bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-line PARP inhibitors (PARPi) with androgen receptor pathway inhibitors (ARPi) in metastatic castration-resistant prostate cancer (mCRPC): A systematic review and meta-analysis.
Authors: Khan Muhammad Ali , Naqvi Syed Arsalan Ahmed , Imran Manal , Channar Aneeta , Saxena Akshat , Raina Ammad , Khakwani Kaneez Zahra Rubab , Riaz Zaryab Bin , Kase Adam McLain , Humphreys Mitchell R. , Moore Cassandra N. , Orme Jacob , Childs Daniel S , Singh Parminder , Bryce Alan Haruo , Palmer Jeanne M. , Riaz Irbaz Bin 
Published: January 2024

173 Background: The data for combining PARPi and ARPi in mCRPC have shown conflicting results. Here, we report a quantitative summary of benefits by clinically meaningful subgroups (HRR mutation status, BRCA mutation status) to guide the use of PARPi and ARPi combination in mCRPC setting. Methods: MEDLINE, EMBASE, and CENTRAL were systematically searched from each database’s inception through September 7, 2023. Phase III studies comparing PARPi + ARPi with ARPi + placebo in mCRPC were included. Radiographic progression-free survival (rPFS) and overall survival (OS) in patient subgroups based on HRR and BRCA mutation status were assessed. Hazard ratios for rPFS and OS with 95% CI were collected at the level of each trial, and a random-effects meta-analysis was conducted using an inverse variance approach. Subgroup differences were assessed and p-value of interaction <0.1 was considered statistically significant. Results: The literature search identified 4976 studies from which 3 trials (11 references) – TALAPRO2, PROpel and MAGNITUDE met the inclusion criteria. A total of 2254 participants were eligible for analysis. PARPi + ARPi prolonged rPFS in patients with HRR mutations (HR: 0.55, 95%CI: 0.38-0.78) as well as in patients without HRR mutations (HR: 0.74, 95%CI: 0.63-0.88). There is no evidence of treatment interaction by HRR mutation status (p = 0.14). In patients harboring HRR mutations, improved rPFS was observed in those with BRCA mutations (HR: 0.28, 95%CI: 0.13-0.62) as well as those without BRCA mutations (HR: 0.72, 95%CI: 0.59-0.87). However, there is evidence that patients with BRCA mutations derived greater rPFS benefit as compared to patients without BRCA mutations (p =0.02). PARPi + ARPi showed no significant improvement in overall survival either in patients with HRR mutations (HR: 0.79, 95%CI: 0.59-1.05) or in patients without HRR mutations (HR: 0.92, 95%CI: 0.74-1.14). Conclusions: Genomic testing for HRR genes is mandatory to guide clinical decision making in mCRPC patients. Patients harboring BRCA mutations are most likely to derive clinically meaningful benefit from combination PARPi + ARPi treatment. [Table: see text]
Detection of neuroendocrine prostate cancer through plasma-based epigenomic profiling.
Authors: Eid Marc , Semaan Karl , Seo Ji-Heui , Davidsohn Matthew P. , Fortunato Brad , Lakshminarayanan Gitanjali , El Zarif Talal , Savignano Hunter , Canniff John , Saliby Renee Maria , Saad Eddy , Pomerantz Mark , Baca Sylvan , Freedman Matthew , Berchuck Jacob E , Choueiri Toni K. 
