bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive genomic profiling unravels molecular targets in patients with metastatic spinal cord compression from prostate cancer.
Authors: Duong Tony , Wang Jue
Published: February 2022

147

Background: Spinal cord compression (SCC) from prostatic cancer is an oncologic emergency with significant negative impact on morbidity and survival. However, the molecular mechanisms involved in spinal metastases remains largely unclear. The aim of this study was to evaluate the histopathology, molecular profiles, and outcome in these patients. Methods: Twenty patients with magnetic resonance imaging-confirmed metastatic SCC from prostate cancer were identified at Dignity health Cancer Institute. Pathology slides were reviewed and the molecular analysis of 324 cancer-related genes was performed on tumor specimens using targeted next-generation sequencing. Characteristics including age, Gleason score, SCC anatomical site, time to diagnosis of SCC, gene alterations, number of lines of treatment and clinical outcome were analyzed. Results: At the time of diagnosis of SCC, the median age at diagnosis of SCC was 60.5 years old (range=50-76). The median PSA value was 626 ng/ml, 100% of patients have a Gleason score above 7, 30% of patients had visceral metastases. The thoracic spine affecting (15/20) patients is the most common site of SCC. Seventeen patients (75%) were initially treated with surgery combined with radiation therapy (RT), whereas 3 (15%) were managed with RT alone. At the time of this study, 11 patients remain alive (55%), median overall survival (OS) is 20 months, 18 months in treatment naive and 22 months in hormone refractory patients. Molecular analysis revealed gene mutations in all (100%) tumors, The most common gene alterations were PTEN (16%), followed by AR alterations AR (13%), TP53 (11%), TMPRSS2-ERG (8 %), BRCA1/2(4%), RB1(1%) and ATM (1%). Conclusions: Comprehensive genomic profiling revealed several molecular targets in patients with metastatic spinal cord compression from prostate cancer.[Table: see text]
Clinical and molecular features of low prostate-specific membrane antigen (PSMA) expression in patients (pts) with metastatic castration resistant prostate cancer (mCRPC).
Authors: de Kouchkovsky Ivan , Zhang Li , Huang Jiaoti , Trepka Kai , Chou Jonathan , Foye Adam , Shui David , Wong Chris , Friedl Verena , Weinstein Alana , Hope Thomas A , Quigley David A. , Stuart Josh , Beer Tomasz M. , Reiter Robert Evan , Gleave Martin E. , Evans Christopher P , Feng Felix Y , Small Eric Jay , Aggarwal Rahul Raj
Published: February 2022

167

Background: Low PSMA uptake on positron-emission tomography is seen in up to 30% of mCRPC pts and represents a clinically distinct subgroup with adverse outcomes. We assessed transcriptional and clinical features associated with low PSMA ( FOLH1) gene expression in mCRPC. Methods: A retrospective analysis of mCRPC biopsy samples with RNA-seq data was undertaken. Normalized FOLH1 expression was compared across histologic subtypes and sites of disease. We assessed the association between FOLH1 expression, selected androgen receptor (AR) target genes, master regulators of neuroendocrine differentiation, and previously validated AR activity and treatment-associated small cell neuroendocrine carcinoma (t-SCNC) transcriptional signature scores using Pearson correlations. Associations between FOLH1 and both PSA50 response to subsequent AR-targeted therapy and overall survival (OS) were examined by logistic regression and Cox proportional hazard models, respectively. Results: Samples from 97 pts were identified, of which 18% harbored t-SCNC histology. 45% of pts had visceral metastases at the time of biopsy, and 41% received subsequent AR-targeted therapy. Median FOLH1 expression was lower in pts with visceral metastases vs no visceral metastases (14.7 vs 15.6, p = 0.02) but was not significantly different across t-SCNC vs adenocarcinoma biopsies (14.3 vs 15.4, p = 0.13). FOLH1 expression was positively correlated with AR transcriptional activity and AR target genes, and negatively correlated with master regulators of neuroendocrine differentiation and t-SCNC transcriptional signature scores (Table). Low FOLH1 expression did not predict PSA50 response to subsequent AR-targeted therapy (OR 0.97, p = 0.8), but was associated with shorter OS on univariate analysis (HR 1.09, 95% CI 1.02-1.16, p=0.01). A post-hoc analysis revealed a trend towards decreased median OS in pts with FOLH1 expression <12 (7.5 vs 17.1 months, log-rank p = 0.06). Conclusions: In this retrospective analysis of mCRPC pts, low FOLH1 expression was associated with transcriptional features of t-SCNC, decreased AR activity, and shorter OS. These findings are hypothesis-generating and prospective validation is needed.[Table: see text]
Evaluation of ctDNA alterations in mCRPC patients with germline pathogenic mutations.
Authors: Light Malcolm , Jaeger Ellen B. , Caputo Sydney , Fleming William , Manogue Charlotte , Huang Minqi , Sussman Isabelle P. , Lieberman Alex , Miller Patrick , Barata Pedro C. , Layton Jodi Lyn , Lewis Brian E. , Ledet Elisa M. , Sartor A. Oliver
Published: February 2022

