bluuebunny/crossref_metadata_2025_split huggingface dataset:
PSA velocity to predict clinical progression in African American and non-Hispanic White patients with low-risk prostate cancer undergoing active surveillance.
Authors: Javier-Desloges Juan , Nelson Tyler , Courtney Patrick Travis , Deka Rishi , Nalawade Vinit , Mell Loren K. , Murphy James Don , Parsons J Kellogg , Rose Brent S. 
Published: March 2021

196 Background: The utility of prostate-specific antigen velocity (PSAV) to predict clinical progression in patients with localized prostate cancer (PC) on active surveillance remains unclear, and in African American (AA) patients on active surveillance remains undefined. Methods: We performed a cohort analysis using the national US Veterans Affairs Informatics and Computing Infrastructure (VINCI). We identified 5296 patients diagnosed with localized prostate cancer (PC) from 2001 to 2015 managed with active surveillance. Follow-up extended through March 31, 2020. We defined low-risk PC as ISUP grade group 1 (GG1) clinical tumor stage ≤ 2A, and PSA level ≤ 10 ng/dl; and active surveillance as no definitive treatment within the first year after diagnosis with at least one additional staging biopsy after diagnostic biopsy. The primary outcome was grade progression on repeat biopsy/prostatectomy defined as GG2 or GG3. The secondary outcome was incident metastases. Cumulative incidence functions and multivariable Cox proportional hazards models were used to test associations between PSAV and outcomes. Results: The final cohort included 3919 Non-Hispanic White patients (NHW) (74%) and 1377 AA (26%) patients. GG2 progression on repeat biopsy occurred in 2062 (38.9%) patients, with a cumulative incidence (CI) of 43.2 % and GG3 progression occurred in 728 (13.7%) patients, with a CI of 18% at seven years. Fifty-four (0.8%) patients developed metastases, with a CI of 1.4% at ten years. In unadjusted analyses, compared to NHW patients, AA patients were significantly more likely to progress to GG2 (52.8% vs 39.8%, p<0.001), and GG3 (22.2% vs 16.8%, p=0.01). On MV analysis, PSAV was a significant predictor of GG2 (HR 1.32 [1.26-1.39]), GG3 (1.5 [1.40-1.62]), and metastases (1.38 [1.10-1.74]). A significant interaction term between race and PSAV indicated the need for different PSAV thresholds for AA and NHW men. Based on maximally selected rank statistics, optimal thresholds for separating outcomes were different in AA vs NHW men. (0.44 vs. 1.18). Conclusions: In this analysis of PSAV in low-risk prostate cancer patients on AS—to our knowledge, the largest to date for AA patients—we observed that PSAV is a robust predictor of upgrading on restaging biopsy as well as metastasis. Compared to NHW patients, AA patients were more likely to progress at lower values of PSAV and therefore merit close follow-up on active surveillance protocols.
An FDA pooled analysis: Characteristics and outcomes of patients with nonmetastatic castration-resistant prostate cancer, based on prior history of prostatectomy and/or radiation therapy.
Authors: Fallah Jaleh , Zhang Lijun , Weinstock Chana , Suzman Daniel L. , Tang Shenghui , Goldberg Kirsten B. , Kluetz Paul Gustav , Beaver Julia A. , Pazdur Richard , Ibrahim Amna , Amiri-Kordestani Laleh 
Published: March 2021