Published: January 2024

201 Background: Neuroendocrine prostate cancer (NEPC) is an aggressive resistance phenotype that can develop in men with metastatic prostate adenocarcinoma (PRAD). Early detection of NEPC has prognostic and therapeutic implications, but is challenging due to spatial heterogeneity, sampling error associated with tissue biopsy, and a lack of distinguishing genetic mutations that can be assessed from cell-free DNA (cfDNA). Herein, we introduce a novel epigenomic-based approach to non-invasively identify NEPC from cfDNA. Methods: Plasma was collected from patients with NEPC and PRAD at the Dana-Farber Cancer Institute. Chromatin immunoprecipitation and sequencing on cfDNA (cfChIP-seq) was performed on 1mL of plasma for the post-translational histone modifications H3K4me3 and H3K27ac. Activity of gene promoters and enhancers was inferred based on H3K4me3 and H3K27ac cfChIP-seq signal normalized to signal at constitutively active regulatory elements. A classifier was built to distinguish NEPC from PRAD based on H3K27ac signal at a published set of regulatory elements with increased chromatin accessibility in neuroendocrine tumors compared to adenocarcinomas (NE-REs). The classifier performance was evaluated using the area under the receiver operating characteristic (AUROC) curve. Results: Our cohort included 30 patients, 10 with NEPC and 20 with PRAD. H3K4me3 signal at the promoter of chromogranin A ( CHGA), a diagnostic marker gene of NE-differentiation, was significantly elevated in plasma from patients with NEPC vs. PRAD (p=4x10-11, Wilcoxon rank-sum test). H3K27ac signal at binding sites for ASCL1, a master transcription factor driving NE-differentiation, was significantly elevated in NEPC vs. PRAD plasma samples (p=7.2x10-5, Wilcoxon rank-sum test). H3K27ac signal at NE-REs accurately distinguished patients with NEPC from patients with PRAD with an AUROC curve of 0.97. Conclusions: We present a non-invasive approach to identify NE-differentiation in patients with metastatic prostate cancer using 1mL of plasma. This method could help overcome practical challenges associated with NEPC detection and further guide therapy selection.
Evaluation of ctDNA in patients with mCRPC with liver metastases.
Authors: Huang Minqi , Gebrael Georges , Sayegh Nicolas , Casado Crystal , Habibian Nicholas , Akerele Opeoluwa , Gupta Kanika , Lieberman Alexandra , Schwartz Jennifer , Layton Jodi Lyn , Sweeney Patrick L , Lewis Brian E. , Agarwal Neeraj , Sartor A. Oliver , Ledet Elisa M. 
Published: January 2024

212 Background: Patients with prostate cancer with liver metastases are known to have a worse prognosis. In this study, we evaluated ctDNA in mCRPC (metastatic castration-resistant prostate cancer) patients with and without liver metastases. Methods: A retrospective chart review identified mCRPC patients with liver metastases at Tulane Cancer Center and Huntsman Cancer Institute. Liver metastases were confirmed via molecular or conventional imaging. All patients had ctDNA assessed with a multi-gene cancer panel via the Guardant 360 assay. Alterations with <0.1% allelic fraction, synonymous alterations, and variants of unknown significance were excluded from analyses. Statistical analyses were performed using Fisher’s Exact and Wilcoxon Rank Sum Tests. Correction for multiple testing was not performed, hence these alterations may be subject to a type 1 error. Results: 53 mCRPC patients with liver metastases and 144 mCRPC patients without liver metastases were included in the study. We found seven genes that are more likely to be pathologically altered in ctDNA in mCRPC patients with liver metastases (See Tables 1-3): AR (OR=2.38, 95% CI: [1.25, 4.52], p=0.01), BRAF (OR=2.74, 95% CI:[1.05, 7.18], p=0.05), BRCA2 (OR=5.33, 95% CI:[1.49, 19.02], p=0.01), CDK6 (OR=4.09, 95% CI:[1.35, 12.42], p=0.01), EGFR (OR=3.12, 95% CI:[1.22, 7.99], p=0.02), FGFR1 (OR=5.69, 95% CI:[1.81, 17.86], p-value=0.003), MYC (OR=4.55, 95% CI:[1.63, 12.68], p=0.004), and PIK3CA (OR=4.34, 95% CI:[1.87, 10.06], p=0.01). Additionally, mCRPC patients with liver metastases are more likely to have copy number alterations (CNA) (p= 0.01) compared to mCRPC patients without liver involvement. There were no other significant differences in the remaining 70 genes interrogated. Germline pathogenic alterations did not vary between the two groups. Conclusions: In mCRPC patients with liver metastases, these exploratory analyses suggest ctDNA testing is more likely to detect pathologic alterations in AR, BRAF, BRCA2, CDK6, EGFR, FGFR1, MYC, and PIK3CA. Additionally, mCRPC patients were more likely to have copy number alterations (CNA). Limitations of the Guardant 360 assays are notable in this setting given the incomplete ascertainment of gene deletions and the incomplete number of prostate-relevant genes assessed. [Table: see text]
The impact of SPOP gene alterations in men with metastatic prostate cancer: Results from the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) consortium.
