Biomarker and MRI-enhanced strategies comparable for prostate cancer screening, study finds

26th April 2024

A biomarker-based strategy is comparable to a magnetic resonance imaging (MRI)-enhanced approach for prostate cancer screening but results in more biopsies and increased detection of less aggressive cancers, a randomised trial has found.

Prostate cancer guidelines often recommended obtaining an MRI before a biopsy, yet MRI access was limited and using blood-based biomarkers with systematic biopsies could provide an alternative approach, Swedish researchers wrote in the journal JAMA Network Open.

In the open-label randomised trial, 12,743 men aged 50 to 74 with no previous cancer diagnosis underwent blood sampling for prostate specific antigen (PSA) levels and Stockholm3 tests to estimate their risk of clinically significant prostate cancer.

After the blood tests, men were randomly assigned in a 2:3 ratio to receive a Stockholm3 test with systematic biopsy (biomarker group) or a PSA test followed by MRI with systematic and targeted biopsy (MRI-enhanced group).

The Stockholm3 test, combines patient age, previous prostate biopsy results, family history of prostate cancer, single-nucleotide variations and levels of total PSA, free PSA, human kallikrein 2, β-microseminoprotein and growth differentiation factor 15 to estimate the risk of clinically significant cancer (Gleason score ≥ 3 + 4).

In the biomarker group (5,134 men), 8.0% of participants (413) had a Stockholm3 risk score of 0.15 or higher and underwent systematic biopsies, researchers said.

In the MRI-enhanced group (7,609 men), 12.2% participants (929) had a PSA level of 3ng/mL or higher and were referred for an MRI with biopsies if they had a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3 or higher.

Detection rates of clinically significant prostate cancer were comparable between the two groups: 2.3% in the biomarker group and 2.5% in the MRI-enhanced group.

However, researchers reported more biopsies were performed in the biomarker group than in the MRI-enhanced group (326 of 5,134 [6.3%] vs 338 of 7,609 [4.4%]).

There were also more indolent cancers detected in the biomarker group (61 [1.2%] vs 41 [0.5%]).

Senior author Professor Anna Lantz, associate professor in urology at Karolinska Institute and consultant urologist at Karolinska University Hospital Solna in Stockholm, Sweden, noted that certain areas and healthcare systems lacked the capacity to implement the diagnostic chain required for MRI-based screening and the cost of MRI of the prostate varied by setting.

Given their findings, they concluded the Stockholm3 test could be a feasible alternative in regions with limited access to MRI.

‘Nevertheless, the biomarker-based approach comes at the expense of more biopsy procedures and increased detection of less aggressive cancers,’ Professor Lantz and colleagues said.

Strengths of the study included its randomised design, large-size and population-based screening setting.

Regarding limitations, the authors noted that optimal PSA cut-off values for triggering a Stockholm3 test and guiding biopsy decisions were undetermined.

‘Finally, we focused on detecting clinically significant prostate cancer, and long-term prostate cancer mortality implications remain uncertain,’ they wrote.

Last month, a Cancer Research UK study found fewer middle-aged people are dying of cancer in the UK than at any point over the last 25 years, despite a rise in cases of cancer, partly due to improvements in screening programmes.

Another recent artificial intelligence-based study found that prostate tumours evolve in two distinct disease types, which may lead to better diagnosis and tailored treatments in future.

Novel prostate cancer screening test highly accurate

13th February 2023

A novel prostate cancer epigenetic screening test which incorporates PSA values has been found to have an accuracy of 94%

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.

Citation
Pchejetski D et al. Circulating Chromosome Conformation Signatures Significantly Enhance PSA Positive Predicting Value and Overall Accuracy for Prostate Cancer Detection. Cancers 2023

Prostate cancer screening with MRI after PSA a cost-effective strategy

21st November 2022

Prostate cancer screening that involves an MRI scan following a PSA test and then targeted biopsies was shown to be a cost-effective approach

A prostate cancer screening strategy that involves an MRI scan following a prostate specific antigen (PSA) test with subsequent targeted biopsies, is a more cost-effective strategy than using just a PSA and standard biopsy according to a cost-effectiveness analysis by Swedish researchers.

Prostate cancer (PCa) screening based on PSA, has been shown in a 16-year follow-up study, to reduce prostate cancer mortality. A biopsy is normally used to confirm the diagnosis of PCa though in recent years there has been an increase in the role of magnetic resonance imaging (MRI) as an alternative means for the identification of PCa. In fact, data suggests that the use of multi-parametric magnetic resonance imaging (MP-MRI) might allow 27% of patients to avoid a primary biopsy. In a 2021 study which compared MRI-targeted or standard biopsy for the purposes of screening for PCa, it was found that in men with a PSA level > 3 ng/ml, an MRI result suggestive of prostate cancer was non-inferior to standard biopsy for detecting clinically significant prostate cancer. In the trial, men were randomised to either a 10 to 12-core standard biopsy or to undergo a triage MRI and then a standard biopsy if the MRI results suggested prostate cancer. Given the non-inferior findings of this study, the Swedish team set out to determine the cost-effectiveness of the MRI-based screening approach in men aged 55 to 69 years of age.

The researchers modelled three scenarios: no screening (strategy 1); PSA and standard biopsy every four years (strategy 2) and finally, MRI following an elevated PSA and then a standard biopsy if the men had a PI-RADS value of between 3 and 5, i.e., which is suggestive of PCa. For each of the three strategies, the team modelled several different outcomes including the mean lifetime number of screening tests, MRIs, over-diagnosis (where screening was positive but would not have presented with symptoms before death due to other causes) and deaths. The incremental cost-effectiveness ratio (ICER), which represents the additional cost of one unit of outcome gained by one strategy compared with another, was calculated for each scenario. The ICER was calculated by dividing the difference in costs by the difference in quality-adjusted life-years (QALYs) for the no screening and the two alternative strategies.

Prostate cancer screening and cost-effectiveness

A total of 603 men were randomised to the standard arm and 929 to the MRI arm and of whom, 11.9% underwent MRI or any biopsy.

When compared against a strategy of no screening, the ICER for the MRI and combined biopsies was $53,736 per QALY gained compared to $69,254 for the PSA and standard biopsy strategy and which the authors designated as a moderate cost per QALY gain. Furthermore, MRI-based screening reduced the number of lifetime biopsies and over-diagnosis by approximately 50% and had a high probability of being cost-effective compared to the alternative strategies.

The authors concluded that a strategy for prostate cancer screening based on PSA followed by MRI with subsequent combined targeted and standard biopsies, had a high probability to be more cost-effective compared with the traditional screening pathway using PSA and a standard biopsy.

Citation
Hao S et al. Cost-effectiveness of Prostate Cancer Screening Using Magnetic Resonance Imaging or Standard Biopsy Based on the STHLM3-MRI Study. JAMA Oncol 2022