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While the 5-year survival rate for local and regional prostate cancer is nearly 100%, it decreases dramatically for advanced tumours. Accessibility to health care is an important factor for cancer prognosis. The U.S. Military Health System (MHS) provides universal health care to its beneficiaries, reducing financial barriers to medical care. However, whether the universal care translates into improved survival among patients with advanced prostate cancer in the MHS is unknown. In this study, we compared the MHS and the U.S. general population in survival of patients with advanced prostate cancer (stages III and IV).The MHS patients (N = 5379) were identified from the Department of Defense's (DoD) Automated Central Tumor Registry (ACTUR). Patients in the U.S. general population (N = 21,516) were identified from the Surveillance, Epidemiology, and End Results (SEER) programme. The two populations were matched on age, race, and diagnosis year.The ACTUR patients exhibited longer 5-year survival than the matched SEER patients (HR = 0.74, 95% CI = 0.67-0.83), after adjustment for the potential confounders. The improved survival was observed for ages 50 years or older, both White patients and Black patients, all tumour stages and grades. This was also demonstrated despite the receipt of surgery or radiation treatment.MHS beneficiaries with advanced prostate cancer had longer survival than their counterparts in the U.S. general population.

PURPOSE: Frailty is associated with adverse outcomes following radical cystectomy. Prospective tools to identify factors affecting outcomes are needed. We describe a novel electronic rapid fitness assessment to evaluate geriatric patients undergoing radical cystectomy. MATERIALS AND METHODS: Prior to undergoing radical cystectomy between February 2015 and February 2018, 80 patients over the age of 75 completed the electronic rapid fitness assessment and were perioperatively comanaged by the Geriatrics Service. Physical and cognitive function over 12 domains were evaluated and an accumulated geriatric deficit score compiled. Hospital length of stay, discharge disposition, unplanned intensive care unit admissions, urgent care visits, readmissions, complications, and deaths were assessed. RESULTS: Sixty-five patients who underwent radical cystectomy for bladder cancer without concomitant procedures completed the assessment. Median age was 80 (77, 84), and 52 (80%) were male. A higher proportion of patients with intensive care unit admission, urgent care visit, and major complications had impairments identified within electronic rapid fitness assessment domains, including Timed Up and Go. Readmission rates were similar between patients with or without deficits identified. Higher accumulated geriatric deficit score was significantly associated with intensive care unit admission (p=0.035), death within 90 days (p=0.037), and discharge to other than home (p=0.0002). CONCLUSIONS: We demonstrated the feasibility of assessing fitness in patients over 75 undergoing radical cystectomy using a novel electronic fitness tool. Physical limitations and overall impairment corresponded to higher intensive care unit admission rates and adverse postoperative outcomes. Larger studies in less resourced environments are required to validate these findings.

Racial differences in Health-Related Quality of Life (HRQoL) after treatment of prostate cancer (PCa) are not well studied. We compared treatment patterns and HRQoL in African American (AA) and non-AA men undergoing active surveillance (AS), radical prostatectomy (RP), or radiation (XRT).Men diagnosed with PCa from 2007-2017 in the Center for Prostate Disease Research Database were identified. HRQoL was evaluated using Expanded PCa Index Composite and SF-36 Health Survey.In 1006 men with localized PCa, 223 (22.2%) were AA (mean follow up 5.2 yrs). AA men with low-risk disease were less likely to undergo AS (28.5 vs. 38.8%) and more likely to undergo XRT (22.3 vs. 10.6%) than non-AA men, p0.001. In intermediate-risk disease, AA received more XRT (43.0 vs. 26.9%) and less RP (50.5 vs 66.8%), p = 0.016. In all men, RP resulted in worse urinary function and sexual HRQoL compared to AS and XRT. Bowel HRQoL did not vary by treatment in AA men, however, in non-AA men, XRT resulted in worse bowel scores than AS and RP. HRQoL was then compared for each treatment modality. AA men had worse sexual bother (p = 0.024) after RP than non-AA men, No racial differences were found in urinary, bowel, hormonal, or SF-36 scores for men undergoing AS, RP or XRT.AA men are less often treated with AS for low-risk disease and are more likely to undergo XRT. AA men experience worse sexual bother after RP, however, the effect of XRT on bowel symptoms is worse in non-AA men.