Authors: Yamamoto Kyra Lee , Henderson Nicholas , Hwang Clara , Barata Pedro C. , Bilen Mehmet Asim , Kilari Deepak , Graham Laura , Garje Rohan , Rothstein Shoshana , Koshkin Vadim S , Tripathi Abhishek , Cackowski Frank Cameron , Nauseef Jones T. , Schweizer Michael Thomas , Armstrong Andrew J. , Dorff Tanya B. , Alva Ajjai Shivaram , McKay Rana R. 
Published: January 2024

225 Background: Inactivating mutations in the SPOP gene, encoding speckled-type poxvirus and zinc-finger protein, are common among men with localized and metastatic prostate cancer, occurring at a frequency of 6-15%. Previous studies have suggested the presence of an inactivating mutation in SPOP results in increased sensitivity to androgen deprivation therapy (ADT). In this multi-institutional clinical-genomic database, we evaluated the impact of SPOP alterations on survival outcomes in men with metastatic prostate cancer. Methods: Retrospective data from the PROMISE Consortium were utilized for this analysis. Eligible patients had metastatic prostate cancer and had undergone standard of care next-generation sequencing (NGS). Patients with inactivating mutations in SPOP were defined as SPOP mutated, where. as those lacking such alterations were defined as SPOP wild-type. The primary endpoint was overall survival defined as the time from diagnosis of metastatic prostate cancer to death from any cause, censored at the date of last follow-up. Secondary endpoints included time from metastatic disease to castration resistance and time from castration resistance to death. Results: Of the 2097 patients with available NGS testing, 5.5% (n=115) had SPOP alterations. The median age at diagnosis was 63 years, 427 were Black, and 83 were Hispanic. At last assessment, 66% had bone metastases, 7% lung metastases, and 5% liver metastases. The most frequent co-occurring alterations in the SPOP-mutated group were: TP53 (30.4%), APC (25.2%), and AR (21.7%). 1832 patients were included in the survival analysis [n=96 (5.2%) with and n=1736 (94.8%) without SPOP alterations]. Median overall survival was numerically longer, though not statistically significant, in the SPOP-mutated compared SPOP-wild-type group (75.9 versus 59.5 months, p=0.12). In patients with metastatic disease, median time to castration resistance was 14.6 months in the SPOP-mutated group versus 12.2 months in the SPOP-wild-type group (p=0.30). Median time from metastatic castration resistant to death was 45.0 months in the SPOP-mutated group and 40.2 months in the SPOP-wild type group. Conclusions: Our hypothesis generating data support that SPOP-mutated prostate cancer likely represents a unique molecular subtype of prostate cancer that may confer prolonged survival. Future studies of novel androgen-receptor targeting treatments should be tested in this molecular population.
Trends in preferred place of death for prostate cancer in the United States from 2003 to 2020: Analysis of CDC WONDER database.
