Plasma metabolomics profiling of 580 patients from an Early Detection Research Network prostate cancer cohort.

Prostate cancer is the second most common cancer in men and affects 1 in 9 men in the United States. Early screening for prostate cancer often involves monitoring levels of prostate-specific antigen (PSA) and performing digital rectal exams. However, a prostate biopsy is always required for definitive cancer diagnosis. The Early Detection Research Network (EDRN) is a consortium within the National Cancer Institute aimed at improving screening approaches and early detection of cancers. As part of this effort, the Weill Cornell EDRN Prostate Cancer has collected and biobanked specimens from men undergoing a prostate biopsy between 2008 and 2017. In this report, we describe blood metabolomics measurements for a subset of this population. The dataset includes detailed clinical and prospective records for 580 patients who underwent prostate biopsy, 287 of which were subsequentially diagnosed with prostate cancer, combined with profiling of 1,482 metabolites from plasma samples collected at the time of biopsy. We expect this dataset to provide a valuable resource for scientists investigating prostate cancer metabolism.

Randomized phase II trial of MRI-guided salvage radiotherapy for prostate cancer in 4 weeks versus 2 weeks (SHORTER).

BACKGROUND: Ultra-hypofractionated image-guided stereotactic body radiotherapy (SBRT) is increasingly used for definitive treatment of localized prostate cancer. Magnetic resonance imaging-guided radiotherapy (MRgRT) facilitates improved visualization, real-time tracking of targets and/or organs-at-risk (OAR), and capacity for adaptive planning which may translate to improved targeting and reduced toxicity to surrounding tissues. Given promising results from NRG-GU003 comparing conventional and moderate hypofractionation in the post-operative setting, there is growing interest in exploring ultra-hypofractionated post-operative regimens. It remains unclear whether this can be done safely and whether MRgRT may help mitigate potential toxicity. SHORTER (NCT04422132) is a phase II randomized trial prospectively evaluating whether salvage MRgRT delivered in 5 fractions versus 20 fractions is non-inferior with respect to gastrointestinal (GI) and genitourinary (GU) toxicities at 2-years post-treatment. METHODS: A total of 136 patients will be randomized in a 1:1 ratio to salvage MRgRT in 5 fractions or 20 fractions using permuted block randomization. Patients will be stratified according to baseline Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domain scores as well as nodal treatment and androgen deprivation therapy (ADT). Patients undergoing 5 fractions will receive a total of 32.5 Gy over 2 weeks and patients undergoing 20 fractions will receive a total of 55 Gy over 4 weeks, with or without nodal coverage (25.5 Gy over 2 weeks and 42 Gy over 4 weeks) and ADT as per the investigator's discretion. The co-primary endpoints are change scores in the bowel and the urinary domains of the EPIC. The change scores will reflect the 2-year score minus the pre-treatment (baseline) score. The secondary endpoints include safety endpoints, including change in GI and GU symptoms at 3, 6, 12 and 60 months from completion of treatment, and efficacy endpoints, including time to progression, prostate cancer specific survival and overall survival. DISCUSSION: The SHORTER trial is the first randomized phase II trial comparing toxicity of ultra-hypofractionated and hypofractionated MRgRT in the salvage setting. The primary hypothesis is that salvage MRgRT delivered in 5 fractions will not significantly increase GI and GU toxicities when compared to salvage MRgRT delivered in 20 fractions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04422132. Date of registration: June 9, 2020.

Study protocol for a prospective, multi-centered randomized controlled trial comparing pelvic fascia-sparing radical prostatectomy with conventional robotic-assisted prostatectomy: The PARTIAL trial.