OBJECTIVES To determine whether utilisation of a serum microRNA (miRNA) test could improve treatment appropriateness and cost-effectiveness for patients with Stage I non-seminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS A decision tree model was built to investigate treatment course, clinical and cost outcomes for patients with Stage IA (T1N0M0S0) and IB (T2-4N0M0S0) NSGCT. The model compared outcomes and cost of standard approach using histopathology, conventional serum tumour markers and radiographic staging (standard model) to a miRNA-based approach using the standard model + post-orchidectomy serum miR-371a-3p (marker model). Probabilities of expected treatment and outcomes were based on presence/absence of cancer upon entering into the model. Overtreatment was defined as adjuvant chemotherapy or primary retroperitoneal lymph node dissection in a patient without cancer. Undertreatment was defined as initial surveillance for a patient with cancer. RESULTS Utilising the miRNA marker-based approach, 26% of patients avoid overtreatment and 8% avoid undertreatment in Stage IA NSGCT; 27% avoid overtreatment and 23% avoid undertreatment in Stage IB disease. Appropriate treatment decision-making increased from 65% to 94% and 50% to 92% for Stage IA and IB, respectively. The miRNA-based approach remained cost-effective over a wide range of performance characteristics with savings of ~$1400 (American dollars)/patient for both Stage IA and IB disease. CONCLUSION A miRNA-based approach may potentially select patients with Stage I NSGCT for correct treatment in a cost-effective manner. Identification of residual teratoma-only remains an issue. Prospective studies are necessary to validate these findings.

We are presenting a compelling case of a 61-year-old female with a history of appendiceal mucinous adenocarcinoma (AMA) with a new complaint of irritative lower urinary tract symptoms. Magnetic resonance imaging (MRI) showed a semi-circumferential, T2 hyperintense, rim enhancing, and lacking restricted diffusion lesion involving the urethra and infiltrating the right perineal and internal obturator muscles. The suspected differential diagnosis was urethral malignancy, based on her cancer history and MRI findings. After interdisciplinary consensus, the patient underwent excision of the lesion, and pathology was consistent with metastasis from the primary tumor. The urethra is a rare site of primary malignancy and metastatic disease. In particular, a non-contiguous metastatic disease involving the urethra is exceedingly rare. To the best of our knowledge, this is the first report of an AMA metastasizing to the urethra.

BACKGROUND: Active surveillance (AS) protocols rely on rectal examination, prostate-specific antigen, imaging, and biopsy to identify disease progression. OBJECTIVE: To evaluate whether an AS regimen based on magnetic resonance imaging (MRI) or clinical stage changes can detect reclassification to grade group (GG) ≥2 disease compared with scheduled systematic biopsies. DESIGN, SETTING, AND PARTICIPANTS: We identified a cohort of men initiated on AS between January 2013 and April 2016 at a single tertiary-care center. Patients completed confirmatory testing and prostate MRI prior to enrollment, then underwent laboratory and physical evaluation every 6 mo, MRI every 18 mo, and biopsy every 3 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: MRI results were evaluated using composite Likert/Prostate Imaging Reporting and Data System v2 scoring. MRI and clinical changes were assessed for association with disease progression. Univariable and multivariable regression models were used to predict upgrading on 3-yr biopsy. RESULTS AND LIMITATIONS: At 3 yr, of 207 men, 66 (32%) had ≥GG2 at biopsy: 55 (83%) with GG2, 10 (15%) with GG3, and one (1.5%) with GG4. Among patients with a 3-yr MRI score of ≥3, 41% had ≥GG2 disease, compared with 15% with an MRI score of

We assessed the concordance among urologists' judgment of health quartiles for patients with localized prostate cancer, and compared the life expectancy (LE) and ensuing treatment recommendations when following National Comprehensive Cancer Network (NCCN) guidelines based on actuarial life tables versus the Kent model, a validated LE prediction model.NCCN suggests using actuarial life tables and relying on surgeon assessment of patient health to increase (for the best quartile) or decrease (for the worst quartile) LE by 50%. Eleven urologic surgeons allocated quartile of health and recommended treatments for ten patient vignettes. The 10-year survival probability was calculated using the Kent model and compared to the life-table estimate based on health quartile by surgeon consensus.Surgeon assessment agreed with the presumed true quartile of health based on a validated model in 41% of cases. For no case did three-quarters of surgeons assign health quartile correctly; in half of cases,50% of surgeons assigned the correct quartile. The NCCN comorbidity-adjusted LE estimates underestimated risk of death in the best health quartile and overestimated risk of death in the worst health quartile, compared to the Kent model. Patients with LE 10 years on NCCN estimation were recommended more frequently for surgery (81%) and those with ≤10 years estimated LE were more commonly recommended for radiation (57%) or observation (29%).A method based on physician-assessed health quartiles for LE estimation, as suggested by the NCCN guidelines, appears too crude to be used in the treatment counseling of men with localized prostate cancer, as compared to a validated prediction model, such as the Kent model.

