bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cohort study evaluating the clinical, environmental and genetic profiles of men with early-onset, aggressive prostate cancer.
Authors: Fenton Sarah Elizabeth , Kocherginsky Masha , VanderWeele David James , Morgans Alicia K. , Palmbos Phillip Lee , Meeks Joshua J , Benning James , Kenny Siobhan , Martone Brenda K. , Szymaniak Brittany , Hussain Maha H. A. 
Published: March 2023

266 Background: The frequency of young men with aggressive prostate cancer (PC) at diagnosis is increasing. Clinical, environmental, and genetic drivers of this change have not been well characterized. Methods: This multi-institutional study evaluated two cohorts; Cohort 1 completed enrollment and is reported here. Eligible patients (pts) had early-onset (age ≤ 60 years) PC with metastasis (N+ or M+) at diagnosis, or within 5 years of curative intent local therapy. Data were collected to define clinical, environmental, and genetic profiles, including ctDNA and whole genome and transcriptome sequencing using Tempus xE. Standard descriptive statistics were used. Results: 46 pts were enrolled. Median age at diagnosis was 55 (range 41-60 years); 85% were White, 15% were Black; 4% served in the military and 4% reported biochemical exposure. 85% reported a family history of cancer, 46% had family history of PC. Median PSA at diagnosis was 19 (range 1-534 ng/mL), 56% had a Gleason score of 9-10, and 56% had de novo metastatic PC. 46% had prior local therapy. Genetic data is available for 40 pts. The most frequent clinically significant mutations (≥10% for somatic, ≥2.5% for germline) are summarized. 23 unique germline and over 1,000 unique somatic mutations were identified. Germline mutations associated with hereditary PC were found in 15%, all were associated with DNA damage repair (DDR). Somatic mutations in DDR genes were found in 10%. Co-mutations in TP53 and BRAF were seen in 30%. Interestingly, there were also incidental germline mutations identified that are associated with cardiac ( MYBPC, MYH7) and vascular ( MYH11, ACTA2) conditions, among others. Conclusions: In this cohort study we identified an unexpectedly high frequency of family histories that were positive for cancer (85%), and specifically PC (46%). However, rates of germline mutations associated with hereditary PC were similar to previous studies (15%), suggesting the possibility that other novel hereditary mutations driving increased PC risk may be present. Increased rates of somatic mutations in BRAF (35%) were also seen. The high frequency of BRAF mutations, particularly those that co-occur with TP53 mutations, may be driving more aggressive disease. We also found enrichment of mutations associated with non-cancer hereditary syndromes, including hypertrophic cardiomyopathy. These are not usually included in cancer-focused genetic studies, suggesting broader testing that includes potentially actionable incidental findings should be considered. More work is needed to define characteristics of this high-risk population and optimize management. [Table: see text]
Racial differences in survival and healthcare resource utilization among Medicaid-insured adults with metastatic castration-resistant prostate cancer.
Authors: DerSarkissian Maral , Gupta Deepshekhar , Ivanova Jasmina , Niyazov Alexander , Zanardo Enrico , Guo Tracy , Wang Jingru , Duh Mei Sheng , Freedland Stephen J. 