Authors: Jatwani Karan , Sukaina Mahnoor , Khosla Atulya Aman , Singh Rohit , Singh Navpreet , Walia Kamalpreet Singh , Patel Archit , Muthusamy Kumarasamy Vasanthan , Gopalakrishnan Dharmesh 
Published: January 2024

231 Background: Prostate Cancer (PCa) is the most common cancer in men and the second cause of cancer mortality. The identification of the preferred place of death (PPOD) has been shown to improve the delivery of palliative care, reduce healthcare costs, and improve quality of care. We evaluated the trends in PPOD for patients and hospice utilization with PCa in the USA from 2003 to 2020 based on the CDC WONDER (Centers for Disease Control and Prevention for Wide-ranging Online Data for Epidemiologic Research) database. Methods: The US nationwide and state-level data was pooled using the CDC WONDER database from January 01, 2003, to December 31, 2020. The data trends of PPOD for prostate cancer were pooled using the International Classification of Diseases, Tenth Revision as C61: malignant neoplasm of prostate. The analysis of trends in mortality over the past decade was stratified according to age, census region, race, and place of death. Results: The analysis demonstrated that overall mortality due to PCa was 526,783 from 2003 to 2020. Of these deaths, 43,813 (8.32%) were recorded in hospice facilities. The hospice mortality steadily increased from 0.4% in 2003 to the highest of 9.20% in 2019, with a notable decline to 7.6% in 2020. We noticed that the PPOD differed based on racial subgroups. More than half of mortality in the Native American (NA) and African-American (AA) subgroups was observed in a medical facility (51.81% and 58.21%, respectively) compared to Whites (49.15%). Hospice or death at home in NA and AA groups were (48.11% and 41.11%, respectively) compared to Whites (50.85%). The age-stratified mortality analysis revealed increased hospice utilization in 25-44 years (11.95%) vs. 65+ years (8.13%). Upon stratifying the results by census showed the highest hospice utilization in Florida, compared to the lowest in North Dakota (22.6% vs. 0.02%). Conclusions: To our knowledge, this is the first study utilizing the CDC WONDER database to analyze PPOD in PCa-related deaths. We observed a steady increase in hospice utilization from 2003 to 2019 throughout the US, with a decline in 2020, possibly due to the COVID-19 pandemic. The AA and NA groups had higher mortality in medical facilities compared to Whites, whereas the White population utilized more hospice services or died at home. This highlights the existing disparities in end-of-life care in PCa and promotes policy-level changes in the states with lower utilization of hospice services to improve access of care in PCa patients.
Use of the Prostatype P-score to predict adverse pathology (AP) at radical prostatectomy (RP).
Authors: Andriole Gerald L. , Berglund Emelie , Gaal Steven , Bykov Vladimir J.N. 
Published: January 2024

276 Background: Men with low or favorable intermediate risk prostate cancer (PCa) may undergo Active Surveillance (AS) or curative treatment. Among the factors patients and clinicians use to determine which approach to take is the likelihood of AP at RP. Nomograms using clinical parameters alone or along with GC’s have been used to aid in the prediction of AP at RP. The Prostatype test has been developed from prostate biopsy specimens of men with localized PCa. It has been validated in 2 large studies to accurately predict 10-year Prostate Cancer Specific Mortality and 10-year Prostate Cancer Metastasis. The Prostatype test is generated from the signature of 3 embryonic stem cell genes (IGFBP3, F3, and VGLL3) measured from the biopsy along with clinical data (PSA, Gleason Score, and T-stage). Its intended use is to guide treatment decisions in men currently on or considering AS. The Prostatype test is CE marked and is available for clinical use in Europe. Methods: To validate the ability of the Prostatype test performed on prostate biopsy tissue to predict AP (Gleason score 4+3 or higher and/or non-organ confined disease (pT3)) at RP, we studied 214 patients (Median age 65 (59,68); Median PSA 7.6 (5.3, 11.1); 20% Gleason 6; 64% Gleason 7; 16% Gleason >8) who underwent RP, of which 117 (55%) had AP. The model to predict AP at RP is an Artificial Neural Network (ANN) algorithm. Results: This ANN showed excellent performance, e.g., great balance between precision and sensitivity and had a high overall accuracy (AUC of 0.88) at predicting AP at RP. This 5-layer ANN model includes IGFBP3, F3, % positive biopsies and biopsy primary Gleason score. Confusion matrix measurement of the performance of the model shows it minimizes misclassification of patients with AP, and together with the Matthews Correlation coefficient (0.639) provides evidence that the ANN model manages false positives and false negatives correctly. Conclusions: This study shows that the Prostatype test is a strong predictor of AP at RP and may be used to guide decision making of clinicians and patients who are currently on or considering AS.
