New research evaluates strategies for prostate cancer screening

Prostate-specific antigen (PSA) screening reduced mortality over the long term, magnetic resonance imaging (MRI) and targeted biopsies improved early detection, and a multistep screening protocol involving a PSA test, a 4-kallikrein panel, and an MRI showed promise.

Three recent studies looked at different ways to screen men for prostate cancer.

The first, a secondary analysis of a clinical trial published April 6 by JAMA, compared the effect of a single invitation to prostate-specific antigen (PSA) screening versus no screening on long-term prostate cancer-specific mortality at 573 randomized primary care practices in England and Wales. In the intervention and control groups, respectively, there were 12,013 and 12,958 men ages 50 to 69 years who eventually received a prostate cancer diagnosis. At a median follow-up of 15 years, 1,199 men in the intervention group and 1,451 men in the control group had died of prostate cancer (0.69% [95% CI, 0.65% to 0.73%] and 0.78% [95% CI, 0.73% to 0.82%], respectively; rate ratio [RR], 0.92 [95% CI, 0.85 to 0.99]; P=0.03).

The PSA screening intervention increased detection of low-grade and localized disease but not intermediate, high-grade, locally advanced, or distally advanced tumors. Overall, there were 45,084 all-cause deaths in the intervention group versus 50,336 all-cause deaths in the control group (23.2% [95% CI, 23.0% to 23.4%] vs. 23.3% [95% CI, 23.1% to 23.5%]; RR, 0.97 [95% CI, 0.94 to 1.01]; P=0.11). Eight deaths from prostate cancer in the intervention group and seven in the control group (0.7% vs. 0.5%) were related to a diagnostic biopsy or to prostate cancer treatment.

The authors noted that the intervention involved only a single PSA screening invitation, that diagnosis and treatment have improved since the study began in 2002, and that few Black men were included, among other limitations. They concluded that a single invitation to PSA screening reduced prostate cancer deaths at 15 years compared with no routine screening but that the absolute reduction in deaths was small.

The second study, published April 5 by JAMA Oncology, was a systematic review and meta-analysis that examined whether screening pathways that included magnetic resonance imaging (MRI) and targeted biopsies outperformed those that used only PSA testing and systematic biopsy. Randomized clinical trials and prospective cohort studies published through May 2023 were eligible for inclusion if they reported data on the diagnostic utility of prostate MRI for prostate cancer screening. The primary outcome was the rate of detection of clinically significant prostate cancer, defined as International Society of Urological Pathology grade 2 or higher. Detection of clinically insignificant prostate cancer, biopsy indication rates, and positive predictive value for detection of clinically significant prostate cancer were secondary outcomes.

Twelve studies involving 80,114 men were included in the analysis. A positive result on the MRI pathway, which used sequential screening and a Prostate Imaging Reporting and Data System (PI-RADS) score of 3 or greater as a cutoff for biopsy, was associated with higher odds of clinically significant prostate compared with standard PSA-based screening cancer (odds ratio [OR], 4.15 [95% CI, 2.93 to 5.88]; P≤0.001). In addition, the MRI pathway was associated with decreased odds of biopsies (OR, 0.28 [95% CI, 0.22 to 0.36]; P≤0.001) and detection of insignificant cancer (OR, 0.34 [95% CI, 0.23 to 0.49]; P=0.002) without significant differences in detection of clinically significant cancer (OR, 1.02 [95% CI, 0.75 to 1.37]; P=0.86). Using a higher PI-RADS score as a biopsy cutoff was associated with additional reductions in odds of detecting insignificant disease and biopsies performed without any change in detection of clinically significant disease.

The authors concluded that based on their results, a strategy of prostate MRI with targeted biopsies appears to be effective for early detection of prostate cancer. "We found that MRI mitigates pitfalls of standard PSA-based strategies, as it can be associated with fewer unnecessary biopsies and helps to avoid the detection of insignificant cancers while not comprising significant disease detection," they wrote. "Our results highlight the need to reassess our approach to population-based screening; however, the optimal setup of MRI and biopsy scheme in the screening process requires further evaluation."

Finally, a preliminary report from the ProScreen Randomized Trial, published April 6 by JAMA, described rates of low-grade and high-grade prostate cancer among men participating in a screening protocol involving a PSA test, a 4-kallikrein panel, and an MRI. In the trial, which is being conducted in Finland, 61,193 men ages 50 through 63 years were randomly assigned to receive a screening invitation or not. Those in the intervention group had PSA testing, then a 4-kallikrein panel risk score if their PSA level was 3.0 ng/mL or higher. The kallikrein panel score was based on total PSA, free PSA, intact PSA, and human kallikrein-2. Those whose score was 7.5% or higher had an MRI of the prostate, with targeted biopsies for abnormal results.

Overall, 15,201 men were invited to participate in the screening protocol and 45,444 were not. Of those in the former group, 7,744 (51%) participated. Thirty-two low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected. In the 7,457 invited men (49%) who declined to participate, there were seven low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%). Cumulative incidence of low- and high-grade prostate cancer for the entire invited screening group was 0.26% and 1.13%, respectively. During a median of 3.2 years of follow-up, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected in the group not invited to screening, for a risk difference of 0.11% (95% CI, 0.03% to 0.20%) for low-grade cancer and 0.51% (95% CI, 0.33% to 0.70%) for high-grade cancer compared with the invited group.

"In this preliminary descriptive report from a randomized clinical trial, compared with a control group not offered screening, a single prostate cancer screening intervention that included a PSA test, a kallikrein panel for patients with PSA values of 3.0 ng/mL or higher, and an MRI, the screening intervention detected 1 additional high-grade cancer per 196 men invited to screening and 1 low-grade cancer per 909 men invited to the screening group," they wrote. "These preliminary findings should be interpreted provisionally, pending results of the primary mortality outcome."

An accompanying editorial commended the authors for their work and said that their trial evaluates a more contemporary and pragmatic approach to screening, although the lack of diversity among the included patients is an important limitation. "Although the long-term benefits of this approach will be better elucidated with follow-up, these early data already reflect more favorable stage distribution, more frequent management with active surveillance, and reduced use of androgen deprivation therapy in the screened population," the editorialists wrote. "With additional, collaborative efforts spanning research and clinical practice, even better care of patients is on the horizon."