ExoDx Urine Prostate Test to Evaluate Risk of Aggressive Prostate Cancer Prior to First Biopsy.

The ExoDx Prostate Test is a non-invasive, non-digital rectal exam, urine test used as a risk assessment tool to provide risk probabilities for aggressive prostate cancer.

The technology relies on cancer-specific genomic biomarkers found in the urine. The test analyzes three cancer-specific biomarkers found in the urine associated with aggressive prostate cancer: ERG, PCA and SPDEF. It purposefully does not analyze prostate specific antigen (PSA). Patients below the cut-point of 15.6 are considered at low risk of having high-grade prostate cancer. Patients above the cut-point of 15.6 are considered to have higher risk of high-grade prostate cancer.

The test is intended for men over 50 with PSA’s from 2-10 ng/mL and considering an initial biopsy. The doctor and the patient should discuss the patients’ ExoDx Prostate score in a shared decision-making process including all relevant factors and make a decision as to whether or not to proceed with a prostate biopsy.

This urine-exosome, pre-biopsy risk stratification technology is now commercialized. See the following link.

New Genetic Risk Test for Prostate Cancer

Using a comprehensive analysis of all the genetic risk data concerning prostate cancer for African American men, Dr. Chris Haiman of the University of Southern California and his team of over 200 researchers were able to determine that it was possible to create an affordable test, based solely on a man’s saliva or blood sample, to assess his risk of developing prostate cancer. The challenge now is to optimize the accuracy of this test and design a way to deliver it to all men.

Information about this test is available from the following link from the Prostate Cancer Foundation. You can also use the following link to sign up for the Smith Polygenic Risk Test and other related information.

Molecular Imaging PSMA PET/CT Could Transform Management of People with Aggressive Cancer

Upon recent discussions with my urologist and oncologist, they both informed me that the following is a highly significant development in imaging of prostate cancer.

A medical imaging technique, known as PSMA PET/CT, that provides detailed body scans while detecting levels of a molecule associated with prostate cancer could help doctors better tailor treatments for their patients, by determining the extent of disease spread at the time of diagnosis. This was the finding of a randomized, controlled trial involving 300 patients in Australia recently published in The Lancet journal.

The approach combines two imaging technologies – positron emission tomography (PET) and computed tomography (CT) – and is almost one third more accurate than standard CT and bone scans at pinpointing the spread of prostate cancer throughout the body. PSMA PET/CT proved to be 92% accurate compared with only 65% accuracy with standard imaging. Although the study did not assess whether the scans had any effect on patient survival, the researchers say this approach could improve outcomes by helping doctors decide whether to offer a localized treatment, such as surgery or radiotherapy, or to use more advanced treatments to treat the whole body if the cancer has already spread.

Prostate cancer is commonly treated by surgery to remove the prostate or intensive radiotherapy to target the tumor. If there is a high risk the cancer may have spread to other parts of the body, patients may be offered medical imaging – typically CT and bone scans – to help doctors determine if additional treatments are needed. Study lead Professor Michael Hofman of the Peter MacCallum Cancer Centre, Melbourne, said: “Taken together, our findings indicate that PSMA-PET/CT scans offer greater accuracy than conventional imaging and can better inform treatment decisions. We recommend that clinical guidelines should be updated to include PSMA PET/CT as part of the diagnostic pathway for men with high risk prostate cancer.” Both imaging techniques involve exposure to radiation but the dose associated with PSMA-PET/CT was less than half that associated with conventional imaging (8.4mSv vs 19.2mSv).

Researchers sought to investigate if a molecular imaging approach could help doctors better define the extent of disease at the time of diagnosis. This approach involves giving patients a radioactive substance that detects a molecule called Prostate Specific Membrane Antigen (PSMA), which is found at high levels on prostate cancer cells. They then undergo a PET/CT scan. The CT scan produces detailed images of the body’s organs and structures, while the PET scan lights up areas where PSMA is present at high levels, indicating the presence of prostate cancer cells.

