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

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.).

Bi- or multiparametric MRI in a sequential screening program for prostate cancer with PSA followed by MRI? Results from the Göteborg prostate cancer screening 2 trial.

OBJECTIVES: The PIRADS Steering Committee has called for "higher quality data before making evidence-based recommendations on MRI without contrast enhancement as an initial diagnostic work up," however, recognizing biparametric (bp) MRI as a reasonable option in a low-risk setting such as screening. With bpMRI, more men can undergo MRI at a lower cost and they can be spared the invasiveness of intravenous access. The aim of this study was to assess cancer detection in bpMRI vs mpMRI in sequential screening for prostate cancer (PCa). METHODS: Within the ongoing Göteborg PCa screening 2 trial, we assessed cancer detection in 551 consecutive participants undergoing prostate MRI. In the same session, readers first assessed bpMRI and then mpMRI. Four targeted biopsies were performed for lesions scored PIRADS 3-5 with bpMRI and/or mpMRI. RESULTS: Cancer was detected in 84/551 cases (15.2%; 95% CI: 12.4-18.4) with mpMRI and in 83/551 cases (15.1%; 95% CI: 12.3-18.2%) with bpMRI. The relative risk (RR) for cancer detection with bpMRI compared to mpMRI was 0.99 (95% one-sided CI: > 94.8); bpMRI was non-inferior to mpMRI (10% non-inferiority margin). bpMRI resulted in fewer false positives, 45/128 (35.2%), compared to mpMRI, 52/136 (38.2%), RR = 0.92; 95% CI: 0.84-0.98. Of 8 lesions scored positive only with mpMRI, 7 were false positives. The PPV for MRI and targeted biopsy was 83/128 (64.8%) for bpMRI and 84/136 (61.8%) for mpMRI, RR = 1.05, 95% CI: 1.01-1.10. CONCLUSIONS: In a PSA-screened population, bpMRI was non-inferior to mpMRI for cancer detection and resulted in fewer false positives. KEY POINTS: • In screening for prostate cancer with PSA followed by MRI, biparametric MRI allows radiologists to detect an almost similar number of prostate cancers and score fewer false positive lesions compared to multiparametric MRI. • In a screening program, high sensitivity should be weighed against cost and risks for healthy men; a large number of men can be saved the exposure of gadolinium contrast medium by adopting biparametric MRI and at the same time allowing for a higher turnover in the MRI room.

Performance of 4Kscore as a Reflex Test to Prostate-specific Antigen in the GÖTEBORG-2 Prostate Cancer Screening Trial.

BACKGROUND AND OBJECTIVE: We investigated whether adding 4Kscore as a reflex test to prostate-specific antigen (PSA) could improve the screening algorithm for prostate cancer (PC). METHODS: In the GÖTEBORG-2 PC screening trial, 38 000men (50-60 yr) were invited to PSA testing and, if elevated, followed by magnetic resonance imaging (MRI). For 571 men with PSA ≥3.0 ng/ml and evaluable outcomes, 4Kscore was calculated. The performance using a prespecified 4Kscore cutoff of 7.5% was evaluated. KEY FINDINGS AND LIMITATIONS: The area under the curve for 4Kscore to identify intermediate- and high-risk PC was 0.84 (95% confidence interval 0.79-0.89), and the positive predictive value, and negative predictive value were 15% (0.12-0.20) and 99% (97-100%), respectively. Of the 54 men diagnosed with intermediate- or high-grade PC, two had a 4Kscore cutoff below 7.5%, both with organ-confined intermediate-risk PC. Per 1000 men with elevated PSA, adding 4Kscore would have resulted in avoidance of MRI for 408 (41%) men, biopsies for 95 (28% reduction) men, and diagnosis of 23 low-grade cancers (23% reduction) while delaying the diagnosis of four men with intermediate-grade cancers (4%). CONCLUSIONS AND CLINICAL IMPLICATIONS: Including 4Kscore as a reflex test for men with elevated PSA reduces the need for MRI and biopsy markedly, and results in less overdiagnosis of low-grade PC at the cost of delaying the diagnosis of intermediate-grade PC in a few men. These results add further evidence for including new blood-based biomarkers in addition to PSA to improve the harm and benefit ratio of PC screening and reduce the need for resource-demanding MRI and biopsies. PATIENT SUMMARY: In this study, 4Kscore, a blood-based biomarker, as a reflex test for men with elevated prostate-specific antigen (PSA), reduces the need for magnetic resonance imaging and biopsy. These results support the inclusion of new blood-based biomarkers in addition to PSA.