Published: March 2023

29 Background: Prostate cancer (PC) disproportionately affects Black or African American (BAA) men in the United States (US), but racial disparities in outcomes are not well understood. This study analyzed racial disparities in OS, healthcare resource utilization (HRU), and PC treatments in Medicaid-insured metastatic castration resistant PC (mCRPC) patients. Methods: This retrospective longitudinal cohort study evaluated de-identified data from the Centers for Medicare and Medicaid Services 100% Medicaid data files from 01/01/2010 – 12/31/2018. The study included adult patients with a diagnosis of PC and metastasis, and a claim for at least one of the following drugs prior to 9/30/2018, which is specific to mCRPC (date defined index): ≥1 claim for cabazitaxel, mitoxantrone, enzalutamide, radium-223, or sipuleucel-T, ≥1 claim for abiraterone acetate before June 2017, ≥1 claim for docetaxel at least 90 days after initiation of hormone therapy, or evidence of castration resistance. Patients were required to be continuously enrolled for ≥6 months pre-index (i.e., baseline period) and ≥3 months post-index. Outcomes were assessed from the index date to the earliest of end of continuous enrollment, data availability, or death. A multivariable Cox proportional hazards model of OS, and a multivariable Poisson model of HRU were implemented and controlled for age, plan type, region, median state income, residence in a state with Medicaid expansion, index year, Charlson comorbidity index, baseline HRU, baseline PC treatments, and clinical characteristics. Results: The study included 1,095 mCRPC patients (320 [29%] White [W], 278 [25%] BAA, 190 [17%] Hispanic [H], 307 [28%] Other races [O]). H had the highest mean age of 69 years, followed by 68 years for O, and 63 years for both W and BAA. Median unadjusted OS was 46.7 months in H, 40.5 months in BAA, 35.3 months in O, and 32.3 months in W. After adjustment, H had significantly lower risk of death vs. W (hazard ratio [95% confidence interval (CI)]: 0.62 [0.42, 0.90]) and BAA had comparable survival to W (0.85 [0.62, 1.16]). BAA had significantly fewer PC-related outpatient (OP) visits vs. W (adjusted incidence rate ratios [IRR] [95% CI]: 0.67 [0.48, 0.93]), but significantly more PC-related emergency room (ER) visits (5.03 [2.03, 12.47]) per patient per year. Race cohorts differed in the proportions of patients treated with novel hormonal therapy (70% W, 63% BAA, 58% H, 67% O) and chemotherapy use (29% BAA, 26% H, 24% W, 19% O). Conclusions: Among Medicaid-insured adult mCRPC patients, H were more likely to live longer than W patients, while BAA and W patients had similar OS. BAA patients had a higher rate of PC-related ER visits but fewer PC-related OP visits as compared to W, showing differential use of PC-related healthcare resources.
Genomic profiling between Hispanic Americans (HA) and non-Hispanic (NHW) with advanced prostate cancer: A retrospective analysis of tissue, liquid, and germline testing.
Authors: Dhaliwal Armaan , Taylor Megan Kathleen , Bertolo Aaron , Estrada-Mendizabal Ricardo J. , Saboda Kathylynn , Roe Denise , Chipollini Juan , Heimark Ronald , Batai Ken , Boiles Alejandro Recio 
Published: March 2023

30 Background: Genomic testing through the employment of somatic and germline testing has become increasingly relevant in determining the prognosis and targeted therapies for advanced prostate cancer patients. Prostate cancer health disparities resulting in worse presentations and clinical outcomes have been observed in HA compared to NHW. Understanding the prevalence of different genomic alterations is paramount to bridge the gap between the two ethnic groups. Methods: This is a retrospective analysis of 190 metastatic prostate adenocarcinoma patients with 24.2% HA who presented to the University of Arizona Cancer Center from 2015 to 2022. Patients in both groups may have undergone more than one type of testing. Homologous recombination repair (HRR) included ATM, BRCA1/2, BARD1, BRIP1, CDK12, CHEK1/2, FANCA/L, HDAC2, PALB2, RAD-51B/1C/51D, or 54L. Tissue-agnostic therapy approvals are dMMR, MSI-H, TMB-High, BRAF V600E, and NTRK/RET fusion. The proportion of HA and NHW was determined, and the statistical significance of the differences was reported using Chi2 or Fisher’s Exact test. Results: 43.6%, 34.7%, and 38.9% of patients had somatic tissue, liquid, and germline testing, respectively analyzed for pathogenic variants. TMB-High >10 (30% vs 3.6%, p=0.02), PD-L1 CPS>5 (9.4% vs 0%, p=0.03) and TMPRSS2-ERG fusion (37.5 vs 7.8%, p=0.0009) had higher proportion in HA compared to NHW. No test showed a difference in BRCA 1/2 or another HRR deficiency actionable mutation between the two ethnicities. There were no other statistically significant differences in common mutations or variants of unknown significance among groups. Conclusions: Liquid and tissue biopsies indicated a difference in proportions for tissue-agnostic and immune-oncology therapeutic indications, being more prevalent in HA. TMPRSS2-ERG fusions have differences in PC development and progression by race and now potentially by ethnicity, as shown by our study. Our review revealed increased germline and somatic testing over time according to targeted therapies approval and guideline recommendations, although, there remains a critical need for advancing genomic sequencing efforts for underrepresented HA. The Hispanic Americans Prostate Cancer Comprehensive Genomic Profiling Study's (THAPCA-GPS) future investigations aim to delineate the pathogenetic differences between HA and NHW and may reduce healthcare disparities and improve clinical outcomes in HA patients. [Table: see text]
Persistent need for systematic biopsy for those on active surveillance for early-stage prostate cancer.
