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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 5039-5039
    Abstract: 5039 Background: The Intermediate Clinical Endpoints (ICEs) in Cancer of the Prostate (ICECaP) working group identified metastasis-free survival as a valid surrogate endpoint for overall survival (OS) for patients with localized prostate cancer. No comparably validated surrogate endpoints for OS exist in advanced prostate cancer. Methods: In this meta-analysis, PubMed was searched for trials in advanced prostate cancer, defined as node positive (N1M0), metastatic castration-sensitive (mCSPC), non-metastatic (M0CRPC), or metastatic castration-resistant prostate cancer (mCRPC). Eligible randomized trials were required to report OS and ≥1 intermediate clinical endpoint (ICE). ICEs included biochemical-failure (BF), clinical failure (CF), BF-free survival (BFS), progression-free survival (PFS), radiographic PFS (radiographic +/- other study defined endpoints). Candidacy for surrogacy was assessed using the second condition of the meta-analytic approach, correlation of the treatment effect of the ICE and OS, using R 2 weighted by the inverse variance of the log ICE hazard ratio and defined as an R 2 〉 0.70. Results: A total of 143 randomized trials (n = 75,601 patients) were included. No candidate endpoints met criteria for surrogacy; R 2 BF (n = 28,922) 0.42 (95%CI 0.18-0.64), BFS (n = 25,741) 0.57 (95%CI 0.37-0.73), CF (n = 22,616) 0.31 (95%CI 0.0075-0.56), PFS (n = 52,639) 0.50 (95%CI 0.35-0.63), and radiographic PFS (n = 52,548) 0.50 (95%CI 0.35-0.63). Within preplanned subgroups by castration sensitive or resistant disease, or by treatment type, neither BFS nor PFS met criteria for surrogacy. When assessing radiographically-defined progression (exclusive or with clinical progression), PFS for the overall group and by castration status did not meet criteria for surrogacy. Sensitivity analyses demonstrated that candidacy for surrogacy of all endpoints tested did not change over time. Conclusions: Our aggregate screening method for surrogate endpoints in advanced prostate cancer demonstrated commonly used clinical endpoints are not valid surrogate endpoints for OS, and further composite endpoint construction is necessary.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 5019-5019
    Abstract: 5019 Background: Patients (pts) with laUC who are C-ineligible have inferior survival compared to counterparts who receive C based N-therapy and have a pathologic response at radical cystectomy (RC). Cohort 2 (C2) of the GU14-188 trial is designed to assess the tolerability and efficacy of N- G and P in laUC pts who are C-ineligible. Methods: Eligible pts for C2 were surgical candidates and C-ineligible with cT2-4aN0M0 bladder UC or mixed histology. Enrollment followed a Simon 2-stage design for H 0 of interval futility which was rejected at stage 1, and fully enrolled. Pts were treated with N- G (1000mg/m 2 ) on days 1, 8, and 15 of a 28 day cycle (cy) for a total of 3 cy, and overlapped with P 200mg every 3wks starting on cy 1 day 8 x 5 doses. Minimum criteria for evaluation of safety: 1 dose of P, and for efficacy: 2 doses P and RC. The primary endpoint of pathologic muscle invasive response rate (PaIR, ≤pT1N0) was assessed at RC and designed for 86% power, 4% significance to detect PaIR difference from 18 to 40%. Molecular subtyping is planned. Results: 37 pts were enrolled to C2 with a median (mdn) age of 72, 70% male, 55% 〉 cT2. C-ineligibility was due to renal function (49%), hearing (30%), neuropathy (12%). Mdn per-pt doses given (intended) for P:5(5) and G:9(9). The PaIR was 51.6% (95%CI 0.35, 0.68), P0 (ypT0N0) rate of 45.2%, and neither correlated with baseline PD-L1 score. Downstage to PaIR occurred in 57% of pts with cT2, and 47% of 〉 cT2. Mdn time to RC from last dose was 5.6wks. Six were not included in the primary analysis: 3 (8.1%) did not have RC due to progression (RFS censored), 2 did not receive required protocol therapy, and 1 withdrew consent. At mdn follow up of 10.8mo (4-24), the estimated 12mo RFS, OS, and DSS is 74.9%, 93.8%, and 100%, respectively. Treatment related AE included grade (gr) 3/4 neutropenia (24%), anemia (13%), and platelets (5%). There were no gr 4 non-heme AE, and of 14 (36%) pts with gr 3, 12 did not preclude RC. Of these, there were 4 gr 3 investigator assessed immune related adverse events (IAirAE) of pneumonitis (5%), colitis (3%), and AST elevation (3%). Though IAirAE improved, protocol therapy was discontinued in 3 pts: 2 did not have RC due to progression. Conclusion: N- G with P in C-ineligible pts with laUC is feasible with manageable toxicity, and has a pathologic downstage rate comparable to standard of care in the C-eligible population. G and P warrants further study with component contribution as a C- free N- option in laUC. Clinical trial information: NCT02365766 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 5047-5047