197 Background: Patients (pts) enrolled in trials of androgen receptor inhibitors (ARI) in the non-metastatic castration resistant prostate cancer (nmCRPC) setting may or may not have received definitive treatment with prostatectomy and/or radiation therapy (Surg/RT). We investigated the characteristics and outcomes of pts with nmCRPC based on prior history of Surg/RT. Methods: Data were pooled from all trials of ARI in nmCRPC submitted to the FDA as of October 2020. Pts baseline characteristics were summarized by prior history of Surg/RT. The Kaplan-Meier method was used to estimate median metastatic-free survival (MFS) and overall survival (OS) of each treatment arm by prior history of Surg/RT status. Hazard Ratios (HR) with corresponding 95% confidence intervals (CI) were estimated using a Cox proportional hazards model stratified by trial and adjusted for baseline characteristics. Results: Three trials met the inclusion criteria. Of 4117 pts enrolled, 2251 (55%) had prior surg/RT. The median age at the time of enrollment was 72 and 76 years in pts with and without prior Surg/RT, respectively. The median time from initial diagnosis of prostate cancer to enrollment on the trials of ARI was 9.1 and 5.7 years in pts with and without prior Surg/RT, respectively. PSA doubling time and number of prior hormonal therapies were similar between the two groups with and without prior Surg/RT. History of prior Surg/RT varied by geographic region: 76% (N = 611/807) in North America, 50% (N = 1110/2229) in Europe, 39% (N = 220/570) in Asia/Pacific, 52% (135/262) in South America, and 73% (171/233) in Australia/New Zealand. ECOG performance status (PS) at the time of enrollment was 0 and 1 in 80% and 20% of the pts with prior Surg/RT, respectively. In pts without prior Surg/RT, ECOG PS was 0 in 65% and 1 in 35% of pts. Gleason score was ≥8 in 36% and 47% of pts with and without prior Surg/RT, respectively. MFS and OS results in pts with and without prior Surg/RT are in the table. Conclusions: In this retrospective analysis, MFS and OS was improved in pts who received ARIs compared to placebo, regardless of prior history of Surg/RT. Any relative differences based on prior history of Surg/RT can only be considered hypothesis generating. [Table: see text]
Utilization and survival outcomes between definitive versus conservative treatments among elderly men with high-risk prostate cancer.
Authors: Patel Sagar Anil , Gay Hiram Alberto , Michalski Jeff M. , Baumann Brian Christopher , Brenneman Randall , Hershatter Bruce Warren , Jani Ashesh B. , Fischer-Valuck Benjamin Walker 
Published: March 2021

204 Background: Prostate cancer (PCa) is the second leading cause of cancer death in men > 80 years old. However, studies have shown that older men are less likely to undergo curative treatment for localized PCa, possibly due to competing comorbidities or inability to accurately estimate life expectancy. Herein, we investigate utilization trends and survival outcomes amongst guideline-supported treatment options in elderly men with high-risk PCa in the United States. Methods: Men ≥ 80 years diagnosed with high-risk PCa (cT3-4 or Gleason 8-10 or PSA > 20) between 2004-2016 were analyzed from the National Cancer Database. Those missing risk-stratification or treatment data were excluded. Eligible patients were grouped based on their primary treatment modality: no treatment (observation), androgen deprivation therapy (ADT) alone, radiation therapy (RT) alone, RT + ADT, or radical prostatectomy (RP). Cochran-Armitage was used to evaluate treatment trends over time, and multivariable logistic regression was used to identify sociodemographic predictors of treatment. Overall survival (OS) between treatments was evaluated using Kaplan-Meier, log-rank, and multivariable Cox proportional hazards. Results: With a median follow up of 42 months, 19,920 men were eligible for analysis. The most utilized treatment modality was RT+ADT (37.2%), followed by ADT alone (29.4%), observation (23.9%), RT alone (7.8%), and RP (1.7%). There was a significant increase in use of RT+ADT and RT alone (p < 0.001) and decrease in use of ADT alone and observation ( p< 0.001); no change was seen in RP use. There was no OS difference between observation versus ADT alone (aHR 1.04, 95% CI 0.99-1.09, p = 0.11). Definitive local treatment was associated with improved OS compared to ADT alone (RT+ADT: aHR 0.48, 95% CI 0.46-0.50, p < 0.0001; RT alone: aHR 0.54, 95% CI 0.50-0.59, p < 0.0001; RP: aHR 0.50, 95% CI 0.42-0.59, p < 0.0001). Black men and uninsured status were independently associated with lower likelihood of undergoing definitive treatment (i.e. RT+ADT, RT, or RP). Conclusions: For men ≥ 80 years old with high-risk PCa in this large US registry, definitive local therapy using RT +/- ADT or RP was associated with a 50% reduction in overall mortality compared to observation or ADT alone. Less than half of men in this time period underwent a definitive treatment, and Black and uninsured men remained at particularly high risk of undertreatment.
Pinpointing uncharacterized prostate cancer in active surveillance patients through mpMRI biopsy.
Authors: Greenberg Jacob W. , Sanekommu Ganesh , Hughes William M. , Shelton Thomas M. , Koller Christopher R. , Natale Caleb , Miller Stephanie , Silberstein Jonathan L. , Krane L. Spencer 
Published: March 2021

