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13th February 2023
A team of UK researchers have developed a novel prostate cancer (PaC) screening test based on measurement of five chromosome conformations that were originally detected in association with advanced PaC and which, together with the prostate specific antigen (PSA) test, has a high degree of accuracy for detecting the cancer.
Prostate cancer is the second most common cancer in men and in 2020, there were just over 1.4 million new cases worldwide. Further investigations for suspected PaC are based on the results of a PSA test and the threshold has conventionally been set at 3 to 4 to differentiate between ‘normal’ and ‘abnormal’ although cancer can be present at lower PSA levels. However, while other tests have been developed, these all generally have a low positive predictive value. While imaging modalities have shown promise as screening tests, the recent PROSTAGRAM study which compared PSA test, MRI and ultrasound, found that all provided a similar level of accuracy for detecting PaC.
In the current study, researchers developed an assay based on specific chromosome conformation changes in certain genes in the blood of men with PaC. Using samples from the PROSTAGRAM study, which included men diagnosed with PaC and control patients, the team set out to establish whether their novel assay (EpiSwitch) in combination with a PSA test could improve the accuracy of PaC diagnosis.
Novel prostate cancer test performance
Samples from 109 men (88 control and 21 with PaC) were analysed. Based on a PSA cut-off level of 3 ng/mL, the test had an accuracy of 79%. The EpiSwitch test alone had an accuracy of only 64% but when the EpiSwitch test was combined with the PSA test, the accuracy was 94%.
The researchers reported that using the EpiSwitch test and the PSA level taken as a continuous variable, there was a high positive predictive (92%) and negative predictive value (94%) for the diagnosis of PaC. Although the study was based on a relatively small number of patient samples, the authors called for further studies to examine the value of the test in larger patient samples.
Pchejetski D et al. Circulating Chromosome Conformation Signatures Significantly Enhance PSA Positive Predicting Value and Overall Accuracy for Prostate Cancer Detection. Cancers 2023
15th November 2021
The presence of racial and ethnic disparities over an 8-year period have been revealed in a study of men with an elevated prostate-specific antigen (PSA) result according to researchers from the School of Economics, Georgia Institute of Technology, Atlanta, USA. Ethnic disparities in the diagnosis and treatment of prostate cancer are not new and have been associated with a complex interaction of several factors including socioeconomic status, detection at advanced stages, biological aggressiveness, family history, and genetic susceptibility. Moreover, this disparity also appears to be present among those deemed at low risk and for whom active surveillance has been advised. In fact, there is a significantly difference in prostate cancer mortality between Black and White males which is likely due in part, to low levels of PSA testing among Black, low income males.
An accurate prostate cancer diagnosis might help to reduce ethnic disparities and recently, a study using prostate magnetic resonance (MRI) has shown that this imaging modality might allow 27% of patients to avoid a primary biopsy and the diagnosis of 5% fewer clinically insignificant cancers. Furthermore, research suggests that prostate MRI is able to successfully detect prostate cancer to a similar extent in both Black and White males.
For the present study, the researchers turned to the Optum claims database which covers a diverse population and individuals from over 50 US states. They collected data from 2011 to 2017 and focused on men aged 40 years of age and older who had a single documented PSA result and no previous PSA screening or prostate MRI claims. Using PSA thresholds of above 2.5 ng/ml, 4 ng/ml and 10 ng.ml, the team set their main outcome of interest was the association between an elevated PSA result and a follow-up prostate MRI and stratified their analysis by race, ethnicity and age.
From a total of 795,809 participants with a mean age of 59.8 years, 51,500 (6.5%) had a PSA level above 4 ng/ml, of whom only 1524 (3%) underwent a subsequent prostate MRI within 180 days. When considering ethnicity, 9.6% of patients were Black, 13.6% Hispanic, 3.9% Asian and 57.3% White.
The study revealed important racial and ethnic disparities. For example, when compared to White males, Black males with a PSA of 4 ng/ml were 22% less likely to undergo a prostate MRI (odds ratio, OR = 0.78, 95% CI 0.65 – 0.89). Such ethnic disparities were also apparent for other races such that Asians with a PSA of 4 ng/ml were 24% less likely to undergo a prostate MRI (OR = 0.76, 95% CI 0.59 – 0.99). This ethnic disparity was also apparent across age groups, with Black patients aged between 65 and 74 and a PSA above 4, 23% less likely to have a prostate MRI (OR = 0.76).
The authors concluded that racial and ethnic disparities were apparent among men with an elevated PSA result in their subsequent use of a prostrate MRI. They called for future research to better understand and mitigate physician’s decision-making biases.
Abasgidze N et al. Racial and Ethnic Disparities in the Use of Prostate Magnetic Resonance Imaging Following an Elevated Prostate-Specific Antigen Test. JAMA Netw Open 2021