177

Background: Germline alterations are found in approximately 12-17% of CRPC patients. Similarly, evaluating tumoral changes with circulating tumor DNA (ctDNA) has become an increasingly useful tool for understanding mechanisms underpinning disease progression. In this study, we evaluated both germline and somatic genetic changes in patients with mCRPC. Methods: Patients included had germline screening and ctDNA analyzed with the Guardant 360 assay. All patients were CRPC at the time of Guardant testing. Germline alterations were classified as pathogenic/likely-pathogenic or not pathogenic. Only ctDNA alterations with an alleleic fraction greater than 0.5% were included in analyses. Additional evaluation of CRPC status, treatment history, family history and other clinical covariates are ongoing. Chi-square and Fischer’s Exact tests were used for comparison of cohorts. Results: A total of 168 Caucasian CRPC patients had Guardant 360 testing at time of progression and germline testing between 2015-2021. 61% (n = 102/168) of patients have previously had treatment with abiraterone, 49% (n = 82/168) have had Enzalutamide and 40% (n = 68/168) have had treatment with taxanes. 12% (n = 20/168) of CRPC patients had a pathogenic/likely-pathogenic (P/LPv) germline alteration, 46% (n = 77/168) had a germline variant of unknown significance (VUS), 42% (n = 71/168) were germline negative. CRPC patients with pathogenic germline mutations were significantly more likely to have subsequent somatic alterations in BRCA2 (OR = 5.05, 95% C.I. (1.11, 23.01), p = 0.055), NF1 (OR = 7.89, 95% C.I. (2.15, 28.10), p = 0.004), and TP53 (OR = 3.52, 95% C.I. (1.28, 9.68), p = 0.015). In TP53, among germline positive patients, 45% (n = 9/20) had TP53 alterations compared to 30% (n = 45/148) of germline negative patients. Conclusions: Germline positive (P/LPv) CRPC patients were significantly more likely to have somatic alterations in BRCA2, NF1, and TP53. Understanding the totality of genetic changes, both germline and acquired somatic alterations is essential as the arsenal of targeted treatment for CRPC continues to expand. Additional studies including longitudinal assessment genetic changes and clinical correlates will be necessary to evaluate these findings in the context of treatment outcomes and disease progression.
Virtual genetics board for enhancing knowledge and practice of prostate cancer genetic testing: The ENGAGEMENT study.
Authors: Giri Veda N. , Gross Laura , Cheng Heather H. , Russo Jessica , Paller Channing Judith , Johnson Jennifer M , Weg Emily Steinberger , Loeb Stacy
Published: February 2022

184

Background: With the increasing indications for germline testing for prostate cancer (PCA), there is a growing need for a spectrum of providers to develop working knowledge and understand considerations of germline testing and genetic counseling. A virtual genetics board was developed to provide case-based discussion of PCA germline testing, standard of care and clinical trial management, hereditary cancer management, and genetic counseling. Methods: A virtual genetics board was launched including experts in GU medical oncology, prostate cancer genetics, radiation oncology, urology, clinical trials, genetic counseling, and molecular oncology. Conferences are held monthly, with cases covering metastatic PCA, high-risk disease, early-stage PCA, or PCA screening. Participants complete a baseline survey of demographic information and cancer genetics knowledge. Post-conference survey includes retaking knowledge questions and feedback on cases and Zoom format. Results: At the time of this report, 57 participants have engaged in the virtual genetics board. Participants include genetic counselors (21%), nurse practitioners (21%), medical oncologists (14%), researchers/scientists (14%), nurses (9%), urologists (5%), radiation oncologists (4%), and other specialties. Practice settings include academic centers (49%), public hospitals (16%), private hospitals (11%), and other settings. The baseline survey was completed by 55 participants, and post-conference survey by 34 participants. Knowledge scores increased regarding cancer inheritance, rates of mutations in metastatic PCA, BRCA2-related cancers, risk of PCA for HOXB13 carriers, and risk for PCA in African American males. Feedback was positive, with over 90% favorable responses on usability of technology, usefulness of case discussions, and relevance to informational needs. Conclusions: Initial results support a virtual genetics board to increase PCA genetic evaluation knowledge. The ENGAGEMENT study is ongoing with monthly live case discussions that are also recorded for on-demand viewing; registration is available at www.prostategenetics.com/engagement.[Table: see text]
Trends in disease burden from prostate cancer amongst different regions of the world and extensively the European Union 15+ countries, from 1990 to 2019: Estimates from the Global Burden of Disease study.
Authors: Mouchati Christian , Abdallah Nour , Jani Chinmay , Mariano Melissa , Jani Ruchi Tusharkumar , Marshall Dominic C , Singh Harpreet , Shalhoub Joseph , Salciccioli Justin , McKay Rana R.
Published: February 2022

187

Background: Prostate cancer was the third most commonly diagnosed cancer in 2020 and the fifth leading cause of cancer mortality worldwide. Global variations in the burden of prostate cancer have been observed in the past decades. This study aimed to assess the trends in incidence, mortality, and disability-adjusted life years from prostate cancer in the World Health Organization (WHO) regions and extensively in the European Union (EU) 15+ countries from 1990 to 2019. Methods: The Global Burden of Disease Study database was used to extract the mortality data of prostate cancer, based on the International Classification of Diseases versions 10 and 9. Data acquired for different WHO regions and each country of the EU15+ nations, per year from 1990 to 2019, included age-standardized incidence rates (ASIR), age-standardized death rates (ASDR), and disability-adjusted life years (DALYs). Mortality-to-incidence ratios (MIR) were then computed. Trends were assessed using Joinpoint regression. Results: Between 1990 and 2019, ASIRs increased worldwide (+13.16%), except in the American region, with the largest growth in the Eastern Mediterranean Region (EMR) (+72.43%). While ASDRs and DALYs increased in Africa, South-East Asia, and EMR, they decreased in the Americas, Europe, and Western Pacific Region (WPR). MIRs decreased universally (-25.52%), mainly in the WPR (-43.49%). In EU15+ countries, ASIRs increased in all countries, except for Canada (-11.27%) and the United States of America (USA) (-10.37%), with the largest rise in Finland (+75.11%). ASDRs decreased in all countries, with the widest drop in Luxembourg (-41.89%) and the lowest in Denmark (-13.96%). MIRs decreased in all countries, with the highest drop in Finland (-55.37%). Similarly, DALYs decreased in all countries, with the highest decrease in Luxembourg (-40.56%). In 2019, the highest ASIR was in the USA (118.24/100,000), whereas Denmark had the highest ASDR (31.35/100,000), MIR (0.38/100,000), and DALY (498.03/100,000). Conclusions: Over the 30 years, the incidence of prostate cancer has been rising worldwide, excluding Canada and the USA. However, the universal decrease of MIRs highlights improved outcomes and efficient screening and therapeutic strategies. All indices are represented per 100,000 population.[Table: see text]
Prevalence of Fanconi anemia gene mutations among men undergoing multigene germline testing for prostate cancer: Interim results from the EMPOWeR study.
Authors: Giri Veda N. , Gross Laura , Russo Jessica , Shimada Ayako , McNair Christopher , Kelly William Kevin , Gomella Leonard G.
Published: February 2022

