A Four-kallikrein Panel and β-Microseminoprotein in Predicting High-grade Prostate Cancer on Biopsy: An Independent Replication from the Finnish Section of the European Randomized Study of Screening for Prostate Cancer

Assel, Melissa; Sjöblom, Liisa; Murtola, Teemu J.; Talala, Kirsi; Kujala, Paula; Stenman, Ulf Håkan; Taari, Kimmo; Auvinen, Anssi; Visakorpi, Tapio; Tammela, Teuvo L.J.; Lilja, Hans

doi:10.1016/j.euf.2017.11.002

Cited by 8 publications

(9 citation statements)

References 29 publications

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“…Available results about the PCA3 showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. On the other hand, recent diagnostic accuracy studies assessing a 4K Score and Phi showed an AUC ranging from 0.71 to 0.74 for high--grade PCa detection (24,25). Those values are similar to the ones of the AUC of [CITRATE] for csPCa detection measured in the present study (0.748).…”

Section: Discussionsupporting

confidence: 89%

Seminal citrate is superior to PSA for detecting clinically significant prostate cancer

et al. 2019

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Purpose: To establish whether the citrate concentration in the seminal fl uid ([CI-TRATE]) measured by means of high-resolution nuclear magnetic resonance spectroscopy (1HNMRS) is superior to the serum prostate-specifi c antigen (PSA) concentration in detecting of clinically signifi cant prostate cancer (csPCa) in men with persistently elevated PSA. Materials and Methods: The group of patients consisted of 31 consecutively seen men with histological diagnosis of clinically localized csPCa. The control group consisted of 28 men under long-term follow-up (mean of 8.7 ± 3.0 years) for benign prostate hyperplasia (BPH), with persistently elevated PSA (above 4 ng/mL) and several prostate biopsies negative for cancer (mean of 2.7 ± 1.3 biopsies per control). Samples of blood and seminal fl uid (by masturbation) for measurement of PSA and citrate concentration, respectively, were collected from patients and controls. Citrate concentration in the seminal fl uid ([CITRATE]) was determined by means of 1HNMRS. The capacities of PSA and [CITRATE] to predict csPCa were compared by means of univariate analysis and receiver operating characteristic (ROC) curves. Results: Median [CITRATE] was signifi cantly lower among patients with csPCa compared to controls (3.93 mM/l vs. 15.53 mM/l). There was no signifi cant difference in mean PSA between patients and controls (9.42 ng/mL vs. 8.57 ng/mL). The accuracy of [CITRATE] for detecting csPCa was signifi cantly superior compared to PSA (74.8% vs. 54.8%). Conclusion: Measurement of [CITRATE] by means of 1HNMRS is superior to PSA for early detection of csPCa in men with elevated PSA.

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Section: Discussionsupporting

confidence: 89%

Seminal citrate is superior to PSA for detecting clinically significant prostate cancer

et al. 2019

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“…The controversies of using prostate-specific antigen (PSA) screening in the general population are well documented, but PSA remains the most effective PrCa biomarker currently available [10], [11], [12]. Efforts to improve sensitivity and specificity of PSA by incorporating other biological markers, such as the 4 kallikrein (4 K) marker panel [13], [14], PrCa risk calculators [15], [16], magnetic resonance imaging (MRI) [17], [18], and genetic markers [19], [20], into screening algorithms are under evaluation.…”

Section: Introductionmentioning

confidence: 99%

Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers

et al. 2019

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BackgroundMutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations.ObjectiveTo report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status.Design, setting, and participantsMen aged 40–69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy.Outcome measurements and statistical analysisPSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians.Results and limitationsA total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65).ConclusionsAfter 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers.Patient summaryWe demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening.

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“…The four kallikrein marker panel was evaluated in cryopreserved samples using the AutoDelfia 1235 automatic immunoassay system (Perkin‐Elmer, Turku, Finland) in H.L.’s laboratory at Lund University, Malmö, Sweden [14–16]. The panel was also validated for precision, concordance, and accuracy using Victor instruments (Perkin‐Elmer) at all three local laboratories.…”

Section: Methodsmentioning

confidence: 99%

“…Two USA‐based studies, the Multi‐ethnic Cohort study and the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial, both reported an association between MSP and high‐grade prostate cancer on biopsy [13,14]. However, two European‐based studies found that adding MSP to the four kallikrein model increased discrimination for GG ≥2 prostate cancer either very marginally [15] or not at all [16].…”

Section: Introductionmentioning

confidence: 99%

Prospective validation of microseminoprotein‐β added to the 4Kscore in predicting high‐grade prostate cancer in an international multicentre cohort

et al. 2020

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To prospectively evaluate the performance of a pre-specified statistical model based on four kallikrein markers in blood (total prostate-specific antigen [PSA], free PSA, intact PSA, and human kallikrein-related peptidase 2), commercially available as the 4Kscore, in predicting Gleason Grade Group (GG) ≥2 prostate cancer at biopsy in an international multicentre study at three academic medical centres, and whether microseminoprotein-b (MSP) adds predictive value. Patients and MethodsA total of 984 men were prospectively enrolled at three academic centres. The primary outcome was GG ≥2 on prostate biopsy. Three pre-specified statistical models were used: a base model including PSA, age, digital rectal examination and prior negative biopsy; a model that added free PSA to the base model; and the 4Kscore. ResultsA total of 947 men were included in the final analysis and 273 (29%) had GG ≥2 on prostate biopsy. The base model area under the receiver operating characteristic curve of 0.775 increased to 0.802 with the addition of free PSA, and to 0.824 for the 4Kscore. Adding MSP to the 4Kscore model yielded an increase (0.014-0.019) in discrimination. In decision-curve analysis of clinical utility, the 4Kscore showed a benefit starting at a 7.5% threshold. ConclusionA prospective multicentre evaluation of a pre-specified model based on four kallikrein markers (4Kscore) with the addition of MSP improves the predictive discrimination for GG ≥2 prostate cancer on biopsy and could be used to inform biopsy decision-making.

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A Four-kallikrein Panel and β-Microseminoprotein in Predicting High-grade Prostate Cancer on Biopsy: An Independent Replication from the Finnish Section of the European Randomized Study of Screening for Prostate Cancer

Abstract: Four kallikrein markers and β-microseminoprotein in blood improve discrimination of high-grade prostate cancer at biopsy in men with elevated prostate-specific antigen.

Cited by 8 publications

References 29 publications

Seminal citrate is superior to PSA for detecting clinically significant prostate cancer

Seminal citrate is superior to PSA for detecting clinically significant prostate cancer

Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers

Prospective validation of microseminoprotein‐β added to the 4Kscore in predicting high‐grade prostate cancer in an international multicentre cohort

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