In a screening population, a non-negligible number of men with prostate-specific antigen (PSA) 1.8–3.0 ng/ml have clinically significant prostate cancer. Lowering the PSA threshold for magnetic ...resonance imaging (MRI) would lead to a large increase in MRI examinations, and whether the benefits of lowering the PSA threshold outweigh the harms is not yet known.
Magnetic resonance imaging(MRI) and targeted biopsies reduce overdiagnosis of prostate cancer(PC). It is uncertain how this strategy performs for low PSA levels. The objective was to investigate the PI-RADS distribution, frequency and characteristics of screen-detected PC with PSA of 1.8–<3ng/ml and 3–<10ng/ml.
In the population-based Göteborg-2 screening study, 17 974 men choose to participate by having a PSA(2015–2020). One-third of the participants(n=6006) were randomized to Arm 3, men with a PSA ≥1.8ng/ml were recommended MRI. Men with positive MRI(PI-RADS3–5) had four targeted biopsies from each MRI-visible lesion. Clinically significant PC was defined as Gleason score ≥3+4.
6006 men were included. Median age was 55.9 years. 670(11%) had PSA of 1.8–<3ng/ml(low-PSA group), median PSA 2.1ng/ml, and 377(6.3%) had PSA of 3–<10ng/ml(high-PSA group), median PSA 3.9ng/ml. PI-RADS scores of 3, 4, and 5 were observed in 7.8%, 15%, and 1.0% in the low-PSA group, and in 6.9%, 17%, and 5.3% in the high-PSA group, respectively. PC was found in 64 men (41%, 95%CI 0.33-0.49) with positive MRI findings in the low-PSA group, 33(21%) had Gleason 6 and 31(20%) had Gleason ≥7. In the high-PSA group, PC was detected in 61men (56%, 95%CI 0.46-0.66), 26(24%) had Gleason 6 and 35(32%) had Gleason ≥7. Limitations include results from only a single screening round.
A non-negligible number of men with PSA 1.8-3ng/ml have clinically significant PC. Whether a delay in the diagnosis of these tumors until they reached PSA ≥3ng/ml would impair their chance of cure remains to be evaluated.
Abstract
Background: Long-term frozen storage may alter the results of prostate-specific antigen (PSA) measurements, mainly because of degradation of free PSA (fPSA) in vitro. We compared the effects ...of long-term storage on fPSA, total PSA (tPSA), and complexed PSA (cPSA) in serum vs EDTA-plasma samples.
Methods: We measured fPSA and tPSA concentrations in matched pairs of archival serum and EDTA-plasma samples (stored frozen at −20 °C for 20 years) from a large population-based cohort in Malmö, Sweden. We also compared concentrations in age-matched men with those in samples not subjected to long-term storage, obtained from participants in a population-based study of prostate cancer screening in Göteborg, Sweden. These contemporary samples were handled according to standardized preanalytical and analytical protocols aimed at minimizing in vitro degradation. tPSA and fPSA measurements were performed with a commercial assay (Prostatus Dual Assay; Perkin-Elmer Life Sciences).
Results: Concentrations of tPSA and fPSA and calculated cPSA (tPSA − fPSA) in archival plasma were not significantly different from those in contemporary serum from age-matched men. In archival serum, however, random variability of fPSA was higher vs plasma than in contemporary samples, whereas systematic error of fPSA analyses was similarly small in archival and contemporary serum and plasma.
Conclusions: Concentrations of tPSA and calculated cPSA were highly stable in plasma and serum samples subjected to long-term storage at −20 °C. Greater random variability, rather than a systematic decrease, may explain differences in fPSA analyses observed in archival serum.
