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Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

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221 hot topic(s) found with the query "Prostate cancer"

Germline Sequencing Analysis to Inform Clinical Gene Panel Testing for Aggressive Prostate Cancer.
Burcu F Darst et al. JAMA Oncol 2023 9 (Posted: Sep-22-2023 2PM)

From the abstract: " Do rare pathogenic variants in genes beyond previously established prostate cancer risk genes contribute to risk of aggressive prostate cancer? In this exome-sequencing genetic association study of 17?546 men with aggressive and nonaggressive prostate cancer, an association between known genes BRCA2, ATM, and NBN with aggressive prostate cancer was found. Nominal association evidence was observed for MSH2, XRCC2, and MRE11A. The findings of this study suggest that DNA repair and cancer susceptibility genes can inform disease management in men with nonaggressive prostate cancer, as men carrying deleterious variants in these genes are likely to develop advanced disease."

Biomarker-Directed Therapy in Black and White Men With Metastatic Castration-Resistant Prostate Cancer.
Clara Hwang et al. JAMA Netw Open 2023 9 (9) e2334208 (Posted: Sep-21-2023 2PM)

From the abstract: "Do disparities exist in the application of precision medicine for Black and White men with metastatic prostate cancer? In this cohort study of 962 men with metastatic castration-resistant prostate cancer, mismatch repair deficiency or microsatellite instability-high was significantly more frequent in Black men than White men. However, Black men were significantly less likely to receive molecularly matched targeted therapy than White men. These findings suggest that although precision medicine in metastatic prostate cancer has become more common, opportunities remain to improve access to precision medicine to benefit Black men with prostate cancer. "

An international multi-institutional validation study of the algorithm for prostate cancer detection and Gleason grading
Y Tolkach et al, NPJ Precision Oncology, August 15, 2023 (Posted: Aug-16-2023 8AM)

Pathologic examination of prostate biopsies is time consuming due to the large number of slides per case. In this retrospective study, we validate a deep learning-based classifier for prostate cancer (PCA) detection and Gleason grading (AI tool) in biopsy samples. Five external cohorts of patients with multifocal prostate biopsy were analyzed from high-volume pathology institutes. A total of 5922 H&E sections representing 7473 biopsy cores from 423 patient cases (digitized using three scanners) were assessed concerning tumor detection.

BRCA-deficient metastatic prostate cancer has an adverse prognosis and distinct genomic phenotype
H Fettle et al, ebiomedicine, August 5, 2023 (Posted: Aug-07-2023 9AM)

Genomic alterations in DNA damage response (DDR) genes are common in metastatic castration-resistant prostate cancer (mCRPC). Understanding how these genomic events impact prognosis and/or treatment response is vital for optimising clinical outcomes. These data emphasise that the BRCA genes, in particular BRCA2, are key prognostic biomarkers in mCRPC. The clinical utility of BRCA2 as a marker of poor outcomes may, at least in cfDNA assays, be independent of the zygosity state detected.

Meeting the need for germline testing
Lancet Oncology editorial, July 2023 (Posted: Jul-05-2023 7AM)

Germline genetic testing for pathogenic mutations in people diagnosed with cancer is recommended for several cancer types and has been shown to have a positive effect on survival. The US NCCN guidelines recommend that all, or a high proportion of, patients with a personal history of breast, ovarian, endometrial, pancreatic, colorectal, and prostate cancer should undergo germline testing. Yet, in a new study, only 6·8% of patients diagnosed with one of seven cancers in California and Georgia, USA, between 2013 and 2019, underwent genetic testing.

Precision medicine meets cancer vaccines.
et al. Nat Med 2023 6 (Posted: Jun-22-2023 7AM)

Vaccines for treating cancer have been in development for decades, but their clinical efficacy has been elusive. Thus far, only one therapeutic vaccine against cancer has been approved by the US Food and Drug Administration for the treatment of prostate cancer, extending patient survival by only 4 months. Now, two independent efforts using mRNA vaccines tailor-made to target each patient’s tumor have reported initial success in melanoma and pancreatic cancer and are energizing the field of anti-cancer vaccines.

Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry.
Burcu F Darst et al. Am J Hum Genet 2023 6 (Posted: Jun-15-2023 8AM)

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies. The investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping.

Genetically adjusted PSA levels for prostate cancer screening.
Linda Kachuri et al. Nat Med 2023 6 (Posted: Jun-02-2023 6AM)

In this study, we discovered 128 genome-wide significant associations (P?<?5?×?10-8) in a multi-ancestry meta-analysis of 95,768 men and developed a PSA polygenic score (PGSPSA) that explains 9.61% of constitutive PSA variation. Genetically adjusted PSA was more predictive of aggressive prostate cancer (odds ratio (OR)?=?3.44, P?=?6.2?×?10-14, area under the curve (AUC)?=?0.755) than unadjusted PSA (OR?=?3.31, P?=?1.1?×?10-12, AUC?=?0.738) in 106 cases and 23,667 controls. Compared to a prostate cancer PGS alone (AUC?=?0.712), including genetically adjusted PSA improved detection of aggressive disease (AUC?=?0.786, P?=?7.2?×?10-4). Our findings highlight the potential utility of incorporating PGS for personalized biomarkers in prostate cancer screening.

