invasive bladder cancer (NMIBC). Acupuncture has been shown to reduce pain and urinary urgency/frequency in other patient populations. OBJECTIVE: To evaluate the feasibility, safety, and tolerability of weekly in-clinic preprocedural acupuncture among patients receiving induction BCG. DESIGN, SETTING, AND PARTICIPANTS: Patients with high-risk NMIBC undergoing induction BCG were randomized 2:1 to a standardized acupuncture protocol (acupuncture) versus the standard-of-care control arm. INTERVENTION: In-office acupuncture prior to each BCG instillation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Feasibility was assessed via recruitment, retention, and intervention adherence. Acupuncture safety and tolerability were assessed via physician-reported Common Terminology Criteria for Adverse Events version 5.0 and adverse events (AEs). Secondary endpoints included BCG treatment adherence, patient-reported BCG-related toxicity, and bladder cancer-specific and generic (European Organisation for Research and Treatment of Cancer [EORTC]-QLQ-NMIBC-24 and EORTC-QLQ-NMIBC-C30) quality of life (QOL). Subjective assessments of acupuncture acceptability were performed through patient surveys. RESULTS AND LIMITATIONS: A total of 43 individuals were randomized 2:1 to the acupuncture (n = 28) versus control (n = 15) group. The median age was 70.3 yr, and 76% were male. Week 7 follow-up surveys were completed by 93%; six participants withdrew early due to disease progression, refractory gross hematuria, or preference. Acupuncture was delivered successfully prior to each BCG treatment, with no acupuncture-related AEs or interruptions to induction BCG. BCG-attributed AEs were reported by 91% acupuncture and 100% control individuals, including pain (28% vs 43%, p = 0.34) and urinary symptoms (62% vs 79%, p = 0.31). Comparing acupuncture patients with controls, change in QOL over the study period demonstrated greater improvements in median urinary symptoms (9.5, interquartile range [IQR] 0.0-19.0 vs 0.0, IQR -14.3 to 7.1; p = 0.02) among patients in the acupuncture arm. Of the acupuncture patients, 96% reported that acupuncture was "very/extremely helpful," and 91% would recommend acupuncture to other patients. Limitations include modest sample size and single-institution design. CONCLUSIONS: Acupuncture prior to induction BCG treatments is feasible and safe. In this phase 1/2 trial, improved urinary function scores were observed among patients undergoing acupuncture. Patients receiving acupuncture reported high degrees of satisfaction with treatments. PATIENT SUMMARY: We evaluated the safety and feasibility of delivering acupuncture in a urology clinic prior to weekly intravesical bladder cancer treatments with bacillus Calmette-Guérin (BCG) in a randomized controlled trial. We found that acupuncture could be delivered safely prior to weekly BCG instillations and that the use of acupuncture was associated with high patient satisfaction and a decrease in patient-reported urinary symptoms compared with usual care.

Isolating the Drivers of Racial Inequities in Prostate Cancer Treatment.

BACKGROUND: Black individuals in the United States are less likely than White individuals to receive curative therapies despite a 2-fold higher risk of prostate cancer death. While research has described treatment inequities, few studies have investigated underlying causes. METHODS: We analyzed a cohort of 40,137 Medicare beneficiaries (66 and older) linked to the Surveillance Epidemiology and End Results (SEER) cancer registry who had clinically significant, non-metastatic (cT1-4N0M0, grade group 2-5) prostate cancer (diagnosed 2010-2015). Using the Kitagawa-Oaxaca-Blinder decomposition, we assessed the contributions of patient health and health care delivery on the racial difference in localized prostate cancer treatments (radical prostatectomy or radiation). Patient health consisted of comorbid diagnoses, tumor characteristics, SEER site, diagnosis year, and age. Health care delivery was captured as a prediction model with these health variables as predictors of treatment, reflecting current treatment patterns. RESULTS: A total of 72.1% and 78.6% of Black and White patients received definitive treatment, respectively, a difference of 6.5 percentage points. An estimated 15% [95% confidence interval (CI): 6-24] of this treatment difference was explained by measured differences in patient health, leaving the remaining estimated 85% (95% CI: 74-94) attributable to a potentially broad range of health care delivery factors. Limitations included insufficient data to explore how specific health care delivery factors, including structural racism and social determinants, impact differential treatment. CONCLUSIONS: Our results show the inadequacy of patient health differences as an explanation of the treatment inequity. IMPACT: Investing in studies and interventions that support equitable health care delivery for Black individuals with prostate cancer will contribute to improved outcomes.