188

Background: Germline testing for prostate cancer (PCA) is now central to treatment, screening, and hereditary cancer management. The Fanconi anemia (FA) pathway is a key DNA repair pathway involved in PCA biology and treatment. Prevalence of FA genes BRCA2, PALB2, and BRIP1 is well-described; however, multiple other FA genes are not routinely tested, with limited prevalence data. Here we report mutation prevalence of a spectrum of FA genes among men undergoing PCA multigene testing on the Evaluation and Management for Prostate Oncology, Wellness, and Risk (EMPOWeR) study. Methods: Eligibility includes any male with PCA or at-risk for PCA. Multigene testing includes 51 genes; FA pathway genes include BRCA2, PALB2, BRIP1, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, and FANCM. Multiple additional cancer risk genes were tested. Fisher’s exact tests were conducted to compare the prevalence of FA gene mutations between participants in the EMPOWeR study vs population prevalence reported in the literature. Statistical significance level of all tests was set a priori to 0.05. Results: The current cohort includes 235 participants. Characteristics are White (83.3%), Black (13.7%), PCA diagnosis (83.4%), mean age of PCA diagnosis 61.7 + 7.69 years, Gleason score >=7 (66.2%), and T3 or higher (29.4%). Genetic results were available for 179 participants. Overall, 11.1% of participants (n=20) had a pathogenic/likely pathogenic mutation identified. Among mutation carriers, 45% (n=9) had mutations in FA genes, including FANCA (n=3), BRCA2 (n=2), FANCM (n=1), FANCD2 (n=1), PALB2 (n=1), and BRIP1 (n=1). Table shows clinical characteristics of participants with mutations in FANCA, FANCM, and FANCD2. Further mutation spectrum included: CHEK2 (n=3), NBN (n=2), MUTYH (n=2), BRCA (n=1), ATM (n=1), HOXB13 (n=1), APC (n=1). Compared to population prevalence, FA mutation prevalence was significantly higher overall (5.0% vs. 0.6%, p = 0.010) and among mutation carriers (45% vs. 0.6%, p<0.001). Conclusions: While prevalence of FA genes BRCA2, PALB2, and BRIP1 is well-described, our study supports testing a broader range of FA genes given the prevalence rates, potential implications for clinical trials, targeted therapy, inherited syndromes, and reproductive implications.[Table: see text]
Association between prostate-specific antigen screening and prostate cancer mortality in a racially diverse cohort of United States veterans.
Authors: Sherer Michael Vincent , Qiao Edmund Men , Kotha Nikhil V. , Qian Alexander , Rose Brent S.
Published: February 2022

225

Background: African American (AA) men are known to develop more aggressive forms of prostate cancer at a younger age compared to their Non-Hispanic White (NHW) counterparts. However, few AA men were included in the major randomized trials assessing the efficacy of Prostate-Specific Antigen (PSA) screening. It is thus unknown whether PSA screening may be more beneficial in the AA population. Methods: We conducted a retrospective analysis of men diagnosed with prostate cancer in the United States (US) Veterans Affairs Health System (VA) using the VA Informatics and Computing Infrastructure. Inclusion criteria were AA or NHW men aged 55-69 diagnosed with intermediate or high-risk prostate cancer between 2004 and 2017. Patients were classified as never screened with PSA prior to diagnosis, screened at least once prior to diagnosis (some screening), or screened in 5 consecutive years prior to diagnosis (annual screening). A lead-time bias adjusted multivariate regression model was implemented to assess the effect of screening on prostate cancer specific mortality (PCSM), with covariates including age, comorbidities, BMI, smoking history, marital status and primary care utilization. Results: A total of 45,825 men met the inclusion criteria and were included in the analysis, including 14,294 (31.1%) AA men and 31,151 (68.9%) NHW men. When compared to no screening, any prior PSA screening was associated with improved PCSM for both AA (subdistribution hazard ratio (SHR) 0.64, p < 0.001) and NHW (SHR 0.62, p < 0.001) patients. Annual PSA screening (vs no or some screening) was associated with improved PCSM for AA men (SHR 0.68, p = 0.013) but not NHW men (SHR 0.90, p = 0.240). Other significant predictors of worse PCSM in both AA and NHW men included older age, earlier year of diagnosis, greater comorbidity burden, and cigarette smoking. Conclusions: In a diverse population of US veterans, at least one prior screening PSA was associated with improved PCSM in both AA and NHW patients. Annual PSA screening was associated with reduced PCSM in AA but not NHW men, suggesting that more intensive screening protocols may be beneficial for AA patients.
Comparison of prostate specific antigen testing in men aged 55 to 69 with and without a history of cancer.
Authors: Lazarovich Alon , Chandrasekar Thenappan , Shapiro Oleg , Jacob Joseph M , Basnet Alina , Bratslavsky Gennady , Goldberg Hanan
Published: February 2022