Clinical utility of polygenic risk scores: a critical 2023 appraisal
S Koch et al, J Comm Genetics, May 3, 2023 (Posted: May-03-2023 7AM)

We surveyed the current state of PRSs for various diseases, including breast cancer, diabetes, prostate cancer, coronary artery disease, and Parkinson disease, with an extra focus upon the potential improvement of clinical scores by their combination with PRSs. We observed that the diagnostic and prognostic performance of PRSs alone is consistently low, as expected. Moreover, combining a PRS with a clinical score at best led to moderate improvement of the power of either risk marker. Despite the large number of PRSs reported in the scientific literature, prospective studies of their clinical utility, particularly of the PRS-associated improvement of standard screening or therapeutic procedures, are still rare.

Predicting response to enzalutamide and abiraterone in metastatic prostate cancer using whole-omics machine learning.
Anouk C de Jong et al. Nature communications 2023 4 (1) 1968 (Posted: Apr-10-2023 7AM)

Response to androgen receptor signaling inhibitors (ARSI) varies widely in metastatic castration resistant prostate cancer (mCRPC). To improve treatment guidance, biomarkers are needed. We use whole-genomics (WGS; n?=?155) with matching whole-transcriptomics (WTS; n?=?113) from biopsies of ARSI-treated mCRPC patients for unbiased discovery of biomarkers and development of machine learning-based prediction models. Tumor mutational burden (q?<?0.001), structural variants (q?<?0.05), tandem duplications (q?<?0.05) and deletions (q?<?0.05) are enriched in poor responders, coupled with distinct transcriptomic expression profiles.

A Polygenic Risk Score for Prostate Cancer Risk Prediction.
Kerry R Schaffer et al. JAMA internal medicine 2023 3 (Posted: Mar-07-2023 6PM)

In this study, a prostate cancer polygenic risk score did not improve risk prediction of aggressive prostate cancer compared with a contemporary clinical risk predictor. Although the PRS269 improved model discrimination for all cancers, improvement was less than has been observed for other validated prostate cancer biomarker predictors such as the Prostate Health Index.

Bringing Prostate Cancer Polygenic Risk Scores to the Clinic.
Robert J Klein et al. JAMA internal medicine 2023 3 (Posted: Mar-07-2023 6PM)

The PRS as currently formulated will not enhance clinical decision-making. There is a need to demonstrate accuracy and utility—defined for the relevant clinical context—before rolling such scores out on a large scale. Given the experience with PSA testing, where a marker for any prostate cancer resulted in detection of many indolent cancers that did not need treatment, care will need to be taken that any PRS that makes it to the clinic can discriminate between indolent and potentially lethal prostate cancer.

Association between genetically proxied PCSK9 inhibition and prostate cancer risk: A Mendelian randomisation study.
Fang Si et al. PLoS medicine 2023 1 (1) e1003988 (Posted: Jan-04-2023 6AM)

Using genetic variants associated with LDL cholesterol, liver-derived gene expression, and plasma protein levels, the researchers applied drug target Mendelian randomization (MR) and colocalization to examine the association between lipid-lowering drug targets and the risk of overall, early-onset, and advanced prostate cancer. Additional MR analyses were conducted to explore putative mediators of drug effects. This study provided evidence of an association between genetically proxied PCSK9 inhibition and lower risk of overall and early-onset prostate cancer supported by both MR and colocalization approaches.

Genetic determinants for the racial disparities in the risk of prostate and testicular cancers
I Uzamere et al, Comm Med, November 2, 2022 (Posted: Nov-02-2022 6AM)

It has been observed that men of African ancestry have a higher incidence of prostate cancer and lower incidence of testicular cancer compared to men of European ancestry. However, little is known about underlying mechanisms accounting for these observations. The current study compares frequencies of all genetic alterations associated with risks of prostate cancer or testicular cancer between the two racial groups. Our findings suggest that differences in the frequencies of genetic alterations between the groups may help to explain the racial disparities in the risk of prostate and testicular cancers.

Polygenic risk of any, metastatic, and fatal prostate cancer in the Million Veteran Program.
Pagadala Meghana S et al. Journal of the National Cancer Institute 2022 10 (Posted: Oct-29-2022 10AM)

90,750 male participants were included. Median age at last follow-up was 69 years. PHS290 was associated with fatal prostate cancer in the full cohort and for each racial and ethnic group (p<0.001). Comparing men in the highest 20% of PHS290 to those in the lowest 20% (based on percentiles from an independent training cohort), the hazard ratio for fatal prostate cancer was 4.42 [95%CI: 3.91-5.02]. When accounting for guideline-recommended risk factors (family history, race and ethnicity), PHS290 remained a strong independent predictor of any, metastatic, and fatal prostate cancer.

Two Factors to ID Men at Highest Risk for Prostate Cancer Death
R Nelson, Medscape, September 2022 (Posted: Oct-03-2022 7AM)

A family history of prostate cancer has long been one of the few universally accepted risk factors for the disease. New findings now provide evidence that risk stratification based on family history and inherited polygenic risk can identify men at highest risk of dying from the disease before age 75. Men in the upper quartile of polygenic risk score or who had a family history of prostate or breast cancer accounted for close to 100% of prostate cancer deaths by age 75. This strategy can also identify men at low risk for prostate cancer, potentially sparing them from intensive prostate cancer screening.