Prostate cancer screening in African American men: a review of the evidence.

BACKGROUND: Prostate cancer is the most diagnosed cancer in African American men, yet prostate cancer screening regimens in this group are poorly guided by existing evidence, given underrepresentation of African American men in prostate cancer screening trials. It is critical to optimize prostate cancer screening and early detection in this high-risk group because underdiagnosis may lead to later-stage cancers at diagnosis and higher mortality while overdiagnosis may lead to unnecessary treatment. METHODS: We performed a review of the literature related to prostate cancer screening and early detection specific to African American men to summarize the existing evidence available to guide health-care practice. RESULTS: Limited evidence from observational and modeling studies suggests that African American men should be screened for prostate cancer. Consideration should be given to initiating screening of African American men at younger ages (eg, 45-50 years) and at more frequent intervals relative to other racial groups in the United States. Screening intervals can be optimized by using a baseline prostate-specific antigen measurement in midlife. Finally, no evidence has indicated that African American men would benefit from screening beyond 75 years of age; in fact, this group may experience higher rates of overdiagnosis at older ages. CONCLUSIONS: The evidence base for prostate cancer screening in African American men is limited by the lack of large, randomized studies. Our literature search supported the need for African American men to be screened for prostate cancer, for initiating screening at younger ages (45-50 years), and perhaps screening at more frequent intervals relative to men of other racial groups in the United States.

Chronic Glucocorticoid Use and Risk for Advanced Prostate Cancer at Presentation: A SEER-Medicare Cohort Study.

BACKGROUND: Examine the relationship between exposure to systemic glucocorticoids (steroids) and advanced prostate cancer (PCa) at presentation. Prior work suggested that steroid use may be associated with increased PCa risk. MATERIALS AND METHODS: We queried the linked SEER-Medicare database (2004-2015) to identify PSA screened patients diagnosed with PCa. Criteria for screening included a PSA lab test or DRE exam in both the 12 month and 13 to 36 month periods prior to diagnosis of PCa. Steroid exposure was determined using Medicare Part D and groups were divided based on duration of use in the 3 years prior to diagnosis: controls with no exposure, <30 days, 30 days - 1 year, 1 to 2 years, and >2+ years. Advanced PCa was defined as systemic metastases or regional lymph node metastasis at presentation. Risk estimates for advanced PCa at presentation for steroid exposure groups vs. controls were assessed with univariable and multivariable logistic regression models. RESULTS: We identified 22,920 PSA screened patients diagnosed with PCa of which 29% used glucocorticoids in the exposure period. The mean (SD) duration for glucocorticoid use (in days) among all steroid users was 76.7 days (192.1). On univariable and multivariable analyses, > 2 years of steroid exposure was associated with significantly increased risk for advanced PCa (OR 2.06, 95% CI 1.35-3.14 and OR 1.74, 95% CI 1.12-2.69, respectively). CONCLUSION: In this population-based PSA-screened cohort, prolonged steroid use was associated with increased risk of advanced PCa at diagnosis. With the widespread use of glucocorticoids, it is important to consider the role steroids may play in PCa pathogenesis.

Interstate Telemedicine for Urologic Cancer Care.

PURPOSE: US states eased licensing restrictions on telemedicine during the COVID-19 pandemic, allowing interstate use. As waivers expire, optimal uses of telemedicine must be assessed to inform policy, legislation, and clinical care. We assessed whether telemedicine visits provided the same patient experience as in-person visits, stratified by in- vs out-of-state residence, and examined the financial burden. MATERIALS AND METHODS: Patients seen in person and via telemedicine for urologic cancer care at a major regional cancer center received a survey after their first appointment (August 2019-June 2022) on satisfaction with care, perceptions of communication during their visit, travel time, travel costs, and days of work missed. RESULTS: Surveys were completed for 1058 patient visits (N = 178 in-person, N = 880 telemedicine). Satisfaction rates were high for all visit types, both interstate and in-state care (mean score 60.1-60.8 [maximum 63], P > .05). More patients convening interstate telemedicine would repeat that modality (71%) than interstate in-person care (61%) or in-state telemedicine (57%). Patients receiving interstate care had significantly higher travel costs (median estimated visit costs $200, IQR $0-$800 vs median $0, IQR $0-$20 for in-state care, P < .001); 55% of patients receiving interstate in-person care required plane travel and 60% required a hotel stay. CONCLUSIONS: Telemedicine appointments may increase access for rural-residing patients with cancer. Satisfaction outcomes among patients with urologic cancer receiving interstate care were similar to those of patients cared for in state; costs were markedly lower. Extending interstate exemptions beyond COVID-19 licensing waivers would permit continued delivery of high-quality urologic cancer care to rural-residing patients.