The study involved 300 men recruited to ten sites across Australia. All of the men had been diagnosed with prostate cancer, confirmed by tests on prostate tissue samples, and were deemed to be at high risk of having aggressive disease. The men were randomly assigned to receive either conventional CT and bone scans (152 patients) or PSMA-PET/CT (148 patients). Men then swapped over and were given the scans using the alternative imaging arm unless more than three sites of cancer spread were detected on the initial scans (18 patients). A second round of scans were undertaken at six months if there was any concern about ongoing prostate cancer following treatment. The results of these scans were used to confirm tumor spread, in addition to biopsies and change in blood tests.

Overall, the researchers found the PSMA-PET/CT scans were much more accurate than conventional CT and bone scans at detecting cancer spread (92% vs 65%). This is because the new technique was better at detecting small sites of tumor spread. Conventional imaging failed to detect that the cancer had spread in 29 patients, giving a false negative result. By comparison, PSMA-PET/CT gave false negative results in just six patients. Furthermore, fewer men had false positive results obtained with the new technique (2 with PSMA-PET/CT and 9 with conventional imaging)

PSMA-PET/CT scans had greater impact on the way patients’ disease was managed, with 28% having their treatment plans changed after the scans (41/147) compared with 15% following conventional imaging (23/152). When PSMA-PET/CT was given at the second round of imaging after conventional imaging, disease management plans were still changed in more than a quarter of cases (39/146, 27%). When conventional imaging was used at the second round, however, just 5% of patients had their treatment plans changed (7/135 patients).

Professor Declan Murphy, senior author, of Peter MacCallum Cancer Centre, Melbourne, said “Around one in three prostate cancer patients will experience a disease relapse after surgery or radiotherapy. This is partly because current medical imaging techniques often fail to detect when the cancer has spread, which means some men are not given the additional treatments they need. Our findings suggest PSMA-PET/CT could help identify these men sooner, so they get the most appropriate care.”

For further details, see the following from the Prostate Cancer Foundation, March 22, 2020.

Gleason 6 Prostate Cancer is not Deadly

Tumor samples from a prostate biopsy are graded (Gleason score) which is an indication of a tumor’s aggressiveness. The tumor grade reflects how far the cancer cells deviate from normal healthy cells. Gleason 6 cancer looks almost like normal prostate gland tissue while higher Gleason scores are indicative of more serious cancers. The Prostate Cancer Research Institute (PCRI) recently published an e mail video from Dr. Mark Scholz stating that in a survey of 26,000 men, it was concluded that surgically-proven Gleason 6 prostate cancer does not metastasize. Men diagnosed with grade 6 cancer should be followed by “watching” and not “treating”. In this study, 22 men with positive nodes were regraded to Gleason 7 or higher. If this study is applicable to your case, please be advised to discuss this video and its conclusions with your personal urologist or oncologist.

Pyl Imaging Agent Accurately Detects Recurrent Prostate Cancer Lesions

Progenics Pharmaceuticals’ PyL, a new imaging agent for positron emission tomography (PET) scans, can accurately detect the location of recurrent prostate cancer lesions, according to data from the Phase 3 CONDOR clinical trial.

“There is a need for improved diagnostics for prostate cancer to replace conventional imaging tests that have limited performance characteristics, especially in men with biochemical recurrence of their disease,” said Barry Siegel, MD, CONDOR’s principal investigator at the Mallinckrodt Institute of Radiology at Washington University School of Medicine clinical site.

PyL (18F-DCFPyl) is a tracing agent composed of DCFPyL, a small molecule that specifically targets the prostate specific membrane antigen (PSMA) protein — present at high levels in prostate cancer cells — coupled with a radioactive compound labelled with fluorine 18. After PyL is injected intravenously into the patient, it travels through the blood and accumulates at prostate cancer sites, making them “light up” during PET scans. PyL has the potential to allow clinicians to detect very small lesions that are currently missed with conventional imaging methods, so can they determine if the disease has returned or spread to distant organs and adjust treatment plans accordingly.

The open-label CONDOR study (NCT03739684) evaluated whether PyL could safely, successfully, and accurately detect new prostate cancer lesions in 208 men suspected of prostate cancer relapse. These suspicions, which were based on biochemical relapse — rising levels of prostate-specific antigen (PSA), a biomarker of the disease — were accompanied by negative or ambiguous findings on conventional imaging scans.