The potential of polygenic risk scores for prostate cancer
Genomics education program blog, September 30, 2022 (Posted: Oct-02-2022 9AM)

In a recent paper, researchers used polygenic risk scores (also known as genetic risk scores) to triage patients with possible prostate cancer symptoms. The study explains that this method, deployable in local GP surgeries, is shown to be more reliable than current first-line tests for prostate cancer, and that it could remove the need for invasive tests for men presenting with prostate cancer symptoms and increase survivability for those testing positive.

How to improve the diagnosis of prostate cancer
B Plackett, Nature, September 2022 (Posted: Sep-18-2022 4AM)

There are two main schools of thought on how to replace PSA screening. The first is to look for better biomarkers in the blood or urine, and the second eschews testing samples altogether in favour of sophisticated imaging techniques. Whichever approach wins out, better screening with fewer false positives should mean fewer patients undergo needless biopsies.

Accumulation of copy number alterations and clinical progression across advanced prostate cancer
A Grist et al, Genome Medicine, September 5, 2022 (Posted: Sep-06-2022 7AM)

The burden of copy number alterations positively associated with radiologically evident distant metastases at diagnosis (P=0.00006) and showed a non-linear relationship with clinical outcome on univariable and multivariable analysis, characterized by a sharp increase in the relative risk of progression (P=0.003) and death (P=0.045) for each unit increase.

Genomic testing in localized prostate cancer can identify subsets of African-Americans with aggressive disease.
Awasthi Shivanshu et al. Journal of the National Cancer Institute 2022 9 (Posted: Sep-04-2022 9AM)

This is a prospective study of the Decipher genomic classifier for NCCN low- and intermediate–risk PCa. Study eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. We found that integration of genomic classifiers with clinically-based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease.

Developing machine learning algorithms for dynamic estimation of progression during active surveillance for prostate cancer.
Lee Changhee et al. NPJ digital medicine 2022 8 (1) 110 (Posted: Aug-08-2022 10AM)

Active Surveillance (AS) for prostate cancer is a management option that continually monitors early disease and considers intervention if progression occurs. A robust method to incorporate “live” updates of progression risk during follow-up has hitherto been lacking. To address this, we developed a deep learning-based individualised longitudinal survival model using Dynamic-DeepHit-Lite (DDHL) that learns data-driven distribution of time-to-event outcomes.

Insight into how patients with prostate cancer interpret and communicate genetic test results: implications for families.
Leader Amy E et al. Journal of community genetics 2022 7 (Posted: Jul-28-2022 6AM)

An appraisal of genetic testing for prostate cancer susceptibility
A Finch et al, NPJ Precision Oncology, June 22, 2022 (Posted: Jun-22-2022 10AM)

We review and summarize the literature describing germline pathogenic variants in genes associated with increased prostate cancer risk and aggressivity. Important questions include: what is our ability to screen for and prevent prostate cancer in a man with a germline pathogenic variant and how does knowledge of a germline pathogenic variant influence treatment of men with nonmetastatic disease, with hormone-resistant disease and with metastatic disease? The frequency of germline pathogenic variants in prostate cancer is well described, according to personal and family history of cancer and by stage and grade of disease. The role of these genes in aggressive prostate cancer is also discussed. It is timely to consider whether or not genetic testing should be offered to all men with prostate cancer. The goals of testing are to facilitate screening for early cancers in unaffected high-risk men and to prevent advanced disease in men with cancer.

Prostate cancer therapy personalization via multi-modal deep learning on randomized phase III clinical trials
A Esteva et al, NPJ Digital Medicine, June 8, 2022 (Posted: Jun-08-2022 6AM)

Here we demonstrate prostate cancer therapy personalization by predicting long-term, clinically relevant outcomes using a multimodal deep learning architecture and train models using clinical data and digital histopathology from prostate biopsies. We train and validate models using five phase III randomized trials conducted across hundreds of clinical centers. Histopathological data was available for 5654 of 7764 randomized patients (71%) with a median follow-up of 11.4?years.

Comparative Effectiveness of Immune Checkpoint Inhibitors vs Chemotherapy by Tumor Mutational Burden in Metastatic Castration-Resistant Prostate Cancer
RP Graf et al, JAMA Network Open, March 31, 2022 (Posted: Apr-01-2022 8AM)

What is the comparative effectiveness of single-agent immune checkpoint inhibitors (ICIs) vs taxane chemotherapy in populations of patients with metastatic castration-resistant prostate cancer (mCRPC) defined by levels of tumor mutational burden (TMB)? In this comparative effectiveness study of 741 patients with mCRPC, patients with TMB of 10 mutations per megabase (mt/Mb) or greater had significantly longer time to next treatment and overall survival with ICIs vs taxanes.

Care of men with cancer-predisposing BRCA variants
R Horton et al, BMJ, October 14,2021 (Posted: Oct-15-2021 6AM)

Men and women are equally likely to inherit or pass on a cancer-predisposing BRCA variant—family history of cancers needs to encompass both sides of the family- Men with cancer-predisposing BRCA variants have an increased risk of developing breast cancer and are advised to be breast aware- Men with cancer-predisposing BRCA2 variants have an increased risk of developing aggressive prostate cancer (men with cancer-predisposing BRCA1 variants may also have an increased risk); it is not yet known whether prostate specific antigen screening reduces mortality in men with cancer-predisposing BRCA variants.

