Come to ASPI's July webinar: 'Why All Men Diagnosed with Prostate Cancer Should Undergo Germline Genetic Testing'
Happy July 4th: 'Democratization' of germline testing: universal testing--please anser the survey
By Howard Wolinsky
Have you you undergone germline testing—analysis of the genes you inherit from your parents that you can pass on to your children?
Odds are you haven’t. Active Surveillance Patients International (ASPI) this month is holding a webinar on why you should.
ASPI has assembled panel of genetics experts to address the topic. The session will run from noon to 1:30 pm Eastern time on Saturday, July 26.
Please register for the meeting here.
There will be a Question-and-Answer session following remarks by the panel. Please send questions in advance to: contactus@aspatients.org
What’s the deal with germline testing?
Germline testing is considered standard of care for breast, ovarian, colorectal, and pancreatic cancers.
But prostate cancers, especially not lower-risk cases? Not really, though data on certain mutations can impact the course of treatment and flush out genes that have significance for your closest relations.
Leaders in the field in January called for universal testing inan article in JCO Oncology Practice entitled “Implementation of Universal Germline Genetic Testing Into Standard of Care for Patients With Prostate Cancer: The Time Is Now.”
Researchers, led by Dr. Neal Shore, wrote: “Universal germline genetic testing (GGT) allows all patients with cancer, regardless of stage, pathology, or family history, to undergo GGT. The importance of universal GGT has been highlighted by several studies which have demonstrated that guideline-directed GGT may miss up to 55% of patients with actionable pathogenic germline variants (PGVs) transition from guideline-directed to universal GGT has been recommended for breast, ovarian, and pancreatic cancers.”
They stressed: “[H}owever, universal testing has not yet been recommended for prostate cancer.”
Shore et al. wrote: “The complexity of the current criteria impedes real-world adoption of prostate cancer GGT. Accordingly, prostate cancer has one of the lowest rates of GGT utilization, with one contemporaneous study finding that only 1% of affected individuals underwent GGT. Even in patients with metastatic and/or castration-resistant disease, for whom GGT is recommended, uptake of only 4%-13% has been reported.”
Testing in non-White, rural and economically disadvantaged populations is even worse.
The presence of BRCA 2 mutations, for example, is linked not only to breast cancer, ovarian cancer and pancreatic cancer, but also prostate cancer, and can impact recommendations on Active Surveillancc. AScan be more intense. Some doctors may recommend based on the genetic findings that it’s time for treatment.
Read about Joel Axler’s genetic journey on Active Surveillance.
'Wildcard’: A journey of genetics, waiting, frustration, desperation, and, finally, a big decision
February 7, 2022
(Editor’s note: Joel Axler faced some serious issues. On the surface, appeared to have low-risk prostate cancer. A perfect Gleason 6? But he had a plot twist—genetic mutations that doctors increasingly are taking seriously in finding a path to treat prostate cancer. Just how ‘active’ should hi…
So it’s time for us to get schooled on genetic testing.
The panel for the ASPI program includes:
—Neal Shore, MD, a urologic oncologist and Medical Director for the Carolina Urologic Research Center in Myrtle Beach, S.C. He has conducted many major studies on medications and immunotherapy that could significance for patients with low-risk disease.
—Channing Paller, MD, a medical oncologist at Sibley Memorial Hospital, an associate professor of oncology at the Johns Hopkins University School of Medicine and lead investigator of the Promise study of genetics and prostate cancer. She is a coauthor of the paper mentioned above.
Promise is enrolling 5,000 patients with prostate cancer for a free germline spit test to recruit 500 prostate patients with mutations. Enroll here for a free germline test. https://www.prostatecancerpromise.org/
Sorry, U.S. PCap atients only.
—Neil Perlman, M.D., medical director of Colon Cancer Alliance for Research and Education for Lynch Syndrome, will round out our panel. Not only is Dr. Perlman a Chicago-based internist, he also is a patient with Lynch syndrome and an advocate for patients with this hereditary disorder, which carries a significantly increased risk of cancer of the prostate, colon, uterus, and ovary. Perlman has been lobbying for changes in state laws to protect patients’ genetic rights and access to insurance.
Please respond to my confidential survey on genetic testing and PCa. I will present the findings in this newslatter. Click here: https://forms.gle/Uv9d5gaZYHadZ5Qh9
NCCN adds MyProstateScore 2.0 and Stockholm3 to guidelines to help patients with rising PSAs avoid biopses
By Howard Wolinsky
NCCN (National Comprehensive Cancer Network) has added two new tests to its approved list of tests for early detection of prostate cancer.
These tests, aimed at slightly different groups, potentially can spare men from unnecessary testing—and unnecessary diagnoses of prostate cancer,
The tests are MyProstateScore 2.0 (MPS2), a urine test, from Lynx Dx in Ann Arbor, Michigan, and Stockholm3, a blood test, from A3P Biomedical in Stockholm, Sweden. Both MPS2 and Stockholm3 are now included in NCCN Guidelines for for Prostate Cancer Early Detection and in the most-recent updates to the NCCN Guidelines for Prostate Cancer.
These tests are part of a raft new secondary or backup tests that are creating a new market with the goal of reducing the number of unnecessary biopsies and avoiding risks that biopsies pose, especially sepsis with transrectal biopsies—though there’s a lot of debate about this in the U.S. ]
How do these two tests compare?
