Social Vulnerability and Receipt of Neoadjuvant Chemotherapy in Patients Undergoing Radical Cystectomy for Bladder Cancer.

OBJECTIVE: To evaluate the association between a population-level measure of social determinants of health, the Centers for Disease Control and Prevention Social Vulnerability Index (SVI), and receipt of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy. METHODS: We queried our institutional database for patients with nonmetastatic MIBC treated with radical cystectomy between 2000 and 2022. Patients were assigned an SVI via ZIP code of residence and grouped into quintiles of SVI (ie, least vulnerable to most vulnerable). Multivariable logistic regression was performed to evaluate the association between SVI and receipt of neoadjuvant chemotherapy, adjusting for age, race, gender, and cancer stage. A sub-analysis was performed to evaluate the association between subthemes of SVI (socioeconomic status, household composition/disability, race/ethnicity/language, and housing/transportation) and receipt of neoadjuvant chemotherapy. RESULTS: Of the 978 patients identified, 490 (50.1%) received neoadjuvant chemotherapy. Patients that received neoadjuvant chemotherapy had a lower SVI, were younger, and had >cT2 stage (all, P <.05). The most vulnerable patients had lower odds of receiving neoadjuvant chemotherapy (OR 0.61, 0.39-0.95) compared to the least vulnerable patients. Analysis of subthemes of SVI demonstrated similar associations by socioeconomic status (OR 0.56, 0.36-0.86) and household composition/disability (OR 0.57, 0.33-0.99). CONCLUSION: Adverse social determinants of health, or social vulnerability, are associated with suboptimal and disparate utilization of neoadjuvant chemotherapy in patients with MIBC undergoing radical cystectomy. Strategies for identifying vulnerable populations may allow for more targeted interventions that would improve equity in bladder cancer care.

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.

Underutilization of Surgical Standard of Care for Insured Men with Invasive Penile Cancer.

PURPOSE: Prior studies of mixed insurance populations have demonstrated poor adherence to surgical standard of care (SOC) for penile cancer. We used data from the Surveillance, Epidemiology and End Results (SEER) cancer registry linked to Medicare to calculate SOC adherence to surgical treatment of penile cancer in insured men over the age of 65, focusing on potential social and racial disparities. METHODS: This is an observational analysis of patients with T2-4 penile cancer of any histologic subtype without metastasis in the SEER-Medicare database (2004-2015). SOC was defined as penectomy (partial or radical) with bilateral inguinal lymph node dissection (ILND) based on the National Comprehensive Cancer Network guidelines. We calculated proportions of those receiving SOC and constructed multivariate models to identify factors associated with receiving SOC. RESULTS: A total of 447 men were included. Of these men, 22.1% (99/447) received SOC while 18.8% (84/447) received no treatment at all. Only 23.3% (104/447) had ILND while 80.9% (362/447) underwent total or partial penectomy. Race and socioeconomic status (SES) were not associated with decreased SOC. Increasing age (OR 0.93, 95%CI:0.89-0.96), Charlson Comorbidity Index score ≥ 2 (OR 0.53, 95%CI:0.29-0.97), and T3-T4 disease (OR 0.34, 95%CI:0.18-0.65) were associated with not receiving SOC on adjusted analysis. CONCLUSIONS: Rates of SOC are low among insured men 65 years of age or older with invasive penile cancer, regardless of race or SES. This finding is largely driven by low rates of ILND. Strategies are needed to overcome barriers to SOC treatment for men with invasive penile cancer.

Patterns and timing of perioperative blood transfusion and association with outcomes after radical cystectomy.

BACKGROUND: Perioperative blood transfusion (PBT) has been associated with worse outcomes across tumor types, including bladder cancer. We report our institutional experience with PBT utilization in the setting of radical cystectomy (RC) for patients with bladder cancer, exploring whether timing of PBT receipt influences perioperative and oncologic outcomes. METHODS: Consecutive patients with bladder cancer treated with RC were identified. PBT was defined as red blood cell transfusion during RC or the postoperative admission. Clinicopathologic and peri and/or postoperative parameters were extracted and compared between patients who did and did not receive PBT using Mann Whitney U Test, chi-square, and log-rank test. Overall (OS) and recurrence-free survival (RFS) were estimated with the Kaplan Meier method. Univariate/multivariate logistic and Cox proportional hazards regression were used to identify variables associated with postoperative and oncologic outcomes, respectively. RESULTS: The cohort consisted of 747 patients (77% men; median age 67 years). Median follow-up was 61.5 months (95% CI 55.8-67.2) At least one postoperative complication (90-day morbidity) occurred in 394 (53%) patients. Median OS and RFS were 91.8 months (95% CI: 76.0-107.6) and 66.0 months (95% CI: 48.3-83.7), respectively. On multivariate analysis, intraoperative, but not postoperative, BT was independently associated with shorter OS (HR: 1.74, 95% CI: 1.32-2.29) and RFS (HR: 1.55, 95%CI: 1.20-2.01), after adjusting for relevant clinicopathologic variables. PBT (intra- or post- operative) was significantly associated with prolonged postoperative hospitalization ≥10 days. CONCLUSIONS: Intraoperative BT was associated with inferior OS and RFS, and PBT overall was associated with prolonged hospitalization following RC. Further studies are needed to validate this finding and explore potential causes for this observation.