Adoption of New Risk Stratification Technologies Within US Hospital Referral Regions and Association With Prostate Cancer Management
MS Leapman et al, JAMA Network Open, October 8, 2021 (Posted: Oct-11-2021 11AM)

n this cohort study of 65 530 commercially insured patients with prostate cancer, uptake of prostate MRI and genomic testing was associated with increased use of observation vs active treatment as initial management. Although prostate MRI, genomic testing, and observation increased overall, use was highly varied across hospital referral regions. The findings of this study suggest that adoption of technologies designed to improve decision-making may lead to perceivable reductions in overtreatment of prostate cancer.

How I faced my prostate cancer: a molecular biologist’s perspective
M Zuradelli, NPJ Precision Oncology, September 2021 (Posted: Sep-28-2021 6AM)

Hippocrates reminds us that “It is more important to know what sort of person has a disease than to know what sort of disease a person has”. This is still true today and reflects the emerging role of personalized medicine for patient-specific risk stratification and treatment programs. This report documents my personal experience as a patient with aggressive prostate cancer, who, as a scientist, had the privilege to access cutting-edge medical care and molecular profiling.

Uptake and acceptability of a mainstreaming model of hereditary cancer multigene panel testing among patients with ovarian, pancreatic, and prostate cancer
JG Hamilton et al, Genetics in Medicine, July 13, 2021 (Posted: Jul-14-2021 7AM)

Only 10% of eligible patients declined participation. Among 1,054 tested participants, 10% had pathogenic variants (PV), 16% had variants of uncertain significance (VUS), and 74% had no variant identified (NV). Participants reported high initial acceptability, including high satisfaction with their testing decision.

Yet Another Automated Gleason Grading System (YAAGGS) by weakly supervised deep learning
Y Munn et al, NPJ Digital Medicine, June 14, 2021 (Posted: Jun-14-2021 6AM)

The Gleason score contributes significantly in predicting prostate cancer outcomes and selecting the appropriate treatment option, which is affected by well-known inter-observer variations. We present a novel deep learning-based automated Gleason grading system that does not require extensive region-level manual annotations by experts and/or complex algorithms for the automatic generation of region-level annotations.

Urinary exosome microRNA signatures as a noninvasive prognostic biomarker for prostate cancer
S Shin et al, NPJ Digital Medicine, June 11, 2021 (Posted: Jun-12-2021 7AM)

we developed a “Prostate Cancer Metastasis Risk Scoring (PCa-MRS)” model. The PCa-MRS showed superior stratification power (AUC?=?0.925) to preoperative PSA or clinical Gleason score. Patients with high scores showed significantly poorer biochemical recurrence-free survival than those with low scores (P?=?6.53?×?10-10). Our results showed the potential of urinary exosomal miRNAs as noninvasive markers for predicting metastasis and prognosis in PCa patients.

Intrinsic Biologic Differences Unlikely to Be Driving Prostate Cancer Disparities
ASCO Daily News, June 8, 2021 (Posted: Jun-09-2021 7AM)

Although there were intrinsic biologic differences in gene alterations between men of European ancestry and men of African ancestry with advanced prostate cancer, a new study presented at the 2021 ASCO Annual Meeting showed that there were largely similar rates of alterations in genes with therapy implications. Outcomes could become more equivalent with equitable treatment delivery.

Concordance of DNA Repair Gene Mutations in Paired Primary Prostate Cancer Samples and Metastatic Tissue or Cell-Free DNA.
Schweizer Michael T et al. JAMA oncology 2021 6 (Posted: Jun-09-2021 7AM)

In this genetic association study, which included primary samples with paired cell-free circulating tumor DNA and/or metastatic tissue from 51 men from 3 cohorts, gene alterations in DNA repair genes detected in cell-free circulating tumor DNA or metastatic tissue were concordant with primary prostate cancer when clonal hematopoiesis was excluded

Validation of a 22-Gene Genomic Classifier in Patients With Recurrent Prostate Cancer: An Ancillary Study of the NRG/RTOG 9601 Randomized Clinical Trial.
Feng Felix Y et al. JAMA oncology 2021 Feb (Posted: Feb-12-2021 0PM)

In this ancillary study of 352 men randomized to placebo or hormone therapy in the NRG/RTOG 9601 clinical trial of salvage radiation, the Decipher genomic classifier was independently associated with the risk of metastasis, prostate cancer–specific mortality, and overall survival.

Deciphering Genomic Risk in Prostate Cancer-Ready for Prime Time.
McGuire Sean E et al. JAMA oncology 2021 Feb (Posted: Feb-12-2021 0PM)

Individualizing treatment recommendations for men with a diagnosis of prostate cancer remains a major challenge for clinicians. These challenges occupy many clinical scenarios ranging from newly diagnosed disease localized to the prostate to biochemically recurrent disease in the postprostatectomy setting, and in the distant metastatic settings. To date, clinical decision-making has largely rested on traditional clinicopathologic features.