Prospective randomized pilot study of a novel patient-centered pathology report for colorectal polyps.

Objective: US patients have increased access to their medical records, yet the information is not always understandable. To improve patient understanding, we tested a patient-centered pathology report (PCPR) containing results for recent colon cancer screening or surveillance colonoscopy. Methods: A pilot randomized trial assessed the impact of addition of the PCPR to a standard pathology report on knowledge accuracy, decisional self-efficacy and control, and therapeutic alliance. Results: 55 participants were enrolled; 20 participants in the intervention group and 24 controls completed follow-up. There was no significant difference in polyp knowledge between groups at baseline or 30-days, with similar confidence in understanding their diagnoses, decisional self-efficacy, and therapeutic alliance. Most participants receiving a PCPR felt that it helped them understand their diagnosis better and should always be provided with the standard pathology report. Conclusion: Although patient attitudes toward the PCPR were positive, receiving it did not significantly improve knowledge accuracy or measures of self-efficacy. Further iterations should be explored to communicate key knowledge about colorectal polyp results. Innovation: A stakeholder-driven approach to PCPR development facilitated construction of a personalized document that has potential to increase patient's understanding for their results and needed follow-up.

Inequities in Definitive Treatment for Localized Prostate Cancer Among Those With Clinically Significant Mental Health Disorders.

INTRODUCTION: Patients with mental health disorders are at risk for receiving inequitable cancer treatment, likely resulting from various structural, social, and health-related factors. This study aims to assess the relationship between mental health disorders and the use of definitive treatment in a population-based cohort of those with localized, clinically significant prostate cancer. METHODS: We conducted a cohort study analysis in SEER (Surveillance, Epidemiology, and End Results)-Medicare (2004-2015). History of a mental health disorder was defined as presence of specific ICD (International Classification of Diseases)-9 or ICD-10 diagnostic codes in the 2 years preceding cancer diagnosis. Descriptive statistics were performed using Wilcoxon rank-sum and χ2 testing. Multivariable logistic regression was used to evaluate the relationship between mental health disorders and definitive treatment utilization (defined as surgery or radiation). RESULTS: Of 101,042 individuals with prostate cancer, 7,945 (7.8%) had a diagnosis of a mental health disorder. They were more likely to be unpartnered, have a lower socioeconomic status, and less likely to receive definitive treatment (61.8% vs 68.2%, P < .001). Definitive treatment rates were >66%, 62.8%, 60.3%, 58.2%, 54.3%, and 48.1% for post-traumatic stress disorder, depressive disorder, bipolar disorder, anxiety disorder, substance abuse disorder, and schizophrenia, respectively. After adjusting for age, race and ethnicity, marital status and socioeconomic status, history of a mental health disorder was associated with decreased odds of receiving definitive treatment (OR 0.74, 95% CI 0.66-0.83). CONCLUSIONS: Individuals with mental health disorders and prostate cancer represent a vulnerable population; careful attention to clinical and social needs is required to support appropriate use of beneficial treatments.

Patient-centered outcomes of telehealth for the care of rural-residing patients with urologic cancer.