BACKGROUND: Pelvic fascia-sparing robotic-assisted radical prostatectomy (PFS-RARP) is a novel approach that spares the endopelvic fascia ventral to the prostate. The preservation of more native structures compared to conventional robotic-assisted radical prostatectomy (RARP) may lead to faster recovery of urinary function, fewer penile changes, and decreased inguinal hernia sequelae, but may have a higher risk for positive surgical margins and poorer cancer control. However, high-level evidence is absent. The PARTIAL trial is a surgical randomized controlled trial (RCT) aiming to bridge this evidence gap (NCT05155501). METHODS: We describe a prospective RCT with a projected enrollment of 600 men randomized to PFS-RARP vs. RARP. The primary outcome is cancer control (positive surgical margins and prostate-specific antigen failure) and secondary outcomes include health-related quality of life pertaining to urinary and sexual function, decision regret, and adverse events (30-day complications, inguinal hernias, penile shortening, and Peyronie's disease). The anticipated duration of trial participation is 24 months. Study participation is incentivized with the use of innovative methodologies such as a novel, two-stage informed consent and a validated web-based interface to monitor patient-reported symptoms and empower individuals to improve their recovery. CONCLUSION: If PFS-RARP is non-inferior to RARP in terms of cancer control and has better functional outcomes, it should be the surgical standard of care for men with localized prostate cancer. Using the innovative two-stage consent process, completion of the trial will not only provide much needed evidence on one of the most common cancer surgeries but also insight on improving surgical RCT methodology. Trial status This trial is registered at ClinicalTrials.gov (NCT05155501; first posted on December 13, 2021); Institutional approval number: WCM IRB # 21-07023781, BRANY's initial approval event ID # 186333. The trial is not yet recruiting.

National Adherence to Guidelines for Antimicrobial Prophylaxis for Patients Undergoing Radical Cystectomy.

PURPOSE: The sentinel reference for antibiotic prophylaxis for radical cystectomy with ileal conduit in the AUA Guidelines reports data from 2003-2013 and has not been updated in the interim. Here, we assess adherence to antibiotic prophylaxis guidelines among patients undergoing radical cystectomy with ileal conduit for bladder cancer using a large national database. As a secondary objective, we assess the association between antimicrobial use and postoperative infection during the index admission following cystectomy. MATERIALS AND METHODS: The Premier Healthcare Database was queried for all patients undergoing cystectomy with ileal conduit with diagnosis of bladder cancer between 2015 and 2020. Antibiotics used and the duration of use was determined by charge codes and grouped as guidelines-based or not according to 2019 AUA Guidelines. Association with infectious complications was assessed by logistic mixed effects regression models. RESULTS: Among 6,708 patients undergoing cystectomy with ileal conduit, only 28% (1,843/6,708) were given prophylaxis according to AUA guidelines; 1.8% (121/6,708) of patients received an antifungal and 37% (2,482/6,708) received extended duration prophylaxis beyond postoperative day 1. Patients who received guidelines-based prophylaxis were less likely to be diagnosed with a urinary tract infection (21% vs 24%, P = .04), pyelonephritis (5.1% vs 7.7%, P < .001), bacterial infection (24% vs 27%, P = .03), or pneumonia (12% vs 17%, P < .001). There was no statistically significant difference in clostridium difficile infection between guidelines-based and nonguidelines-based prophylaxis (3.2% vs 3.7%, P = .32). In a multivariable logistic regression adjusting for age, race, insurance, and hospital and provider characteristics, nonguideline antibiotic prophylaxis (OR 1.27 [1.12, 1.43], P < .001) was associated with an increased odds of infectious events, whereas a robotic approach (OR 0.82 [0.73, 0.92], P < .001) was associated with lower odds. CONCLUSIONS: Seventy-three percent of patients fail to receive guideline-based antibiotic prophylaxis when undergoing radical cystectomy with conduit, which was largely driven by extended duration antibiotic use. Despite the shorter duration of antibiotics, we found that guideline-based prophylaxis was associated with a 25% decrease in the odds of infectious complications. While residual confounding is possible, these data support current AUA guidelines and suggest a need for outreach to improve guideline adherence.

A multidisciplinary approach to optimize primary prostate cancer biobanking.

PURPOSE: Biobanking tissue of high quality and fidelity is imperative for cancer genomics research. Since it is a challenging process, we sought to develop a protocol that improves the fidelity and quantity of biobanked primary prostate cancer (CaP) tissue. MATERIALS AND METHODS: We conducted a pilot study evaluating pathologic concordance of biobanked tissue and the radical prostatectomy specimen using either standard protocol (SP) vs. next-generation protocol (NGP). RESULTS: There were no significant differences in clinical and pathologic characteristics (age, BMI, preoperative PSA, prostate weight, race, final prostatectomy Gleason score, or pathologic tumor and nodal stages) between the two protocol arms. Utilization of the NGP compared to the standard protocol resulted in a significantly higher rate of pathologic concordance between the biobanked and RP specimens (61.8% vs. 37.9%, P = 0.0231) as well as a nearly two-fold increase in the amount of biobanked tumor tissue (330 mm3 vs. 174 mm3, P < 0.001). When looking at relevant clinical and pathologic characteristics, NGP was associated with pathologic concordance on both univariate [OR 2.65 (95% CI 1.13-6.21), P = 0.025] and multivariate analysis [OR 3.11 (95% CI 1.09-8.88), P = 0.034]. CONCLUSIONS: Our study validates the NGP as a multidisciplinary approach for improving the fidelity and amount of biobanked primary CaP tissue for future studies. Given the challenges to banking tissue from primary CaP as tumors are often difficult to visualize grossly and are frequently multifocal, optimizing the fidelity and volume of biobanked tissue is an important step forward to improve the generalizability of genomic data as we move towards precision medicine.