Application of a novel machine learning framework for predicting non-metastatic prostate cancer-specific mortality in men using the Surveillance, Epidemiology, and End Results (SEER) database
C Lee et al, Lancet Digital Health ,February 3, 2021 (Posted: Feb-05-2021 7AM)

A novel machine learning-based approach produced a prognostic model, Survival Quilts, with discrimination for 10-year prostate cancer-specific mortality similar to the top-ranked prognostic models, using only standard clinicopathological variables. Additional data will likely improve model performance and accuracy for personalized prognostics.

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.
Conti David V et al. Nature genetics 2021 Jan (Posted: Jan-06-2021 8AM)

We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 for men of European ancestry to 3.74 for men of African ancestry.

Prostate Cancer Progression and the Epigenome
W Arap et al, NEJM, December 2, 2020 (Posted: Dec-03-2020 7AM)

Prostate cancer is driven by interrelated genetic and epigenetic alterations. Known genetic contributors to sporadic prostate cancer are the presence of germline genetic variants that increase the risk of prostate cancer and of somatic mutations, rearrangements, or irregular expression of noncoding RNAs that promote tumorigenesis and metastasis. Central to the pathophysiological mechanisms of prostate cancer is the androgen receptor.

Prognostic Genomic Biomarkers in Patients With Localized Prostate Cancer: Is Rising Utilization Justified by Evidence?
Lin Daniel W et al. JAMA oncology 2020 Nov (Posted: Nov-28-2020 0PM)

Although genomic tests are widely available and used, the lack of adoption into the standard-of-care pathways and guidelines is primarily attributed to the fact that none have been prospectively tested or shown to improve long-term outcomes, such as quality of life, need for treatment, or survival.

Regional Adoption of Commercial Gene Expression Testing for Prostate Cancer.
Leapman Michael S et al. JAMA oncology 2020 Nov (Posted: Nov-28-2020 0PM)

This cohort study of commercially insured patients with prostate cancer found that although adoption of genomic testing was highly variable, there were distinct regional trajectories of adoption. Rapid regional adoption of genomic testing was associated with higher contextual measures of income, education, and prostate cancer services.

Accelerating precision medicine in metastatic prostate cancer
J Mateo, Nature Cancer, November 17, 2020 (Posted: Nov-20-2020 9AM)

Disease classification based on genomic sequencing is a promising approach for identifying patients whose tumors exhibit actionable targets and for making more informed treatment decisions. Here we discuss how precision oncology can be accelerated to inform broader genomically driven clinical decisions for men with advanced prostate cancer.

Detection of Pathogenic Variants With Germline Genetic Testing Using Deep Learning vs Standard Methods in Patients With Prostate Cancer and Melanoma.
AlDubayan Saud H et al. JAMA 2020 Nov (19) 1957-1969 (Posted: Nov-18-2020 8AM)

In this analysis of 2 cohorts of patients with prostate cancer and melanoma, more pathogenic variants in 118 cancer-predisposition genes were found using deep learning technology compared with a standard genetic analysis method (198 vs 182 variants identified in 1072 patients with prostate cancer; 93 vs 74 variants identified in 1295 patients with melanoma). The number of cancer-predisposing pathogenic variants depends partially on the automated approach used.

Association of Clonal Hematopoiesis in DNA Repair Genes With Prostate Cancer Plasma Cell-free DNA Testing Interference
K Jensen et al, JAMA Oncology, November 5, 2020 (Posted: Nov-06-2020 7AM)

In this case series study of 69 men with advanced prostate cancer, 7 (10%) had CHIP variants in genes used for US Food and Drug Administration-approved indications of PARPi treatment, most frequently in ATM. Men with prostate cancer are at high risk of being misdiagnosed as being eligible for PARPi therapy using current cfDNA tests.

Activity of Platinum-Based Chemotherapy in Patients With Advanced Prostate Cancer With and Without DNA Repair Gene Aberrations
S Shmid et al, JAMA Network Open, October 28, 2020 (Posted: Oct-29-2020 11AM)

In a case series of 508 patients, platinum-based therapy was associated with antitumor activity, especially among patients with known DNA repair gene aberrations. In patients with DNA repair gene aberrations, nearly half had a decrease in prostate-specific antigen levels of at least 50% and experienced soft tissue responses.

Racial Differences in Genomic Profiling of Prostate Cancer.
Mahal Brandon A et al. The New England journal of medicine 2020 Sep (11) 1083-1085 (Posted: Sep-10-2020 7AM)

Clinically significant alterations may occur at different frequencies across races. Notably, Black men with metastatic prostate cancer were more likely than either White or Asian men to have tumor mutations in AR, along with mutations in DNA-repair genes and actionable genetic mutations. This finding could have implications for prognosis, response to therapy.

Germline sequencing DNA repair genes in 5,545 men with aggressive and non-aggressive prostate cancer.
Darst Burcu F et al. Journal of the National Cancer Institute 2020 Aug (Posted: Sep-01-2020 8AM)

Participants were 5,545 European-ancestry men, including 2,775 non-aggressive and 2,770 aggressive PCa cases, which included 467 metastatic cases (16.9%). Risk conveyed by DNA repair genes is largely driven by rare P/LP/D alleles within BRCA2, PALB2, and ATM. The study supports the use of these genes in both screening and disease management considerations.