Participants were recruited, dosed, and imaged with PyL at 14 sites in the U.S. and Canada. CONDOR’s primary goal was to assess the predictive value of PyL in detecting the right location of new cancer lesions that confirmed the disease had returned. For that, three blinded, independent researchers compared the results of PyL PET scans with those of confirmatory biopsy or surgery, conventional imaging, and/or changes in PSA levels following radiation therapy of PyL-suspected lesions, performed within 60 days after PyL imaging. The study’s secondary goal was determining the percentage of patients whose treatment plan was changed based on PyL imaging results.

Results showed that the trial met its primary goal, with PyL imaging detecting at least one posteriorly confirmed new lesion in 84.8% to 87% of the cases. This exceeded by far the 20% threshold established by the FDA “for the trial to be deemed a success,” reflecting “the impactful clinical utility of PyL imaging.”

As far as safety, the imaging agent was well-tolerated, consistent with data from the previous Phase 2/3 OSPREY clinical trial (NCT02981368). The most frequently reported adverse side effect (in 1.9% of patients) was headache, and one man had a serious immune reaction (hypersensitivity) to PyL.

“The high positive predictive value demonstrated in this study reflects the clinical utility of PSMA-targeted PET imaging agents providing actionable information to physicians to guide treatment plans and improve disease management of one of the most prevalent cancers in the U.S.,” Siegel said.

“The positive results of our Phase 3 CONDOR trial reinforce our belief in the potential of PyL to enable better physician treatment decisions and, ultimately, improve patient outcomes,” David Mims, Progenics’ interim CEO, said in a press release. The company plans to submit a new drug application for PyL to the U.S. Food and Drug Administration in the second half of this year, according to Mims.

Material cited above was received on January 13th in the Prostate Cancer News Today Weekly Digest to which I recommend a subscription.

PSMA PET-CT Offers Best Detection Rates in Recurrent Prostate Cancer.

In a recent study, investigators reported the findings of a clinical trial designed to compare the rates for detecting recurrent cancer sites using the prostate-specific membrane antigen (PSMA) PET-CT imaging agent (68Ga-PSMA-11) to those of 18F-fluciclovine in a group of men with recurrent prostate cancer who had already undergone prostatectomy and had very low levels of PSA (less than 2.0 ng/mL).

Whole-body positron emission tomography–computed tomography (PET-CT) scans are necessary to determine the location and extent of disease in men whose prostate cancer has returned, to select the best course of treatment. However, there is no consensus among different health authorities as to which specific PET-CT imaging agent should be used to identify suspected sites of prostate cancer recurrence in these patients.

Guidelines defined by the National Comprehensive Cancer Network (NCNN) have established that 18F-fluciclovine is the most suitable imaging agent for these cases, while the European Association of Urology (EAU) recommends the use of prostate-specific membrane antigen (PSMA) PET-CT imaging agents. 18F-fluciclovine labels prostate cancer cells by exploiting their increased amino acid (the building blocks of proteins) transport, whereas PSMA PET-CT agents label prostate cancer cells containing high amounts of PSMA, a marker of disease. Preliminary reports suggest superior detection rates of PSMA PET-CT compared with 18F-fluciclovine PET-CT. However, these imaging tests have not been compared prospectively and directly.

To ascertain this, a prospective, single-center, open-label, single-arm trial (NCT02940262) was carried out at the University of California Los Angeles. All men enrolled in the study had PET-CT scans with both imaging agents within a period of 15 days. The study’s primary endpoint was to determine the detection rates for both imaging agents on a per-patient and per-region level. Each PET-CT scan was analyzed by three independent experts. The opinion of the majority was considered the correct interpretation of the findings. Between February, 2018 and September, 2018, 143 men suspected of having recurrent prostate cancer were screened for eligibility and 50 were enrolled into the trial for a median follow-up period of eight months.

Study findings revealed the PSMA PET-CT imaging agent had significantly higher overall detection rates per patient, compared to those of 18F-fluciclovine (56% vs. 26%). The difference remained significant regardless of PSA levels at the time of the imaging scans. In addition, on a per-region level, the detection rates of the PSMA PET-CT imaging agent were also higher than those of 18F-fluciclovine on pelvic lymph nodes (30% vs. 8%), lymph nodes in other regions (16% vs. 0%), bone (8% vs. 0%) and other organs (4% vs. 0%).