Response to Neoadjuvant Chemotherapy and Survival in Micropapillary Urothelial Carcinoma: Data From a Tertiary Referral Center and the Surveillance, Epidemiology, and End Results (SEER) Program.

BACKGROUND: Micropapillary urothelial carcinoma (MPC) is a rare urothelial carcinoma variant with conflicting data guiding clinical practice. In this study, we explored oncologic outcomes in relation to neoadjuvant chemotherapy (NAC) in a retrospective cohort of patients with MPC, alongside data from Surveillance, Epidemiology, and End Results (SEER)-Medicare. PATIENTS AND METHODS: We retrospectively identified patients with MPC or conventional urothelial carcinoma (CUC) without any variant histology undergoing radical cystectomy (RC) in our institution (2003-2018). SEER-Medicare was also queried to identify patients diagnosed with MPC (2004-2015). Clinicopathologic data and treatment modalities were extracted. Overall survival (OS) was estimated with the Kaplan-Meier method. Mann-Whitney-Wilcoxon and chi-square tests were used for comparative analysis and Cox regression for identifying clinical covariates associated with OS. RESULTS: Our institutional database yielded 46 patients with MPC and 457 with CUC. In SEER-Medicare, 183 patients with MPC were identified, and 63 (34%) underwent RC. In the institutional cohort, patients with MPC had significantly higher incidence of cN+ (17% vs. 8%), pN+ stage (30% vs. 17%), carcinoma-in-situ (43% vs. 25%), and lymphovascular invasion (30% vs. 16%) at RC versus those with CUC (all P < .05). Pathologic complete response (ypT0N0) to NAC was 33% for MPC and 35% for CUC (P = .899). Median OS was lower for institutional MPC versus CUC in univariate analysis (43.6 vs. 105.3 months, P = .006); however, MPC was not independently associated with OS in the multivariate model. Median OS was 25 months in the SEER MPC cohort for patients undergoing RC, while NAC was not associated with improved OS in that group. CONCLUSION: Pathologic response to NAC was not significantly different between MPC and CUC, while MPC histology was not an independent predictor of OS. Further studies are needed to better understand biological mechanisms behind its aggressive features as well as the role of NAC in this histology variant.

Firework-related genitourinary trauma: a single institution case series.

PURPOSE: The clinical impact of firework-related genitourinary trauma remains unknown. In this study, we aim to characterize injury patterns, interventions, and clinical outcomes of firework-related genitourinary injuries and evaluate the relationship with certain firework types. METHODS: A retrospective case series was conducted for patients treated at a level I trauma center from 2005 to 2019 who experienced firework-related genitourinary trauma. Fifteen patients sustained firework-related genitourinary injuries. Injury patterns, operative interventions, clinical outcomes, as well as details of firework type were examined. RESULTS: Firework-related genitourinary injuries were identified in 15 trauma patients. Mean age was 29.7 years (± 14.3, standard deviation), all (100%) patients were male, and most (11; 73.3%) were Caucasian. Average length of stay (LOS) was 10.5 days, and 4 (26.7%) patients required ICU admission. Ten (66.7%) patients underwent 28 operative interventions (mean 1.9 per patient), 7 (46.7%) of whom underwent 15 urologic specific intervention (mean 1.0 per patient). No injury-related deaths occurred. Considering firework type, 10 (66.7%) patients had mortar or shell-related injuries, while 3 (20.0%) involved firecrackers, and 2 (13.3%) involved bottle rockets. All (100%) patients sustained injuries that occurred with the use of legally obtained fireworks and 11 (73.3%) were active users. CONCLUSIONS: Firework-related genitourinary injuries occurred most frequently in young men, lead to polytrauma with the scrotum and penis being the most common urologic sites, had high operative rates, and were most commonly associated with legally obtained fireworks, specifically mortar and shell fireworks. Further investigation is needed to understand the long-term sequelae of these injuries.

Evaluation of programmed cell death protein 1 (PD-1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma.