In the United States, prostate cancer (CaP) remains the second leading cause of cancer deaths in men. CaP is predominantly indolent at diagnosis, with a small fraction (25–30%) representing an aggressive subtype (Gleason score 7–10) that is prone to metastatic progression. This fact, coupled with the criticism surrounding the role of prostate specific antigen in prostate cancer screening, demonstrates the current need for a biomarker(s) that can identify clinically significant CaP and avoid unnecessary biopsy procedures and psychological implications of being diagnosed with low-risk prostate cancer. Although several diagnostic biomarkers are available to clinicians, very few comparative trials have been performed to assess the clinical effectiveness of these biomarkers. It is of note, however, that a majority of these clinical trials have been over-represented by men of Caucasian origin, despite the fact that African American men have a 1.7 times higher incidence and 2.1 times higher rate of mortality from prostate cancer. Biomarkers for CaP diagnosis based on the tissue of origin include urine-based gene expression assays (PCA3, Select MDx, ExoDx Prostate IntelliScore, Mi-Prostate Score, PCA3-PCGEM1 gene panel), blood-based protein biomarkers (4K, PHI), and tissue-based DNA biomarker (Confirm MDx). Another potential direction that has emerged to aid in the CaP diagnosis include multi-parametric magnetic resonance imaging (mpMRI) and bi-parametric magnetic resonance imaging (bpMRI), which in conjunction with clinically validated biomarkers may provide a better approach to predict clinically significant CaP at diagnosis. In this review, we discuss some of the adjunctive biomarker tests along with newer imaging modalities that are currently available to help clinicians decide which patients are at risk of having high-grade CaP on prostate biopsy with the emphasis on clinical utility of the tests across African American (AA) and Caucasian (CA) men.

INTRODUCTION AND OBJECTIVE:DNA damage repair genes (DDRGs) play a critical role in genomic stability and their dysfunction contributes to mutagenesis in several cancer types. In prostate cancer (Ca...

Existing tumor markers for testicular germ cell tumor (TGCT) cannot detect the presence of pure teratoma. Serum miRNAs have strong performance detecting other subtypes of TGCT. Previous reports suggest high levels of miR-375 expression in teratoma tissue. The purpose of this study was to explore the role of serum miRNA, including miR-375, in detecting the presence of teratoma at postchemotherapy retroperitoneal lymph node dissection (PC-RPLND).We prospectively collected presurgical serum from 40 TGCT patients undergoing PC-RPLND (21 with teratoma at RPLND and 19 with no evidence of disease). We examined the utility of serum miR-375-3p and miR-375-5p by quantitative polymerase chain reaction, and searched for other putative serum miRNAs with small RNA sequencing. The area under the receiver operating characteristic curve (AUC) and univariate analyses were utilized to evaluate test characteristics and predictors of teratoma.Both serum miR-375-3p and miR-375-5p exhibited poor performance (miR-375-3p: 86% sensitivity, 32% specificity, AUC: 0.506; miR-375-5p: 55% sensitivity, 67% specificity, AUC: 0.556). Teratoma at orchiectomy was the only predictor of PC-RPLND teratoma. Small RNA sequencing identified three potentially discriminatory miRNAs, but further validation demonstrated no utility. Our results confirm prior reports that serum miR-375 cannot predict teratoma, and suggest that there may not exist a predictive serum miRNA for teratoma. Patient summary: We found that serum miR-375 cannot detect the presence of teratoma at postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). We are also unable to find any other serum miRNAs predictive of pure teratoma at PC-RPLND. Hence, the lack of a reliable circulating marker of teratoma remains a critical clinical need.

To investigate impact of age and race on health-related quality of life (HRQoL) in men undergoing radical prostatectomy (RP) using a prospectively maintained, racially diverse cohort.The Center for Prostate Disease Research Multicenter National Database was used to identify patients receiving RP from 2007-2017. The Expanded PCa Index Composite and 36 Item Short-Form Health Survey were completed at baseline and regular intervals. Groups were stratified based on age:60, 60-70,70. Longitudinal patterns in HRQoL were assessed using linear regression models, adjusting for baseline HRQoL, demographics, and clinical characteristics.In 626 patients undergoing RP, 278 (44.4%) were60, 291 (46.5%) were 60-70, 57 (9.1%) were70. Older men had worse baseline urinary bother (P.01) and sexual HRQoL (P.01). Baseline urinary function was similar for older and younger men. Post-RP urinary and sexual HRQoL was significantly lower in men70. However, when adjusting for baseline HRQoL, race, NCCN risk, and comorbidities, no difference was found between age groups in urinary function or bother, or sexual function. Sexual bother was worse in older men until 48 months post-operatively but subsequently improved to levels similar to younger patients. Race independently affected HRQoL outcomes with older African American men reporting worse urinary function and sexual bother.When accounting for baseline HRQoL, age does not independently predict worse HRQoL outcomes. Older and younger men experience similar declines in urinary and sexual domain scores after RP. Our findings may be used to better inform patients regarding their expected post RP HRQoL and guide treatment decision-making.