Men's Acceptance of Screening for Prostate Cancer with Prostate-specific Antigen, Magnetic Resonance Imaging, and Prostate Biopsy.

BACKGROUND: A prerequisite before introducing a screening program is that the screening examinations are acceptable to participants. OBJECTIVE: To evaluate the acceptance and bother of prostate cancer screening examinations. DESIGN, SETTING, AND PARTICIPANTS: The randomized population-based GÖTEBORG-2 prostate cancer screening trial invited >37 000 men for prostate-specific antigen (PSA) testing followed by magnetic resonance imaging (MRI) in case of elevated PSA and prostate biopsy (targeted and/or systematic) if indicated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Participants were asked to fill out a questionnaire and rate the level of bother associated with each examination (PSA, MRI, and prostate biopsy) on a categorical scale ranging from 1 to 5 (1 = "not at all bothersome" and 5 = "very bothersome"), and to rate their willingness to repeat the examinations, by marking an X on a continuous scale ranging from 0 to 10 (0 = "yes, without any hesitation" and 10 = "no, absolutely not"). Wilcoxon signed rank test was used. RESULTS AND LIMITATIONS: Compliance with MRI was 96% (1790/1872), compliance with biopsy was 89% (810/907), and the response rate to the questionnaire was 75% (608/810). Men who underwent all examinations (n = 577) responded that biopsy was more bothersome than PSA test (p < 0.001) and MRI (p < 0.001). High levels of bother (≥4 out of 5) were reported by 2% (12/577) for PSA test, 8% (46/577) for MRI, and 43% (247/577) for biopsy. Men were more willing to repeat MRI than biopsy (p < 0.001), but the difference was small (median 0.2 [interquartile range 0.1-0.6] vs 0.5 [0.1-2.0]). CONCLUSIONS: Biopsies are more bothersome than MRI, but a large majority of men accept to repeat both examinations if necessary. Omitting biopsy for MRI-negative men and shifting to targeted biopsies only will reduce bother for men participating in prostate cancer screening. PATIENT SUMMARY: We asked men how bothersome they found the prostate-specific antigen (PSA) test, magnetic resonance imaging (MRI), and prostate biopsies. Biopsies were more bothersome than PSA and MRI, but most men were willing to repeat all procedures if necessary.

Prostate Cancer Screening with Magnetic Resonance Imaging: Results from the Second Round of the Göteborg Prostate Cancer Screening 2 Trial.

BACKGROUND: The Göteborg 2 prostate cancer (PC) screening (G2) trial evaluates screening with prostate-specific antigen (PSA) followed by magnetic resonance imaging (MRI) in case of elevated PSA levels. OBJECTIVE: To assess the safety of using a 2-yr interval in men who were previously screened positive with PSA but had negative MRI or positive MRI with a negative biopsy. DESIGN, SETTING, AND PARTICIPANTS: A total of 61 201 men aged 50-60 yr were randomized and 38 366 were invited for screening (years 2015-2020). Men with positive MRI (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3) were scheduled for targeted biopsies. Men with negative MRI or negative biopsies were reinvited after 2 yr. Round 1 and 2 MRI scans (PI-RADS ≥3) of men not diagnosed with PC in round 1 were re-read and classified according to Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) by two radiologists. Interval PCs (detected outside the program before invitation to round 2) were identified by linking to the Regional PC Registry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Tabulation of overall detection of PC was done. RESULTS AND LIMITATIONS: Between October 2017 and June 2020, 474 men with round 1 elevated PSA and MRI underwent a second screening. Of those, 19% had nonelevated PSA in round 2 and were not examined further. Of the remaining 376 men, 89% had negative MRI. Targeted biopsies yielded 14 PCs: nine grade group (GG) 1 and five GG 2-3. In men with PI-RADS ≥3 and PC diagnosed in round 2, only two (GG 1) progressed according to the PRECISE criteria and the remainder were stable. Ten interval PCs were diagnosed: seven GG 1, one GG 2, and two GG 5. The two GG 5 PCs were PI-RADS 4 and 5 with negative round 1 biopsy. CONCLUSIONS: A 2-yr interval seems to be safe in men with negative MRI, while men with PI-RADS 4 and 5 lesions with negative biopsies should have a closer follow-up. PATIENT SUMMARY: In prostate cancer screening, a 2-yr follow-up seems to be safe if magnetic resonance imaging did not show highly suspicious findings.

