Delivering clarity
for a better tomorrow
for a better tomorrow
PROSTATENOW is a comprehensive germline panel offered by GoPath Diagnostics. The test content, result interpretation, and corresponding clinical actions are developed and supported by a national leader in urology.
PROSTATENOW provides valuable insights in determining
a patient’s risk and potential treatment plans
Assess risk of developing prostate cancer
Family history, rare pathogenic mutations (RPMs) and genetic risk score (GRS) are three measures of inherited risk, allowing for a comprehensive analysis of risk of developing prostate cancer. Men with an increased risk of prostate cancer may consider earlier and more frequent prostate cancer screening and may evaluate their chances of passing on this risk to their offspring.
Assess prognosis for localized prostate cancer
ProstateNow supplements traditional clinical variables like Gleason score and PSA levels in determining risk for disease progression and can inform decisions on prostate cancer treatment, such as pursuing active surveillance versus definitive treatment with surgery or radiation.
Predict therapeutic responses for advanced prostate cancer
ProstateNow screens for pathogenic mutations in DNA repair genes and identifies patients who may respond better to targeted treatments, such as PARP inhibitors and platinum-based chemotherapies.
LEVERAGING DATA TO IMPROVE RESULTS
Reliability of RPMs and GRS in Multiple Races:
- PROSTATENOW includes all known prostate cancer susceptibility genes
- Includes >200 prostate cancer risk-associated SNPs for calculating GRS in multiple races
The Largest Mutation Database:
- Following the guidelines of the American College of Medical Genetics (ACMG), we have the largest germline mutation database with data gathered from more than 300,000 men with or without prostate cancer.
RARE PATHOGENIC MUTATIONS (RPMs)
Genetic Risk Score (GRS)
Family History
- RPMs are detected in 23 genes known to be associated with prostate cancer risk and disease aggression.
- Those with RPMs have an approximately 2-to 8-fold increased risk of developing prostate cancer in their lifetime, depending on the affected gene.
- Some RPMs are associated with more aggressive disease and a higher risk of metastatic progression10, and screening for these variants supplements clinical variables in risk stratification of patients with localized prostate cancer.
- RPMs in genes involved in homologous recombination are associated with sensitivity to targeted therapies, such as PARP inhibitors and platinum-based chemotherapies. Among patients with advanced prostate cancer, screening for these variants provides valuable insights into treatment planning.
- The GRS is a calculation of a man’s relative risk for prostate cancer, with GRS of 1.0 being the average risk within the general population. This score is used to calculate a man’s remaining lifetime risk for prostate cancer, providing clinicians with an absolute risk calculation that is easily interpreted.
- Men with high GRS are more likely to develop prostate cancer and this information may inform decisions regarding screening.
- GRS is also associated with the number of prostate tumors. Patients with high GRS are more likely to harbor multifocal tumors,11 which are in turn associated with development of higher-grade tumors on active surveillance.
- A medical family history is gathered by a genetic counselor and is included to complete the comprehensive analysis of a patient’s inherited risk for prostate cancer.
A clear, easy-to-read report with clinically actionable results
A clear, easy-to-read report with clinically actionable results
- Rare pathogenic mutations
2.Genetic risk score
3.Family history
23 GENE PANEL
HSD3B1
PROSTATENOW is the only germline panel that includes genotyping of HSD3B1 1245C, an important biomarker in predicting response to androgen deprivation therapy (ADT). This common risk allele in HSD3B1 is associated with increased resistance to ADT and patients carrying this variant display a shorter time to development of castrate-resistant prostate cancer.
Who Should Be Tested?
Most prostate cancer patients and their families can benefit from germline testing. NCCN guidelines recommend germline testing for the following groups:
For prostate cancer patients
High-risk family history includes:
For unaffected men
- Metastatic, regional (node-positive), or high-risk or very-high-risk localized prostate cancer;
- High-risk family history, intraductal histologies, or other conditions, regardless of risk.
High-risk family history includes:
- ≥1 first-degree relative with prostate cancer at age ≤60 years;
- ≥1 first-, second-, or third-degree relative with breast cancer, colorectal cancer, or endometrial cancer before age 50; male breast cancer, ovarian cancer, exocrine pancreatic cancer at any age; or metastatic, regional, high- or very high-risk prostate cancer at any age;
- ≥2 first-, second-, or third-degree relatives with breast cancer or prostate cancer at any age;
- ≥3 first- or second-degree relatives with Lynch syndrome-related cancers;
- A known family history of a high-risk germline mutation;
- Ashkenazi Jewish ancestry.
For unaffected men
- Men with a family history of hereditary cancer syndromes (HBOC, Lynch, or others);
- Men with a family history of high-risk germline mutations.
Genetic Counseling
GoPath is proud to offer in-house genetic counseling services to guide patients and providers through the genetic testing process. Our experienced genetic counselors are available to meet both before and after testing, providing patients with the information, support, and resources needed to understand the risks and benefits of genetic testing and the interpretation of test results.