Prognostic Role of Preoperative Vascular Cell Adhesion Molecule-1 Plasma Levels in Urothelial Carcinoma of the Bladder Treated With Radical Cystectomy.

BACKGROUND: Angiogenesis-related marker vascular cell adhesion molecule-1 (VCAM-1) has been shown to be elevated in urothelial carcinoma of the bladder (UCB), but its predictive/prognostic role has not been determined. Thus, this study aimed to investigate the predictive/prognostic role of VCAM-1 for patients who have UCB treated with radical cystectomy (RC). METHODS: The study enrolled 1036 patients with clinically non-metastatic advanced UCB who underwent RC, and plasma VCAM-1 was evaluated preoperatively. The correlation of plasma VCAM-1 with pathologic and survival outcomes was assessed using binominal logistic regression and multivariable Cox regression analyses. Discrimination was assessed using the area under the curve and concordance indices. The clinical net benefit was evaluated using decision curve analysis (DCA). RESULTS: Preoperative VCAM-1 was significantly elevated in patients with adverse pathologic features. Higher VCAM-1 levels were independently associated with increased risk of lymph-node-metastasis (LNM), ≥pT3 disease, and non-organ-confined disease (NOCD (p < 0.001 for each). Preoperative plasma VCAM-1 was independently associated with recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) in pre- and postoperative multivariable models. Adding VCAM-1 to these predictive models improved their discriminatory ability to predict all outcomes by a significant margin. In the DCA, VCAM-1 addition to the reference models for prediction of LNM, NOCD, RFS, and CSS resulted in relevant improvement. CONCLUSIONS: Elevated plasma VCAM-1 was associated with biologically and clinically aggressive UCB disease features. After validation, preoperative VCAM-1 may serve as a biomarker to help identify patients likely to benefit from intensified/multimodal therapy. In addition, VCAM-1 improved the discriminatory power of predictive/prognostic models and can be used to refine personalized clinical decision-making.

Novel nomograms to predict muscle invasion and lymph node metastasis in upper tract urothelial carcinoma.

OBJECTIVES: To develop accurate preoperative nomograms for prediction of muscle-invasive disease and lymph node metastasis in upper tract urothelial carcinoma (UTUC), to assist surgeons in risk stratifying patients and help guide treatment decisions. MATERIALS/METHODS: The National Cancer Database was used to identify all patients from 2004 to 2016 with UTUC who underwent extirpative surgery and lymphadenectomy. Univariate and multivariate logistic regression was performed to identify variables predicting muscle-invasive and node-positive disease. The data set was split 80:20 into a derivation and validation cohort and used to generate and test two nomograms. Nomograms were assessed using area under the curve (AUC) and calibration plots. RESULTS: A total of 6,143 patients met inclusion criteria. Predictors of muscle-invasive disease were age, grade, lymphovascular invasion (LVI), tumor size, and positive clinical lymph node status. Predictors of node-positive disease were grade, LVI, tumor size, and positive clinical lymph node status. The accuracy of the final nomogram predicting muscle-invasive disease was 80.0% (AUC 0.800, corrected C-index 0.813), and the accuracy of the nomogram predicting node-positive disease was 87.8% (AUC 0.878, corrected C-index 0.887). CONCLUSIONS: With data readily available after imaging and biopsy (age, tumor grade, LVI status, tumor size, and clinical lymph node status), we developed the first preoperative nomograms to quantitatively predict muscle-invasive disease and lymph node metastasis in UTUC, with an accuracy of 80.0% and 87.8% respectively. This information could be helpful to assist surgeons with pre-operative risk stratification.

Collision tumors revealed by prospectively assessing subtype-defining molecular alterations in 904 individual prostate cancer foci.