Authors: Fakunle Mary , Cowan Janet E. , Washington Samuel L. , Nguyen Hao G , Cooperberg Matthew R. , Carroll Peter 
Published: March 2023

322 Background: Serial biopsy is a mainstay of surveillance for patients on active surveillance for prostate cancer. mpMRI targeting has become a standard for targeting lesions during biopsy as it allows for better identification of the dominant lesion (grade and/or volume). It is unclear whether “targeted biopsy” alone reliably identifies the dominant lesion on serial biopsy, thereby obviating the need for systematic biopsy. The aim of this study was to assess whether targeting alone can consistently identify the dominant lesion on serial biopsies for active surveillance. Methods: Participants enrolled in active surveillance with early-stage prostate cancer (PSA <20, cT1-2, GG1 and 2) at diagnosis and underwent two or more MR fusion biopsy sessions that include both systematic and targeted sampling. Timing and frequency of Gleason upgrading were assessed. Grade and sextant location within the prostate were compared between the systematic and targeted cores to determine concordance. Results: Of 619 men who had multiple MR targeted biopsies, 80% were GG 1 at time of diagnosis and 20% were GG 2. Fifteen percent had their first MR fusion biopsy as their diagnostic, 41% on confirmatory biopsy, and 44% on subsequent surveillance biopsy. The highest grade was sampled by MR targeting from 70% to 91% of the time. In a subset of 106 men with GG1 at first MR fusion biopsy and a subsequent MR fusion biopsy within 36 months, Gleason upgrading was detected in 47 men (44%) on the 2nd MR fusion biopsy. When comparing upgrading between systematic and MRI targeting, 20 men (42%) upgraded inside the target only. Twenty-one men (45%) upgraded on both systematic and MR targeted biopsy. And 6 men (13%) upgraded on systematic biopsy only. Conclusions: In those with serial MR-targeted biopsies, targeting alone identified a majority of upgrading. However, it missed a portion of with upgrading outside the target. This suggests that those on active surveillance, with MR targets, still benefit from systematic biopsies.
Impact of MRI and targeted biopsy on oncological outcomes of prostate cancer after treatment.
Authors: Debnath Neha , Tayebi Shima , Tobler Juliana , Verma Sadhna , Sidana Abhinav 
Published: March 2023

323 Background: To determine the impact of pre-biopsy prostate MRI followed by a targeted biopsy (TBx) approach for initial diagnosis on oncological outcomes after prostate cancer (PCa) treatment. Methods: We performed a retrospective review of all patients who underwent prostate biopsy followed by radiation therapy (RT) or radical prostatectomy (RP) as their first treatment from 2014-2020. Patients were separated into two cohorts based on the diagnostic approach: pre-biopsy prostate MRI during the initial evaluation and those who did not receive MRI. Patients with positive MRI findings underwent a combination of TBx and systematic biopsy (SBx) to confirm the diagnosis, while those without MRI underwent SBx only. Patients with PSA >20 were excluded. Kaplan-Meier curve analysis was used to compare biochemical recurrence (BCR, defined as PSA > 0.2ng/ml after RP or a rise of 2ng/ml after RT) between cohorts. Cox proportional hazard analysis was done to determine the predictors of the BCR. Results: 366 patients (174 diagnosed by SBx only, and 192 diagnosed by pre-biopsy MRI and TBx) with a median follow-up of 40 months were included in the study. 245 men (67%) had RP as their first treatment. Median age and PSA were 64.7 and 7.9, respectively in the SBx cohort and 65.0 and 8.3, respectively in the TBx cohort. There was a significant difference in BCR rate between the TBx (7.98%) versus SBx (19.28%, p<0.05 by log-rank). After adjusting for age, race, PSA, biopsy path, DRE, and family hx, pre-biopsy the MRI and TBx approach for diagnosis was found to be an independent negative predictor (p=0.001); with patients diagnosed with the above approach 71% less likely to have BCR during the study period. Conclusions: Our study shows that patients undergoing pre-biopsy MRI followed by TBx have lower rates of biochemical recurrence compared to men diagnosed without pre-biopsy MRI. To our knowledge, this study is the first to show the positive impact of pre-biopsy MRI on oncological outcomes, likely due to its role in risk stratification, treatment selection, surgical staging, and planning. Further longitudinal studies are needed to discern the true long-term benefits of pre-biopsy MRI on oncological outcomes.