Stockholm3: Aims to detect aggressive prostate cancer earlier, including in men with low PSA, while significantly reducing unnecessary biopsies and MRI examinations.
MPS2: Provides a comprehensive, genetically driven risk assessment, particularly useful for men with elevated PSA to determine the necessity of a biopsy.
Stockholm3 can be used by all men aged 45-74 who have not previously been diagnosed with prostate cancer.
MPS2 calculates a personalized risk score for prostate cancer based on genetic markers.
What’s wrong with screening with PSA, a protein marker,used to detect and follow prostate cancer? Many doctors say it’s the best biomarker they have with some caveats.
Dr. Eric Klein, chair emeritus at Cleveland Clinic and developer of the previously included test IsoPSA, told me a while back, “PSA has 95% sensitivity for grade 6 or higher cancer. It misses about 8% of high-grade cancers that don’t make PSA. [PSA’s] main limitation is its low specificity, meaning it’s frequently elevated just by BPH.”
Hari Vigneswaran, MD, an American urologist and researcher at Karolinska Institutet in Stockholm, told me: “Stockholm3, by design, predicts risk of significant cancer (which is Gleason 3+4 or higher). Gleason 3+3 is not of interest to be detected, thus showing its ability to reduce overdetection.”
Stockholm3 is a blood test that includes five protein biomarkers (including total PSA and free PSA); genetic markers (specifically 101 single nucleotide polymorphisms or SNPs); and clinical information (such as age, family history, and previous biopsy results).
These factors are combined in an algorithm to provide a risk score.
Vigneswaran said Stockholm3 is mainly used by urologists and primary care providers in Europe. “The major benefit is in the primary care setting which can act as a rule-in test and rule-out test. In the urology setting, it acts more as a rule-out test,” he said.
MyProstateScore 2.0 is a urine test that primarily analyzes genetic markers, including 18 unique gene transcripts associated with prostate cancer; the novel gene fusion T2:ERG, a highly specific biomarker for prostate cancer.
The test is the only one on the market that detects the T2:ERG gene fusion, which is present in most men with prostate cancer. Analysis of these 18 genetic markers uncovers information not available through PSA screening alone.
MPS2 can be used as a biomarker-only test or incorporate clinical risk factors. It can be an in-home test. (Note: The Active Surveillor will run an interview soon of one of the developers of MPS2.)
MPS2 is not a screening tool, nor is it intended to replace PSA. The MyProstateScore test is designed to provide additional information for patients who have undergone PSA testing.
An NCCN expert told The Active Surveillor:
In the NCCN Guidelines for Prostate Cancer Early Detection (interim update posted on June 24, 2025), the MyProstateScore 2.0 (MPS2) and the Stockholm3 biomarker tests were added as options among other available tests as follows:
Prior to initial biopsy: The probability of high-grade cancer (Grade Group ≥2) may be further defined prior to initial biopsy utilizing tools such as the Prostate Health Index (PHI), SelectMDx, 4Kscore, ExoDx Prostate Test, MyProstateScore (MPS), MPS 2.0 (MPS2) (category 2B), Stockholm3, and IsoPSA.
In layman's terms: These tests can help some patients with an elevated PSA better define their risk of having prostate cancer that needs to be treated. Some patients may be able to delay or forgo biopsy. They should have follow-up in 6-12 months with a PSA test and a DRE (digital rectal exam).
After initial biopsy: Tests that improve specificity in the post-biopsy setting may be considered in patients thought to be higher risk despite a negative prostate biopsy. Tests to be considered are percent-free PSA, 4Kscore, PHI, PCA3, ConfirmMDx, ExoDx Prostate Test, MPS, MPS2 (category 2B), and IsoPSA.
In layman’s terms: These tests can be used in patients who have a negative biopsy if the physician is still concerned that they may have prostate cancer. These tests can inform whether the patient should have a repeat biopsy. Regardless, PSA and DRE should be performed at 12- to 24-month intervals.
Also, NCCN said about updated guidelines :
In the NCCN Guidelines for Prostate Cancer (during the 1.2025 update posted on December 4, 2024 [current version is 2.2025]), for patients with localized prostate cancer treated with radiation or surgery, the post-treatment pathways were streamlined.
After radiation therapy:
Patients without biochemical recurrence (defined in footnote u of the Guidelines) should undergo monitoring.
Those with biochemical recurrence have different options depending on the results of imaging: monitoring, ADT with or without abiraterone, additional therapy to the prostate (such as surgery or cryotherapy) with or without ADT.
After radical prostatectomy:
Patients with undetectable PSA without any adverse features should undergo monitoring.
For patients with undetectable PSA who do have adverse features, monitoring is still preferred, but treatment (see below) can be considered.
For patients with undetectable PSA who have lymph node metastases, monitoring or treatment are the options.
For patients with PSA persistence after surgery, treatment options depend on the results of imaging (if done): radiation therapy with or without ADT, radiation with ADT and abiraterone, and monitoring.
Also, please you fill in a survey on biopsies?
—Please answer this questionnaire on transperineal biopsies vs. transrectal biopsies: https://forms.gle/GShpHwegEPtAVgTs9 I have a relevant story coming, and you can take a few minutes and help if you haven’t already. One more and I’ll have 100 respondents.—Howard Wolinsky.