Screening for prostate cancer is burdened by a high rate of overdiagnosis. The most appropriate algorithm for population-based screening is unknown.
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.
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.
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.).
The New England journal of medicine. 2022 Dec 08 [Epub]
Jonas Hugosson, Marianne Månsson, Jonas Wallström, Ulrika Axcrona, Sigrid V Carlsson, Lars Egevad, Kjell Geterud, Ali Khatami, Kimia Kohestani, Carl-Gustaf Pihl, Andreas Socratous, Johan Stranne, Rebecka Arnsrud Godtman, Mikael Hellström, GÖTEBORG-2 Trial Investigators
From the Departments of Urology (J.H., A.K., K.K., J.S., R.A.G.), Radiology (J.W., K.G., A.S., M.H.), and Pathology (C.-G.P.), Sahlgrenska University Hospital-Sahlgrenska Academy at Gothenburg University, and the Department of Urology, Sahlgrenska Academy at Gothenburg University (J.H., M.M., S.V.C.), Gothenburg, and the Department of Oncology-Pathology, Karolinska Institute, Stockholm (L.E.) - all in Sweden; the Departments of Pathology and Molecular Oncology, Oslo University Hospital-Radiumhospitalet, Oslo (U.A.); and the Departments of Surgery (Urology Service) and Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (S.V.C.).