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.).

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.

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.

Role of Magnetic Resonance Imaging in Prostate Cancer Screening: A Pilot Study Within the Göteborg Randomised Screening Trial.

BACKGROUND: Magnetic resonance imaging (MRI) and targeted biopsies (TB) have shown potential to more accurately detect significant prostate cancer compared with prostate-specific antigen (PSA) and systematic biopsies (SB). OBJECTIVE: To compare sequential screening (PSA+MRI) with conventional PSA screening. DESIGN, SETTING, AND PARTICIPANTS: Of 384 attendees in the 10th screening round of the Göteborg randomised screening trial, 124 men, median age 69.5 yr, had a PSA of ≥ 1.8 ng/ml and underwent a prebiopsy MRI. Men with suspicious lesions on MRI and/or PSA ≥ 3.0ng/ml were referred for biopsy. SB was performed blinded to MRI results and TB was performed in men with tumour-suspicious findings on MRI. Three screening strategies were compared (PSA ≥ 3.0+SB; PSA ≥ 3.0+MRI+TB and PSA ≥ 1.8+MRI+TB). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cancer detection rates, sensitivity, and specificity were calculated per screening strategy and compared using McNemar's test. RESULTS AND LIMITATIONS: In total, 28 cases of prostate cancer were detected, of which 20 were diagnosed in biopsy-naïve men. Both PSA ≥ 3.0+MRI and PSA ≥ 1.8+MRI significantly increased specificity compared with PSA ≥ 3.0+SB (0.92 and 0.79 vs 0.52; p<0.002 for both), while sensitivity was significantly higher for PSA ≥ 1.8+MRI compared with PSA ≥ 3.0+MRI (0.73 vs 0.46, p=0.008). The detection rate of significant cancer was higher with PSA ≥ 1.8+MRI compared with PSA ≥ 3.0+SB (5.9% vs 4.0%), while the detection rate of insignificant cancer was lowered by PSA ≥ 3.0+MRI (0.3% vs 1.2%). The primary limitation of this study is the small sample of men. CONCLUSION: A screening strategy with a lowered PSA cut-off followed by TB in MRI-positive men seems to increase the detection of significant cancers while improving specificity. If replicated, these results may contribute to a paradigm shift in future screening. PATIENT SUMMARY: Major concerns in prostate-specific antigen screening are overdiagnosis and underdiagnosis. We evaluated whether prostate magnetic resonance imaging could improve the balance of benefits to harm in prostate cancer screening screening, and we found a promising potential of using magnetic resonance imaging in addition to prostate-specific antigen.

Inadequate testosterone suppression after medical and subsequent surgical castration in a patient with prostate cancer.

Androgen deprivation is a cornerstone in prostate cancer management. We present a 69-year-old man, with a poorly differentiated prostate cancer with skeletal and lymph node metastases. After medical and subsequent surgical castration serum testosterone concentrations remained inappropriately high (4.9 and 4.5 nmol/L; castration range < 0.5). For cancer staging a CT was performed which showed bilateral adrenal enlargement. Endocrine workup revealed elevated levels of adrenal androgens and adrenal precursors. Mutation analysis confirmed a non-classical 21-hydroxylase deficiency, that is, a mild form of congenital adrenal hyperplasia (CAH). To suppress adrenocorticotrophic hormone and the excess adrenal androgen secretion, treatment with hydrocortisone and prednisolone was started with success. Inadequate testosterone suppression after castration due to previously undiagnosed CAH has not previously been reported. Considering the estimated prevalence of 1% in selected populations, non-classical CAH should be considered when testosterone is not adequately suppressed after castration in men with prostate cancer.

Optimisation of tube voltage for conventional urography using a Gd2O2S:Tb flat panel detector.