BackgroundAfrican American (AA) men have significantly higher mortality rates from prostate cancer (PC) than individuals of European ancestry (EA). Therapeutically targetable molecular differences may hold the potential to reduce this disparity.ObjectiveTo investigate chromodomain helicase DNA-binding protein 1 (CHD1) deletion both as a cause of aggressive disease and therapeutic vulnerability in the prostate cancer of AA men.Design, setting, and participants91 AA and 109 EA prostate cancer cases were analyzed by fluorescence in situ hybridization (FISH) for the deletion of CHD1. Whole exome and whole genome sequencing data from prostate adenocarcinoma cases were analyzed for mutational signatures from AA and EA individuals.Outcome measurements and statistical analysisAssociations with biochemical recurrence were evaluated using Cox proportional hazard regression models. Association between mutational signatures and CHD1 deletion were assessed by Wilcoxon ranked sum tests.Results and limitationsSubclonal deletion of CHD1 is nearly three times as frequent in prostate tumors of men than in EA men. CHD1 deletion is associated with some of the homologous recombination deficiency associated mutational signatures in prostate cancer. In a cell line model CHD1 deletion induced 1-10 kb deletions resembling those induced by BRCA2 deficiency. CHD1 deficient cells showed markedly increased sensitivity to both talazoparib and the radiomimetic bleomycin.ConclusionsCHD1 is more frequently deleted in the prostate cancer of AA men. This deletion is both associated with and induces mutational signatures characteristic of BRCA2 deficiency. CHD1 deficient prostate cancer is more sensitive to talazoparib or bleomycin treatment.Patient summarySubclonal deletion of CHD1 is more frequent in the prostate cancer of AA men and this could be one of the reasons behind more aggressive disease. CHD1 deletion, however, also constitutes a therapeutic vulnerability to the PARP inhibitor talazoparib. This treatment may significantly improve the outcome of disease in AA men.

The multifocality and highly variable molecular pathology of prostate cancer are underlying features of this clinically heterogeneous disease. Most patients harbor multiple molecularly distinct cancer foci at diagnosis that likely arose as independent clones. There is a critical need for molecular biomarkers that can distinguish the multifocality and inter-focal heterogeneity of tumors and help stratify patients for treatment. PTEN loss and ETS gene rearrangements are among the most prevalent genomic alterations in prostate carcinogenesis. The detection of both ERG overexpression and PTEN protein loss by immunohistochemistry (IHC) have proven to be reliable substitutes for detecting genomic alterations by fluorescence in situ hybridization (FISH) assay. We developed monoclonal antibodies against ETV1 and ETV4 and evaluated their performance in prostate cancer specimens. The expression of ETV1, ETV4, were examined in relation to ERG and loss of PTEN expression in TMAs constructed from primary prostate cancer specimens of two independent patient cohorts. The first TMA was constructed from multiple 1 mm cores representing distinct tumor focus from multifocal tumors from 50 African American (AA) and 50 Caucasian American (CA) men. The second was constructed from a single 2 mm core of individual tumors from an independent cohort of 152 AA and 304 CA men. We present results on the expression of each protein biomarker in the context of patient race and their association with clinico-pathologic features, together with concurrence or mutual exclusiveness for each event. These results support the application of ETS monoclonal antibodies in IHC assays to detect prostate cancer tumor heterogeneity and to identify subsets of prostate cancer. Citation Format: Cara Schafer, Denise Young, Yingjie Song, Jiji Jiang, Albert Dobi, Gyorgy Petrovics, Bettina F. Drake, Gregory T. Chesnut, Isabell A. Sesterhenn, Shyh-Han Tan. Immunohistochemical detection of prostate cancer heterogeneity by using ETS and PTEN monoclonal antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2220.

Objectives: Diagnosis with prostate cancer (PCa) at younger age is a serious challenge in Military Health System. PCa onset at younger age is more likely to be aggressive in African American (AA) population. Also, application of formalin fixed paraffin embedded (FFPE) tissue in RNA based study was significantly hindered due to poor quality/quantity of RNA in archived pathology slides. This study is aimed to examine age/race associated gene signatures in military cohort with high representation of AA and younger population in FFPE samples for potential genetic mechanisms of health disparities and broaden tissue sample availability. Methods: A cohort of 41 Caucasian American (CA) and 20 AA non-familial PCa patients from the biospecimen bank of CPDR, WRNMMC were used. Specimens donated by radical prostatectomy patients who provided written consent and protocols approved by Institutional Review Boards. Total RNA was extracted from tumor and the adjacent normal epithelium of whole-mount FFPE tissue of matched specimens. Differential gene expression, in tumor versus normal tissues, between younger and older AA and CA patients were analyzed by NanoString using a customized CodeSet of 151 probes. The panel designed to detect 135 target transcripts, compiled from 34 genes implicated/associated with PCa progression, 27 PCa specific gene fusions, 25 cancer-associated genes, and 5 genes encoding ETS-family of transcription factors. The 27 over-expressed genes and 17 under-expressed genes in PCa were included as comparison to matched, benign epithelium. Additionally, 5 prostate stroma or epithelium specific genes were selected as control and 11 housekeeping genes were included for biological normalization. Results: The differentially expressed genes related to tumor-normal differences between AA older (66-73 years) and younger (42-58 years) as well as CA older and younger PCa patients with moderate Gleason score (3+3 and 3+4) sum were identified. After controlling for false discovery rates, panel of nine genes (ANXA2, C-MYC, VEGFR1, ERG, NPY, PSMA/FOLH1, TWIST1, MAOA, MYCN) uniquely associated with age/race were identified. Tumor vs normal ratios of ANXA2 and C-MYC expression in prostate tumors of older and younger patients were significantly enhanced. We found a clear association of VEGFR1 gene expression with CA young and c-MYC gene with AA young PCa. Conclusions: Using age/race as endpoint, we identified ANXA2, c-MYC and VEGFR1 as age and race associated PCa gene. Our findings highlight distinct racial and age-related differences and addresses the clinical utility of available genetic tests across old and young AA and CA men, which needs to be further validated in lager cohort. Further, our study also highlighted the utilization of FFPE tissue for NanoString assay and subsequent genetic signature analyses. Citation Format: Shashwat Sharad, Darryl Nousome, Gregory T. Chesnut, Hua Li. The study of age and race genetic signatures of prostate cancer with formalin fixed paraffin embedded (FFPE) samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2210.