Real-world clinical outcomes of patients with localized prostate cancer (LPC) treated with external beam radiation therapy (EBRT).
Authors: Karsh Lawrence Ivan , Du Shawn , He Jinghua , Waters Dexter , Muser Erik , Shore Neal D. 
Published: March 2023

330 Background: Patients (pts) with localized prostate cancer (LPC) or locally advanced prostate cancer (PC) have several treatment options, including external beam radiation therapy (EBRT) and radical prostatectomy, which can be curative in some pts. However, limited real-world evidence exists on the long-term clinical outcomes of these pts, particularly those with high-risk LPC (HRLPC). This study examines real-world clinical outcomes for HRLPC and low/intermediate risk LPC (LIRLPC) pts treated with EBRT in the US. Methods: A retrospective study using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked registry-claims data from 2012−2019 included LPC pts aged ≥65 treated with EBRT as initial definitive therapy. Baseline demographic and clinical characteristics were summarized for HRLPC and LIRLPC pts. Clinical outcomes of interest (overall survival, metastasis-free survival [MFS] and time to initiation of advanced PC treatment) were compared using Kaplan-Meier (KM) and Cox proportional hazards (PH) models. Results: Of 11,127 LPC pts treated with EBRT within 6 months of LPC diagnosis, ~40% (n=4,414) were HRLPC and ~60% (N=6,713) were LIRLPC. Patient characteristics for both groups appeared similar, with mean age at EBRT initiation >70 years, 86% white, and mean follow-up time >40 months. ADT was used with EBRT in 78% HRLPC and 34% LIRLPC. Median (IQR) duration of ADT therapy (via KM analysis) was 9.9 (5.8, 21.5) months for HRLPC and 7.2 (5.3, 9.8) months for LIRLPC. A higher proportion of HRLPC vs LIRLPC pts experienced metastasis, death, and progression to advanced PC therapies (medians were not reached). Unadjusted Cox PH survival analyses showed higher risk of mortality, metastasis, and advanced PC therapy use for HRLPC vs LIRLPC pts. Conclusions: This real-world study of clinical outcomes in pts with HRLPC and LIRLPC treated with EBRT suggested substantial additional disease burden in pts with HRLPC and highlights the need for additional strategies and treatments to improve clinical outcomes in pts with HRLPC. [Table: see text]
Survival outcomes in metastatic castration-resistant prostate cancer in the up-front treatment era.