Abstract Background Active surveillance (AS) has emerged as a treatment strategy for reducing overtreatment of screen-detected, low-risk prostate cancer (PCa). Objective To assess outcomes following ...AS of men with screen-detected PCa. Design, setting, and participants Of the 968 men who were diagnosed with screen-detected PCa between 1995 and 2010 in the Göteborg randomised, population-based PCa screening trial, 439 were managed with AS and were included in this study. Median age at diagnosis was 65.4 yr of age, and median follow-up was 6.0 yr from diagnosis. Intervention The study participants were followed at intervals of 3–12 mo and were recommended to switch to deferred active treatment in case of a progression in prostate-specific antigen, grade, or stage. Outcome measurements and statistical analysis The end points—overall survival (OS), treatment-free survival, failure-free (no relapse after radical treatment) survival, and cancer-specific survival—were calculated for various risk groups (very low, low, intermediate, and high) with Kaplan-Meier estimates. A Cox proportional hazards model as well as a competing risk analysis were used to assess whether risk group or age at diagnosis was associated with failure after AS. Results and limitations Forty-five per cent of all screen-detected PCa were managed with AS, and very low-risk and low-risk PCa constituted 60% of all screen-detected PCa. Thirty-seven per cent (162 of 439) switched from surveillance to deferred active treatment, and 39 men failed AS. The 10-yr OS, treatment-free survival, and failure-free survival were 81.1%, 45.4%, and 86.4%, respectively (Kaplan-Meier estimates). Men with low-, intermediate-, and high-risk tumours had a hazard ratio for failure of 2.1 ( p = 0.09), 3.6 ( p = 0.002), and 4.6 ( p = 0.15), respectively, compared to very low-risk tumours (Cox regression). Only one PCa death occurred, and one patient developed metastasis (both in the intermediate-risk group). The main limitation of this study is the relatively short follow-up. Conclusions A large proportion of men with screen-detected PCa can be managed with AS. AS appears safe for men with low-risk PCa.
Abstract Context There is great interest in using magnetic resonance imaging (MRI) for men on active surveillance for prostate cancer. Objective To systematically review evidence regarding the use of ...MRI in men with low- or intermediate-risk prostate cancer suitable for active surveillance. Evidence acquisition Ovid Medline and Embase databases were searched for active surveillance, prostate cancer, and MRI from inception until April 25, 2014 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses process. Identified reports were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. Evidence synthesis A lesion on MRI suspicious for prostate cancer (positive MRI) is seen in two-thirds of men otherwise suitable for active surveillance. A positive MRI makes the identification of clinically significant disease at repeat biopsy more likely, especially when biopsies are targeted to suspicious MRI lesions. Radical prostatectomy data show that positive MRI is more likely to be associated with upgrading (Gleason score >3 + 3) than a negative MRI (43% vs 27%). A positive MRI is not significantly more likely to be associated with upstaging at radical prostatectomy (>T2) than a negative MRI (10% vs 8%). Although MRI is of interest in the monitoring of men on active surveillance, robust data on the use of repeat MRI in active surveillance are lacking. Prospective studies with clear definitions of radiological significance and progression are needed before this approach can be adopted. Conclusions MRI is useful for detection of clinically significant disease at initial assessment of men considering active surveillance. To use MRI as a monitoring tool in surveillance, it will be necessary to define both radiological significance and radiological progression. Patient summary This review assesses evidence for the use of magnetic resonance imaging (MRI) in men on active surveillance for prostate cancer. MRI at the start of surveillance can detect clinically significant disease in one-third to half of men. There are few data to assess the use of MRI as a monitoring tool during surveillance, so there is a need to define significant disease on MRI and significant changes over time.
Higher age increased the risk of prostate cancer and the risk of higher Gleason score. These findings should be considered when counseling men for early diagnosis and treatment for prostate cancer.
...Studies have suggested associations between greater age, increased risk of prostate cancer (PC), and higher Gleason score.
The present study aimed at investigating these associations within the Göteborg-1 randomized, population-based PC screening trial.
The screening arm of the Göteborg-1 screening trial comprises 10000 randomly selected men (aged 50–64 yr at randomization) from the Göteborg region of Sweden. Between 1995 and 2014, they were biennially invited to prostate-specific antigen (PSA) testing to an upper age limit of 70 yr (range 67–71 yr). PSA ≥3 ng/ml triggered a prostate biopsy (sextant biopsy 1995–2009, thereafter a ten-core biopsy).
The impact of age on Gleason score, given a screen-detected PC, was investigated with multinomial logistic regression analyses adjusted for year of testing and screening round.
Overall, 7625 men had at least one PSA test and 1022 men were diagnosed with PC. For men with screen-detected PC, age was associated with the risk of clinically significant PC above and beyond screening round and year of testing (p < 0.001). For each 1-yr increase in age, the risk of being diagnosed with a Gleason score ≥3 + 4 cancer (vs <7) increased by 11% (95% confidence interval CI 4.7–17), whereas the risk of being diagnosed with a Gleason score ≥4 + 3 cancer (vs <7) increased by 8.5% (95% CI –1.6 to 20).