BACKGROUNDProstate cancer is multifocal with distinct molecular subtypes. The utility of genomic subtyping has been challenged due to inter- and intrafocal heterogeneity. We sought to characterize the subtype-defining molecular alterations of primary prostate cancer across all tumor foci within radical prostatectomy (RP) specimens and determine the prevalence of collision tumors.METHODSFrom the Early Detection Research Network cohort, we identified 333 prospectively collected RPs from 2010 to 2014 and assessed ETS-related gene (ERG), serine peptidase inhibitor Kazal type 1 (SPINK1), phosphatase and tensin homolog (PTEN), and speckle type BTB/POZ protein (SPOP) molecular status. We utilized dual ERG/SPINK1 immunohistochemistry and fluorescence in situ hybridization to confirm ERG rearrangements and characterize PTEN deletion, as well as high-resolution melting curve analysis and Sanger sequencing to determine SPOP mutation status.RESULTSBased on index focus alone, ERG, SPINK1, PTEN, and SPOP alterations were identified in 47.5%, 10.8%, 14.3%, and 5.1% of RP specimens, respectively. In 233 multifocal RPs with ERG/SPINK1 status in all foci, 139 (59.7%) had discordant molecular alterations between foci. Collision tumors, as defined by discrepant ERG/SPINK1 status within a single focus, were identified in 29 (9.4%) RP specimens.CONCLUSIONInterfocal molecular heterogeneity was identified in about 60% of multifocal RP specimens, and collision tumors were present in about 10%. We present this phenomenon as a model for the intrafocal heterogeneity observed in previous studies and propose that future genomic studies screen for collision tumors to better characterize molecular heterogeneity.FUNDINGEarly Detection Research Network US National Cancer Institute (NCI) 5U01 CA111275-09, Center for Translational Pathology at Weill Cornell Medicine (WCM) Department of Pathology and Laboratory Medicine, US NCI (WCM SPORE in Prostate Cancer, P50CA211024-01), R37CA215040, Damon Runyon Cancer Research Foundation, US MetLife Foundation Family Clinical Investigator Award, Norwegian Cancer Society (grant 208197), and South-Eastern Norway Regional Health Authority (grant 2019016 and 2020063).

Pilot study of the diagnostic utility of 89 Zr-df-IAB2M and 68 Ga-PSMA-11 PET imaging and multiparametric MRI in localized prostate cancer.

BACKGROUND: Accurate diagnosis of localized prostate cancer (PCa) is limited by inadequacy of multiparametric (mp) MRI to fully identify and differentiate localized malignant tissue from benign pathologies. Prostate-specific membrane antigen (PSMA) represents an excellent target for molecular imaging. IAB2M, an 85-kD minibody derived from a de-immunized monoclonal antibody directed at the extracellular domain of human PSMA (huJ591), and PSMA-11, a small molecule ligand have been previously tested as probes for visualization of recurrent/metastatic PCa with PET/CT. This pilot, non-randomized trial studied their diagnostic utility in patients (pts) with localized PCa. METHODS: Pts planned for radical prostatectomy (RP) were enrolled and underwent mpMRI and PET/CT imaging with 89 Zr-df-IAB2M and/or 68 Ga-PSMA-PET/CT. Image results were read by a radiologist blinded to clinical information and pathology results, mapped and compared to corresponding histopathology findings from all lesions, both clinically significant and nonsignificant. The detection rates of all three imaging modalities were measured and correlated. RESULTS: 20 pts with median age of 64.5 (46-79) years and PSA level of 7.5 (1.6-36.56) ng/ml were enrolled. 19 pts underwent RP and were imaged pre-operatively with 89 Zr-Df-IAB2M PET/CT and mpMRI. Nine of those were imaged using 68 Ga-PSMA-11 as well. Out of 48 intraprostatic lesions verified on surgical pathology, IAB2M PET/CT was able to detect 36 (75%). A similar proportion of pathologically confirmed, clinically significant lesions (22/29, 76%) was detected. IAB2M PET/CT was also able to identify 14/19 (74%) extraprostatic lesions. The performance of mpMRI was inferior, with 24/48 detectable lesions (50%) and 18/29 clinically significant intraprostatic lesions (62%). Compared to the current standard (mpMRI), IAB2M PET/CT had a sensitivity of 88%, specificity 38%, positive predictive value 58%, and accuracy 63%. In 9 pts who underwent Ga-PSMA-11 as well, the latter yielded a detection rate of 70% (14/20), which was also seen in clinically significant lesions (10/14, 71%). Ga-PSMA-11 PET/CT also detected 4/6 (67%) extraprostatic lesions. CONCLUSIONS: In this pilot study, the performance of 89 Zr-df-IAB2M was superior to mpMRI and similar to 68 Ga-PSMA-11 PET/CT. The higher detection rate of PSMA-PET supports its use as a diagnostic tool with consequent management change implications in men with localized PCa.

