Prostate Cancer Screening with PSA and MRI Followed by Targeted Biopsy Only

Abstract

Background: Screening for prostate cancer is burdened by a high rate of overdiagnosis. The most appropriate algorithm for population-based screening is unknown.

Methods: We invited 37,887 men who were 50 to 60 years of age to undergo regular prostate-specific antigen (PSA) screening. Participants with a PSA level of 3 ng per milliliter or higher underwent magnetic resonance imaging (MRI) of the prostate; one third of the participants were randomly assigned to a reference group that underwent systematic biopsy as well as targeted biopsy of suspicious lesions shown on MRI. The remaining participants were assigned to the experimental group and underwent MRI-targeted biopsy only. The primary outcome was clinically insignificant prostate cancer, defined as a Gleason score of 3+3. The secondary outcome was clinically significant prostate cancer, defined as a Gleason score of at least 3+4. Safety was also assessed.

Results: Of the men who were invited to undergo screening, 17,980 (47%) participated in the trial. A total of 66 of the 11,986 participants in the experimental group (0.6%) received a diagnosis of clinically insignificant prostate cancer, as compared with 72 of 5994 participants (1.2%) in the reference group, a difference of -0.7 percentage points (95% confidence interval [CI], -1.0 to -0.4; relative risk, 0.46; 95% CI, 0.33 to 0.64; P<0.001). The relative risk of clinically significant prostate cancer in the experimental group as compared with the reference group was 0.81 (95% CI, 0.60 to 1.1). Clinically significant cancer that was detected only by systematic biopsy was diagnosed in 10 participants in the reference group; all cases were of intermediate risk and involved mainly low-volume disease that was managed with active surveillance. Serious adverse events were rare (<0.1%) in the two groups.

Conclusions: The avoidance of systematic biopsy in favor of MRI-directed targeted biopsy for screening and early detection in persons with elevated PSA levels reduced the risk of overdiagnosis by half at the cost of delaying detection of intermediate-risk tumors in a small proportion of patients. (Funded by Karin and Christer Johansson's Foundation and others; GÖTEBORG-2 ISRCTN Registry number, ISRCTN94604465.).

Figure 1.. Randomization and Enrollment.

Men 50 to 60 years of age identified from a population registry were invited to screening. Those who agreed to undergo screening and prostate-specific antigen (PSA) testing were randomly assigned to the reference group or to the experimental group. Men in both groups who had a PSA level of at least 3 ng per milliliter were offered multiparametric magnetic resonance image (MRI) screening. Participants in the reference group underwent systematic prostate biopsies (10 to 12 cores) irrespective of their MRI results and, possibly, targeted biopsies (4 cores) in case of positive MRI findings (Prostate Imaging Reporting and Data System [PI-RADS] score 3 to 5; scores range from 1 to 5, with higher scores indicating more clinically suspicious lesions). Men in the experimental group underwent only targeted prostate biopsy if the MRI showed suspicious lesions (PI-RADS score, 3 to 5) unless the PSA level was 10 ng per milliliter or higher.