The increased risk of a higher Gleason score in older men should be considered when counseling men regarding early diagnosis and treatment for PC.
We found that older age increased both the risk of prostate cancer and the risk of more aggressive prostate cancer.
Our goal was to analyze results from 22 years of followup in the Göteborg randomized prostate cancer (PC) screening trial.
In December 1994, 20,000 men born 1930-1944 were randomly extracted from the ...Swedish population register and were randomized (1:1) into either a screening group (SG) or to a control group (CG). Men in the SG were repeatedly invited for biennial prostate specific antigen testing up to an average age of 69 years. Main endpoints were PC incidence and mortality (intention-to-screen principle).
After 22 years, 1,528 men in the SG and 1,124 men in the CG had been diagnosed with PC. In total, 112 PC deaths occurred in the SG and 158 in the CG. Compared with the CG, the SG showed a PC incidence rate ratio (RR) of 1.42 (95% CI, 1.31-1.53) and a PC mortality RR of 0.71 (95% CI, 0.55-0.91). The 22-year cumulative PC mortality rate was 1.55% (95% CI, 1.29-1.86) in the SG and 2.13% (95% CI, 1.83-2.49) in the CG. Correction for nonattendance (Cuzick method) yielded a RR of PC mortality of 0.59 (95% CI, 0.43-0.80). Number needed to invite and number needed to diagnose was estimated to 221 and 9, respectively. PC death risk was increased in the following groups: nontesting men, men entering the program after age 60 and men with >10 years of followup after screening termination.
Prostate specific antigen-based screening substantially decreases PC mortality. However, not attending, starting after age 60 and stopping at age 70 seem to be major pitfalls regarding PC death risk.
Background
Diffusion‐weighted magnetic resonance imaging plays an important role in multiparametric assessment of prostate lesions. The derived apparent diffusion coefficient (ADC) could be a useful ...quantitative biomarker for malignant growth, but lacks acceptance because of low reproducibility.
Purpose
To investigate the impact of the choice of diffusion‐weighting levels (b‐values) on contrast‐to‐noise ratio and quantitative measures in prostate diffusion‐weighted MRI.
Study Type
Retrospective and simulation based on published data.
Subjects
Patient cohort (21 men with Prostate Imaging‐Reporting and Data System (PI‐RADS) version 2 score ≥3) from a single‐center study.
Field Strength/Sequence
3 T/diffusion‐weighted imaging with single‐shot echo‐planar imaging.
Assessment
Both clinical data and simulations based on previously acquired data were used to quantify the influence of b‐value choice in normal peripheral zone (PZ) and PZ tumor lesions. For clinical data, ADC was determined for different combinations of b‐values. Contrast‐to‐noise ratio and quantitative diffusion measures were simulated for a wide range of b‐values.
Statistical Tests
Tissue ADC and the lesion‐to‐normal tissue ADC ratios of different b‐value combinations were compared with paired two‐tailed Student's t‐tests. A P‐value <0.05 was considered statistically significant.
Results
Findings about b‐value dependence derived from clinical data and from simulations agreed with each other. Provided measurement was limited to two b‐values, simulation‐derived optimal b‐value choices coincided with PI‐RADSv2 recommendations. For two‐point measurements, ADC decreased by 15% when the maximum b‐value increased from 1000 to 1500 seconds/mm2, but corresponding lesion‐to‐normal tissue ADC ratio showed no significant change (P = 0.86 for acquired data). Simulations with three or more measurement points produced ADCs that declined by only 8% over this range of maximum b‐value. Corresponding ADC ratios declined between 2.6% (three points) and 3.8% (21 points). Simulations also revealed an ADC reduction of about 19% with the shorter echo and diffusion time evaluated.
Data Conclusion
The comprehensive assessment of b‐value dependence permits better formulation of protocol and analysis recommendations for obtaining reproducible results in prostate cancer diffusion‐weighted MRI.
Level of Evidence
4
Technical Efficacy
Stage 2
In the present study, we show that a blood-based biomarker “4Kscore” as a reflex test in men with prostate-specific antigen ≥3.0 ng/ml would reduce the number of magnetic resonance imaging scans ...needed by 41%, and more importantly, 28% of men would be spared a biopsy.