Racial and ethnic differences in the receipt of metabolic syndrome risk factor screening and treatment among individuals with prostate cancer treated with androgen deprivation therapy.
Authors: Barqawi Yazan K. , Borrego Matthew E , Roberts Melissa H , Thompson Todd , Hashemi-Sadraei Neda 
Published: January 2024

29 Background: Racial and ethnic health disparities in prostate cancer screening, and treatment constitute the largest of all cancer disparities. Androgen deprivation therapy (ADT) is widely used in the treatment of localized or metastatic prostate cancer. However, ADT is associated with toxic cardiovascular and metabolic adverse events that may occur as early as 6 months of therapy initiation. This study aimed to assess racial/ethnic differences and longitudinal changes in metabolic syndrome risk factor (MSRF) screening/treatment among patients with prostate cancer treated with ADT at a university-affiliated comprehensive cancer center in the southwestern U.S. between 2010-2021. We also aimed to identify patient and healthcare provider factors that influence MSRF screening among study sample. Methods: A retrospective observational cohort study of 803 patients treated with ADT for at least six months at the cancer center was conducted. Patients were followed three months pre- to 12 months post-ADT initiation to evaluate MSRF screening/treatment. Determination of MSRF screening was based on primary care provider referral for MSRF screening/treatment or receipt of blood glucose, lipid profile, and blood pressure screening within six months post-treatment with ADT. Patients were considered treated for MSRF if they were started or continued therapy (within six months of ADT initiation) with science advisory guideline recommended treatments. Results: Guideline-concordant MSRF screening rate approached 23.5%; MSRF treatment rate was 76.9%. A higher treatment rate in MSRF treatment was found for NHW compared to Hispanic men ( p=0.02). We found a significant difference in the proportion of patients receiving MSRF screening across all racial/ethnic groups ( p=0.03). MSRF screening rates from 13.9% to 35.6% were observed over the 10-year data collection period. Patients with dyslipidemia at baseline had higher odds of having MSRF screening than patients without dyslipidemia ( p<0.0001). Oncologists with >20 years of experience had higher odds of providing MSRF screening compared with <10 years of experience ( p=0.006). Conclusions: Minority populations had significantly lower odds of having MSRF screening than NHW patients after adjusting for clinical and socio-economic variables. Closer clinical attention and education, as well as the development and implementation of innovative practice tools and interventions to optimize MSRF screening and treatment are warranted to mitigate the harmful adverse effects of ADT in patients with prostate cancer.
The Capio Prostate Cancer Center model for prostate cancer diagnostics using Stockholm3, MRI, and targeted biopsies: Real-world evidence from 2018 to 2022.