The Genetics of Prostate Cancer
Prostate cancer is the most common malignancy in men, with an annual incidence of more than 250,000 cases and over 30,000 deaths in the US per year, accounting for 27% of all male cancers and 11% of male cancer-related deaths. Although not traditionally thought of as a hereditary disease, accumulating evidence from genetic studies has demonstrated a consistent impact of heritable gene variants and family history on the development of prostate cancer. In fact, inherited factors may account for as much as 57% of the risk for developing prostate cancer.
Current data supports the use of three independent tools for measuring inherited risk:
Family History
Family history is a common but indirect measurement of inherited risk. Those with a family history of prostate cancer have a 1.5-to-2.5-fold increased risk of developing prostate cancer, and the relative risk increases with:
i. Increased number of affected family members,
ii. Closer relation to those affected, and
iii. Decreased age at diagnosis of affected family members.
i. Increased number of affected family members,
ii. Closer relation to those affected, and
iii. Decreased age at diagnosis of affected family members.
Rare Pathogenic Mutations (RPMs)
ProstateNow detects germline mutations in 23 genes associated with increased risk of prostate cancer. Certain mutations (such as those in DNA repair genes) are also prognostic indicators, associated with more aggressive disease, and some confer sensitivity to targeted therapies, providing valuable insights in treatment planning.
Genetic Risk Score (GRS)
GRS is a polygenic risk score that analyzes >200 prostate cancer risk-associated single nucleotide polymorphisms (SNPs) to predict inherited risk for prostate cancer. Utilizing GRS allows for the identification of high-risk patients who may otherwise be missed by an analysis of family history and RPMs alone.
Men at High Risk
for Prostate Cancer
for Prostate Cancer
Schematic Venn diagram of men in the general population at high-risk for prostate cancer, identified by family history (FH), rare pathogenic mutations (RPMs), and genetic risk score (GRS). The size of the circle indicates the proportion of high-risk men in the general population identified by each measure of inherited risk. The color indicates the degree of risk, with darker blue denoting a higher risk.
Because family history, RPMs, and GRS each measure risk independently, a comprehensive inherited risk assessment should include all three tools.
Because family history, RPMs, and GRS each measure risk independently, a comprehensive inherited risk assessment should include all three tools.
Adapted from: Xu J, Labbate CV, Isaacs WB, Helfand BT. Inherited risk assessment of prostate cancer: it takes three to do it right. Prostate Cancer Prostatic Dis. 2020;23(1):59-61. doi:10.1038/s41391-019-0165-y
This COMPREHENSIVE GERMLINE PANEL analyzes 88 clinically-relevant genes that are associated with genetic disorders, including most hereditary cancers.
BRCANOW is a next-generation sequencing panel for people with a personal or family history of breast or ovarian cancer.
LYNCHNOW is a cost-effective, screening tool that rapidly detects mutations that cause Lynch syndrome.
DIABETESNOW is a unique genetic panel that tests for 16 genes associated with MODY, syndromic, neonatal, and mitochondrial causes of monogenic diabetes. It also includes pan-ancestry type 1 and 2 diabetes polygenic risk scores (PRS) and the probability of type 1 diabetes (GenProb-T1D).
We're here to guide you through the process.
Part of PROSTATENOW includes genetic counseling to walk you through our process and test results, along with any lifestyle or treatment alternatives depending on your results.
References:
1.Rawla P. Epidemiology of Prostate Cancer. World J Oncol. 2019;10(2):63–89. doi:10.14740/wjon.1191 2.American Cancer Society. Cancer Facts & Figures 2022. Atlanta: American Cancer Society; 2022. 3.Pilié PG, et al. Germline genetic variants in men with prostate cancer
and one or more additional cancers. Cancer. 2017;123(20):3925-3932. doi:10.1002/cncr.30817 4.Mucci LA, Hjelmborg JB, Harris JR, et al. Familial risk and heritability of cancer among twins in Nordic countries. JAMA. 2016;315(1):68-76. doi: 10.1001/jama.2015.17703 5.Bhanji W, Isaacs
WB, Xu J, et al. Prostate Cancer Predisposition. Urol Clin North Am. 2021;48(3):283-296. doi:10.1016/j.ucl.2021.03.001 6.Xu J, Labbate CV, Isaacs WB, Helfand BT. Inherited risk assessment of prostate cancer: it takes three to do it right. Prostate Cancer Prostatic Dis. 2020;23(1):59-61.
