The Position of Liquid Biomarker for Early Detection of Prostate Most cancers

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US PREVALENCE OF PROSTATE CANCER AND PSA TEST SCREENING

According to Moul, the incidence of prostate cancer in the US has dropped to about 200,000 cases per year, compared to 330,000 cases per year for the past 15 to 20 years. Previously, the U.S. Preventive Services Task Force had given PSA test screening a low rating, but Moul said more primary care physicians are resuming PSA test screening.

Albala added that when the PSA test was first introduced, the incidence of prostate cancer in the US was about 1 in 6 or 7 men. “But we saw a break in [number of] Patient [with metastatic disease] who we saw, ”remarked Albala. “I remember when I was in the [Veterans Health Administration], we would see a lot of them [patients with meta-static disease] come, and the PSA era has really changed that. “

CONSIDERATIONS FOR PSA TEST SCREENING

Although PSA test screening needs refinement, it should continue as it is an effective baseline screening, Moul said, with secondary tests often used to “refine” decisions before completing a biopsy. Albala added that urologists recognize that the PSA test has limitations because it is not cancer-specific. The widespread criticism of PSA test screening could be due to how the medical field has used the information generated by the test, Moul said. In fact, the PSA test does not match the accuracy of tissue-based biopsy tests and is not recommended for diagnosis.3 However, since high PSA levels can indicate metastatic disease, PSA screening can help detect metastatic prostate cancer. Albala reiterated Mouls’ endorsement of PSA testing as a major contributor to prostate cancer detection; it has been used in a number of ways to test the ratios of free to total PSA, PSA velocity and PSA density in patients.

“Back when I did [was] in training, 1 out of 5 men [who presented with prostate cancer] typically presented with metastases. And then, in the PSA era, that dropped to 2% or 3%, which means that only 2% to 3% of men presenting with prostate cancer had it [metastases]”, Explained Moul.

USING NEW LIQUID BIOMARKER TESTS IN PROSTATE CANCER SCREENING

Albala says numerous next-generation tests for screening for prostate cancer are commercially available, including blood-based (e.g. [PHI], 4Kscore) and urine-based tests (e.g. Exosom, SelectMDx, PCA3).

An exosome test does not require practitioners to do a rectal exam, Moul explained, while a PCA3 test requires an attentive digital rectal exam prior to the urine test. At the completion of the exosome test, patients empty the urine through a special device; Previously this was done in-house, but as tests have become available in the mail, patients can now collect the urine sample at home, mail it back, and receive the result within a week. Regarding blood tests, Moul said he has more experience with the PHI than other tests; the PHI predicts the likelihood of cancer in 4 risk groups: low, low-medium, medium and high. Crucially, however, the exosome test does not predict cancer or no cancer, but rather the probability of Gleason 7 or higher. Moul believes that the PHI and the exosome complement each other.

Albala said that when most patients arrive at his clinic, they are asked to leave a urine sample and it is often difficult to produce a second sample during the same visit. He used the exosome test because patients can complete their second sample at home, but the exosome and SelectMDx urine tests are comparable, Albala believes. A rectal massage is not necessary with the SelectMDx test. Since urine tests predict prostate cancer a little more accurately than blood tests, Albala’s institution has focused more on urine testing. “When a new test comes out, I look at effectiveness, costs, [adverse] Effect profile, the ease with which the test was carried out and then the durability. I always think of these 5 things – be it a new drug, a new procedure or whatever – in the back of my mind to put these tests in perspective because when new tests come out there is a lot of hype, a lot of excitement … you want [come] back to earth, “and use tests when it’s really appropriate,” Albala said.

EFFECTS OF COVID-19 ON SCREENING

With the COVID-19 pandemic, the use of telemedicine skyrocketed, so patients who did not want to come to the practice could continue to meet with their doctors. One benefit of this trend, Moul said, is that it has helped him develop good therapeutic relationships with new patients, especially those with elevated PSA who would otherwise have physically attended the cancer center and felt very uncomfortable and nervous . With telemedicine, some initial visits were more relaxed and open. Mail exosome tests were particularly useful during this time, Moul said.

SELECTING SECONDARY TESTS IN PROSTATE CANCER SCREENING

After a standard PSA test shows that PSA is elevated, borderline, or in the “gray area,” many patients request more data before undergoing an invasive tissue biopsy, Moul said. These data can be generated by various secondary tests. A blood test (like PHI) can be used to measure a patient’s risk for prostate cancer. The benefits of a PHI include fewer potential biopsies and more accurate detection of prostate cancer, which helps doctors not only know if a more aggressive cancer is being detected, but also better targeting the treatment that is needed. Urine tests can detect overexpression of PCA3 and assess risk of prostate cancer.5 The PHI test is Duke’s first choice for secondary blood tests, Moul said, because it is done in-house and can be done immediately. They have even started training general practitioners to take this test.