With the increasing use of computed tomography (CT) for urography examinations, the indications for 'conventional' projection urography have changed and are more focused on high-contrast details. The purpose of the present study was to optimise the beam quality for urography examinations performed with a Gd(2)O(2)S:Tb flat-panel detector for the new conditions. Images of an anthropomorphic phantom were collected at different tube voltages with a CXDI-40G detector (Canon Inc., Tokyo, Japan). The images were analysed by radiologists and residents in a visual grading characteristics (VGCs) study. The tube voltage resulting in the best image quality was 55 kV, which therefore was selected for a clinical study. Images from 62 patients exposed with either 55 or 73 kV (original tube voltage) at constant effective doses were included. The 55-kV images underwent simulated dose reduction to represent images collected at 80, 64, 50, 40 and 32 % of the original dose level. All images were included in a VGC study where the observers rated the visibility of important anatomical landmarks. For images collected at 55 kV, an effective dose of approximately 85 % resulted in the same image quality as for images collected at 73 kV at 100 % dose. In conclusion, a low tube voltage should be used for conventional urography focused on high-contrast details. The study indicates that using a tube voltage of 55 kV instead of 73 kV for a Gd(2)O(2)S:Tb flat-panel detector, the effective dose can be reduced by approximately 10-20 % for normal-sized patients while maintaining image quality.

Efficacy and safety of gadodiamide (Gd-DTPA-BMA) in renal 3D-magnetic resonance angiography (MRA): a phase II study.

PURPOSE: To determine the most efficacious dose of gadodiamide for three-dimensional (3D) contrast-enhanced (CE) magnetic resonance angiography (MRA) of the renal arteries on a patient level based on the sensitivity in detecting the main hemodynamically relevant (> or =50% or occlusion) renal artery stenosis (RAS) using intra-arterial digital subtraction angiography (IA DSA) as the gold standard. MATERIALS AND METHODS: This prospective, randomized, double-blind, parallel-group, multicenter study included 273 patients referred to IA DSA for suspected RAS. Patients underwent 3D CE MRA after injection of 0.01, 0.05, 0.1, or 0.2mmol/kg of body weight gadodiamide (0.5mmol/ml). The images were assessed for location and degree of RAS by independent blinded readers (MRA: three readers, IA DSA: one reader). Hypothesis testing for a significant trend in sensitivity across dose groups was based on the one-sided Cochran-Armitage style trend test for each independent MRA reader. RESULTS: The lowest dose group (0.01mmol/kg) proved non-efficacious in detecting hemodynamically relevant (i.e., > or =50% or occlusion) RAS. A statistically significant dose trend (p<0.001) was shown for each of the three independent readers. Depending on reader, the sensitivity obtained with 0.05, 0.1, and 0.2mmol/kg was 63.9-86.1%, 75.8-91.4% and 80.6-90.6%, the specificity was 66.7-73.9%, 59.3-75.0%, and 59.3-75.0% and accuracy was 67.8-78.9%, 75.4-77.4%, and 76.3-81.0%, for the three dose groups, respectively. There were eight non-severe adverse events (AEs). Three serious AEs occurring in one patient were judged not related to gadodiamide by the on-site investigator. CONCLUSION: A significant dose trend between the four doses examined was observed. The lowest dose (0.01mmol/kg) differed significantly from those of the other three doses. Based on the analysis of the primary and secondary endpoints, 0.1mmol/kg gadodiamide appears to be the most suitable dose in diagnosing hemodynamically relevant RAS. The present study also demonstrated gadodiamide to be safe and well tolerated.

Prospective randomized study comparing ultrasound-guided thrombin injection to compression in the treatment of femoral pseudoaneurysms.

PURPOSE: To compare in a randomized prospective study the treatment of femoral pseudoaneurysms with ultrasound-guided thrombin injection versus ultrasound-guided compression. METHODS: Thirty consecutive patients (22 men; mean age 67+/-8 years, range 53-82) with iatrogenic femoral pseudoaneurysms were randomized to treatment with either ultrasound-guided compression (n=15) or injection of bovine thrombin (n=15). The primary outcome measure was thrombosis of the pseudoaneurysm within 24 hours. Secondary outcome measures were complications and hospitalization time (LOS). RESULTS: Thrombosis within 24 hours was achieved in 15 (100%) patients given thrombin versus 2 (13%) in the compression group (p<0.001). Of 13 pseudoaneurysms failing the initial compression treatment, 7 were retreated, 4 successfully. Thus, only 6 (40%) lesions were thrombosed within 48 hours after 1 or 2 compression sessions. The other 9 cases were successfully treated with thrombin injection. LOS was 2.8+/-1.5 days and 3.5+/-2.4 days in the thrombin and compression groups, respectively (p>0.05). No complications were noted in either group. CONCLUSIONS: Ultrasound-guided thrombin injection induces a fast, effective, and safe thrombosis of postcatheterization pseudoaneurysms. The technique is clearly superior to compression treatment and is recommended as the therapy of choice.