doi:10.1038/s41391-019-0165-y 7.Ewing CM, Ray AM, Lange EM, et al. Germline Mutations in HOXB13 and Prostate-Cancer Risk. N Engl J Med. 2012;366(2):141–149. doi: 10.1056/NEJMoa1110000 8.Leongamornlert D, Saunders E, Dadaev T, et al. Frequent germline deleterious mutations
in DNA repair genes in familial prostate cancer cases are associated with advanced disease. Br J Cancer. 2014;110(6),1663–1672. doi:10.1038/bjc.2014.30 9.Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J
Med. 2016;375(5):443-453. doi:10.1056/NEJMoa1603144 10. Shi Z, Lu L, Resurreccion WK, et al. Association of germline rare pathogenic mutations in guideline-recommended genes with prostate cancer progression: A meta-analysis. Prostate. 2022;82(1):107-119. doi:10.1002/pros.24252
11.Xu J, Isaacs WB, Mamawala M, et al. Association of prostate cancer polygenic risk score with number and laterality of tumor cores in active surveillance patients. Prostate. 2021;81(10):703-709. doi:10.1002/pros.24140 12.Hettel, D., Sharifi, N. HSD3B1 status as a biomarker of androgen
deprivation resistance and implications for prostate cancer. Nat Rev Urol . 2018;15(3):191-196. doi:10.1038/nrurol.2017.201 13.Chang KH, Li R, Kuri B, et al. A Gain-of-Function Mutation in DHT Synthesis in Castration-Resistant Prostate Cancer. Cell. 2013;154(5):1074-1084. doi:10.1016/j.-
cell.2013.07.029 14.Hearn JWD, AbuAli G, Reichard CA, et al. HSD3B1 and resistance to androgen-deprivation therapy in prostate cancer: a retrospective, multicohort study. Lancet Oncol. 2016;17(10):1435-1444. doi:10.1016/S1470-2045(16)30227-3 15.Chandrasekar T, Yang JC, Gao AC,
et al. Mechanisms of resistance in castration-resistant prostate cancer (CRPC). Transl Androl Urol. 2015;4(3):365-380. doi:10.3978/j.issn.2223-4683.2015.05.02 16.Hearn JWD, Sweeney CJ, Almassi N, et al. HSD3B1 Genotype and Clinical Outcomes in Metastatic Castration-Sensitive
Prostate Cancer. JAMA Oncol. 2020;6(4):e196496. doi:10.1001/jamaoncol.2019.6496
1.Rawla P. Epidemiology of Prostate Cancer. World J Oncol. 2019;10(2):63–89. doi:10.14740/wjon.1191 2.American Cancer Society. Cancer Facts & Figures 2022. Atlanta: American Cancer Society; 2022. 3.Pilié PG, et al. Germline genetic variants in men with prostate cancer
and one or more additional cancers. Cancer. 2017;123(20):3925-3932. doi:10.1002/cncr.30817 4.Mucci LA, Hjelmborg JB, Harris JR, et al. Familial risk and heritability of cancer among twins in Nordic countries. JAMA. 2016;315(1):68-76. doi: 10.1001/jama.2015.17703 5.Bhanji W, Isaacs
WB, Xu J, et al. Prostate Cancer Predisposition. Urol Clin North Am. 2021;48(3):283-296. doi:10.1016/j.ucl.2021.03.001 6.Xu J, Labbate CV, Isaacs WB, Helfand BT. Inherited risk assessment of prostate cancer: it takes three to do it right. Prostate Cancer Prostatic Dis. 2020;23(1):59-61.
doi:10.1038/s41391-019-0165-y 7.Ewing CM, Ray AM, Lange EM, et al. Germline Mutations in HOXB13 and Prostate-Cancer Risk. N Engl J Med. 2012;366(2):141–149. doi: 10.1056/NEJMoa1110000 8.Leongamornlert D, Saunders E, Dadaev T, et al. Frequent germline deleterious mutations
in DNA repair genes in familial prostate cancer cases are associated with advanced disease. Br J Cancer. 2014;110(6),1663–1672. doi:10.1038/bjc.2014.30 9.Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J
Med. 2016;375(5):443-453. doi:10.1056/NEJMoa1603144 10. Shi Z, Lu L, Resurreccion WK, et al. Association of germline rare pathogenic mutations in guideline-recommended genes with prostate cancer progression: A meta-analysis. Prostate. 2022;82(1):107-119. doi:10.1002/pros.24252
11.Xu J, Isaacs WB, Mamawala M, et al. Association of prostate cancer polygenic risk score with number and laterality of tumor cores in active surveillance patients. Prostate. 2021;81(10):703-709. doi:10.1002/pros.24140 12.Hettel, D., Sharifi, N. HSD3B1 status as a biomarker of androgen
deprivation resistance and implications for prostate cancer. Nat Rev Urol . 2018;15(3):191-196. doi:10.1038/nrurol.2017.201 13.Chang KH, Li R, Kuri B, et al. A Gain-of-Function Mutation in DHT Synthesis in Castration-Resistant Prostate Cancer. Cell. 2013;154(5):1074-1084. doi:10.1016/j.-
cell.2013.07.029 14.Hearn JWD, AbuAli G, Reichard CA, et al. HSD3B1 and resistance to androgen-deprivation therapy in prostate cancer: a retrospective, multicohort study. Lancet Oncol. 2016;17(10):1435-1444. doi:10.1016/S1470-2045(16)30227-3 15.Chandrasekar T, Yang JC, Gao AC,
et al. Mechanisms of resistance in castration-resistant prostate cancer (CRPC). Transl Androl Urol. 2015;4(3):365-380. doi:10.3978/j.issn.2223-4683.2015.05.02 16.Hearn JWD, Sweeney CJ, Almassi N, et al. HSD3B1 Genotype and Clinical Outcomes in Metastatic Castration-Sensitive
Prostate Cancer. JAMA Oncol. 2020;6(4):e196496. doi:10.1001/jamaoncol.2019.6496