230

Background: Prostate specific antigen (PSA) screening remains a controversial issue. However, most urological guidelines recommend PSA testing through a shared decision-making process with the patient. The rate of PSA screening in men with a history of cancer compared to men with no cancer history is not well known. We aimed to compare PSA testing in men aged 55-69 years with and without a history of cancer (excluding prostate cancer patients). Methods: Utilizing the National Health Interview Survey (NHIS) a retrospective cross-sectional study between the years 2015 and 2018 was carried out to analyze and compare PSA testing rates in men aged 55-69 years. Multivariable logistic regression model was implemented do demonstrate potential associations with PSA testing. Results: A total of 13,850 men aged 55-69 years included in the NHIS Survey were analyzed. 1519 (10.9%) men had a history of cancer (non-prostate). On multivariable analysis, men who were previously diagnosed with cancer had a higher rate of PSA testing compared to men with no history of cancer (OR: 1.88, 95% CI 1.39-2.54, p < 0.001). Other factors associated with an increased likelihood of undergoing PSA testing included: age, homosexual orientation, and married men. In contrast, current smokers, American Indians and Alaskan Natives and Asians were less likely to undergo PSA testing. Conclusions: Our data suggest that men aged 55-69 with a history of cancer are more likely to undergo PSA testing than men with no cancer history.[Table: see text]
The BARCODE1 study in primary care: Early results targeting men with increased genetic risk of developing prostate cancer—Examining the interim data from a community-based screening program using polygenic risk score to target screening.
Authors: McHugh Jana Kathlyn , ni Raghallaigh Holly , Bancroft Elizabeth , Kote-Jarai Zsofia , Benafif Sarah , Eeles Ros A.
Published: February 2022

231

Background: A significant proportion of Prostate cancer (PrCa) risk is attributable to heritable risk factors of which only a minority are high risk Mendelian traits. A greater proportion of PrCa is due to the combined effect of multiple low risk variants. There have been approximately 170 single nucleotide polymorphisms (SNPs) identified that are associated with PrCa risk in Europeans. Although each of these confer a low to moderate risk of PrCa, the cumulative risk (polygenic risk score, PRS) of increasing numbers of these risk alleles may confer a substantial relative risk. In PrCa genetic profiling, using PRS, could be used to target population screening to those at highest risk. BARCODE1 is the first study to prospectively review the use of a genetic profile in PrCa screening in the general population in the UK. Methods: Our study invited healthy males aged 55-69 to participate through their Primary Care physicians. Collection kits were mailed to retrieve saliva samples. Genotyping was carried out after DNA extraction using a study specific assay and the PRS was calculated for each participant using the sum of weighted alleles for 130 risk loci. Prostate MRI and Biopsy were then offered to men in the top 10% of the genetic risk profile. Results: 40,292 men were invited by letter to participate. The uptake was 22%, of whom 91% of men were eligible for inclusion. Following DNA extraction, genotyping, and quality control checks, data were available for 5008 men. 573 participants had PRS in the top 10% and were invited for screening; 180 underwent a prostate MRI, and 100 went on to have a systematic +/- targeted prostate biopsy. There were 42 diagnoses of PrCa (42%). 52% of cancers detected were low-risk and are being managed with Active Surveillance (AS). Conclusions: The early data from BARCODE1 have shown the feasibility of this population-based study, with an overall uptake of 22% and a cancer incidence of 42% of men in the top decile of PRS. We have identified clinically significant PrCa in 48%. The BARCODE1 study results will be important in defining the role of PRS genetic profiling in targeted PrCa population screening. Clinical trial information: NCT03857477.
Predictive accuracy of PSA density in the UCSF-CAPRA score.
Authors: Parker Robert , Bell Alexander , Greenberg Scott , Washington Samuel L. , Cowan Janet E. , Cooperberg Matthew R. , Carroll Peter
Published: February 2022