Background Overprescribing of opioids after surgery contributes to long-term abuse. Evaluating opioid prescription patterns and patient-reported opioid use offers an evidence-based method to identify potential overprescription. This quality improvement initiative aimed to reduce and standardize opioid prescriptions upon discharge from an ambulatory oncologic surgery center and evaluate the effect of this change on patients’ subsequent opioid use and reported pain. Methods Between March 2018 and January 2019, consecutive opioid-naive patients aged ≥ 18 years who underwent robotic or laparoscopic hysterectomy, radical prostatectomy, or partial nephrectomy, or total mastectomy with or without immediate reconstruction were surveyed 7–10 days postoperatively. Data collected in the pre- (n = 551) and post-standardization (n = 480) cohorts included perception of pain relief, opioids prescribed (verified by electronic medical record review) and consumed, and refills received. Results Pre-standardization, the median opioid prescription at discharge was 20 pills (interquartile range [IQR] 20–28) or 140 oral morphine milligram equivalents (MME) (IQR 100–150). Median opioid consumption was 2 pills (IQR 0–7) or 10 MME (IQR 0–40) among all services. Opioid prescriptions were later standardized to 7, 8, and 10 pills (35, 40, and 75 MME), in the gynecology, urology, and breast services, respectively. The change was not associated with an increase in reported pain. Refill requests increased postintervention across all surgeries from 4.4% to 7.7%, with the largest increase among patients who underwent breast surgery. Conclusion The number of opioid pills given at discharge to patients undergoing ambulatory or short-stay cancer surgery can safely be reduced.

INTRODUCTION AND OBJECTIVE:Coaching is used in many professions from athletics to business. In surgery, it is traditionally implemented during medical school and residency but formalized programs f...

INTRODUCTION AND OBJECTIVE:Guidelines recognize the critical role life expectancy (LE) plays in shared decision making for localized prostate cancer treatment. The National Comprehensive Cancer Net...

INTRODUCTION AND OBJECTIVE:Upper tract urothelial carcinoma (UTUC) is a rare disease associated with poor prognosis. Increasing recent attention has been paid to surgical care and multidisciplinary...

Background Salvage partial gland ablation (sPGA) has been proposed to treat some localized radiorecurrent prostate cancer. The role of prostate biopsy and magnetic resonance imaging (MRI) characteristics to identify patients eligible for sPGA is unknown. Objective To evaluate the ability of MRI and prostate biopsy characteristics to identify an index lesion suitable for sPGA and validate this selection using detailed tumor maps created from whole-mount slides from salvage radical prostatectomy (sRP) specimens. Design, setting, and participants Men who underwent sRP for recurrent prostate cancer following primary radiotherapy with external beam radiotherapy (EBRT) and/or brachytherapy between 2000 and 2014 at a single high-volume cancer center were eligible. Those with tumor maps, MRI and biopsy data were included in analysis. Outcome measurements and statistical analysis Primary outcome was the ability of clinicopathologic and imaging criteria to identify patients who may be eligible for sPGA based on detailed tumor map from whole-mount sRP slides. Results and limitations Of 216 men who underwent sRP following whole gland radiotherapy, tumor maps, MRI, and biopsy data were available for 77. Of these, 15 (19%) were determined to be eligible for sPGA based on biopsy-proven unilateral disease in contiguous sextant segments, a dominant lesion on MRI concordant with biopsy location or no focal region of interest, and no imaging evidence of extraprostatic disease. Review of tumor maps identified 6 additional men who would have met criteria for sPGA, resulting in sensitivity of 71% (95% C.I. 48%–89%) and specificity of 100% (lower bound of 95% C.I. 94%). None of the 15 men who met the criteria for sPGA on clinical data were identified incorrectly on tumor maps to require full gland surgery (upper bound of 95% C.I. 22%). Median tumor volume of the index lesion was 0.4 cc and recurrent cancer was noted in the apex, mid-gland, and base in 81%, 100%, and 29% of men. Conclusions In men with recurrent prostate cancer after radiotherapy, biopsy findings and MRI can be used to select index lesions potentially amenable for sPGA and can guide patient evaluation for inclusion in clinical trials of sPGA following radiation failure. Larger, prospective studies are required to evaluate both the role of MRI and clinical criteria in guiding focal salvage therapy and the effectiveness of this modality for radiorecurrent prostate cancer.