The GÖTEBORG prostate cancer screening 2 trial: a prospective, randomised, population-based prostate cancer screening trial with prostate-specific antigen testing followed by magnetic resonance imaging of the prostate.

OBJECTIVE: To describe the study design of the GÖTEBORG prostate cancer screening (PC) 2 (Göteborg-2), a prospective, randomised, population-based trial of PC screening. This trial evaluates whether prostate-specific antigen (PSA) testing followed by 3 Tesla prostate magnetic resonance imaging (MRI) and targeted biopsy can reduce overdiagnosis, while maintaining the detection of clinically significant cancer, compared to PSA-screening and systematic biopsy. MATERIALS AND METHODS: A random sample of men 50-60 years in the Göteborg area, Sweden, identified from the Total Population Register, were randomised to either a screening or control group (CG). Participants in the screening group (SG) were further randomised into one of three arms: (1) PSA-test; if PSA ≥ 3 ng/mL, then MRI and systematic biopsy, plus targeted biopsy to suspicious lesions as per Prostate Imaging - Reporting and Data System, version 2 (PI-RADSv2) 3-5; (2) PSA-test; if PSA ≥ 3 ng/mL, then MRI, and targeted biopsy only if PI-RADSv2 3-5; (3) identical to Arm 2, except lower PSA-cut-off ≥1.8 ng/mL. The primary outcome is the detection rate of clinically insignificant PC (defined as Gleason Score 3 + 3 [Grade Group 1]) comparing all men with PSA ≥ 3 ng/mL in Arm 1 vs. Arm 2 + 3. RESULTS: Randomisation and enrolment started in September 2015. Accrual has hitherto resulted in 38,770 men randomised to the SG. The participation rate is 50%. Invitation to the first screening round was completed in June 2020. CONCLUSIONS: The Göteborg-2 trial will provide new knowledge about the performance of prostate MRI in a screening setting.

Performance and inter-observer variability of prostate MRI (PI-RADS version 2) outside high-volume centres.

Objective: Despite the growing trend to embrace pre-biopsy MRI in the diagnostic pathway for prostate cancer (PC), its performance and inter-observer variability outside high-volume centres remains unknown. This study aims to evaluate sensitivity of and variability between readers of prostate MRI outside specialized units with radical prostatectomy (RP) specimen as the reference standard.Materials and methods: Retrospective study comprising a consecutive cohort of all 97 men who underwent MRI and subsequent RP between January 2012 and December 2014 at a private hospital in Sweden. Three readers, blinded to clinical data, reviewed all images (including 11 extra prostate MRI to reduce bias). A tumour was considered detected if the overall PI-RADS v2 score was 3-5 and there was an approximate match (same or neighbouring sector) of tumour sector according to a 24 sector system used for both MRI and whole mount sections.Results: Detection rate for the index tumour ranged from 67 to 76%, if PI-RADS 3-5 lesions were considered positive and 54-66% if only PI-RADS score 4-5 tumours were included. Detection rate for aggressive tumours (GS ≥ 4 + 3) was higher; 83.1% for PI-RADS 3-5 and 79.2% for PI-RADS 4-5. The agreement between readers showed average [Formula: see text] values of 0.41 for PI-RADS score 3-5 and 0.51 for PI-RADS score 4-5.Conclusions: Prostate MRI evidenced a moderate detection rate for clinically significant PC with a rather large variability between readers. Clinics outside specialized units must have knowledge of their performance of prostate MRI before considering omitting biopsies in men with negative MRI.

Prostate cancer screening-when to start and how to screen?

Prostate-specific antigen (PSA) screening reduces prostate cancer (PCa) mortality; however such screening may lead to harm in terms of overdiagnosis and overtreatment. Therefore, upfront shared decision making involving a discussion about pros and cons between a physician and a patient is crucial. Total PSA remains the most commonly used screening tool and is a strong predictor of future life-threatening PCa. Currently there is no strong consensus on the age at which to start PSA screening. Most guidelines recommend PSA screening to start no later than at age 55 and involve well-informed men in good health and a life expectancy of at least 10-15 years. Some suggest to start screening in early midlife for men with familial predisposition and men of African-American descent. Others suggest starting conversations at age 45 for all men. Re-screening intervals can be risk-stratified as guided by the man's age, general health and PSA-value; longer intervals for those at lower risk and shorter intervals for those at higher risk. Overdiagnosis and unnecessary biopsies can be reduced using reflex tests. Magnetic resonance imaging in the pre-diagnostic setting holds promise in pilot studies and large-scale prospective studies are ongoing.