    Abstract: 5047 Background: Patients (pts) with laUC who are C-eligible for N- therapy may benefit from combination chemo-immunotherapy. Cohort 1 (C1) of the GU14-188 trial is a phase 1b/2 trial designed to assess the tolerability and efficacy of N- gemcitabine (G), C, and P in pts with laUC. The current standard of care is ddMVAC with a pathologic non-muscle invasive rate (PaIR, ≤pT1N0) of ~44%. Methods: Eligible pts for C1 were surgical candidates and C-eligible with cT2-4aN0M0 bladder UC. Enrollment followed a Simon 2-stage design for H 0 of interval futility which was rejected at stage 1, and fully enrolled. Phase 1b (no DLT) /2 treatments were the same: P 200mg q3wks on day 8 x5 doses; with C (70mg/m2) day 1, and G (1000mg/m2) days 1 and 8 of a 21 day cycle (cy), for 4 cy; followed by radical cystectomy (RC). Minimum criteria for evaluation of safety: 1 dose of P, and for efficacy: 2 doses P and RC. The primary endpoint of PaIR was assessed at RC and designed for 86% power with 4% significance to detect a difference from 23 to 48%. Secondary endpoints include relapse free survival and overall survival. Results: 43 pts were enrolled to C1 with a median (mdn) age 64, 63% male, 51% 〉 cT2. Mdn per-pt doses given (attempted) for: P:5(5), C:4(4), G:8(8). The PaIR was 61.1% (95%CI 0.45, 0.75), P0 (ypT0N0) rate of 44.4%, and did not correlate with baseline PD-L1 score. Downstage to PaIR occurred in 53% of cT2, and 74% of cT3/4. Mdn time to RC from last dose was 5.3wks. Seven were not included in the primary analysis: 4 (9.3%) without RC, 1 progressed, 1 lost to f/u during C1, 1 did not receive required protocol therapy. There was 1 death on post-RC day 9 due to mesenteric ischemia. Of 4 pts who did not have RC, 3 refused and 1 due to gr4 thrombocytopenic purpura; 4pts are alive and without recurrence at mdn f/u of 32mo. One pt with presumed gr3 MI during cy 4 had a negative inpt cardiac workup and completed therapy and RC without further AE. One gr4 hyponatremia and ten gr3 events did not preclude RC (2-each thromboembolism, elevated creatinine, hyponatremia;1-each: dehydration, emesis, neutropenic fever, infection). Gr 3/4 cytopenias occurred in 57% of pts. At mdn f/u of 34.2mo (3.9-47.4), the estimated 36mo RFS, OS, and DSS is 63%, 82%, and 87%, respectively. Conclusion: Neoadjuvant GC with P in laUC has manageable toxicity and has improved pathologic outcomes compared to historic controls. Durable long-term survival in those with- and without -RC is noteworthy in this advanced cohort. KEYNOTE 866, NCT03924856, is a Phase III study of GC with perioperative P. Clinical trial information: NCT02365766 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 541-541
    Abstract: 541 Background: The role of microbiome in genitourinary cancer is an emerging field, with evidence implicating the important role of microbiome as causative factors or cofactors in tumorigenesis and drug metabolism. Our study aims to characterize healthy and bladder cancer enterotypes in the gut and identify functional alterations through the use of metagenomics data. Methods: After prospective collection of 29 rectal swab samples of bladder cancer (BCa) patients undergoing cystectomy, and 32 healthy volunteers, we perform 16S rRNA amplicon sequencing on 61 samples (29 with bladder cancer, 32 without cancer). Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was applied to infer functional categories associated with taxonomic composition. The p values were adjusted using the false discovery rate. The a- and b-diversity analyses were performed using QIIME. The Mann-Whitney U test was employed to evaluate the statistical significance of b-diversity distances within and between groups of interest. Results: Across all the bladder cancer stool samples, estimation of relative abundance revealed of the five most dominant bacterial populations was Bacteroidales ( 46.21%), Clostridiales ( 32.29%), Burkholderiales (9.07%), Erysipelotrichales (3.20%) and Lactobacillales ( 2.20%). In contrast, healthy controls exhibited an increased relative abundance of Enterobacteriales ( 10.75% vs 0.52%) and Pseudomonadales (8.33% vs 0.18%) as compared to tumor samples. The microbial diversity differences between Bca and normal samples showed no differences across alpha diversity metrics (Shannon diversity p 〉 0.05) as compared to normal tissue. However, there was significant difference in clustering of organisms as determined by principal coordinate analysis ( PCoA) ordination of unweighted UniFrac Distances, (p=0.002). Furthermore, upon stratification of patients on smoking status (all healthy=nonsmokers), clustering persisted, albeit non smokers with bladder cancer displayed an intermediate across PCoA. Bca samples exhibited higher LDA score Campylobacterales (log change 8.0, p 〈 0.001, p adj 〈 0.001) ,Fusobacteriales (log change 6.11, p 〈 0.001/ p adj 〈 0.01), Epysipelotrichales (log 2.55, p 〈 0.001/ p adj 〈 0.001 ), Actinomycetales (log change 1.86, p=0.001/ p adj 〈 0.001), Verrucomicrobiales (log change 1.78, p=0.017/p adj =0.031) and Enterobacteriales (log change -1.54,p=0.017/ p adj = 0.132). Conclusions: In conclusion, our study provides preliminary evidence that the GI microbiota is different in bladder cancer patients. Collectively, our study highlights distinct microbial overexpression of Campylobacter and Fusobacterium in Bca cohort not previously reported, both implicated in tumorigenesis, and could serve as a target that could be modulated to enhance treatment response.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 5
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    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e17510-e17510
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e17510-e17510
    Abstract: e17510 Background: The co-occurrence of cancer and end-stage-renal disease (ESRD) may pose significant challenge in the management of both diseases. Further complicating clinical decisions is our limited understanding of the comorbidity burden (CB), which also affects their outcomes to a considerable extent. The purpose of this study is to characterize the CB in prostate cancer patients, with and without ESRD. Methods: Using SEER-Medicare database between years 2000-2016, we retrieved sociodemographic variables, including age (40-54, 55-64, 65-74, and 75+), race (African American vs. all others), marital status (married/partnered vs. all others), residence in a census tract with poverty rate 〉 20%, and dual Medicare-Medicaid enrollment status; chronic conditions identified in the year of cancer diagnosis; and ESRD status preceding prostate cancer diagnosis. We limited our study population to cancer patients enrolled in Medicare at the time of cancer diagnosis, and were receiving their care through the fee-for-service system. In this descriptive analysis, we compared the prevalence of these conditions between prostate cancer patients by ESRD status. Results: Our study population included 2,046 ESRD and 302,136 non-ESRD men diagnosed with incident prostate cancer during the study period. Compared to non-ESRD patients, a disproportionately higher percentage of ESRD patients were in the 40-54 and 55-64 age groups compared to non-ESRD (11.0 vs 0.95% and 32.2% vs. 8.51%, respectively). Similarly, the percentage of prostate cancer patients who were African American was 44.1% among ESRD patients, compared with 13.6% in their non-ESRD counterparts. With regard to comorbidities, several conditions were significantly higher in ESRD than non-ESRD patients, including: anemia (65.4% vs. 15.3%), congestive heart failure (31.1% vs. 8.9%), ischemic heart disease (38.9% vs. 25.2%), diabetes (40.7% vs. 17.0%), hypertension (68.0% vs. 42.6%), hypothyroidism (4.6% vs. 2.9%), hyperlipidemia (43.1% vs. 35.1%), and stroke (3.7% vs. 2.5%). Conclusions: Compared to their non-ESRD counterparts, ESRD patients present with high CB, severely compromising their physiologic reserve and tolerance for various cancer treatment modalities, and affecting outcomes. Future studies should compare the prevalence of specific combinations of conditions constituting multimorbidity between ESRD and non-ESRD patients, and identify multimorbidity profiles associated with a lower likelihood to receive standard treatment. Such detailed analysis will be foundational to clinical management and outcome studies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 2_suppl ( 2016-01-10), p. 27-27