Purpose The purpose of this paper is to determine the impact of having a patient-designated caregiver remain overnight with ambulatory extended recovery patients on early postoperative clinical outcomes. Design/methodology/approach This was a retrospective cohort study of patients undergoing surgery requiring overnight stay in a highly resourced free-standing oncology ambulatory surgery center. Postoperative outcomes in patients who had caregivers stay with them overnight were compared with outcomes in those who did not. All other care was standardized. Primary outcomes were postoperative length of stay, hospital readmission rates, urgent care center (UCC) visits within 30 days and perioperative complication rates. Findings Among patients staying overnight, 2,462 (57 percent) were accompanied by overnight caregivers. In this group, time to discharge was significantly lower. Readmissions (though rare) were slightly higher, though the difference was not statistically significant (p=0.059). No difference in early ( Originality/value This study is unique in its evaluation of the clinical impact of having a caregiver stay overnight with ambulatory surgery patients. Little research has focused on the direct impact of the caregiver on patient outcomes, especially in the ambulatory setting. With increased adoption of minimally invasive surgical techniques and enhanced recovery pathways, a larger number of patients are eligible for short-stay ambulatory surgery. Factors that impact discharge and early postoperative complications are important.

Introduction: The addition of targeted prostate biopsy to systemic biopsy impacts patient experience. We examined patient-reported pain, discomfort, anxiety, and tolerability among men undergoing magnetic resonance imaging (MRI)-targeted prostate biopsy in addition to transrectal ultrasound-guided systematic biopsy compared to those undergoing systematic biopsy alone. Methods: All patients underwent transrectal systematic 14-core biopsies. Patients with regions of interest on MRI underwent additional targeted biopsies. All patients received equivalent periprostatic nerve block. Four single-item, standard 11-point numerical rating scales evaluating pain, discomfort, anxiety, and tolerability were completed immediately after biopsy. Differences in means were compared using t-tests. Correlation between rated domains was tested using Spearman’s correlation coefficient. Results: Of 273 consecutive patients, 195 (71%) underwent targeted biopsy and 188 (69%) had undergone prior biopsy. In all men, the median score for pain and tolerability was 3, while the median score for discomfort and anxiety was 4. Pain was rated at 7 or above by 15% of patients. Moderate correlation between pain, discomfort, anxiety, and tolerability of repeat biopsy was observed (Spearman’s p between 0.48 and 0.76). Compared to patients undergoing systematic biopsy alone, men who received both targeted and systematic biopsies reported higher anxiety scores (difference 1.2; 95% confidence interval [CI] 0.4–2.0; p=0.004) and discomfort (difference 1.0; 95% CI 0.3–1.7; p

Objective To describe contemporary management and outcomes of patients experiencing postoperative hemorrhage after minimally invasive radical prostatectomy. Materials and Methods We retrospectively analyzed data from patients who underwent minimally invasive radical prostatectomy at our institution between January 2010 and January 2017. Clinically significant hemorrhage was defined as a decrease in hemoglobin of ≥30% or 4 g/dL from preoperative to 4 or 14 hours postoperative measurement, receiving a blood transfusion within 30 days, or undergoing a secondary procedure to control bleeding. Patients were analyzed in 3 groups: (1) serially monitored only, (2) received a blood transfusion, and (3) underwent a secondary procedure. Outcomes included imaging studies performed, length of stay, emergency room visits, hospital readmissions, complication rates, and functional outcomes. Results Of 3749 men, 4% (151/3749) had clinically significant hemorrhage, 1.6% (60/3749) received a transfusion; 0.32% (12/3749) underwent a secondary procedure to control bleeding. In a 30-day composite outcome, increased healthcare utilization (emergency room visit, readmission, or Grade ≥3 complications), was seen in 25% of the serial monitoring group, 65% of the transfusion group, and 100% in the secondary procedure group. This rate in 3598 men without hemorrhage was 12.5%. One-year erectile function was poorest in men who underwent a secondary procedure. Urinary functional outcomes were similar in the 3 groups. Conclusion Most patients experiencing clinically significant hemorrhage will stabilize without transfusion, and a very small fraction require secondary intervention. Patients experiencing milder bleeding events utilized additional healthcare resources at approximately twice the rate of those who did not, warranting appropriate counseling and postoperative monitoring.

