Introduction of antigen prostate-specific (PSA) in the screening and diagnosis of Prostate Cancer (CaP) represented, from the 90s of the last century to the early 2000s, a paradigm shift in the management of the disease, resulting in an increase in the incidence and prevalence of cases due to early diagnosis of CaP, including «indolent» forms subjected to an excess of radical treatment (1).
In recent years, a slowdown in the reduction in CaP-specific mortality has been observed.This is interpreted as a likely outcome of the increase in late-stage diagnoses and probably related to the reduction in the use of PSA as a screening test since 2008 and following a restrictive recommendation of some guidelines (2).
According to the National Health System (NHS), about three-quarters of men with an elevated PSA level do not have cancer, while about 1 in 7 men with CaP have a normal PSA result.
The use of new bio-markers aims to integrate the role of PSA in patients with suspected prostate cancer and open up scenarios of use beyond PSA with the aim of improving specificity in intercepting CaP and reducing the number of patients subjected to unnecessary treatments.
The Prostate Screening EpiSwitch (PSE) is a test that uses 3D genomics to detect specific chromosomal conformations of the neoplasm present in a patient’s blood sample and stands as a test that could supplement PSA improving its diagnostic performance.
Real-world screening PSA
CaP has a high prevalence of one in six men, but there is currently no widely accepted screening program.The PSA test is widely used at the cut-off of 3.0 ng/mL, but it does not have sufficient accuracy for the detection of any prostate cancer. At this cut-off the PSA test has a sensitivity of 59% with a specificity of 87% including insignificant and slow-growing forms of CaP, resulting in numerous unnecessary prostate biopsies performed in men with benign disease. Alternatively, some men with PSA <3.0 ng/mL may have false reassurances despite being affected by a CaP that in some cases can be aggressive (3).
Epigenetic research and PSE
Aberrant DNA methylation and histone acetylation are epigenetic modifications related to the onset of CaP. Three-dimensional chromatin conformations (CC) are potent epigenetic regulators of gene expression and pathological cell phenotypes. In primary prostate tumors and in the circulating DNA of patients with CaP, long-range epigenetic alterations have been found in CCs.Using EpiSwitch technology, the presence of cancer-specific CCs in peripheral blood mononuclear cells (PBMCs) was demonstrated. A UK research team has developed an epigenetic test for prostate cancer that detects neoplasm-specific CCs in the patient’s blood. The test, called PSE, could detect CaP with 94% accuracy, a significantly better result than PSA.
PSE associated with PSA
A study published in Cancer (4) evaluated the combination of the PSE epigenetic test with the PSA test and used two patient cohorts to determine whether integrating the two tests could achieve better diagnostic accuracy. The results showed an overall accuracy for EpiSwitch of 94%, far superior to PSA, which alone and at a cut-off>3 ng/mL showed a low positive predictive value (VPP) of 0.14 and a high negative predictive value (VPN) of 0.93.In contrast, EpiSwitch alone showed a VPP of 0.91 and a VPN of 0.32.
The combination of the two tests (PSA and Episwitch) significantly increased VPP to 0.81, although it reduced VPN to 0.78. By integrating PSA as a continuous variable (rather than a dichotomized cut-off at 3 ng/mL), with EpiSwitch in a new multivariate layering model, the PSE test produced a combined VPP of 0.92 and a VPN of 0.94 when tested on the independent prospective cohort.
PSE useful for diagnosis and screening
The result of the PSE is surprising, according to the statements of the research team reported in Medscape (4). When tested in the context of screening the at-risk population, PSE produces a rapid and minimally invasive diagnosis of CaP, and because of its high VPP exceeds current screening modalities.In addition, due to its non-invasive nature and low cost, the PSE test can be used for both diagnostic and screening purposes, minimizing unnecessary referrals to MRI and/or biopsy.
The next step, to confirm and expand the use of the PSE test, will be to test it with large prospective studies in a screening cohort of a population with a low prevalence of CaP.
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Source — https://www.univadis.it/viewarticle/pse-un-nuovo-test-il-tumore-della-prostata-2023a10003m8