BACKGROUND: Patients residing in rural areas with urologic cancers confront significant obstacles in obtaining oncologic care. In the Pacific Northwest, a sizeable portion of the population lives in a rural county. Telehealth offers a potential access solution. METHODS: Patients receiving urologic care through telehealth or an in-person appointment at the Fred Hutchinson Cancer Center in Seattle, Washington, were surveyed to assess appointment-related satisfaction and travel costs. Patients' residences were classified as rural or urban based on their self-reported ZIP code. Median patient satisfaction scores and appointment-related travel costs were compared by rural versus urban residence within telehealth and in-person appointment groups using Wilcoxon signed-rank or χ2 testing. RESULTS: A total of 1091 patients seen for urologic cancer care between June 2019 and April 2022 were included, 28.7% of which resided in a rural county. Patients were mostly non-Hispanic White (75%) and covered by Medicare (58%). Among rural-residing patients, telehealth and in-person appointment groups had the same median satisfaction score (61; interquartile ratio, 58, 63). More rural-residing than urban-residing patients in the telehealth appointment groups strongly agreed that "Considering the cost and time commitment of my appointment, I would choose to meet with my provider in this setting in the future" (67% vs. 58%, p = .03). Rural-residing patients with in-person appointments carried a higher financial burden than those with telehealth appointments (medians, $80 vs. $0; p <.001). CONCLUSIONS: Appointment-related costs are high among rural-residing patients traveling for urologic oncologic care. Telehealth provides an affordable solution that does not compromise patient satisfaction.

Sarcomatoid Urothelial Carcinoma Is Associated With Limited Response to Neoadjuvant Chemotherapy and Poor Oncologic Outcomes After Radical Cystectomy.

INTRODUCTION: To examine oncologic outcomes and response to neoadjuvant chemotherapy (NAC) in patients with sarcomatoid urothelial carcinoma (SUC) treated with radical cystectomy (RC). MATERIALS AND METHODS: We retrospectively queried our institutional database (2003-18) and Surveillance, Epidemiology, and End Results (SEER)-Medicare (2004-2015) for patients with cT2-4, N0-2, M0 SUC and conventional UC (CUC) treated with RC. Clinicopathologic characteristics were described using descriptive statistics (t test, χ2-test and log-rank-test for group comparison). Overall (OS) and recurrence-free-survival (RFS) after RC were estimated with the Kaplan Meier method and associations with OS were evaluated with Cox proportional hazards models. RESULTS: We identified 38 patients with SUC and 287 patients with CUC in our database, and 190 patients with SUC in SEER-Medicare. In the institutional cohort, patients with SUC versus CUC had higher rates of pT3/4 stage (66% vs. 35%, P < 0.001), lower rates of ypT0N0 (6% vs. 35%, P = .02), and worse median OS (17.5 vs. 120 months, P < .001). Further, patients with SUC in the institutional versus SEER-Medicare cohort had similar median OS (17.5 vs. 21 months). In both cohorts, OS was comparable between patients with SUC undergoing NAC+RC vs. RC alone (17.5 vs. 18.4 months, P = .98, institutional cohort; 24 vs. 20 months, P = .56, SEER cohort). In Cox proportional hazards models for the institutional RC cohort, SUC was independently associated with worse OS (HR 2.3, CI 1.4-3.8, P = .001). CONCLUSION: SUC demonstrates poor pathologic response to NAC and worse OS compared with CUC, with no OS benefit associated with NAC. A unique pattern of rapid abdominopelvic cystic recurrence was identified.

Racial inequities in the quality of surgical care among Medicare beneficiaries with localized prostate cancer.

BACKGROUND: US Black men are twice as likely to die from prostate cancer as men of other races. Lower quality care may contribute to this higher death rate. METHODS: Sociodemographic and clinical data were obtained for men in Surveillance, Epidemiology, and End Results-Medicare diagnosed with clinically localized prostate cancer (cT1-4N0/xM0/x) and managed primarily by radical prostatectomy (2005-2015). Surgical volume was determined for facility and surgeon. Relationships between race, surgeon and/or facility volume, and characteristics of treating facility with survival (all-cause and cancer-specific) were assessed using multivariable Cox regression and competing risk analysis. RESULTS: Black men represented 6.7% (n = 2123) of 31,478 cohort. They were younger at diagnosis, had longer time from diagnosis to surgery, lower socioeconomic status, higher prostate-specific antigen (PSA), and higher comorbid status compared with men of other races (p < .001). They were less likely to receive care from a surgeon or facility in the top volume percentile (p < .001); less likely to receive surgical care at a National Cancer Institute-designated cancer center and more likely seen at a minority-serving hospital; and less likely to travel ≥50 miles for surgical care. On multivariable analysis stratified by surgical volume, Black men receiving care from a surgeon or facility with lower volumes demonstrated increased risk of prostate cancer mortality (hazard ratio, 1.61; 95% confidence interval, 1.01-2.69) adjusting for age, clinical stage, PSA, and comorbidity index. CONCLUSIONS: Black Medicare beneficiaries with prostate cancer more commonly receive care from surgeons and facilities with lower volumes, likely affecting surgical quality and outcomes. Access to high-quality prostate cancer care may reduce racial inequities in disease outcomes, even among insured men. PLAIN LANGUAGE SUMMARY: Black men are twice as likely to die of prostate cancer than other US men. Lower quality care may contribute to higher rates of prostate cancer death. We used surgical volume to evaluate the relationship between race and quality of care. Black Medicare beneficiaries with prostate cancer more commonly received care from surgeons and facilities with lower volumes, correlating with a higher risk of prostate cancer death and indicating scarce resources for care. Access to high-quality prostate cancer care eases disparities in disease outcomes. Patient-centered interventions that increase access to high-quality care for Black men with prostate cancer are needed.