Introduction: ETV1 is frequently involved in genomic fusions and translocation events that lead to its overexpression in multiple cancers. These events occur in approximately 5% of prostate cancers, which are mutually exclusive from tumors harboring TMPRSS2-ERG fusion or PTEN deletion. Studies suggest a correlation between strong ETV1 protein expression and poor outcome in prostate cancer. ETV1 has been reported to synergistically cooperate with KIT as a lineage survival factor in gastrointestinal stromal tumors. The expression of ETV1 in a subset of sarcomas that harbor CICrearrangements or CIC-DUX4 gene fusions presents a reliable molecular signature for the diagnosis of this cancer. Our understanding of the role that ETV1 plays in the activation of prostate cancer has been limited by the lack of ETV1 specific antibodies. Methods: A novel ETV1 monoclonal antibody (MAb) was raised by immunization of ETV1 peptides in rabbit followed by screening of hybridomas by ELISA and immunoblot assays. Further screening using exogenously expressed ETV1, ETV4, ETV5, ERG, SPDEF, and FLI1 proteins identified the clone with the most reactive MAb. Purified MAb was used to evaluate ETV1 expression on a tissue micro-array (TMA) constructed from radical prostatectomies of 50 African American (AA) and 50 Caucasian American (CA) patients by immunohistochemistry (IHC). Key residues required for Mab binding were mapped by ELISA using overlapping peptides and alanine scanning. Results: IHC evaluation using the ETV1 specific rabbit Mab on a prostate cancer TMA derived from 100 patients identified five ETV1 positive cases, of whom four were CA. The index tumors for these five ETV1 cases were ERG negative. One patient harbored both ERG positive and ERG negative tumor foci, and as expected, the ETV1 positive tumor focus was ERG negative, and vice versa. Conclusions: We developed a novel rabbit monoclonal ETV1 antibody that is suitable for IHC assay in human prostate tissue. An evaluation of prostate cancer specimens confirmed the reported frequency of ETV1 alteration. Further evaluation using tissue specimens from larger cohorts to establish the sensitivity and specificity of this antibody and validate the utility of ETV1 detection in improving the diagnosis and stratification of prostate and other cancers are in progress. Citation Format: Shyh-Han Tan, Denise Young, Sally Elsamanoudi, Jacob Kagan, Sudhir Srivastava, Albert Dobi, Gyorgy Petrovics, Isabell A. Sesterhenn, Gregory T. Chesnut. Detection of ETV1 expression in human prostate tissue specimens using a novel and highly specific rabbit monoclonal antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2565.

Introduction: DNA damage repair genes (DDRGs) play a critical role in genomic stability and their dysfunction contributes to mutagenesis in several cancer types. In prostate cancer (CaP) emerging data provide potential roles of DDR pathways in aggressive disease. However, the association with disease progression and therapeutic stratification based on inherited mutations of DDRGs remains to be defined in African American (AA) CaP patients. Our objective was to genomically profile all known annotated DDRGs in AA and Caucasian American (CA) CaP patient to determine whether DDRG germline variation status can refine patient stratification for targeted therapeutic options. Methods: Germline mutations in all DDRGs (N=276) was evaluated by whole genome sequence (WGS) analysis of archived blood DNA samples from 600 CaP patients (300 AA and 300 CA) who underwent primary treatment at Walter Reed National Military Medical Center. The WGS mean coverage exceeded 37x. Principal Component Analysis (PCA) was used infer axes of genetic variation within AA men and examine individual and population clustering to predict ancestry of each sample using the Peddy program. Variant frequencies in CPDR CaP patients were compared to variant frequencies available from the Exome Aggregation Consortium (ExAC) control cases with no CaP by Fisher's Exact Test, using false discovery rate adjusted p-values. Results: Interrogation of the complete known DDRG set of 276 genes revealed several known and novel mutations in this cohort. The Pathogenic/likely pathogenic (P/LP) variant carrier rate was higher than reported before (23.5%) in both AA and CA patients. However, the analysis revealed that more than 2/3 of the identified 47 DDRGs with P/LP mutation were different between AA and CA patients. Unlike in CA patients, several RAD family genes (RAD51, RAD54L, RAD54B), PMS2, and BRCA1 were among the most frequently mutated DDRGs in AA patients, but not in CA patients. The most frequent (over 1% carrier frequency) and potentially targetable type of mutations were independently validated by ddPCR. These genes are part of targetable DDRG pathways (homologous recombination and mismatch repair), suggesting that targeted therapy could potentially benefit AA patients. AA men harbor more potentially targetable DDRG germline mutations (over 10%) than CA men which may contribute to addressing CaP disparity. Germline mutations in any of the DDRG genes was associated with shorter time to BCR (Kaplan-Meier analysis, log rank p value 0.044) in AA patients, but not in CA patients. Conclusion: Our findings highlight distinct racial differences in DDRGs and addresses the clinical utility by targeted therapy across AA and CA men. The percentage of patients with DDRG germline variation is of suitable threshold (23%) to consider early genetic testing for them in both AA and CA patients. Citation Format: Indu Kohaar, Xijun Zhang, Shyh-Han Tan, Darryl Nousome, Kevin Babcock, Lakshmi Ravindranath, Gauthaman Sukumar, Elisa Mcgrath-Martinez, John Rosenberger, Camille Alba, Amina Ali, Denise Young, Yongmei Chen, Jennifer Cullen, Inger Rosner, Isabella Sesterhenn, Albert Dobi, Gregory Chesnut, Clesson Turner, Clifton Dalgard, Matthew Wilkerson, Shiv Srivastava, Gyorgy Petrovics. Germline mutation landscape of all DNA repair genes in African American prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2074.