233

Background: The UCSF-CAPRA score is a validated risk tool that uses patient factors at diagnosis to predict prostate cancer outcomes after radical prostatectomy. This study aims to evaluate whether the substitution of prostate-specific antigen (PSA) density for serum PSA improves the predictive performance of the clinical CAPRA model. Methods: Participants were diagnosed in 2000-2019 with stage T1/T2 cancer, underwent radical prostatectomy (RP) for prostate cancer, and had at least 6 months of post-surgical follow up. We computed the standard CAPRA clinical risk score using diagnostic age, Gleason grade, percentage of positive cores, clinical T stage, and serum PSA, as well as an alternate score based on the same variables but substituting PSA density (incremental categories) for serum PSA. We reported validated CAPRA categories of low (0-2), intermediate (3-5) and high (6-10) risk. Recurrence was defined as 2 consecutive PSA > = 0.2 ng/ml or receipt of salvage treatment. Life table and Kaplan-Meier analysis was used to evaluate recurrence-free survival after prostatectomy. Two Cox proportional hazards regression models were used to test associations of standard or alternate CAPRA component variables with risk of recurrence. Two additional models tested associations between standard CAPRA score or alternate CAPRA score with risk of recurrence. The Cox log-likelihood ratio test (-2 LOG L) was used to assess model accuracy. Results: A total of 2,557 patients had a median age of 61 years (IQR 56-66), GG1 34% and GG2 30%, median PSA 6.3 (IQR 4.8-9.3), and median PSA density 0.19 (IQR 0.13-0.29). Post-surgical follow up was 49 months (IQR 25-86). The alternate CAPRA model was associated with significant shifts in risk scores, with 16% of patients increasing and 6% decreasing (p < 0.01). Recurrence-free survival after RP was 75% at 5 years and 63% at 10 years. Both CAPRA component models were associated with risk of recurrence after RP on Cox regression. Covariate fit statistics showed significantly better fit (low -2 LOG L) for the standard CAPRA model compared to the alternate model (-p < 0.01). Both standard (HR 1.55; 95% CI 1.49-1.61) and alternate (HR 1.52; 95%CI 1.46-1.58) CAPRA scores were associated with risk of recurrence, with better fit for the standard model p < 0.01). Conclusions: In a cohort of 2,557 men followed for a median of 49 months after RP, a alternate CAPRA model using PSA was associated with higher risk of BCR, but did not perform better than the standard CAPRA model at predicting BCR. While PSA density is well established as an independent prognostic variable in the pre-diagnostic setting and for sub-stratifying otherwise low-risk disease, it does not appear to improve predictive accuracy of BCR models when applied across the full range of cancer risk.
A phase I does-escalation and expansion study of epidiolex (cannabidiol) in patients with biochemically recurrent prostate cancer.
Authors: Myint Zin , St.Clair William H. , Strup Stephen , Wang Peng , James Andrew Callaway , Yan Donglin , Ellis Carleton Scott , Otto Danielle E. , DiPaola Robert S. , Arnold Susanne M. , Kolesar Jill
Published: February 2022

257

Background: There is a need for a low toxicity option for men with prostate cancer with biochemical recurrence (BCR) following primary curative therapy. Cannabinoids (CBD) have anti-tumor activity in preclinical studies, but products may vary in activity without clear standardization. As epidiolex is a standardized FDA approved oral CBD solution for treatment of certain types of seizures, we studied epidiolex in patients with BCR of prostate cancer to determine safety and dosing of this therapy to support future studies. Methods: We present an open-label, single center, phase I dose escalation study followed by a dose expansion. Patients with BCR prostate cancer after primary definitive local therapy (prostatectomy +/- salvage radiotherapy or primary definitive radiotherapy) were eligible. Majority of our patients’ prostate-specific antigen (PSA) doubling time was ≤ 12 months. All patients were screened for urine tetrahydrocannabinol (THC) prior to enrollment. With use of a Bayesian optimal interval design, patients received escalating doses of epidiolex starting at 600mg daily and up to 800mg daily. All patients were treated for 90 days followed by a 10 day taper. The Primary endpoints were safety and tolerability. Patients were monitored for both acute (30 days) and chronic (90 days) treatment-related toxicities. Secondary endpoints included change in PSA levels and testosterone levels from baseline throughout the treatment period. Results: A total of 21 patients were enrolled but four withdrew from the study (one patient was hospitalized with COVID-19 and three patients requested to stop due to grade 2 adverse events (AEs). There were seven patients included in the dose escalation phase. Four patients received 600mg daily; two of the four in this phase did not finish the first 30 days (one with COVID-19 and one withdrew). The other three patients received 800 mg daily. No dose-limiting toxicities were observed at any dose level so an additional 14 patients were enrolled at the 800mg dose. Treatment-related chronic AEs occurring in >10% of patients were grade 1 or 2 diarrhea (47.6%), grade 1 or 2 nausea (23.8%) and grade 1 or 2 fatigue (19%). The mean PSA at baseline was 2.9 ng/ml. One patient developed oligo-metastasis disease, two patients progressed after the study period, and one patient died from a non-treatment or disease-related cause. Conclusions: Epidiolex at a dose of 800mg daily appears to be safe and tolerable in patients with BCR of prostate cancer, supporting a safe dose for future studies to determine if there is clinical activity to delay development of hormone refractory metastatic disease. Clinical trial information: NCT04428203.
External beam radiation therapy with or without brachytherapy boost for low PSA, high-grade prostate cancer.
Authors: Fischer-Valuck Benjamin Walker , Baumann Brian Christopher , Dhere Vishal Ramesh , Brenneman Randall , Gay Hiram Alberto , Andruska Neal , Brown Simon A. , Hershatter Bruce , Michalski Jeff M. , Patel Sagar Anil
Published: February 2022

