Swedish Prostate Cancer Screening Method Cuts MRIs, Biopsies

But Is It Practical Elsewhere?

Nancy A. Melville

August 19, 2021

In a randomized trial of prostate cancer screening methods, a blood-based diagnostic test and MRI with subsequent targeted plus systematic prostate biopsies outperformed the standard approach of prostate specific antigen (PSA) and traditional biopsies, according to results involving 12,000-plus Swedish men.

The experimental screening approach decreased the number of MRIs done by 36% and biopsy procedures done by 8%, while maintaining the ability to detect clinically significant prostate cancer, say the investigators.

The Swedish innovation included the Stockholm3 test, which uses a combination of clinical information, protein measurements (including PSA), and a genetic score based on single-nucleotide polymorphisms to estimate risk.

Dr Tobias Nordström

"These findings might prompt a reevaluation of population-based prostate cancer screening in countries with high prostate cancer mortality," say Tobias Nordström, MD, PhD, of the Karolinska Institutet, Stockholm, Sweden, and colleagues in their study published this month in Lancet Oncology.

However, an American expert observed that the proposed Stockholm3/MRI model could work well with Sweden's health system — but get complicated elsewhere.

"It's a fairly complex diagnostic workflow involving laboratories, imaging protocols, and radiological competence reading MRIs — and that's quite complex," R. Jeffrey Karnes, MD, told Medscape Medical News.

"A non-streamlined health care system could have a hard time adopting this kind of strategy," said Karnes, chair of the Division of Community Urology at the Mayo Clinic, Rochester, Minnesota.

Dr R. Jeffrey Karnes

Karnes, who was not involved in the study, also noted another important limitation to wider use. "The study involves the Stockholm3 score based on Caucasian Scandinavian men and based on their (genetic profiles), so we don't know if it's been validated elsewhere or if it's translatable to a more heterogeneous population of men."

The study authors provided context for the current trial.

They observe that PSA testing followed by standard transrectal ultrasound-guided biopsies in men with elevated PSA is known to be linked to reduced mortality from prostate cancer (in the European Randomized Screening for Prostate Cancer). But the approach has a known disadvantage — namely overdetection of low-grade cancers that are relatively harmless, resulting in unwanted side effects linked to the diagnosis and treatment.

Among various emerging alternatives that have been proposed, the Stockholm3 test combines clinical information (eg, age and cancer history) with protein measurements (including PSA) and a polygenic risk score, in estimating risk prior to a traditional biopsy.

Furthermore, the use of MRI prior to a biopsy, as opposed to the standard ultrasound approach, has also been shown to further reduce overdetection while increasing the detection of prostate cancer that is clinically significant.

Reduced Detection of Low-grade Cancers

To investigate the efficacy of the combination of the Stockholm3 risk prediction model with MRI-targeted biopsy, the authors enrolled 12,750 men men in Sweden and found that 2293 had an elevated risk of prostate cancer, defined either as a PSA of 3 ng/mL or higher or a Stockholm3 score of 0.11 or higher, and thus were eligible for inclusion.

The men, aged between 50 and 74, were randomly assigned to receive either the traditional transrectal-guided ultrasound prostate biopsies (n = 921) or to biparametric MRI, and then, if shown to be positive on MRI, to receive MRI-targeted and systematic biopsies (n = 1372).

The results showed the use of the score of Stockholm3 of 0.11 or higher and MRI follow-up resulted in an improved detection of clinically significant cancers vs standard PSA and systematic biopsy (relative proportion [RP] 1.44; 3% vs 2%).

The Stockholm3 0.11 or higher/MRI group also had a lower detection of low-grade cancers (RP, 0.46; 0.7% vs 1.4%), and was associated with fewer biopsy procedures.

In looking specifically within the group of patients receiving MRI, a Stockholm3 threshold of 0.15 or higher resulted in an identical detection of clinically significant cancer vs the PSA 3 ng/mL cutoff.

Further, the Stockholm3 test with 0.15 as a threshold resulted in fewer MRI procedures (RP, 0.64), fewer biopsy procedures (RP, 0.92), and a reduced detection of low-grade cancers (RP, 0.83) vs the PSA 3 ng/mL group.

Those in the Stockholm3/MRI group also had a lower incidence of antibiotic prescriptions for infection (1.8% vs 4.4%; P = .0002) and a lower incidence of admission to hospital (1.2% vs 3.4%; P = .0003) compared with those in the standard PSA/traditional biopsy group.

Study Uptake an Issue?

In an accompanying editorial on the study, Caroline M. Moore, MD, of University College London, United Kingdom, noted that key factors necessary for the program to gain success is its uptake in a screening invitation. The authors reported a 26% uptake, which is far short of the 70%–80% that formal national screening programs strive for.

"A combination of interventions might be appropriate to increase uptake, and the potential increase in acceptability after removing the need for digital rectal examination seems likely to contribute to a willingness to be screened across many communities," she writes.

Regarding that issue, study author Nordström noted to Medscape Medical News that "it was not surprising that the level of participation in our study was lower than in existing national screening programs" because the study did not include any advertising or reminders, with participants only urged to respond digitally.

"Nonetheless, I completely agree that a national screening program might need to use a combination of interventions to increase uptake," Nordström said.

Another concern is the implementation of high quality MRI in screening, which can be more challenging of a diagnostic strategy compared with standard transrectal ultrasound-guided biopsy, Moore says.

American critic Karnes accented the positive in a final comment. "This is a helpful study to obtain a more ideal way of screening since it is known that exclusive PSA-based screening can reduce mortality, yet at a cost."  

The study received funding from The Swedish Cancer Society, the Swedish Research Council, and Stockholm City Council. The authors and Karnes have disclosed no relevant financial relationships. Moore reported grants from SpectraCure, the Medical Research Council, Movember, Prostate Cancer UK, National Institute for Health Research, Cancer Research UK, and the EAU Research Foundation; consulting fees from Sonablate; and speaker fees from Astellas and Janssen.

Lancet Oncology. Published August 12, 2021. Abstract, Editorial

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