469 Background: Although there have been changes in the treatment paradigm of patients with upper tract urothelial carcinoma (UTUC) over the past 2 decades, there is limited data on the particular management strategies and associated outcomes. We evaluated surgical trends, perioperative management, and oncologic outcomes of patients who underwent radical nephroureterectomy (RNU) for UTUC at Memorial Sloan Kettering Cancer Center over a 24-year period. Methods: Between 1995 and 2018, we identified 760 patients with UTUC who underwent RNU. 15 had multiple RNU and we kept only the first procedure for analysis. Generalized additive models were fitted to examine the association between date of surgery and continuous while generalized additive models with a logit link were used to estimate categorical variables. As surgical approach was defined using three different categories (open, laparoscopic and robotic) a generalized additive multinomial model was used. Generalized additive cox proportional hazards models were used to estimate the association between surgery date and estimate 2-year cancer-specific survival. Results: The use of pre-operative diagnostic endoscopic biopsies also increased from 12% to 72% which coincides with an increased proportion high grade disease on final pathology from 55% to 91%. The rate of open RNU declined from 100% to 54% with a coinciding rise in the utilization of minimally invasive approaches. Laparoscopy peaked in 2008 and then was subsequently replaced by the robotic approach. Mean lymph node yield increased over the study interval with more retroperitoneal lymph node dissections performed. Utilization of neoadjuvant chemotherapy also increased over time with a current rate of 31%, coinciding with an increase in pT0 rate from only 2% to 9%.The 2-year cancer specific survival probability has improved from 76% to 87% over the study period. Conclusions: Several changes in treatment patterns for patients with UTUC over the past 2 decades appear to correspond with an improvement of oncologic outcomes. How these changes directly relate to each other requires further investigation.

Introduction and Objective Robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) has become an increasingly utilized approach to treating various bladder pathologies requiring extirpation. As surgeons have become more experienced with ICUD, especially with lesser-used diversions such as continent cutaneous reservoirs, the technique has evolved. Methods We describe our technique and recent advances in the practical creation of robotic ICUD with a continent catheterizable pouch (CCP) built upon the open principles of the previously described “Indiana Pouch,” which uses the distal ileum and right colon. Modifications in anatomic mobilization and exposure, bowel segmentation using novel robotic bowel staplers, catheterizable channel creation, and addition of ileal chimney for uretero-enteric anastomoses are highlighted. The addition of the ileal chimney allows for ease of reconstruction in a fashion familiar to surgeons accustomed to performing intracorporeal ileal conduit and, therefore, may result in lower ureteroenteric stricture rates. Table 1 demonstrates the supplies used intraoperatively. Use of indocyanine green to assess vascularity in bowel and ureter intraoperatively is demonstrated. The port configurations are demonstrated using the DaVinci ® Xi platform. Also described are short-term outcomes of our initial experience. Results Eleven consecutive patients (5 female) who have undergone ICUD with CCP were included. Of the eleven, seven had malignant indications (bladder or urethral cancer) while 4 were for benign causes (2 radiation cystitis, 2 interstitial cystitis). Mean blood loss was 235cc (range 100–500cc) and mean operative time was 8.5 h (range 7–13). There were no conversions to an open procedure and no patient required a blood transfusion. Hospital stay was 7.2 days on average (range 4–18) with no 30-day post-discharge readmissions. One patient had a Clavien grade 3 or greater complication at 30 days (Table 2). No urine leaks or bowel leaks were observed and no patient experienced stomal stenosis or uretero-enteric stenosis. At three months follow up, all patients were continent and satisfied with their diversion. Conclusions RARC with CCP ICUD is a safe and effective approach to bladder removal and reconstruction. As more surgeons utilize RARC, growing attention to techniques of intracorporeal reconstruction will allow further implementation of this technique to cystectomy patients. Patients with adequate renal function (glomerular filtration rate of 40 mL/min or greater) and hepatic function, who understand the requirement for regular clean-intermittent-catheterization and who possess mental acuity and manual dexterity to empty their pouch 4–6 times daily should be offered CCP ICUD as a reconstructive option following RARC.

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