We investigated whether adding 4Kscore as a reflex test to prostate-specific antigen (PSA) could improve the screening algorithm for prostate cancer (PC).
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.
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%).
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.
The Swedish population-based organised prostate cancer testing programmes are feasible and have high compliance to the diagnostic pathway. Inter-regional differences in diagnostic outcomes show a ...need for standardisation of the diagnostic pathway’s components.
The European Union recently recommended evaluation of the feasibility of organised prostate cancer screening. In Sweden, regional population-based organised prostate cancer testing (OPT) programmes were introduced in 2020.
To describe initial participation rates and diagnostic outcomes.
The three most populated Swedish regions invited all men aged 50 yr to OPT by a letter in 2020–2022. Men with prostate-specific antigen (PSA) ≥3 ng/ml were referred for prostate magnetic resonance imaging (MRI). PSA assays differed across regions. Men with Prostate Imaging Reporting and Data System (PI-RADS) 1–3 and PSA density ≥0.15 ng/ml/cm3 or PI-RADS 4–5 were referred for a biopsy. Data were obtained from the Swedish Register for Organised Prostate Cancer Testing.
Overall and regional participation rates, PSA distributions, PI-RADS score distributions, cancer detection, and treatment were evaluated.
A total of 23 855 (35%) of 68 060 invited men participated; 696 (2.9%) had PSA ≥3 ng/ml, and of them, 306 (44%) had a biopsy indication and 221 (32%) had a biopsy. On biopsy, 93 (42%) had Gleason grade group ≥2 (0.39% of PSA-tested men) and 44 (20%) Gleason grade group 1 cancer. Most men with cancer had treatment with curative intent (70%) or were under active surveillance (28%). Across regions, proportions of men with PSA ≥3 ng/ml ranged from 2.3% to 4.0%, and those with PI-RADS score 4–5 ranged from 12% to 21%. A limitation is that results are applicable only to first testing of men in their early 50s.
The OPT programmes are feasible with good compliance to the diagnostic pathway. The use of MRI and PSA density avoided a biopsy for over half of the men with PSA ≥3 ng/ml. Inter-regional differences in diagnostic outcomes show a need for standardisation of the diagnostic pathway’s components.
We report the diagnostic outcomes of inviting 68 000 50-yr-old men to organised prostate cancer testing.
Background Treatment for localized prostate cancer remains controversial. To our knowledge, there are no outcome studies from contemporary population-based cohorts that include data on stage, Gleason ...score, and serum levels of prostate-specific antigen (PSA). Methods In the National Prostate Cancer Register of Sweden Follow-up Study, a nationwide cohort, we identified 6849 patients aged 70 years or younger. Inclusion criteria were diagnosis with local clinical stage T1–2 prostate cancer from January 1, 1997, through December 31, 2002, a Gleason score of 7 or less, a serum PSA level of less than 20 ng/mL, and treatment with surveillance (including active surveillance and watchful waiting, n = 2021) or curative intent (including radical prostatectomy, n = 3399, and radiation therapy, n = 1429). Among the 6849 patients, 2686 had low-risk prostate cancer (ie, clinical stage T1, Gleason score 2-6, and serum PSA level of <10 ng/mL). The study cohort was linked to the Cause of Death Register, and cumulative incidence of death from prostate cancer and competing causes was calculated. Results For the combination of low- and intermediate-risk prostate cancers, calculated cumulative 10-year prostate cancer–specific mortality was 3.6% (95% confidence interval CI = 2.7% to 4.8%) in the surveillance group and 2.7% (95% CI = 2.1% to 3.45) in the curative intent group. For those with low-risk disease, the corresponding values were 2.4% (95% CI = 1.2% to 4.1%) among the 1085 patients in the surveillance group and 0.7% (95% CI = 0.3% to 1.4%) among the 1601 patients in the curative intent group. The 10-year risk of dying from competing causes was 19.2% (95% CI = 17.2% to 21.3%) in the surveillance group and 10.2% (95% CI = 9.0% to 11.4%) in the curative intent group. Conclusion A 10-year prostate cancer–specific mortality of 2.4% among patients with low-risk prostate cancer in the surveillance group indicates that surveillance may be a suitable treatment option for many patients with low-risk disease.
PDF