This study concluded that the imaging agent 68Ga-PSMA-11 has better detection rates than 18F-fluciclovine in men with recurrent prostate cancer who have already had radical surgery to remove the prostate and whose levels of prostate-specific antigen (PSA, a marker of disease) are very low.

“However, because the PET findings could not be validated by a gold reference standard in two-thirds of patients, neither sensitivity nor specificity could be established,” the researchers said. “Nevertheless, the results of this prospective head-to-head comparison indicate that PSMA should be the PET tracer of choice when PET-CT imaging is considered for subsequent treatment management decisions in patients with biochemical recurrence and low PSA concentrations. Further research is needed to investigate whether higher detection rates translate into improved oncological outcomes.”

The findings of the study, “18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-center, single-arm, comparative imaging trial,” were published in The Lancet Oncology. The information in this post originally was published in the Sept. 16th, 2019 e mail Prostate Cancer News Today by Joana Carvalho. MSc.

PyL Imaging Agent Detects Lesions Outside the Prostate in a Phase 2/3 Trial

In a Phase 2/3 OSPREY clinical trial aimed at examining its diagnostic accuracy, 18F-DCFPyl (PyL), a new imaging agent for positron emission topography (PET) scans, can accurately detect prostate cancer lesions outside the prostate, whether in nearby lymph nodes or in distant locations, clinical trial data show. The tracer — developed by Progenics — is a second generation fluorine 18-labeled small molecule that targets the prostate-specific membrane antigen (PSMA) protein, present at high levels in prostate cancer cells. Once bound to cancer cells, the radioactive fluorine serves as a signal for PET scans, making it possible to obtain an image showing the location of these cells.

Results from a Phase 2/3 trial examining PyL’s safety and accuracy were recently presented orally at the 2019 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting in Anaheim, California.

The completed OSPREY Phase 2/3 trial included 385 men either with high-risk prostate cancer who had been referred for radical treatment — surgical removal of the prostate and lymph nodes — and assigned to group A, or those who had radiological evidence of recurrent or metastatic cancer and were eligible for biopsy (group B).

To determine the safety and accuracy of PyL, these men underwent PET scans a couple of hours after the imaging agent was released into their bloodstream. Imaging results were then compared to specimens obtained during surgery for group A and biopsies from group B. Three independent readers examined the PET scans.

In group A, the scans led to very few false positives, but a sizable proportion of lesions identified as negatives were actually false negatives. (False positives indicate the presence of cancer at locations it’s not, and false negatives detect no cancer in locations where it exists.) In group B, imaging scans were much more accurate, with very few false negatives identified. This high specificity was seen across regions, both in pelvic lymph nodes and in more distant sites.

“[These results] underscore the power of PyL to accurately detect prostate cancer, including high risk and biochemically recurrent disease where more precise imaging can change treatment decisions,” Asha Das, MD, chief medical officer of Progenics, said in a press release. PyL was well-tolerated, with no serious adverse events related to the agent. Most frequent side effects were altered or unpleasant taste sensations and headache. “With our PSMA-targeted approach, we have the potential to detect small nodal and distant metastases, even in men with low PSA scores. We believe that PyL could transform how prostate cancer is detected, monitored, and treated,” Das said.

PyL is now being assessed in the open-label CONDOR Phase 3 study (NCT03739684) in about 200 men suspected of prostate cancer recurrence, who have had negative or equivocal findings on conventional imaging. The trial is currently recruiting at sites across the U.S. and in Quebec. Sites in the U.S. can be found in California, Connecticut, Florida (Moffitt Cancer Center), Iowa, Maryland (Johns Hopkins), Michigan, Missouri, New York, Pennsylvania, and Wisconsin.

The article above was first published in Prostate Cancer News Today, July 25th, 2019.