Authors: Palsdottir Thorgerdur , Söderbäck Harold , Jäderling Fredrik , Bergman Martin , Vigneswaran Hari Thambiah , Gronberg Henrik 
Published: January 2024

295 Background: The Capio Prostate Cancer Center (Capio PCC) handles approximately 25% of prostate cancer care in Stockholm, Sweden. The Capio PCC Model utilizes Stockholm3 and MRI scans to assess prostate cancer risk, followed by targeted and systematic biopsies for those at increased risk. This study describes the clinical process and real-world evidence of the Capio PCC Model. Methods: If eligible for prostate cancer testing, men undergo a blood test for PSA. Men with PSA ≥1.5 ng/ml are additionally tested with Stockholm3 and men with a Stockholm3 ≥15, undergo MRI. Men with elevated risk on MRI undergo targeted and systematic biopsies. Men were included from 2018-2022 at the Capio PCC, if they underwent PSA and Stockholm3 (for PSA ≥1.5 ng/ml). The results on PSA, Stockholm3, MRI, and biopsies are presented, including the number of clinically significant prostate cancer as defined as ISUP grade ≥2. We compare the biopsy results from Capio PCC to other hospital regions in Sweden and evaluate health economics of the diagnostic pathway. Results: A total of 12,406 men aged 45-75 underwent testing for prostate cancer. Median age was 61 years (IQR: 55-67), median PSA was 1.6 ng/ml (IQR: 0.8 – 3.3), median Stockholm3 was 4 (IQR: 3-11) and 1,064 (8.6%) men were biopsied. A total of 611 (57% of biopsied) men were diagnosed with clinically significant prostate cancer. Of the tested men, 3,496 had PSA ≥3 ng/ml and 2,002 had Stockholm3 ≥15, decreasing the number MRIs by 43%. In total, 2,980 men had PSA between 1.5-2.99 ng/ml and of those, 360 (12%) had Stockholm3 ≥15 with 72 (56% of biopsied) men having clinically significant prostate cancer. In total, 330 men had PSA ≥10 ng/ml and of those, 87 men (26%) had Stockholm3 <15, reducing MRI and biopsy in this higher risk group. Comparing national Swedish prostate cancer data, the Capio PCC Model showed fewer diagnoses of low-risk cancers (14% vs. 25%), more intermediate risk cancers (59% vs. 42%), and less high-risk and advanced cancers (26% vs. 30%). Conclusions: The study demonstrates that the protocol-driven and diagnostic process at Capio PCC leads to an effective care, enabling earlier diagnosis of intermediate risk cancer and reducing the number of MRIs as well as incidence of overdiagnosis of low-risk cancers compared to the prostate cancer care in Sweden.[Table: see text]
Urologist practice divestment from radiation vault ownership and treatment patterns for prostate cancer.
Authors: Faraj Kassem S , Kaufman Samuel , Herrel Lindsey A. , Maganty Avinash , Oerline Mary , Caram Megan Veresh , Shahinian Vahakn B. , Hollenbeck Brent K. 
Published: January 2024

304 Background: Urologists practicing in single-specialty groups with ownership in radiation vaults are more likely to treat men with prostate cancer. The effect of urology practice divestment in radiation vault ownership on treatment patterns of men with prostate cancer is unclear. Methods: A 20% sample of national Medicare claims was used to perform a retrospective cohort study of men with prostate cancer, diagnosed between 2010 and 2019, managed by single specialty urology groups. All men were followed through December 31, 2020. Urology groups were categorized by radiation vault ownership for each year as nonowners, owners, and divested owners. The primary outcome was use of treatment and the secondary outcome was use of intensity-modulated radiation therapy (IMRT). Both outcomes were assessed for the 12-month period after diagnosis. Using a difference-in-differences design, multivariable logistic regression was used to measure the effect of radiation vault divestment on outcomes. Subgroup analyses assessed outcomes by non-cancer mortality risk (high (> 50%) vs. low (≤ 50%)) within 10 years of diagnosis. Results: Among 72 urology practices that owned radiation vaults, six divested during the study. Divestment led to a decrease in treatment compared with those managed at continuously owning practices (difference-in-differences estimate, -13%, p=0.03). The use of IMRT also decreased, but this change was not statistically significant (difference-in-differences estimate, -8%, p=0.21). In men with a high non-cancer mortality risk, treatment (difference-in-differences estimate, -28%, p<0.001) and use of IMRT (difference-in-differences estimate, -27%, p<0.001) decreased after divestment. Conclusions: Urology single specialty group divestment in radiation vault ownership leads to a decrease in prostate cancer treatment. This decrease was most pronounced in newly diagnosed men that had a high non-cancer mortality risk. This has important implications for healthcare reform, suggesting that programs that can incentive constraints on utilization may be effective in reducing prostate cancer overtreatment.