A Phase 1/2 Study of Rapamycin and Cisplatin/Gemcitabine for Treatment of Patients With Muscle-Invasive Bladder Cancer.

INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy is the standard for muscle-invasive bladder cancer (MIBC), however, NAC confers only a small survival benefit and new strategies are needed to increase its efficacy. Pre-clinical data suggest that in response to DNA damage the tumor microenvironment (TME) adopts a paracrine secretory phenotype dependent on mTOR signaling which may provide an escape mechanism for tumor resistance, thus offering an opportunity to increase NAC effectiveness with mTOR blockade. PATIENTS & METHODS: We conducted a phase I/II clinical trial to assess the safety and efficacy of gemcitabine-cisplatin-rapamycin combination. Grapefruit juice was administered to enhance rapamycin pharmacokinetics by inhibiting intestinal enzymatic degradation. Phase I was a dose determination/safety study followed by a single arm Phase II study of NAC prior to radical cystectomy evaluating pathologic response with a 26% pCR rate target. RESULTS: In phase I, 6 patients enrolled, and the phase 2 dose of 35 mg rapamycin established. Fifteen patients enrolled in phase II; 13 were evaluable. Rapamycin was tolerated without serious adverse events. At the preplanned analysis, the complete response rate (23%) did not meet the prespecified level for continuing and the study was stopped due to futility. With immunohistochemistry, successful suppression of the mTOR signaling pathway in the tumor was achieved while limited mTOR activity was seen in the TME. CONCLUSION: Adding rapamycin to gemcitabine-cisplatin therapy for patients with MIBC was well tolerated but failed to improve therapeutic efficacy despite evidence of mTOR blockade in tumor cells. Further efforts to understand the role of the tumor microenvironment in chemotherapy resistance is needed.

A multicenter study assessing survival in patients with metastatic renal cell carcinoma receiving immune checkpoint inhibitor therapy with and without cytoreductive nephrectomy.

BACKGROUND: Cytoreductive nephrectomy (CN) for the treatment of metastatic renal cell carcinoma (mRCC) was called into question following the publication of the CARMENA trial. While previous retrospective studies have supported CN alongside targeted therapies, there is minimal research establishing its role in conjunction with immune checkpoint inhibitor (ICI) therapy. OBJECTIVE: To evaluate the association between CN and oncological outcomes in patients with mRCC treated with immunotherapy. MATERIALS AND METHODS: A multicenter retrospective cohort study of patients diagnosed with mRCC between 2000 and 2020 who were treated at the Seattle Cancer Care Alliance and The Ohio State University and who were treated with ICI systemic therapy (ST) at any point in their disease course. Overall survival (OS) was estimated using Kaplan Meier analyses. Multivariable Cox proportional hazards models evaluated associations with mortality. RESULTS: The study cohort consisted of 367 patients (CN+ST n = 232, ST alone n = 135). Among patients undergoing CN, 30 were deferred. Median survivor follow-up was 28.4 months. ICI therapy was first-line in 28.1%, second-line in 17.4%, and third or subsequent line (3L+) in 54.5% of patients. Overall, patients who underwent CN+ST had longer median OS (56.3 months IQR 50.2-79.8) compared to the ST alone group (19.1 months IQR 12.8-23.8). Multivariable analyses demonstrated a 67% reduction in risk of all-cause mortality in patients who received CN+ST vs. ST alone (P < 0.0001). Similar results were noted when first-line ICI therapy recipients were examined as a subgroup. Upfront and deferred CN did not demonstrate significant differences in OS. CONCLUSIONS: CN was independently associated with longer OS in patients with mRCC treated with ICI in any line of therapy. Our data support consideration of CN in well selected patients with mRCC undergoing treatment with ICI.