    Abstract: 27 Background: The considerable interest in short UHR 5-12 fractions(fr) in management of CaP is based on potential radiobiological advantages, patient convenience & resource allocation benefits. Prior to comparison with standard RT regimens (SRTR), a study was undertaken whose primary objective was to demonstrate that 1-year health-related quality of life (HRQOL) for at least one UHR arm was not significantly lower than baseline as measured by the Bowel & Urinary domains EPIC instrument(EPIC B & U). Secondary objectives included acute & late GI & GU toxicity. Methods: RTOG 0938 is a randomized phase II study of CaP patients(pts), (Gleason score 2-6, stage T1-2a & PSA 〈 10 ng/mL) receiving 36.25 Gy (5 fr of 7.25 Gy in 2 wks), or 51.6 Gy (12 fr of 4.3 Gy in 2.5 wks). Pts were stratified according to RT technique – Cyberknife vs IMRT/VMAT or protons. A change in EPIC bowel domain score (baseline to 1-year) 〉 5 points & in EPIC urinary domain score 〉 2 points were felt to be clinically significant. The frequency for 〉 5 point change in bowel score (FREQE-B) in ≤ 35% of pts was considered acceptable, with the frequency ≥ 55% unacceptable. Similarly, the frequency for 〉 2 point change in urinary score (FREQE-U) in ≤ 40% was considered acceptable, with the frequency ≥ 60% unacceptable. A sample size of 156 pts was needed for 95% power with one-sided significance level of 0.025 to preserve an overall level of 0.05. Results: 240 pts were enrolled to ensure adequacy of data for analysis. The compliance for HRQOL completion was good ( 〉 80%). The 1 year FREQE-B for 5 fr was 23.5% (p 〈 0.001) & 12 fr was 23.1% (p 〈 0.001). The 1 year FREQE-U for 5 fr was 35.3% (p 〈 0.001) & 12 fr was 34.7% (p 〈 0.001). Conclusions: This study confirms that based on changes in EPIC B & U (baseline to 1-year), acute & late toxicity, both the 5 & 12 fr regimens are well tolerated. These UHR need to be compared to current SRTR in the context of a RCT with efficacy & toxicity endpoints. Supported by grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, UG1CA189867 from the National Cancer Institute (NCI). Clinical trial information: NCT01434290. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e16523-e16523
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
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  • 8
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    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 6_suppl ( 2022-02-20), p. 542-542
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 542-542
    Abstract: 542 Background: Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon, breast and pancreatic cancer. However, the role of fungal mycobiome has not been evaluated in bladder cancer. With the sexual dimorphism that exists within bladder cancer (Bca) prevalence and survival, our study aims to characterize fungal mycobiome composition in Bca. Methods: This is a single site, non-randomized, prospective study of patients with the diagnosis of muscle invasive bladder cancer (MIBC) undergoing cystectomy from September 2020 to May 2021. Stool samples were collected during surgery using aseptic technique. We utilized the ITS1 region from DNA sample extracts, which was amplified in triplicate using primers with high specificity for ascomycete fungi (fluorescently-labeled forward primer ITS1F (CTTGGTCATTTAGAGGAAGTAA) and unlabeled reverse primer ITS2 (GCTGCGTTCTTCATCGATGC). Fungal PCR products were separated on the SCE 9610 capillary DNA sequencer (Spectrumedix LLC, State College, PA) using GenoSpectrum software to convert fluorescent output into electropherograms. Hierarchical clustering by Bray-Curtis distance was performed using hclust2. Mean normalized abundance for each amplicon was calculated from the three PCR replicates of each sample, excluding means below 1%. Results: A total of 29 patients (17 males and 12 females) were enrolled. The median (IQR) age was 74 yo (63-77), males, and 68.5 yo (58-78), females. Per figure 1, Saccharomycecales dominated the fungal community at order level with mean relative abundance of 36.35% females, and 21.20%, males. (Figure 1D) Tremellales was the second most notable order, composing 8.22% and 5.13% of male and female samples. There were no differences seen in alpha and beta diversity (Figure 1C) (Figure 1A, C), notable differences were seen across orders. The greatest difference between sexes in LDA( M:F) were noted in