Tailoring Intensity of Active Surveillance for Low-Risk Prostate Cancer Based on Individualized Prediction of Risk Stability.
Cooperberg Matthew R et al. JAMA oncology 2020 Aug e203187 (Posted: Aug-28-2020 8AM)

In this multicenter cohort study including 850 men and an independent validation cohort of 533 men, 7 clinical parameters available for nearly all men on surveillance predicted non-reclassification at 4 years, with high negative predictive value. These findings suggest that active surveillance regimens can be tailored to individual risk.

Clinical deployment of AI for prostate cancer diagnosis
A Janowscyk, Lancet Digital Health, August 1, 2020 (Posted: Jul-31-2020 7AM)

Algorithms capable of elevating general pathologists' performance to that of highly trained specialists, in particular drawing attention to cases that might warrant specialist review, have the potential to substantially raise the standard of care.

The DNA methylation landscape of advanced prostate cancer
SG Zhao et al, Nature Genetics, July 13, 2020 (Posted: Jul-14-2020 9AM)

Through whole-genome bisulfite sequencing paired with deep whole-genome and transcriptome sequencing of 100 castration-resistant prostate metastases, we discovered alterations affecting driver genes. 22% of tumors exhibited a novel epigenomic subtype associated with hypermethylation and somatic mutations in TET2, DNMT3B, IDH1 and BRAF.

Combining liquid biopsies and PET-CT for early cancer detection
SQ Wong et al, Nature Medicine, June 29, 2020 (Posted: Jul-01-2020 8AM)

The use of screening in some cancers (such as PSA testing in prostate cancer and mammography in breast cancer) may have minimal impact on mortality, and over-diagnosis may lead to more harm than good. This uncertainty also exists for liquid-biopsy approaches and raises the need to demonstrate the clinical value of the blood test before it can be widely adopted.

The effect of sample size on polygenic hazard models for prostate cancer.
Karunamuni Roshan A et al. European journal of human genetics : EJHG 2020 Jun (Posted: Jun-11-2020 8AM)

We estimate that a study population of 20 thousand men is required to develop Discovery-SNP polygenic hazard score models while 10 thousand men should be sufficient for Established-SNP models.

Diagnosing hereditary cancer predisposition in men with prostate cancer.
Pritzlaff Mary et al. Genetics in medicine : official journal of the American College of Medical Genetics 2020 May (Posted: May-23-2020 9AM)

A yield of 9.4–12.1% was observed among men with no prior genetic testing. In this group, the positive rate of BRCA1 and BRCA2 was 4.6%; the positive rate for the mismatch repair genes was 2.8%. Increasing Gleason score, personal history, and family history were predictors of positive results.

A genomic and epigenomic atlas of prostate cancer in Asian populations
J Li et al, Nature, March 27, 2020 (Posted: Mar-28-2020 8AM)

Risk of Prostate Cancer Associated With Familial and Hereditary Cancer Syndromes.
Beebe-Dimmer Jennifer L et al. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2020 Mar JCO1902808 (Posted: Mar-27-2020 8AM)

In this large, population-based, family database, the risk of prostate cancer varied by family history and was most strongly associated with early onset disease. These results are critically valuable in understanding and targeting high-risk populations that would benefit from genetic screening and enhanced surveillance.

Risk stratification of prostate cancer through quantitative assessment of PTEN loss (qPTEN)
JNCI, March 2020 (Posted: Mar-06-2020 8AM)

Compared to previous qualitative approaches, qPTEN improves risk stratification of post-radical prostatectomy patients and may be considered as a complementary tool to guide disease management after surgery.

HSD3B1 Genotype and Clinical Outcomes in Metastatic Castration-Sensitive Prostate Cancer
JAMA Oncology, February 13, 2020 (Posted: Feb-14-2020 8AM)

In this study including 475 genotyped white men with metastatic prostate cancer, the adrenal-permissive genotype (ie, inheritance of =1 HSD3B1[1245C] allele) was associated with significantly shorter time to castration-resistant disease and significantly lower overall survival.

Single-Nucleotide Polymorphism–Based Genetic Risk Score and Patient Age at Prostate Cancer Diagnosis
R Na et al, JAMA Network Open, December 27, 2019 (Posted: Dec-27-2019 5PM)

In a cohort study of 3225 men, family history alone identified 14% at high risk of prostate cancer. Combining family history and genetic risk score can better stratify inherited risk to develop personalized prostate cancer screening strategies.

Polygenic risk-tailored screening for prostate cancer: A benefit-harm and cost-effectiveness modelling study.
Callender Tom et al. PLoS medicine 2019 Dec (12) e1002998 (Posted: Dec-21-2019 4PM)

Based on the results of this modelling study, offering screening to men at higher risk could potentially reduce overdiagnosis and improve the benefit–harm tradeoff and the cost-effectiveness of a prostate cancer screening program. The optimal threshold will depend on societal judgements of the appropriate balance of benefits–harms and cost-effectiveness.

Appraising causal relationships of dietary, nutritional and physical-activity exposures with overall and aggressive prostate cancer: two-sample Mendelian-randomization study based on 79 148 prostate-cancer cases and 61 106 controls
N Kazmi et al, Int J Epi, December 5, 2019 (Posted: Dec-09-2019 8AM)

The results for physical activity, serum iron, BMI, monounsaturated fat and height are compatible with causality for prostate cancer. The results suggest that interventions aimed at increasing physical activity may reduce prostate-cancer risk, although interventions to change other risk factors may have negative consequences on other diseases.