Programmed cell death protein 1 (PD-1) immune checkpoint inhibitors have shown activity in patients with advanced renal cell carcinoma (RCC). However, the role of PD-1 expression in tumor-infiltrating lymphocytes (TILs) as a biomarker for poor outcome is not clear. In this study, we evaluated the prognostic value of TIL PD-1 expression in patients with clear cell RCC (ccRCC). 82 patients who underwent nephrectomy for localized or metastatic ccRCC and followed up for at least four years were searched from our database and retrospectively enrolled. Their fixed primary tumor specimens were stained with anti-PD-1 (NAT105). The specimens were classified as negative or positive for PD-1 expression, and the positive specimens were further scored in 10% increments. 37 (45.12%) patients were negative (<1% stained), 26 (31.71%) patients were low (<10 and 10%), and 19 (23.17%) patients were high (20-50%) for PD-1 expression. The prognostic value of TIL PD-1 expression was evaluated by univariate Cox proportional hazards regression on overall and recurrence-free survivals. Higher TIL PD-1 expression was not associated with increased risk of death (P = 0.336) or with increased risk of recurrence (P = 0.572). Higher primary tumor stage was associated with increased risk of recurrence (P = 0.003), and higher Fuhrman nuclear grade was associated with increased risk of death (P <0.001) and with increased risk of recurrence (P <0.001). Our study shows that TIL PD-1 expression by immunohistochemistry (IHC) does not correlate with poor clinical outcome in patients with ccRCC and is inferior to established prognosticating tools.

A novel preoperative inflammatory marker prognostic score in patients with localized and metastatic renal cell carcinoma.

OBJECTIVE: Several inflammatory markers have been studied as potential biomarkers in renal cell carcinoma (RCC), however few reports have analyzed their prognostic value in aggregate and in non-clear cell histologies. We hypothesize that a combination of specific inflammatory markers into an RCC Inflammatory Score (RISK) could serve as a rigorous prognostic indicator of overall survival (OS) in patients with clear cell and non-clear cell RCC. METHODS: Combination of preoperative C-reactive protein (CRP), albumin, erythrocyte sedimentation rate (ESR), corrected calcium, and aspartate transaminase to alanine transaminase (AST/ALT) ratio was used to develop RISK. RISK was developed using grid-search methodology, receiver-operating-characteristic (ROC) analysis, and sensitivity-specificity trade-off analysis. Prognostic value of RISK was analyzed using the Kaplan-Meier method and Cox proportional regression models. Predictive accuracy was compared with RISK to Size, Size, Grade, and Necrosis (SSIGN) score, University of California-LOS Angeles (UCLA) Integrated Staging System (UISS), and Leibovich Prognosis Score (LPS). RESULTS: Among 391 RCC patients treated with nephrectomy, area under the curve (AUC) for RISK was 0.783, which was comparable to SSIGN (AUC 0.776, p = 0.82) and UISS (AUC 0.809, p = 0.317). Among patients with localized disease, AUC for RISK and LPS was 0.742 and 0.706, respectively (p = 0.456). On multivariate analysis, we observed a step-wise statistically significant inverse relationship between increasing RISK group and OS (all p < 0.001). CONCLUSION: RISK is an independent and significant predictor of OS for patients treated with nephrectomy for clear cell and non-clear cell RCC, with accuracy comparable to other histopathological prognostic tools.

Major histocompatibility complex I upregulation in clear cell renal cell carcinoma is associated with increased survival.

OBJECTIVE: To examine the prognostic value of tumor major histocompatibility complex I (MHCI) expression on survival and recurrence in patients with clear cell renal cell carcinoma (RCC). METHODS: Fifty-three patients that underwent nephrectomy at our institution for clear cell RCC (T1-T3) with ≥4 years of follow-up were queried from our nephrectomy database. Immunohistochemical staining for MHCI was performed on tumor specimens and MHCI expression was quantified with an automated image analysis technique. Patients were divided into high and low MHCI expression groups in order to study the relationship between MHCI expression and prognosis using the Kaplan-Meier method and log-rank test. RESULTS: Overall survival and recurrence free survival were increased in the high MHCI expression group compared to the low MHCI expression group (log-rank, p = 0.036 and p = 0.028, respectively). Patients alive at the end of the study had higher MHCI expression (mean positivity score 0.82) than those that died of disease (mean positivity score 0.76, t test, p = 0.030). Patients that did not develop recurrence during the study period had higher MHCI expression (mean positivity score 0.83) than those that did develop recurrence (mean positivity score 0.78), but this difference was not significant (t test, p = 0.079). CONCLUSION: Our data demonstrate that high MHCI expression confers improved overall and recurrence free survival in patients with clear cell RCC and could serve as an important prognostic tool in identifying high-risk patients.