When Moul first came to Duke, they used the PCA3 urine test as a secondary test to the standard PSA blood tests, but since it was a first generation test, the data wasn’t robust enough. Now, Moul said, they tend to use exosome as their secondary urine test, and they were happy with it. Exosome diagnostics and the SelectMDx test are widely used, Moul said, and his advice to new urologists is to familiarize themselves with at least 1 secondary blood test and 1 urine test in order to best work with their patients.

Moul does a rectal exam during a patient exam to contextualize PSA based on prostate size, he explained. “Rectal exams aren’t perfect, and it’s hard to train a GP to do them -[plus] many of them are not that interested. But as urologists and urology trainers, we need to make sure that all the interns we train know how to do a good rectal exam, [including assessing the] Prostate size, ”said Moul.

If a patient is borderline on a rectal exam and has a family history of borderline PSA, a PHI is usually the next test Moul will order. Albala said his institution is using PSA as a primary test and previously used a 4K blood test for secondary testing, but has started to focus more on urine testing.

ROLE OF MRI IN PROSTATE CANCER SCREENING

One of the challenges with using MRI to screen for prostate cancer is that MRI quality can vary by facility.

“Sometimes patients come with an MRI [they’ve had done elsewhere], and they want a fusion biopsy based on that outside of the MRI. This is problematic … because … we tell them, ‘Well, you have to do the MRI again at our facility before we do a fusion,’ ”Moul said.

Also, according to Albala and Moul, insurance coverage is another challenge. Moul said that in North Carolina, for example, many insurance plans do not cover MRI if a prior biopsy has not been performed, and the expensive out-of-pocket expenses at their facilities are between $ 800 and $ 2500 -Dollars can lie, explained Albala and Moul.

UNFULFILLED NEEDS

There are several areas of unmet need in prostate cancer screening. Underserved populations are one of them, Moul said; Many underserved patients who are at high risk for prostate cancer present their condition to the clinic too late. Also, patient compliance with the tests is not ideal. Finally, both Moul and Albala emphasized the need for standardization in assessing prostate size through a rectal exam. Moul found that if they could quickly grasp the estimated size of the prostate, they could contextualize the PSA level more effectively.

Albala reiterated the need for a standardized method for assessing prostate size. “I remember the days when Merck gave us the small models of the prostate. It was 30g, 40g, 50g, and I remember trying to feel these. There was a discrepancy with what you felt on the rectal exam and in the models, but that was the best we had 20, 30 years ago. We are [getting] better, I think. “

More education is needed in the urological community, Moul said, to better understand the use of secondary tests, including determining whether to use PHI or 4K, how to use a urine test, and when to order an MRI. Algorithms were introduced at Duke, but there are still many individual variations.

FINAL THOUGHTS

“We have become more demanding. We used these tools [and] put them together, ”Albala concluded. “That’s the beauty of what we do [in] Practice that we assimilate various tests to try and make a decision. Because biopsy is a huge obligation and complication [can happen—although] They are relatively insignificant, they exist for patients – and if we can be better clinicians, they help diagnose them [a higher] Comfort, I think that’s our goal.

REFERENCES

  1. Prostate Cancer Prevention Guidelines. Memorial Sloan Kettering Cancer Center. Accessed May 26, 2021. https://www.mskcc.org/cancer-care/types/prostate/screening/screening-guidelines-prostate
  2. American Cancer Society Recommendations for Early Detection of Prostate Cancer. American Cancer Society. Updated April 23, 2021. Accessed May 26, 2021. https://www.cancer.org/cancer/prostate-cancer/detection-diagnosis-staging/acs-recommendations. html
  3. US Preventive Services Task Force; Grossman DC, Curry SJ, Owens DK et al. Prostate Cancer Screening: US Preventive Services Task Force Recommendation Statement. JAMA. 2018; 319 (18): 1901-1903. doi: 10.1001 / jama.2018.3710.
  4. Boerrierter E., Groen LN, Van Erp NP, et al. Clinical utility of new biomarkers in liquid biopsies of prostate cancer. Expert Rev. Mol Diag. 2020; 20 (2): 219-230. doi: 10.1080 / 14737159.2019.1675515
  5. Prostate cancer: advances in screening. Accessed June 11, 2021. https: //www.hopkinsmedicine. org / health / conditions-and-diseases / prostate cancer / prostate cancer-advances-in-screenings

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