The BRCA gene is about so much more than breast cancer risk
A Goldman, Well and Good, October 27, 2019 (Posted: Nov-01-2019 10AM)

BRCA literally stands for “BReast CAncer gene,” so it makes sense that we think of a person’s breast cancer risk when we talk about BRCA gene mutations. The thing is, though, that harmful BRCA mutations can impact a person’s risk of developing several other cancers—including pancreatic cancer and prostate cancer—and they’re just less talked about.

Ethnic disparities among men with prostate cancer undergoing germline testing.
Kwon Daniel Hyuck-Min et al. Urologic oncology 2019 Oct (Posted: Oct-23-2019 9AM)

We retrospectively examined germline genetic and clinical data of men reporting a diagnosis of prostate cancer referred to Color Genomics by a healthcare provider for testing of 30 genes associated with hereditary cancer risk. Variants were classified as pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign, or benign.

New Precision Medicine Treatment Could Benefit Many Men with Treatment-Resistant Metastatic Prostate Cancer
by Andrea K. Miyahira, Prostate Cancer Foundation, October 1, 2019 (Posted: Oct-11-2019 8AM)

A new study reported positive results from a Phase 3 clinical trial testing the PARP-inhibitor olaparib (Lynparza) in patients with metastatic castration-resistant prostate cancer (mCRPC) who have alterations in certain DNA damage repair (DDR) genes; a result which will likely lead to a new FDA-approval. Roughly 20-30% of mCRPC patients harbor these DDR gene mutations in their tumors and thus may benefit from PARP-inhibition.

Genome-wide germline correlates of the epigenetic landscape of prostate cancer
KE Houlahan et al, Nature Medicine, October 7, 2019 (Posted: Oct-08-2019 8AM)

The study quantified the influence of germline polymorphisms on the somatic epigenome of 589 localized prostate tumors. Predisposition risk loci influence a tumor’s epigenome, uncovering a mechanism for cancer susceptibility. We identified and validated 1,178 loci associated with altered methylation in tumoral but not nonmalignant tissue.

Cancer: more genetic BRCA testing for men
M Marabelli et al, Nature, September 17, 2019 (Posted: Sep-20-2019 8AM)

The most recent guidelines from the US National Comprehensive Cancer Network recommend BRCA testing for men with metastatic or advanced prostate cancer and a family history of the disease. Broader genetic data on males will improve patient diagnosis and management, and increase treatment and clinical-trial options.

Men, It’s Time for Real Talk about Prostate Health
DM Parker, CDC Blog, August 2019 Brand (Posted: Sep-11-2019 0PM)

Research by the United States Preventive Services Task Force (USPSTF), a group of health care experts, shows that men aged 55 to 69 benefit most from screening. Specifically, the USPSTF lists African American men and men with a family history of prostate cancer as higher risk groups.

More Treatment Options Emerging for Some Men with Metastatic Prostate Cancer
NCI, 2019 Brand (Posted: Sep-03-2019 10AM)

Prospective Comprehensive Genomic Profiling of Primary and Metastatic Prostate Tumors.
Chung Jon H et al. JCO precision oncology 2019 3 (Posted: Jun-26-2019 9AM)

Germline pathogenic variants in 7,636 Japanese patients with prostate cancer and 12,366 controls.
Momozawa Yukihide et al. Journal of the National Cancer Institute 2019 Jun (Posted: Jun-24-2019 8AM)

This largest sequencing study of prostate cancer heredity provides additional evidence to the latest consensus among clinicians for developing genetic testing guidelines for prostate cancer

Development and validation of a deep learning algorithm for improving Gleason scoring of prostate cancer
K Nagpal et al, NPJ Digital Medicine, June 7, 2019 (Posted: Jun-07-2019 1PM)

NCCN Guidelines Updates: Management of Prostate Cancer.
Mohler James L et al. Journal of the National Comprehensive Cancer Network : JNCCN 2019 May 17(5.5) 583-586 (Posted: May-29-2019 9AM)

Racial Inequality in Prostate Cancer Outcomes—Socioeconomics, Not Biology
CJ Paller et al, JAMA Oncology, May 23, 2019 (Posted: May-27-2019 5PM)

A new era: artificial intelligence and machine learning in prostate cancer.
Goldenberg S Larry et al. Nature reviews. Urology 2019 May (Posted: May-18-2019 0PM)

Genomic correlates of clinical outcome in advanced prostate cancer.
Abida Wassim et al. Proceedings of the National Academy of Sciences of the United States of America 2019 May (Posted: May-08-2019 8AM)

A Rich Array of Prostate Cancer Molecular Biomarkers: Opportunities and Challenges.
Kohaar Indu et al. International journal of molecular sciences 2019 Apr 20(8) (Posted: May-01-2019 9AM)

A 17-Gene Genomic Prostate Score as a Predictor of Adverse Pathology for Men on Active Surveillance.
Kornberg Zachary et al. The Journal of urology 2019 Apr 101097JU0000000000000290 (Posted: May-01-2019 9AM)