Intravesical BCG and Incidence of Alzheimer Disease in Patients With Bladder Cancer: Results From an Administrative Dataset.

INTRODUCTION: Alzheimer disease (AD) is a common neurodegenerative disease, and immunomodulation offers treatment opportunities. Preclinical data suggest that intravesical Bacillus Calmette-Guerin (BCG) treatment could delay AD development. We investigated this relationship in a population-based cancer database. SAMPLE AND METHODS: We queried the Surveillance, Epidemiology, and End Results-Medicare database for patients with high-risk nonmuscle-invasive bladder cancer (hrNMIBC). BCG dosage and subsequent Alzheimer diagnosis were collected through ICD-9/10 codes. Multivariable Cox regression was performed to assess the association between BCG therapy and subsequent Alzheimer diagnosis. RESULTS: We identified 26,584 hrNMIBC patients; 51% received BCG and 8.3% were diagnosed with Alzheimer. BCG exposure was significantly associated with lower Alzheimer occurrence (hazard ratio: 0.73, P <0.05), which was dose-dependent. Increasing age, female sex, Black race, and increasing comorbidity index were significantly associated with a greater risk of subsequent Alzheimer diagnosis. DISCUSSION: Treatment with intravesical BCG among patients with hrNMIBC was associated with a significantly lower risk for subsequent Alzheimer diagnosis, which seemed dose-dependent.

Changes in skeletal muscle and adipose tissue during cytotoxic chemotherapy for testicular germ cell carcinoma and associations with adverse events.

OBJECTIVES: To quantify changes in body composition during cytotoxic chemotherapy for germ cell carcinoma of the testis (GCT) and evaluate associations between change in skeletal muscle and adipose tissue and chemotherapy-associated adverse events. MATERIALS AND METHODS: This retrospective single-institution study evaluated men with GCT treated with cytotoxic chemotherapy from 2005 to 2018. We measured skeletal muscle index (SMI [cm2/m2]), skeletal muscle density (SMD [Hounsfield Units (HU)]), skeletal muscle gauge (SMG [cm²*HU/m²]), fat mass index (FMI [kg/m2]), visceral adipose index (VAI [cm2/m2]), and subcutaneous adipose index (SAI [cm2/m2]) on axial computed tomography images at the level of the third lumbar vertebra within 75 days before and after chemotherapy. Chemotherapy-associated adverse events (AE) were graded based on the Common Terminology Criteria for Adverse Events (CTCAE v5.0.) Changes in body composition were quantified. Predictors of change in body composition were evaluated with multivariable linear regression. Associations between baseline or change in body composition and AEs were estimated with multivariable logistic regression adjusting for age, comorbidity, performance status, stage, and number/type of chemotherapy cycles. RESULTS: 141 patients (median age, 30 years [IQR 25-39]) including 86 patients (61%) with non-seminomatous GCT were included. Patients received a median of 3 cycles of cisplatin-based chemotherapy, and 124 patients (88%) completed planned chemotherapy. Median observed changes in SMI, SMD, and SMG were -6% (P<0.0001), -2% (P=0.07), and -7% (P<0.0001), respectively, while FMI increased 5.3% (P<0.0001). Overall, 120 patients (85%) experienced at least one AE including one or more ≥grade 3 AE in 57 patients (48%). Decrease in SMI (OR: 0.89, P=0.02), decrease in SMG (OR: 0.88, P=0.01,) and post-chemotherapy SMG (OR: 0.94, P=0.05) were independently associated with higher incidence of AEs, while pre-chemotherapy skeletal muscle parameters and post-chemotherapy SMI and SMD were not associated with AEs (P>0.05 for all). Preoperative adipose tissue or change in adiposity was not associated with incidence of AEs. CONCLUSIONS: In men with GCT receiving cytotoxic chemotherapy, a decrease in skeletal muscle mass and quality during chemotherapy were associated with a higher incidence of chemotherapy-associated AEs. Adipose tissue was not associated with the incidence of AEs.