258

Background: Radiation dose escalation with the addition of a brachytherapy boost (BT) to external beam radiation therapy (EBRT) may be associated with improved survival in certain men with Gleason grade 5 (GG5) prostate cancer (PCa). However, low PSA, high-grade PCa has much worse outcomes, is associated with neuroendocrine genomic features, and may be more resistant to androgen suppression. It is unclear whether the addition of a BT boost in men with this disease subgroup is associated with a survival benefit and is the subject of this analysis. Methods: Men diagnosed with node-negative, non-metastatic GG5 PCa and treated with (1) EBRT plus ADT or (2) EBRT plus BT plus ADT between 2004 and 2015 were identified in the National Cancer Database (NCDB). The EBRT cohort received conventionally fractionated ≥ 74 Gy or moderately hypofractionated (2.5-3.0 Gy x 20-28 fractions) EBRT. EBRT plus BT cohort received external beam doses of conventionally fractionated ≥45 Gy or moderately hypofractionated (2.5 Gy x 15 – 18 fractions) radiation, and either LDR or HDR BT. Men receiving chemotherapy, immunotherapy, or any form of surgery were excluded. Patients were stratified into two groups based on whether the presenting PSA was above or below the normal threshold (≤4 and > 4 ng/mL). OS was compared using the Kaplan-Meier and log-rank test. Multivariable analysis (MVA) using Cox proportional hazards regression modeling was performed, accounting for age, race, year of diagnosis, Charlson-Deyo comorbidity score, insurance status, treatment facility type, Gleason Score (9 versus 10), and clinical T-stage. Results: 8,260 men met study inclusion criteria of which 658 (8%) presented with PSA ≤4. 572 (87%) patients were treated with EBRT monotherapy and 86 (13%) patients were treated with EBRT + BT. 5-year OS for EBRT versus EBRT plus BT was 79.7 +/- 2.3% versus 86.9 +/- 5.0%, respectively (P = 0.49). On MVA analysis, EBRT plus BT was not associated with improved OS versus EBRT (adjusted HR 0.90, 95% CI 0.52-1.87; P = 0.62). In comparison, for men with PSA > 4 and GG5 disease [EBRT: 6,780 patients (89.2%) & EBRT plus BT: 822 patients (10.8%)], EBRT plus BT was associated with improved OS versus EBRT (adjusted HR 0.85, 95% CI 0.66-0.99; P = 0.044). Conclusions: Receipt of dose-escalated prostate radiation by means of a BT boost was not associated with improved survival in men with PSA ≤4 ng/mL and GG5 prostate cancer. By contrast, an association with improved survival was observed in men with GG5 disease and higher initial PSA. This low PSA, high-grade subgroup may represent a unique risk tier for which current treatment paradigms need further investigation, including study of escalated systemic therapy.
M2 macrophage increase in prostate adenocarcinoma after high-dose rate brachytherapy.
Authors: Kundu Palak , Kane Nathanael , Lim Andrew , Ma Ting Martin , Li Yunfeng , Huang Rong Rong , Ye Huihui , Lee Alan , Nickols Nicholas George , Chang Albert
Published: February 2022

271

Background: Brachytherapy delivers high doses of hypofractionated radiation (RT) internally within the prostate tumor. While radiation has been shown to exhibit immunomodulatory effects, the success of combining radiation and immunotherapy in prostate cancer has been limited. M2 macrophages can contribute to an immunosuppressive tumor environment, and we therefore hypothesize that radiation may increase the abundance of M2 macrophage in the prostate tumor immune infiltrate. Methods: 10 Patients with intermediate risk prostate cancer (age 51-78; 7 GS 3+4, 3 GS 4+3) underwent high-dose rate brachytherapy (2 implants, 13.5Gy per implant, 1 week apart). Patients consented to biopsies before each fraction at the first and second implant. Bulk RNA-seq gene expression was performed on formalin-fixed, paraffin-embedded pre- vs. post-RT tumor samples, and then analyzed with a machine learning deconvolution model to resolve immune cell abundances. CD68+CD163+ M2 macrophages were analyzed with multiplex immunohistochemistry and quantified with tissue analysis software. Paired t-test was used to compare M2 macrophage abundance pre- versus post-RT. Results: Bulk RNA-seq deconvolution demonstrated that the most prevalent immune cell types in the pre-RT samples were resting CD4 memory T cells (39.7%), resting mast cells (38.5%), and M2 macrophages (30.4%), while those in the post-RT samples were M2 Macrophages (78.7%), resting mast cells (58.1%), and resting CD4 memory T cells (48%). M2 macrophages demonstrated the greatest increase, which was corroborated by multiplex IHC: average CD68+CD163+ cell counts were significantly elevated after RT (pre-RT 63.7 vs. post-RT 200.1 per mm2, p=0.015). Conclusions: Hypofractionated radiation increases the immunosuppressive M2 macrophage population in prostate cancer, which may present a therapeutic target to augment the efficacy of radiation and immunotherapy combinations.
Patient-reported experience of diagnosis, management, and burden of renal cell carcinomas: Results >2,000 patients in 41 countries, with focus on older patients.
Authors: Giles Rachel H. , Marconi Lorenzo , Martinez Robin , Maskens Deborah , Kastrati Karin , Castro Carlos , Julian Mauro Juan Carlo , Bick Robert , Heng Daniel Yick Chin , Larkin James , Bex Axel , Jonasch Eric , Maclennan Sara Jane , Jewett Michael A.S.
Published: February 2022