210 Background: The UroNav fusion biopsy system allows for the real time visualization of the prostate using multi-parametric MRI (mpMRI) data. This technology has become a valuable instrument for staging prostate cancer at the time of PSA elevation. However, data is still yet emerging over the use of this tool for patients currently being followed on an active surveillance (AS) protocol. In this study we sought to evaluate the efficacy of the UroNav system in patients on AS. Methods: Patients were enrolled into our prospective study, at a single center institution, approved by the Southeast Louisiana Veterans Health Care System (SLVHCS) IRB. Inclusion criteria for this study was men previously enrolled in an active surveillance protocol with a life expectancy ≥10 years. Statical analysis was performed using R 4.0.2 (Ann Arbor, MI). Results: A total of 103 patients were entered into this study for analysis. These patients had a median age of 67.1(62.8 - 70.8) and BMI of 28.6(25.5 - 32.3). The clinical profiles of these patients were median PSA of 6.36(4.65 - 8.89) with a velocity slope of (0.065 (-0.14 - 0.27), TRUS volume of 39.5(32.2 - 56.8), PSAD of 0.15(0.09 - 0.23), and a PI-RAD score of 4(3 – 5). A logistic regression was performed using upgrading on UroNav or Template bx as the outcome. Patients with an increased PSA were more likely to upgrade of Bx (OR = 1.2 (1.05 - 1.39)). Additionally, patients with decreasing MRI volumes were also more likely to upgrade on Bx (OR = 0.97 (0.94 - 0.98)). A total of 42 (40%) patients upgraded on either MRI or Template bx from their initial AS workup. MRI found 13 (12.6%) patients with an upgraded GG that displayed consistent or benign disease on template. Conversely, template also found 13 (12.6%) unique patients who upgraded but were found to have constant or benign disease on mpMRI. Conclusions: mpMRI guided biopsy is a useful tool that can further assist physicians in characterizing prostate cancer in patients being concurrently followed on an active surveillance protocol. MRI is able to find clinically significant cancer that would have otherwise been missed on traditional template biopsies. [Table: see text]
Racial diversity and reporting in FDA registration trials for genitourinary (GU) cancers from 2006-20.
Authors: Lythgoe Mark , Julve Maximilian , Krell Jonathan , Savage Philip , Grivas Petros , Khaki Ali Raza 
Published: March 2021

22 Background: GU cancers account for 1 in 5 of new cancer diagnoses in the USA. Significant racial disparities exist in terms of incidence, treatment and outcomes. Current FDA clinical trial guidance advises race reporting as a minimum of 5 categories (White/Caucasian, Black, Asian, American Indian or Alaskan Native [AIAN] and Native Hawaiian or Pacific Islander [NHPI]). Guidelines from the International Committee of Medical Journal Editors (ICMJE) recommend that authors should as a minimum, provide descriptive data for variables such as race and ethnicity. We analysed racial diversity in GU registration trials and compliance with FDA/ICMJE guidance in reporting. Methods: A retrospective review of new market authorisations in GU cancers from Jan 2006 to Oct 2020 was conducted utilizing the FDA website. Clinical trials cited on the licensing label for market authorization were recorded and corresponding registration trial publication identified. If race was unreported or partially reported (defined ≤3 groups), then the trial report on clinicaltrials.gov or FDA website was analysed. Total proportion of racial group participation and the proportion of registration trials with adequate reporting was determined. Results: We identified 42 new licensing indications, involving 33 unique drugs. Overall 30,316 patients participated in GU cancer registration trials; 21,068 (69.5%) White or Caucasian, 2516 (8.3%) Asian, 621(2%) Black or African American, 92 (0.3%) AIAN, 17 (0.1%) NHPI, 558 (1.8%) other or multiple races and 5463 (18%) unknown. Table shows breakdown by tumour group. Race reporting occurred in 23 (55%) registration trial publications, of which 5 provided only limited information (e.g. Caucasian only). For studies where no race information was reported, a further 10 (24%) had information within the trial report. In the 5 years prior to the introduction of FDA guidance in 2016 only 30% of registration studies met FDA/ICJME requirements. Since 2016 this has improved significantly to 60%. Conclusions: Despite the higher incidence of GU cancers in non-white populations, this study has revealed the relative over-representation of white participants in GU registration trials. The inclusion of black trial participants is in particular disproportionately low when compared to the burden of disease in this population group. Recruitment of black and other minority participants should be a research priority. [Table: see text]
Conditional progression-free survival in men on active surveillance for prostate cancer stratified by NCCN risk.
Authors: Gusev Andrew , Rumpf Florian , Salari Keyan , Twum-Ampofo Jeffrey , Wszolek Matthew F , Dahl Douglas M. , Blute Michael L. , Feldman Adam S. 
Published: March 2021