Ureteral Strictures Following Ureteroscopy for Kidney Stone Disease: A Population-based Assessment.

PURPOSE: As the prevalence of urolithiasis increases and ureteroscopy is used more frequently, the risks of uncommon complications such as ureteral stricture may become more notable. Our objective is to assess the rate and associated risk factors of ureteral stricture formation in patients undergoing ureteroscopy. MATERIALS AND METHODS: Utilizing the IBM MarketScan research database, we evaluated data from 2008 to 2019 and compared ureteral stricture rates and their management following ureteroscopy to subjects who had shock wave lithotripsy. Shock wave lithotripsy was used as a comparison group to represent the rate of stricture from stone disease alone. A third group of those having both shock wave lithotripsy and ureteroscopy was included. Patients and secondary procedures were identified using Current Procedural Terminology, and International Classification of Diseases-9 and -10 codes. RESULTS: A total of 329,776 patients received ureteroscopy, shock wave lithotripsy, or shock wave lithotripsy+ureteroscopy between 2008 and 2019. Stricture developed in 2.9% of patients after ureteroscopy, 1.5% after shock wave lithotripsy, and 2.6% after shock wave lithotripsy+ureteroscopy. In the multivariable model, rates of stricture were 1.7-fold higher after ureteroscopy vs shock wave lithotripsy (OR:1.71, 95% CI 1.62-1.81). Preoperative hydronephrosis, age, prior stones/intervention, and concurrent kidney and ureteral stones were associated with increased risk of stricture. Of those with strictures incurred after ureteroscopy, 35% required drainage, 21% had endoscopic intervention, 4.8% required reconstructive surgery, and 1.7% underwent nephrectomy. CONCLUSIONS: Ureteral stricture rate after ureteroscopy of nearly 3% was higher than expected and approximately twice the rate attributable to stone disease alone. Factors associated with the stone as well as instrumentation were found to be risk factors. The morbidity of stricture disease following ureteroscopy was significant.

Spending and Out-of-Pocket Costs for Genital Gender-Affirming Surgery in the US.

Importance: Genital gender-affirming surgery (GAS) is safe and offers substantial benefits to patients. Geographic accessibility and high out-of-pocket (OOP) costs reportedly hinder access; however, to date, this has not been thoroughly investigated at the national level. Objective: To estimate OOP and total costs for GAS among commercially insured beneficiaries and assess whether costs differed between surgical procedures conducted in and outside the patient's state of residence. Design, Setting, and Participants: This cross-sectional study used previously collected insurance data from the MarketScan Commercial Database (129 million patients) from January 1, 2007, to December 31, 2019. Vaginoplasties and phalloplasties were identified using diagnosis and procedure codes among patients aged 18 to 64 years. Out-of-state surgical procedures were identified based on residence at enrollment and place of service of the surgery. Data analysis took place from July 1 to September 31, 2021. Exposures: Vaginoplasty and phalloplasty. Main Outcomes and Measures: The main outcomes were differences in OOP and total costs by out-of-state designation, census region, age, and insurance type for surgical procedures, estimated using multivariable linear regression models. Results: The study included 771 patients who underwent GAS. A total of 609 underwent vaginoplasty, of whom 249 (41%) underwent surgery in their state of residence (mean [SD] age, 38.7 [13.1] years) and 340 (56%) underwent surgery outside their state (mean [SD] age, 38.1 [13.0] years), and 162 underwent phalloplasty, of whom 66 (41%) underwent surgery in their state of residence (mean [SD] age, of 39.7 [11.6] years) and 81 (50%) underwent surgery outside their state (mean [SD] age, 35.8 [10.9] years); 20 vaginoplasties (3%) and 15 phalloplasties (9%) could not be classified as in or out of state owing to missing data about the facility or residence. Procedures outside the state were associated with 49% (95% CI, 19%-85%) higher OOP costs compared with procedures done in the state of residence. Conclusions and Relevance: In this cross-sectional study, 56% of patients who underwent vaginoplasty and 50% of patients who underwent phalloplasty underwent the procedure outside their state of residence. Patients who underwent these procedures outside their state also experienced higher OOP costs than did those who underwent these procedures in their state. Improving geographic access and understanding patient preferences for surgical care may help reduce the cost burden for those planning to undergo GAS.