Sociodemographic Disparities in Access to Chemotherapy for Bladder Cancer.

BACKGROUND: We sought to evaluate sociodemographic disparities in access to neoadjuvant (NAC) and adjuvant (AC) chemotherapy in the United States and their effect on survival. METHODS: The National Cancer Database was used to identify all patients from 2004 to 2016 eligible for NAC and AC. Univariate and multivariate logistic regression was performed to identify sociodemographic predictors associated with receipt of NAC and AC. Kaplan-Meier and Cox proportional hazard models were used for survival analysis. RESULTS: A total of 17,121 patients were eligible for NAC, and 18,962 for AC. Older (OR 0.94, P < .001), Medicare (OR 0.88, P = .047), Medicaid (OR 0.66, P = .001), uninsured (OR 0.47, P < .001), rural (OR 0.70, P = .042), and community hospital patients (OR 0.72, P < .001) were less likely to receive NAC. Older, (OR 0.95, P < .001), female (OR 0.79, P < .001), Medicaid (OR 0.71, P = .003), uninsured (OR 0.60, P = .001), and lower income patients (OR 0.86, P = .017) were less likely to receive AC. In NAC-eligible patients, older (HR 1.02, P < .001), Medicare (HR 1.11, P = .024), Medicaid (HR 1.25, P = .012), and community hospital patients (HR 1.09, P = .021) were at an increased risk of death. In AC-eligible patients, older (HR 1.01, P < .001), Black (HR 1.15, P = .011), Medicaid (HR 1.14, P = .042), lower income (HR 1.07, P = .038) and community hospital patients (HR 1.07, P = .021) were at an increased risk of death. CONCLUSIONS: Significant sociodemographic disparities currently exist in the United States in access to neoadjuvant and adjuvant chemotherapy for bladder cancer. Uninsured and Medicaid insurance status are the strongest predictors of not receiving chemotherapy. Efforts must be made to deliver this critical standard-of-care treatment to these patients.

Embryonal rhabdomyosarcoma of the adult prostate: case report and review.

Herein is reported a case of embryonal rhabdomyosarcoma of the prostate in a 54-year-old male. The presenting symptoms were dysuria, hematuria, and systemic thrombotic events. Diagnosis was ascertained through a transurethral resection. The treatment course consisted of transurethral resection, prostatic embolization, chemotherapy with dactinomycin, vincristine, and cyclophosphamide, cystoprostatectomy, rectal excision, and external beam radiation. The patient succumbed to the fatality of this disease within six months of diagnosis. Rhabdomyosarcoma is a rare tumor that can arise in the prostate and this case highlights an unusually refractory and rapidly fatal case. Treatment guidelines are not established for adults with this disease.

Durability of Response to Primary Chemoablation of Low-Grade Upper Tract Urothelial Carcinoma Using UGN-101, a Mitomycin-Containing Reverse Thermal Gel: OLYMPUS Trial Final Report.

PURPOSE: Our goal was to evaluate long-term safety and durability of response to UGN-101, a mitomycin-containing reverse thermal gel, as primary chemoablative treatment for low-grade upper tract urothelial carcinoma. MATERIALS AND METHODS: In this open-label, single-arm, multicenter, phase 3 trial (NCT02793128), patients ≥18 years of age with primary or recurrent biopsy-proven low-grade upper tract urothelial carcinoma received 6 once-weekly instillations of UGN-101 via retrograde catheter to the renal pelvis and calyces. Those with complete response (defined as negative ureteroscopic evaluation, negative cytology and negative for-cause biopsy) 4-6 weeks after the last instillation were eligible for up to 11 monthly maintenance instillations and were followed for ≥12 months with quarterly evaluation of response durability. Durability of complete response was determined by ureteroscopic evaluation; duration of response was estimated by the Kaplan-Meier method. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: Of 71 patients who initiated treatment, 41 (58%) had complete response to induction therapy and consented to long-term followup; 23/41 patients (56%) remained in complete response after 12 months (95% CI 40, 72), comprising 6/12 (50%) who did not receive any maintenance instillations and 17/29 (59%) who received ≥1 maintenance instillation. Kaplan-Meier analysis of durability was estimated as 82% (95% CI 66, 91) at 12 months. Ureteric stenosis was the most frequently reported TEAE (31/71, 44%); an increasing number of instillations appeared to be associated with increased incidence of urinary TEAEs. CONCLUSIONS: Durability of response to UGN-101 with or without maintenance treatment is clinically meaningful, offering a kidney-sparing therapeutic alternative for patients with low-grade disease.