306

Background: Renal cell carcinoma (RCC) is increasing in global prevalence, thereby increasing burden to health systems, and most of all, to individual patients and their families. Little is known about the variations in patient experience and best practices among countries. Here, we report on the second biennial Global Patient Survey on the diagnosis, management, and burden of Renal Cell Carcinomas conducted by the International Kidney Coalition (IKCC) worldwide in 13 languages. The aim of the survey was to improve collective understanding and to contribute toward the reduction of the burden of kidney cancer around the world. Methods: A 35-question survey on the diagnosis, management, and burden of RCC was designed by a multi-country steering committee to identify geographic variations in 6 topics: patient education, experience and awareness, access to care and clinical trials, best practices, quality of life, and unmet psychosocial needs. The survey was distributed to patients with kidney cancer and their caregivers in 13 languages, through IKCC’s 46 Affiliate Organisations and social media from 29 Oct 2020 to 5 Jan 2021. Results: 2,012 responses came from 41 countries. Survey results were analysed using cross-tabulations by an independent third-party organisation. The full global report is publicly available, as well as 7 individual country reports where at least 100 responses were received. 42% reported that the likelihood of surviving their cancer beyond 5 years was not explained Just over half (51%) reported that they were involved as much as they wanted to be in developing their treatment plan. 56% experienced barriers to their treatment 41% indicated that “No one” discussed cancer clinical trials with them 31% were invited to take part in a clinical trial 45% self-reported that they were insufficiently active 50% indicated that they ‘very often’ or ‘always’ experienced disease-related anxiety. 26% ‘very often’ or ‘always’ experienced stress related to financial issues 55% indicated that they ‘very often’ or ‘always’ experienced a fear of recurrence 52% reported having talked to their doctor/healthcare professional about their concerns 48% had been offered a biopsy in the past with only 3% refusing; 47% would be willing to undergo biopsy in the future Patients aged ≤65 experienced more barriers to quality care, understood their disease less well, and experienced a longer time to diagnosis. Conclusions: The IKCC and its global affiliates will be using the results to ensure that patients’ voices are heard. Actionable points will suggest future projects. Individual countries can use their reports to advance their understanding of patient experiences and to improve local care.
Characteristics associated with common reasons to pursue genomic profiling among patients with metastatic genitourinary cancers.
Authors: Malhotra Jasnoor , Philip Errol James , Govindarajan Ameish , Salgia Sabrina , Meza Luis A , Zengin Zeynep Busra , Muddasani Ramya , Chawla Neal Shiv , Castro Daniela , Chehrazi-Raffle Alex , Dizman Nazli , Bergerot Paulo Gustavo , Hsu Joann , Dorff Tanya B. , Pal Sumanta K. , Bergerot Cristiane Decat
Published: February 2022

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Background: Patients with cancer may possess limited knowledge of emerging modalities in oncology, including genomic profiling (GP) tests, which can create barriers to shared decision making. Effective provider communication can address such barriers but little is understood regarding patients’ perceptions of GP. Methods: In this cross-sectional study, patients who were diagnosed with advanced genitourinary cancers (bladder, renal, and prostate cancers), and were referred for GP responded to a survey to assess reasons to pursue such testing. Clinicopathologic characteristics were collected via chart review. Kolmogorov-Smirnov tests were used to assess associations between reasons to pursue GP and patient characteristics. Results: Data was obtained from a sample of 126 patients (gender: 75% M, 25% F; average age: 67; marital status: 78% married; education: 76% some college; histology: 67% renal cell carcinoma, 19% urothelial, and 14% prostate). The most common reasons to pursue GP by patient response were: to guide treatment (73%), to improve treatment response (32%), to follow physician’s indication (27%), to predict treatment response (23%), to learn about their disease (19%), and to contribute to the science (12%). Notably, older age was significantly associated with three reasons (guide treatment, P = 0.001; physician’s indication, P = 0.03; contribute to the science, P = 0.001). No association was found among younger patients. A higher level of education was associated with the desire to guide treatment (P = 0.001). In contrast, a lower level of education was associated with physician’s indication (P = 0.002). Conclusions: This study highlights important associations between reasons to pursue GP and age and level of education. Differing strategies for information delivery could be considered when communicating GP benefits to older patients and to patients with lower levels of education.
Rare intrascrotal tumors in a tertiary cancer center: A retrospective case series.
Authors: Cunha Mateus Trinconi , Cardoso Camila , Fialho de Freitas Guilherme , Silva Jamile Almeida , Muniz David Queiroz Borges , Bastos Diogo Assed , Cardili Leonardo , Mota Jose Mauricio
Published: February 2022

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Background: Given their rarity, the literature on non-germ cell testicular tumors and paratesticular malignancies is still scarce. The objective of this study is to describe clinical and pathological features, as well as treatment patterns and outcomes, of patients with non-germ cell intrascrotal malignancies. Methods: Patients (pts) with benign or malignant non-germ cell intrascrotal tumors who were older than 18 years-old were deemed eligible. Electronic health records (EHR) were reviewed to assess pts clinical features, and disease characteristics and outcomes. Descriptive statistics was used to report data. RECIST 1.1 was used to determine radiological response to treatment. Time-to-event variables were estimated by the Kaplan-Meier method. Results: EHR of 885 pts with a primary diagnosis of ICD-10 C62 treated in a tertiary cancer center from January 2009 to June 2020 were reviewed for eligibility. 29 pts fulfilled eligibility criteria (Sertoli cell tumors, N = 3; Leydig cell tumors, N = 6; granulosa cell tumor, N = 1; testicular tumor of the androgenital syndrome, N = 1; mesotheliomas, N = 3; liposarcomas, N = 3; leiomyosarcomas N = 2; rhabdomyosarcomas, N = 3; spindle cell sarcomas, N = 3; lymphomas, N = 2; carcinoma of the rete testis, N = 1; primary neuroendocrine tumor of the testis, N = 1). The majority of pts (N = 25) had non-metastatic disease at diagnosis, and underwent upfront orchiectomy. The remaining four patients had metastatic disease at diagnosis (lymphoma, N = 1; sarcomas, N = 3), all positive for lymph node (LN) involvement; one with concurrent visceral metastasis. Six other pts posteriorly developed metastatic disease after a median follow-up of 13 months (IQR: 5.8–33.1 months) (Leydig tumor, N = 1; mesothelioma, N = 2; sarcomas, N = 3). The most common metastatic sites were LN (N = 8, 80%), lung (N = 4, 40%), bone (N = 3, 30%), adrenal gland (N = 2, 20%), peritoneum (N = 1, 10%), and skin (N = 1, 10%). Nine pts (90%) received systemic treatment: vincristine, doxorubicin and cyclophosphamide for rhabdomyosarcomas (N = 3), cisplatin plus pemetrexed for mesotheliomas (N = 2), doxorubicin for liposarcomas (N = 2), doxorubicin plus ifosfamide for liposarcoma (N = 1) and doxorubicin, vincristine, cyclophosphamide, and prednisone plus rituximab for lymphoma (N = 1). Of those, 2 pts achieved partial response and 2 had stable disease. Metastasectomy of a single lung metastasis was performed in a patient with metastatic Leydig cell tumor. Median overall survival was 51.2 and 24.5 months for patients with localized and metastatic disease, respectively. Conclusions: Paratesticular and non-germ cell testicular tumors are extremely rare entities with relatively good prognosis if treated at early stages depending on the underlying histology. Most metastatic disease cases were due to paratesticular sarcomas.
Role of preoperative albumin in predicting risk of postoperative complications in patients undergoing post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND).
Authors: Badia Rohit , Jafri Farzan , Baky Fady , Howard Jeffrey , Woldu Solomon L. , Margulis Vitaly , Bagrodia Aditya
Published: February 2022