Authors: Kamijo Shunsuke , Naito Yushi , Kato Masashi , Yamamoto Akiyuki , Tsuzuki Toyonori 
Published: March 2023

336 Background: Several studies have shown that the survival outcome of patients with metastatic prostate cancer after progression to metastatic castration-resistant prostate cancer (mCRPC) appears to be independent of a variety of prognostic factors, suggesting that prolonged time-to-CRPC is important for overall survival. However, the findings of these studies are based on data before the clinical application of up-front therapies such as docetaxel, abiraterone, enzalutamide, and apalutamide for hormone-sensitive metastatic prostate cancer (mHSPC), and the survival of patients with mCRPC with disease progression on up-front treatment has not been fully investigated. Methods: We retrospectively identified 318 patients diagnosed with treatment-naïve mHSPC between March 2014 and January 2022 from our database of 13 affiliated institutions. The patients included in this study were those who received the first-line treatment for mHSPC and progressed to mCRPC and received a second-line treatment. We defined the up-front group as patients who received abiraterone, apalutamide, or enzalutamide in addition to androgen deprivation therapy (ADT) as the first-line treatment for mHSPC, and the vintage group as patients who received ADT alone or bicalutamide or flutamide in addition to ADT. We compared the time-to-CRPC in each group, i.e., the time from diagnosis of mHSPC to progression to mCRPC. We also compared the overall survival (OS) after CRPC and the progression-free survival (PFS) after CRPC, calculated from the diagnosis of castration resistance, between the up-front group and the vintage group. To minimize selection bias, we performed propensity score matching between the up-front group and vintage group and adjusted for covariates such as age, metastatic burden, and Gleason score. Results: Of the 318 patients, 100 were in the up-front group and 218 in the vintage group. Fifteen of the up-front group and 205 of the vintage group progressed to mCRPC within the observation period and received second-line treatment. Fourteen patients from each group were extracted for the analysis of survival after CRPC by propensity score matching, and the clinicopathologic variables in each group were well balanced. In the analysis of the propensity score-matched cohort, time-to-CRPC was significantly prolonged in the up-front group compared to the vintage group (median, not-reached vs. 10.7 months; hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.12-0.28; p<0.001), while OS after CRPC (median, 18.2 months vs. not-reached; HR, 13.80; 95% CI, 1.52-125.10; p=0.019) and PFS after CRPC (median, 4.7 months vs. not-reached; HR, 7.73; 95% CI, 2.05-229.19; p=0.003) were significantly shortened in the up-front group. Conclusions: Although overall survival of mHSPC has improved in the up-front therapy era compared to the vintage hormonal therapy era, survival after disease progression to mCRPC may be shortened.
Impact of psychological distress on emergency room utilization and mortality among prostate cancer survivors.
Authors: Jiang Changchuan , Chidester Kaitlin , Sanders Alexandra , Perimbeti Stuthi , Deng Lei , Jatwani Karan , Roy Arya Mariam , Chatta Gurkamal S. , Gopalakrishnan Dharmesh 
Published: March 2023

343 Background: The population of prostate cancer (PCa) survivors has grown over the recent decades, with many reporting long-term treatment-related physical, emotional, and financial adverse effects resulting in greater psychological distress compared to males without a history of PCa. This study analyzes the prevalence of psychological distress among PCa survivors and its impact on emergency room (ER) utilization and overall survival. Methods: We identified a cohort of 3,453 PCa survivors from the 2000-2018 National Health Interview Survey (NHIS) linked to the National Death Index Mortality Files through Dec 31, 2019. Deaths that occurred during the first two years of follow-up were excluded from analyses to minimize the likelihood of reverse causation. The Kessler Psychological Distress Scale (K6) was used to quantify psychological distress. Severe, moderate, and none/low mental distress have been validated for thresholds K6≥13, 13> K6 ≥5, and 5> K6 ≥0. Its association with self-reported ER utilization during the 12 months preceding the survey and all-cause mortality was estimated using weighted multivariable logistic regression and Cox proportional hazards regression, respectively. Models were adjusted for age, sex, race, educational attainment, comorbidities, region, year of survey, smoking status, health insurance, functional limitations, and time since cancer diagnosis. Results: Among the 3,453 PCa survivors (mean [SD] age 68.5 [7.2] years; 2479 (77.9%] non-Hispanic White, 655 (14.1%) non-Hispanic Black; median time since cancer diagnosis:5 years), 435 (11.3%) and 96 (2.4%) reported moderate and severe psychological distress respectively. PCa survivors with psychological distress tend to be younger, less educated, single, and with multiple comorbid conditions, and functional limitations. 812(22.8%) of PCa survivors visited the ER during 12 months preceding the survey. During a median follow-up of 81 months, 937(25.5%) of survivors died of all causes. After adjusting for covariates, PCa survivors with severe psychological distress were at a higher risk of ER utilization and all-cause mortality than those with moderate or no distress. Conclusions: Psychological distress was associated with increased risk of ER utilization and all-cause mortality among PCa survivors. Greater efforts are needed to understand, recognize, and alleviate such distress, as well as to enhance social and mental/physical health support in this rapidly growing community of vulnerable cancer survivors. [Table: see text]