Saccharomycecales (log change -4.686, p=0.001/ p adj = 0.01), Tremellales (log change 5.119, p=0.001/p adj = 0.01), and Sporidiobolales (log change 4.839, p=0.001 p adj = 0.03). (Figure 1B). Female bladder cancer patients demonstrating an increase abundance of Saccharomycecale. When assessing differences in fungal composition in patients with history of neoadjuvant therapy( NAC) (receipt vs none), patients with history of NAC exhibited a 3.48 increase in Saccharomycecale (p adj = 0.015 ), 4.81 increase Tremalles (p adj = 0.009) and 4.37 increase Pleosporales(p adj = 0.009) . Conclusions: Mycobiome is an integral part of gut microbiota, with fungal elements relatively poorly studied. Nevertheless, the association between fungal dysbiosis and carcinogenesis across multiple cancers exists. Our study is the first to characterize fungal profile in bladder cancer patients, stratified by sex and receipt of NAC, with results highlighting key fungal players: Saccharomycecale, Tremallales, Pleosoporales.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 9
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    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Nursing Research Vol. 70, No. 6 ( 2021-11), p. 475-480
    In: Nursing Research, Ovid Technologies (Wolters Kluwer Health), Vol. 70, No. 6 ( 2021-11), p. 475-480
    Type of Medium: Online Resource
    ISSN: 1538-9847 , 0029-6562
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1480527-3
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  • 10
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    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e17513-e17513
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e17513-e17513
    Abstract: e17513 Background: Persons with end-stage renal disease (ESRD) comprise a vulnerable subgroup of the population. Yet, rarely have studies on cancer disparities accounted for ESRD status. We sought to compare prostate cancer stage at diagnosis, treatment, and outcomes among men with and without ESRD. Methods: Utilizing SEER-Medicare database between years 2000-2016, we retrieved sociodemographic variables, including age (40-54, 55-64, 65-74, and 75+), race (African American vs. all others), marital status (married/partnered vs. all others), residence in a census tract with poverty rate 〉 20%; cancer stage at diagnosis (local, regional, distant, and unknown); treatment (surgery and radiation therapy); and overall and cancer specific survival (OS and CSS) from the SEER, and ESRD status preceding prostate cancer diagnosis from the Medicare portion of the file. In addition to descriptive analysis, multivariable survival analysis was utilized to evaluate the association of ESRD status with OS and CSS after adjusting for patient covariates. Results: Our study population included 2,922 ESRD and 600,848 non-ESRD men diagnosed with incident prostate cancer during the study period. A disproportionately higher percentage of ESRD patients were in the 40-54 age group compared to non-ESRD (9.7 vs 3.6%). Similarly, the percentage of prostate cancer patients who were African American was 41.5% among ESRD patients, compared with 14.4% in their non-ESRD counterparts. In addition, more ESRD than non-ESRD patients lived in census tracts with poverty rates greater than 20% (31.2% vs. 18.0%). With regard to stage, 10.6% of ESRD patients but only 4.5% of non-ESRD patients were diagnosed with distant-stage disease; and while only 24.8% of ESRD patients underwent surgery, 36.9% of non-ESRD patients did so. The rate of radiation therapy was similar across the two groups. Multivariable survival models showed that, adjusting for patient covariates, ESRD status was associated with unfavorable OS and CSS (adjusted hazard ratio (AHR): 4.00 (95% confidence interval: 3.82, 4.18), and AHR: 1.54 (1.37, 1.73), respectively). Median follow up was 3.35 and 7.13 years between the ESRD and non-ESRD cohorts. Conclusions: ESRD status in prostate cancer patients is associated with marked sociodemographic and economic disparities. Compared to their non-ESRD counterparts, more ESRD patients are diagnosed with advanced-stage disease, are less likely to undergo surgery, and experience shorter overall and cancer-specific survival. Future studies should be directed to gain insight into factors contributing to unfavorable cancer-specific outcomes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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