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Background: Testicular cancer with retroperitoneal metastases is often treated with chemotherapy, with subsequent post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) performed for residual masses after chemotherapy. While the cure rate is high, the surgery is associated with significant morbidity. Unlike in other genitourinary cancers, perioperative nutritional optimization is typically not prioritized as most patients are young, otherwise healthy men. Albumin is a systemic marker of nutritional status and has been shown to predict adverse outcomes in other urological cancers. We sought to assess whether preoperative albumin level is associated with postoperative outcomes in patients undergoing PC-RPLND. Methods: A database of patients who received PC-RPLND at our institution between 2007 and 2019 was created. Pre-RPLND albumin was obtained and correlated with postoperative outcomes using univariate and multivariable regression models. The primary outcome was the presence of major (Clavien-Dindo grade ≥ III) complications within 90 days of surgery. Results: Of 76 patients who underwent PC-RPLND, 70 patients had preoperative albumin values available. The median age (IQR) of patients at the time of surgery was 26 years (22 - 32) and median (IQR) preoperative albumin level was 4.4 g/dL (4.1 - 4.6). Patients with major postoperative complications had lower median preoperative albumin than those without a complication (4.1 g/dL vs. 4.4 g/dL; p = 0.03). Greater albumin level (per g/dL) was associated with a lower risk of major postoperative complications on multivariable logistic regression (OR = 0.12; p = 0.03). Other preoperative serum markers such as hemoglobin and creatinine did not associate with postoperative complications. Conclusions: To our knowledge, this is the first study to demonstrate that preoperative albumin is an independent predictor of major postoperative complications in patients undergoing PC-RPLND. This finding demonstrates the importance of nutritional optimization even in young, otherwise healthy individuals prior to undergoing this morbid surgery. Additional studies are warranted to more reliably predict which patients may experience complications.
Primary urethral cancer: A GETUG French nationwide cohort study.
Authors: Blazevic Ilfad , Flechon Aude , Pignot Geraldine , Mesnard Benoît , Rigaud Jerome , Roumiguié Mathieu , Soulie Michel , Thibault Constance , Crouzet Laurence , Goislard De Monsabert Camille , Lefort Felix , Gross-Goupil Marine , Campedel Lucas , Laramas Mathieu , Martin Elodie , Chaltiel Leonor , Pouessel Damien
Published: February 2022

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Background: Primary urethral cancer (PUC) is a rare and heterogeneous malignancy. Due to its scarcity, little data are available on the optimal treatment sequence and survival, especially in metastatic patients. Methods: Data from patients diagnosed with a PUC between 01/01/2000 and 12/31/2018 were retrospectively collected from nine French referral centers. Survival rate were estimated with the Kaplan-Meier method and prognostic factors were analyzed using the Cox proportional hazards model and the log-rank test. In order to increase the statistical power of survival analysis in the metastatic stage, patients with synchronous and metachronous metastatic disease were pooled. Results: We identified 44 (62%) males and 27 (38%) females with a PUC. The most frequent histological types were urothelial carcinomas (40.0%), squamous cell carcinomas (34.3%) and adenocarcinomas (14.3%). Twenty-five (35.2%) patients were diagnosed at a localized stage (≤ T2, N0, M0); 35 (49.3%) at a locally advanced stage (≥ T3 or ≥ N1, M0) and 11 (15.5%) at a distant stage (M1). Twenty-seven patients had a metachronous metastatic cancer. Multimodality therapy was used in 24.0% and 57.1% of the patients with a localized and locally advanced disease, respectively. In the entire cohort, median overall survival (OS) was 52.5 months (IC95% 32.2 – 64.1) and stage at diagnosis was a predictor of OS (p < 0.0001). For the 60 patients with a non-metastatic disease, 39 (65%) had a recurrence or were dead and the median disease-free survival (DFS) was 21.2 months (IC95% 16.8 – 34.5). Nodal involvement was the only factor associated with DFS (HR: 2.03, p = 0.0390). Multimodal treatment compared with unimodal treatment was not significantly associated with DFS (HR: 1.22, p = 0.5419). Regarding survival of the 38 metastatic patients, the median OS was 15.2 months (IC95% 8.2 – 23.5) and the median progression-free survival was 6.4 months (IC95% 4.4 – 9.8). Conclusions: This retrospective study showed an important heterogeneity in terms of histology, stage at diagnosis, and treatment of PUC. In this cohort, the multimodal approach did not show any improvement in survival of non-metastatic patients. This study is one of the few to describe the survival in metastatic patients.