 

68-Gallium PSMA PET Scan Better Than Axumin in Detecting Cancer Recurrence

Among men suspected of having prostate cancer recurrence after surgery, the radiotracer 68Ga-PSMA-11 is better at detecting the cancerous lesions and provides better agreement among experts than the standard Axumin (18F-fluciclovine) tracer, a Phase 2 trial shows.

The results were presented at the 2019 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting, held June 22–25 in Anaheim, California. The communication was titled “68Ga-PSMA-11 PET/CT detects prostate cancer at early biochemical recurrence with superior detection rate and reader agreement when compared to 18F-Fluciclovine PET/CT in a prospective head-to-head comparative phase 3 study.”

Radical prostatectomy — surgery to remove the prostate and surrounding tissues — is among the most common treatment options for prostate cancer. However, up to 40% of patients see their PSA levels increase after surgery. This process, called biochemical recurrence, indicates the return of cancer.

Doctors use various imaging methods to estimate the size and location of recurrent tumors before starting treatment. However, traditional techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and bone scans often fail to detect small tumors, especially at the early stages of biochemical recurrence, when PSA levels are low.

Positron emission tomography/computed tomography (PET/CT) is a highly sensitive imaging method that uses radiotracers — molecules that target specific cellular components, linked to small amounts of radioactive materials — and a special camera and computer to evaluate the function of different tissues. Researchers have developed radiotracers that specifically label components of prostate cancer, thus allowing its detection at earlier stages.

Axumin, by Blue Heart Diagnostics, is a radiotracer indicated to identify suspected sites of prostate cancer recurrence. It is a synthetic amino acid that preferentially enters prostate cancer cells due to their increased amino acid transport, labeling them with the radioisotope fluorine-18.

On the other hand, the 68Ga-PSMA-11 tracer consists of a molecule that binds the prostate specific membrane antigen (PSMA) labeled with the radioactive element gallium, Ga. This radiotracer can detect prostate cancer safely and accurately, but has not been compared with standard Axumin in clinical trials.

The Phase 2 trial (NCT03515577) compared the efficacy of PET/CT using either 68Ga-PSMA-11 or Axumin at detecting prostate cancer in 50 men with early biochemical recurrence, whose PSA levels ranged between 0.2 and 2 ng/mL.

Participants underwent Axumin PET/CT within two weeks before or after 68Ga-PSMA-11 PET/CT, and results were assessed by three independent imaging experts.

The study’s main goal was to compare the detection rates by patient and region. Secondary measures included detection rates according to initial PSA levels, the accuracy of each method, and agreement among readers.

Researchers found that the 68Ga-PSMA-11 tracer helped the experts identify prostate cancer lesions in significantly more patients (56%) than Axumin (23%). The PSMA tracer also identified more lesions by region — 30% versus 8% in the pelvic area, and 16% versus 0% in the extra-pelvic area.

Finally, readers agreed more on the results of this tracer, both by patient and by region.

“In patients with biochemical recurrence and low serum PSA levels after radical prostatectomy, PSMA PET/CT has higher detection rates and better reader agreement than Axumin,” researchers concluded. “Therefore, PSMA PET/CT should be the imaging modality of choice in patients with early biochemical recurrence.”

Published on line on July 8th, 2019 in Prostate Cancer News Today.

Simple Blood Tests to Determine Best Treatment Options for Advanced Prostate Cancer

Blood tests that examine circulating tumor cells, CTC’s, (cells that shed from the tumor or metastasis into circulation), for the presence of a mutated AR-V7  protein, could help determine if a patient with advanced prostate cancer would fare better with chemotherapy or with medicines such as enzalutamide (Xtandi) or abiraterone (Zytiga) that target the androgen receptor (a cellular protein that binds male hormones). But as happens with many medications, tumors often develop a resistance to such therapies that target the androgen receptor. Resistance develops because the medicines target a domain of the receptor that is missing in the AR-V7 version.

When a patient is first diagnosed with metastatic hormone-resistant prostate cancer, the preferred treatment involves androgen receptor inhibitors like Xtandi or Zytiga. But if a patient fails a first-line treatment with these inhibitors, there is no guarantee he’ll respond to a second inhibitor. In such cases, researchers need biomarkers that help them select which patients should receive a second androgen receptor inhibitor, and which should switch to chemotherapy.