Aggressive Prostate Cancer at Presentation Following Solid Organ Transplantation.

Solid organ transplant (SOT) candidates and recipients are often subject to intense screening regimens that can potentially delay transplantation and cause unnecessary harm. Although initial studies suggested that SOT recipients had elevated risk of prostate cancer (PCa), contemporary studies have shown that transplant recipients with low- or intermediate-risk PCa have similar outcomes to their counterparts without a transplant. However, there are limited data on the relationship between prior transplant exposure and the risk of clinically significant aggressive PCa at presentation. To provide additional insight, we queried the Surveillance, Epidemiology and End Results-Medicare database to establish a cohort of prostate-specific antigen (PSA)-screened transplant patients who then went on to develop PCa. Procedure and diagnosis codes were then used to identify patients with a history of SOT. Aggressive PCa phenotype was defined as death from PCa or de novo metastasis, regional lymph node metastasis, PSA >20 ng/l, or Gleason score 8-10 at presentation. On univariable and multivariable (adjusted for age and race) analyses, transplant patients (n = 292) were not at significantly higher risk of an aggressive prostate cancer phenotype with odds ratios of 0.95 (95% confidence interval 0.72-1.25) and 1.18, (95% confidence interval 0.90-1.57), respectively. The results suggest that transplant recipients can have similar screening protocols to those for the general population. Patient summary: Using database results for transplant recipients, we investigated their risk of developing aggressive prostate cancer after transplantation. We found that having a transplant did not increase the risk of aggressive prostate cancer. This work suggests that transplant recipients are unlikely to benefit from more rigorous screening protocols than those for the general population.

Efficacy of Platinum Rechallenge in Metastatic Urothelial Carcinoma After Previous Platinum-Based Chemotherapy for Metastatic Disease.

BACKGROUND: Fit patients with metastatic urothelial carcinoma (mUC) receive first-line platinum-based combination chemotherapy (fPBC) as standard of care and may receive additional later-line chemotherapy after progression. Our study compares outcomes with subsequent platinum-based chemotherapy (sPBC) versus subsequent non-platinum-based chemotherapy (sNPBC). MATERIALS AND METHODS: Patients from 27 international centers in the Retrospective International Study of Cancers of the Urothelium (RISC) who received fPBC for mUC and at least two cycles of subsequent chemotherapy were included in this study. A multivariable Cox proportional hazards model compared overall survival (OS) and progression-free survival (PFS). RESULTS: One hundred thirty-five patients received sPBC and 161 received sNPBC. Baseline characteristics were similar between groups, except patients who received sPBC had higher baseline hemoglobin, higher disease control rate with fPBC, and longer time since fPBC. OS was superior in the sPBC group (median 7.9 vs 5.5 months) in a model adjusting for comorbidity burden, performance status, liver metastases, number of fPBC cycles received, best response to fPBC, and time since fPBC (hazard ratio, 0.72; 95% confidence interval, 0.53-0.98; p = .035). There was no difference in PFS. More patients in the sPBC group achieved disease control than in the sNPBC group (57.4% vs 44.8%; p = .041). Factors associated with achieving disease control in the sPBC group but not the sNPBC group included longer time since fPBC, achieving disease control with fPBC, and absence of liver metastases. CONCLUSION: After receiving fPBC for mUC, patients who received sPBC had better OS and disease control. This may help inform the choice of subsequent chemotherapy in patients with mUC. IMPLICATIONS FOR PRACTICE: Patients with progressive metastatic urothelial carcinoma after first-line platinum-based combination chemotherapy may now receive immuno-oncology agents, erdafitinib, enfortumab vedotin, or sacituzumab govitecan-hziy; however, those ineligible for these later-line therapies or who progress after receiving them may be considered for subsequent chemotherapy. In this retrospective study of 296 patients, survival outcomes and disease control rates were better in those receiving subsequent platinum-based rechallenge compared with non-platinum-based chemotherapy, suggesting that patients should receive platinum rechallenge if clinically able. Disease control with platinum rechallenge was more likely with prior first-line platinum having achieved disease control, longer time since first-line platinum, and absence of liver metastases.