222 Background: Active surveillance (AS) is an accepted management strategy for men with very low, low, and select cases of favorable intermediate National Comprehensive Cancer Network (NCCN) risk prostate cancer (PCa). However, how patients’ risk of disease progression evolves over time during AS has not been well defined. Conditional survival measures the probability a patient will continue to survive some number of years, given that they have already survived a certain number without progression. We evaluated our AS cohort to investigate overall and conditional progression free survival on AS, stratified by the NCCN risk groups. Methods: We reviewed our institutional database of 1254 men enrolled in AS for localized PCa from 1996-2016. Our AS protocol includes prostate specific antigen (PSA) and digital rectal exam (DRE) every 4-6 months for 3 years, then annually. Mandatory confirmatory 12 core biopsy is done at 12-18 months. Multiparametric magnetic resonance imagining (mpMRI) or additional systematic or MRI-fusion biopsies are done at the discretion of physician and patient. Overall freedom from pathologic grade progression on follow-up biopsy and treatment free survival were estimated using the Kaplan-Meier method. Survival curves were compared pairwise using the Log-rank test and adjusted for false discovery rates with the Benjamini-Hochberg procedure. Three-year conditional survival estimates were derived for both outcomes from the Kaplan-Meier estimator. Results: Of 1254 men, 521 (41.6%) met criteria for very low, 606 (48.4%) for low, and 125 (10.0%) for favorable intermediate NCCN risk at diagnosis. Median follow-up time was 6.5 years (IQR 4.1-9.4). Median pathologic grade progression free survival in years was significantly longer for very low risk (7.8, 95% CI 6.8-11.2) compared to low risk men (5.6, 95% CI 4.7-6.9), however neither was significantly different from favorable intermediate risk men (5.9). There was no significant difference in treatment free survival between the three risk groups. At diagnosis, the three-year risk for pathologic grade progression (24%, 95% CI 21-27%) and progression to treatment (22%, 95% CI 20-25%) were similar. However, with increasing time of event-free AS, the conditional probability of pathologic grade progression increased, while that of progression to treatment decreased. Conclusions: Our results demonstrate that despite a mild increase in pathologic progression free survival in very low risk men, there was no clear difference in overall treatment free survival between very low, low, and select favorable intermediate NCCN risk men. Further, with increased time spent on AS, despite elevated rates of pathologic progression, patient progression to treatment decreased. This trend may be indicative of changes in goals of care as men with PCa age and should be closely monitored during AS.
Hospital efficiency and quality of prostate cancer care.
Authors: Jayadevappa Ravishankar , Chhatre Sumedha , Malkowicz S. Bruce , Guzzo Thomas J. , Wein Alan J. , Schwartz Jerome Sanford 
Published: March 2021

223 Background: There is no consistent evidence with respect to the role of hospital efficiency in improving quality of prostate cancer care. Study objective was to examine the association between hospital efficiency and quality of care in African American, Hispanic, and white Medicare beneficiaries with prostate cancer. Methods: Population-based cohort study using Surveillance, Epidemiological, and End Results-Medicare (SEER-Medicare) data from 2000–2016 for prostate cancer patients aged 66 or older. SEER-Medicare data was linked to American Hospital Association data. We computed hospital technical efficiency using data envelopment analysis. Outcomes were emergency room visits, complications, hospitalizations, cost, treatment and mortality (all-cause and prostate cancer-specific). We used competing risk analysis for survival, log-link GLM models for cost, and Poisson (zero inflated) models for count data. Propensity score and instrumental variable approaches were used to minimize potential biases. Results: We identified 87,117 eligible prostate cancer patients. Of these, 86% were white, 11% were African American, and 3% were Hispanic. Table shows the association between four quartiles of efficiency and outcomes. Higher hospital efficiency was consistently associated with decreased all-cause mortality, prostate cancer-specific mortality and emergency room visits. Association between hospital efficiency and mortality varied between racial and ethnic groups. Conclusions: Increasing hospital efficiency may reduce some of the disparity in prostate cancer outcomes. Our findings indicate important racial and ethnic differences that should be considered while planning hospital efficiency models to improve quality of prostate cancer care. Policies to redirect minority patients to hospital with higher efficiency may reduce racial and ethnic disparity in quality of care and outcomes. [Table: see text]
High-risk nonmetastatic prostate cancer in the elderly: Does adjuvant chemotherapy affect survival?
Authors: Akhtar Komal , Formica Margaret K , Madhira Bhaskara , Basnet Alina 
Published: March 2021