Impact of preoperative plasma levels of interleukin 6 and interleukin 6 soluble receptor on disease outcomes after radical cystectomy for bladder cancer.

BACKGROUND: Preoperative plasma levels of Interleukin 6 (IL6) and its soluble receptor (IL6sR) have previously been associated with oncologic outcomes in urothelial carcinoma of the bladder (UCB); however, external validation in patients treated with radical cystectomy (RC) for UCB is missing. PATIENTS/METHODS: We prospectively collected preoperative plasma from 1,036 consecutive patients at two institutes. These plasma specimens were assessed for levels of IL6 and IL6sR. Logistic and Cox regression analyses were used to assess the correlation of plasma levels with pathologic and survival outcomes. The additional clinical net benefits of preoperative IL6 and IL6sR were evaluated using decision curve analysis (DCA). RESULTS: Median IL6 and IL6sR plasma levels were significantly higher in patients with adverse pathologic features. Elevated biomarker levels were independently associated with an increased risk for lymph node metastasis and ≥ pT3 disease. Both biomarkers were independently associated with recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The addition to, respectively, fitted pre- and postoperative prognostic models improved the predictive accuracy for lymph node metastasis, ≥ pT3 disease, RFS and CSS on DCA. INTERPRETATION: We confirmed that elevated preoperative plasma levels of IL6 and IL6sR levels are associated with worse oncological disease survival in patients treated with RC for UCB in a large multicenter study. Both biomarkers hold potential in identifying patients with adverse pathological features that may benefit from intensified/multimodal therapy and warrant inclusion into predictive/prognostic models. They demonstrated the ability to improve the discriminatory power of such models and thus guide clinical decision making.

Does neoadjuvant chemotherapy diminish the sex disparity in bladder cancer survival after radical cystectomy?

INTRODUCTION: Sex-specific survival disparities for bladder cancer outcomes after radical cystectomy (RC) have been demonstrated in several studies. However, these studies predate the widespread adoption of neoadjuvant chemotherapy (NAC). We evaluated the differences in sex-specific survival between patients who received NAC with those who did not, using a contemporary national outcomes database. METHODS: The National Cancer Data Base was queried from 2004 to 2015 to identify subjects who underwent RC. Kaplan-Meier method with log-rank test was performed to compare all-cause mortality between men and women at each pathologic (p) TNM stage group: T1-4N0, N+ and M+ disease. Associations for all-cause mortality were identified using an adjusted Cox regression analysis, and our findings were confirmed with a subgroup analysis. RESULTS: A total of 9,835 subjects (7,483 men and 2,532 women) were included in the analysis. Kaplan-Meier survival curves and Cox regression analysis demonstrated female sex was not associated with worse overall survival compared to males (HR 0.947, 95%CI 0.852-1.053, P = 0.947) in the overall cohort. Stratified by pT stage and node positivity, worse overall survival was seen in women with pT4 disease who did not receive NAC compared to men (5-year OS 9.6% women vs. 15.2% men, P < 0.001), but no sex-specific difference was seen across all groups in patients who received NAC. Subgroup multivariable analysis showed that female sex conferred a survival disadvantage for pT4 (HR 1.369, P = 0.026) disease only in patients who did not receive NAC. CONCLUSIONS: In a contemporary cohort of subjects who underwent RC, administration of NAC narrows the sex survival-gap in advanced stage bladder cancer. Strategies to improve NAC usage in women should be adopted to overcome potential sex-specific differences such as delayed diagnosis, anatomic differences in higher stage disease, or altered tumor biology which may contribute to differences in oncologic outcomes.

Prostate Cancer Screening for Gay Men in the United States.