Multicenter optimization and validation of a 2-gene mRNA urine test for detection of clinically significant prostate cancer prior to initial prostate biopsy.
Haese Alexander et al. The Journal of urology 2019 Apr 101097JU0000000000000293 (Posted: May-01-2019 9AM)

The Clinical Utility of the Genomic Prostate Score in Men with Very Low to Intermediate Risk Prostate Cancer.
Gaffney Christopher et al. The Journal of urology 2019 Feb 101097JU0000000000000170 (Posted: Apr-03-2019 9AM)

The association of BRCA1 and BRCA2 mutations with prostate cancer risk, frequency, and mortality: A meta-analysis.
Oh Mok et al. The Prostate 2019 Mar (Posted: Mar-24-2019 9AM)

Defining Prostate Cancer at Favorable Intermediate Risk: the Potential Utility Of Magnetic Resonance Imaging And Genomic Tests.
Falagario Ugo G et al. The Journal of urology 2019 Feb (Posted: Feb-12-2019 10AM)

Bringing prostate cancer germline genetics into clinical practice.
Das Sanjay et al. The Journal of urology 2019 Feb (Posted: Feb-12-2019 10AM)

Prevalence of Germline Variants in Prostate Cancer and Implications for Current Genetic Testing Guidelines
P. Nicolisi et al, JAMA Oncology, February 8, 2019 (Posted: Feb-08-2019 9AM)

epiCaPture: A Urine DNA Methylation Test for Early Detection of Aggressive Prostate Cancer
E. O'Reilly et al, JCO Precision Oncology, January 2019 (Posted: Jan-22-2019 11AM)

Cost Effectiveness of the Oncotype DX Genomic Prostate Score for Guiding Treatment Decisions in Patients With Early Stage Prostate Cancer.
Chang Eric M et al. Urology 2018 Dec (Posted: Jan-02-2019 4PM)

Germline genetic testing for inherited prostate cancer in practice: Implications for genetic testing, precision therapy, and cascade testing.
Giri Veda N et al. The Prostate 2018 Nov (Posted: Nov-28-2018 8AM)

Germline Genetics of Prostate Cancer: Time to Incorporate Genetics into Early Detection Tools.
Fantus Richard J et al. Clinical chemistry 2018 Nov (Posted: Nov-28-2018 8AM)

Germline Mutations in ATM and BRCA1/2 Are Associated with Grade Reclassification in Men on Active Surveillance for Prostate Cancer.
Carter H Ballentine et al. European urology 2018 Oct (Posted: Oct-17-2018 8AM)

Providing clinicians and patients with important information to help guide decisions about prostate cancer screening.
USPSTF, October 8, 2018 (Posted: Oct-09-2018 2PM)

Genetic Counseling Recommended for Advanced Prostate Cancer
M Dalton, Prostate Cancer Advisor, September 17, 2018 (Posted: Sep-18-2018 8AM)

Impact of family history of cancer on risk and mortality of second cancers in patients with prostate cancer.
Chattopadhyay Subhayan et al. Prostate cancer and prostatic diseases 2018 Sep (Posted: Sep-12-2018 9AM)

Genomic Prostate Score, PI-RADSv2, and Progression in Men with Prostate Cancer on Active Surveillance.
Kornberg Zachary et al. The Journal of urology 2018 Sep (Posted: Sep-05-2018 9AM)

Liquid biopsy approach in the management of prostate cancer.
Riaz Irbaz Bin et al. Translational research : the journal of laboratory and clinical medicine 2018 May (Posted: Aug-06-2018 8AM)

Genomic biomarkers in prostate cancer.
Kornberg Zachary et al. Translational andrology and urology 2018 Jun (3) 459-471 (Posted: Aug-06-2018 8AM)

NIH and Prostate Cancer Foundation launch large study on aggressive prostate cancer in African-American men
NCI, July 2018 Brand (Posted: Jul-30-2018 8AM)

Prostate Cancer Diagnostics Using a Combination of the Stockholm3 Blood Test and Multiparametric Magnetic Resonance Imaging.
Grönberg Henrik et al. European urology 2018 Jul (Posted: Jul-18-2018 9AM)

Differences in inherited risk among relatives of hereditary prostate cancer patients using genetic risk score.
Helfand Brian T et al. The Prostate 2018 Jun (Posted: Jun-27-2018 10AM)

Prostate cancer spit test is trialled
BBC News, June 11, 2018 (Posted: Jun-11-2018 7PM)

Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci
FR Shcumacher et al, Nature Genetics, June 11, 2018 (Posted: Jun-11-2018 1PM)

Annual Report to the Nation: overall cancer mortality continues to decline, prostate cancer mortality has stabilized
NCI, Press Release, May 22, 2018 Brand (Posted: May-22-2018 10AM)

Prostate-Specific Antigen–Based Screening for Prostate Cancer- Evidence Report and Systematic Review for the US Preventive Services Task Force
JJ Fenton t al, JAMA, May 2018 (Posted: May-14-2018 8AM)

Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement
JAMA, May 8, 2018 (Posted: May-09-2018 8AM)

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Disclaimer: Articles listed in Hot Topics of the Day are selected by the CDC Office of Genomics and Precision Public Health to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.
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