One international team of researchers tested whether AR-V7, measured by a blood test in circulating tumor cells  could predict the best treatment approach for each patient. The test they used, called  Oncotype DX AR-V7 CTC nuclear protein test, was developed by Epic Sciences and Genomic Health. (A similar test has been developed at Johns Hopkins University and is called CTC AR-V7 RNA test.)

In one study of 142 patients at three institutions, all had been treated with one of the androgen receptor inhibitors (Xtandi or Zytiga) without success. Seventy patients were then moved to another round of treatment with an androgen receptor inhibitor, while 72 patients were treated with taxane-based chemotherapy — Taxotere (docetaxel) or Jevtana (cabazitaxel). Patients were followed for up to 4.3 years.

As expected, researchers found that patients who were negative for AR-V7 survived significantly longer with an androgen receptor inhibitor (19.8 months) than with chemotherapy (12.8 months). Conversely, chemotherapy was a better approach for patients who were positive for AR-V7, nearly doubling survival times compared to the androgen receptor inhibitor — 14.3 vs. 7.3 months. Overall, these results suggest that assessing AR-V7 levels in circulating tumor cells through a blood test may help identify the best second-line therapy for patients with metastatic hormone-resistant prostate cancer. These results were published in an issue of  JAMA Oncology.

Meanwhile, in a second study, investigators at the Duke Cancer Institute designed a multi-center study — called PROPHECY (NCT02269982) – to evaluate how well both blood tests  above predict the effectiveness of these hormone therapies.

A total of 118 men were enrolled at five medical centers to provide external validation for the two tests. For both tests, AR-V7 detection correlated with worse progression-free survival (PFS) — the length of time during or after treatment without disease progression — and overall survival (OS). While the Johns Hopkins test appeared to be more sensitive and flagged more non-responding patients, the Epic test seemed to be more specific, leading to no false-positive data.

“We have therapies to treat recurrent, metastatic prostate cancer, but they don’t work on everyone, and cross-resistance is a major emerging problem in our field. It’s important to know who will be more likely to respond and who has little chance of benefiting in order to rapidly provide alternative, more effective therapies or to develop new therapies for these men,” said Andrew Armstrong, MD, associate director for clinical research in the Duke Prostate and Urologic Cancer Center. “Having this predictive power could spare many men from undergoing therapies that would simply not benefit them, saving time, money and a great deal of emotional distress,” Armstrong said. “The results of this study are clinically useful in guiding care, particularly in men with high-risk disease and those who have already tried enzalutamide or abiraterone.”

Both of the studies were summarized in articles published online in Prostate Cancer News Today, August 8th  and June 18th, 2018 respectively.

 

Seven Causes of Elevated PSA Levels

  1. Age. In general, a normal PSA range for men in their 40’s is 0-2.5 ng/mL; men in their 50’s, 0-4 ng/mL; 60’s, 0-4.5 ng/mL; and 70’s, 0-6.5 ng/mL. Ethnicity may shift these values slightly as well.
  2. Prostate size. A man with a larger-than-normal prostate gland may have a higher PSA level. A digital rectal exam by your physician will detect this.
  3. Prostate inflamation. Bacterial infections e.g. prostatitis produce inflamed, tender or swollen glands thereby elevating one’s PSA level.
  4. Benign Prostatic Hyperplasia (BPH). BPH is an enlarged prostate and differs from simply having a larger-than-usual gland. It is common in men over 50 and may make urination or ejaculation difficult. Additional tests can confirm BPH.
  5. Urinary tract infection or irritation. This infection as well as irritation caused by medical procedures involving the urethra or bladder may cause the gland to produce more PSA. If any such procedures have been performed, give the area some time to heal before running a PSA test.
  6. Prostate stimulation. Stimulation such as through sexual activity, ejaculation or even having a digital rectal exam by your physician may affect PSA results.
  7. Medications. Some medications can artificially lower the PSA, such as finasteride (Proscar or Propecia) or dutasteride (Avodart). Remind your doctor of any of these medications you may be taking so they can factor them in when assessing your PSA results.                                                                                                                                                  This information was obtained from the Prostate Cancer Foundation, www.pcf.org.