OBJECTIVE: To elucidate trends of prostate-cancer (PCa) screening in gay and bisexual men and assess the association of sexual orientation with PCa screening in the United States of America. METHODS: Data for men ≥40 years-old with no history of PCa were collected from the National Health Interview Survey for the years 2013, 2015, and 2018. Multivariable logistic regression models were created to determine the associations between sexual orientation and PCa screening and the discussion of advantages and disadvantages prior to PCa screening. RESULTS: Gay men screened for prostate cancer were younger than their straight counterparts with a median age (IQR) of 58 years (52-66) vs 64 years (56-71). Gay men were more likely to have undergone a screening PSA test (OR 1.56; 95% CI 1.20-2.02) and discuss the advantages of PSA testing with the physician prior to the test (OR 1.64; 95% CI 1.22-2.21) when compared to straight men. In yearly analysis, gay men were more likely to have undergone screening in 2013 (OR 1.65, 95% CI 1.01-2.68) and 2015 (OR 1.95, 95 CI% 1.30-2.91), however, there was no difference when compared to straight men in 2018 (OR 1.32, 95% CI 0.85-2.04). CONCLUSION: Gay men were screened for PCa at a younger age comparted to straight men. They were also more likely to have undergone PCa cancer screening than straight men between 2013 and 2018. Further study is needed to better understand the role of sexual orientation in PCa screening and management.

Preoperative plasma level of endoglin as a predictor for disease outcomes after radical cystectomy for nonmetastatic urothelial carcinoma of the bladder.

Elevated preoperative plasma level of endoglin has been associated with worse oncologic outcomes in various malignancies. The present large-scale study aimed to determine the predictive and prognostic values of preoperative endoglin with regard to clinicopathologic and survival outcomes in patients treated with radical cystectomy (RC) for nonmetastatic urothelial carcinoma of the bladder (UCB). We prospectively collected preoperative blood samples from 1036 consecutive patients treated with RC for UCB. Logistic and Cox regression analyses were undertaken to assess the correlation of endoglin levels with pathologic and survival outcomes, respectively. The AUC and C-index were used to assess the discrimination. Patients with adverse pathologic features had significantly higher median preoperative endoglin plasma levels than their counterparts. Higher preoperative endoglin level was independently associated with an increased risk for lymph node metastasis, ≥pT3 disease, and nonorgan confined disease (NOCD; all p < 0.001). Plasma endoglin level was also independently associated with cancer-specific and overall survival in both pre- and postoperative models (all p < 0.05), as well as with recurrence-free survival (RFS) in the preoperative model (p < 0.001). The addition of endoglin to the preoperative standard model improved its discrimination for prediction of lymph node metastasis, ≥pT3 disease, NOCD, and RFS (differential increases in C-indices: 10%, 5%, 5.8%, and 4%, respectively). Preoperative plasma endoglin is associated with features of biologically and clinically aggressive UCB as well as survival outcomes. Therefore, it seems to hold the potential of identifying UCB patients who may benefit from intensified therapy in addition to RC such as extended lymphadenectomy or/and preoperative systemic therapy.

Underutilization of Blue Light Cystoscopy for Bladder Cancer in the United States.

Blue light cystoscopy (BLC) during transurethral resection of bladder tumor (TURBT) is guideline-recommended as it improves cancer detection and decreases recurrence of the disease. However, the extent to which BLC is used has not been established. We studied BLC use in the Premier Healthcare Database, a large, national sample that captured 158 870 index TURBT procedures between January 2011 and March 2020. Billing data were queried for the administration of hexaminolevulinate at TURBT as a proxy for BLC, and logistic regression models were constructed to identify variables associated with BLC use. BLC was used in 1.2% of index TURBT procedures over the study period. Its use increased following the American Urological Association non-muscle-invasive bladder cancer guideline publication in October 2016 but plateaued in late 2018. After adjusting for patient characteristics, higher odds for BLC use were found for academic hospitals and hospitals with higher TURBT volumes and higher radical cystectomy volumes. Within hospitals with BLC capability, predictors of a surgeon never using BLC included low surgeon TURBT volumes, low surgeon radical cystectomy volumes, and lack of mitomycin C use. Our findings highlight a concerning underutilization and stagnation in the adoption of evidence and guideline-supported intervention. PATIENT SUMMARY: Use of blue light visualization of the bladder improves the detection of cancer during removal of bladder tumors via the urethra. We reviewed records in a large US database for use of this technique and found that it is being underutilized. Since this technique improves detection of cancer in the bladder so that it can be removed to reduce recurrence, blue light visualization should be more widely used.