229 Background: RTOG0521 and STAMPEDE showed improved Overall survival (OS) and progression free survival (PFS) respectively, of ACT (adjuvant chemotherapy) to ADT (androgen deprivation therapy) and RT (adjuvant radiotherapy) in HrPC (High Risk localized Prostate Cancer). The median age of males in these trials is in 60’s. We present an observational study reporting OS on addition of ACT to ADT and RT in male age > 65 with HrPC. Methods: A retrospective national cancer center database (NCDB) (2004-2015) analysis was done. Patients aged >65 years with non-metastatic HrPC who underwent ADT and RT with or without ACT were included. Group1 included RT+ ADT+ ACT, Group2 included RT+ ADT. OS was estimated using Kaplan Meier analysis, reported for sub groups based on age. An adjusted hazard ratio (aHR) was calculated utilizing a Cox proportional hazard regression model. Results: 1,380,357 patients with HrPC were identified. 11734 met our inclusion criteria; 128 in Group1 and 11606 in Group2. Median Age, Gleason and PSA were: Group1- 72, 9, 14.6, Group2- 74, 9 and 14. Patients who received ACT were more likely to be younger and treated in an academic setting. OS stratified by age is depicted in table. Among patients ≥ 75, OS was uniformly worse with ACT with non-significant p value (p=0.08). The aHR, group 1 vs group 2 is 1.22, 95% CI = 0.96-1.57, p=0.11, when adjusted for Age, Facility Type, Insurance, and Charlson-Deyo Score (CDS). Conclusions: Very elderly patients ≥75 years were not likely to get ACT. OS was not improved by addition of chemotherapy, at age ≥ 65yrs and more prominent at age ≥ 75. Limitations of observational database study are lack of randomizations, missing information, physician bias on choices of ACT, RT and ADT. [Table: see text]
Incidence and cost of radical prostatectomy for NCCN low-risk prostate cancer in Utah.
Authors: Gill David Michael , Baumgartner Jessica , Gygi Jesse , Foy Bridget , Crawford Bryan , Sandhu Zoya , Brant Jamie , Barney Brandon M. , Tward Jonathan David 
Published: March 2021

232 Background: Guidelines Support active surveillance (AS) as the preferred treatment for men with NCCN low-risk prostate cancer (Gleason 3+3, prostate-specific antigen [PSA] <10 ng/ml, ≤T2a). Recent work from Mahal BA et al. (JAMA 2019) reports AS rates are increasing, but only 42.1% of men with low-risk prostate cancer underwent AS in 2015. Low-risk prostate cancer accounted for 30.1% of diagnoses. The majority of Utah residents treated for prostate cancer receive therapy at either The Huntsman Cancer Institute or Intermountain Healthcare facilities. We modeled the costs associated with the presumptive overtreatment of men with low-risk disease treated in 2017-2019. Methods: Data from The Huntsman Cancer Institute and Intermountain Healthcare cancer databases from 2017 to 2019 were retrospectively analyzed. Men with available pathologic, laboratory and clinical data who had undergone prostatectomy were stratified by having NCCN low, intermediate, and high-risk disease. Rates of radical prostatectomy by year and institution were analyzed. The cost of prostatectomy compared to AS was estimated to be $14,453 from recent work by Trogdon JG et al. (JAMA Oncol 2019). Results: Data was available for 1,155 Utahn men (Table). Of the 1155 surgeries performed, 69 (6%) were in low-risk patients. The total costs of care that might have been avoided over these three years are estimated to be $1 million. Conclusions: Approximately 6% of prostatectomies performed in Utah are in men with NCCN low-risk prostate cancer. While these rates are lower than the national average, we estimate approximately $1 million in medical costs and toxicities could be deferred had these patients opted for AS. Work is ongoing to characterize clinical toxicity of treatment in these men, and a multi-institutional collaborative education outreach program to reduce overtreatment is in development. [Table: see text]