Reducing unnecessary biopsy during prostate cancer screening using a four-kallikrein panel: an independent replication.
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ABSTRACT:
SUBMITTER: Vickers A
PROVIDER: S-EPMC2881727 | biostudies-other | 2010 May
REPOSITORIES: biostudies-other
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Project description:A statistical model based on four kallikrein markers (total prostate-specific antigen [tPSA], free PSA [fPSA], intact PSA, and human kallikrein-related peptidase 2) in blood can predict risk of Gleason score ≥7 (high-grade) cancer at prostate biopsy.To determine the value of this model in predicting high-grade cancer at biopsy in a community-based setting in which referral criteria included percentage of fPSA to tPSA (%fPSA).We evaluated the model, with or without adding blood levels of microseminoprotein-β (MSMB) in a cohort of 749 men referred for prostate biopsy due to elevated PSA (≥3 ng/ml), low %fPSA (<20%), or suspicious digital rectal examination at Skåne University Hospital, Malmö, Sweden.The kallikrein markers, with or without MSMB levels, measured in cryopreserved anticoagulated blood were combined with age in a published statistical model (Prostate Testing for Cancer and Treatment [ProtecT]) to predict high-grade cancer at biopsy. Predictive accuracy was compared with a base model.The %fPSA was low (median: 17; interquartile range: 13-22) in this cohort because this marker was used as a referral criterion. The ProtecT model improved discrimination over age and PSA for high-grade cancer (0.777 vs 0.720; p=0.002). At one illustrative cut point, use of the panel would reduce the number of biopsies by 236 per 1000 and detect 195 of 208 (94%) but delay diagnosis of 13 of 208 high-grade cancers. MSMB levels in blood did not improve the accuracy of the panel (p=0.2).The kallikrein model is predictive of high-grade cancer if criteria for biopsy referral also include %fPSA, and it can reduce unnecessary biopsies without missing an undue number of tumors.We evaluated a published model to predict biopsy outcome in men biopsied due to low percentage of free to total prostate-specific antigen. The model helps reduce unnecessary biopsies without missing an undue number of high-grade cancers.
| S-EPMC4643413 | biostudies-other
Project description:BackgroundThe four-kallikrein (4K) panel has been demonstrated to improve prediction of aggressive prostate cancer compared with prostate-specific antigen (PSA) among men with moderately elevated PSA levels. However, the development and testing of the 4K panel has been conducted primarily in White men, with limited data in African Americans and no studies in other racial and ethnic groups.MethodsWe evaluated the 4K panel in a nested case-control study among African American, Latino, Japanese, Native Hawaiian, and White men in the Multiethnic Cohort. Prediagnostic blood levels of free, intact, and total PSA and human kallikrein-related peptidase 2 were measured among 1,667 incident prostate cancer cases and 691 controls with PSA ?2 ng/mL. We evaluated the discriminative ability of the 4K panel within and across all racial/ethnic groups.ResultsThe 4K panel enhanced discrimination of overall prostate cancer compared with free plus total PSA and total PSA alone (AUC 0.748 vs. 0.711 and 0.669, respectively). Discrimination was further enhanced for Gleason 8+ prostate cancer, aggressive prostate cancer, and death due to prostate cancer, and to a lesser degree for nonaggressive prostate cancer. Improvement of the 4K panel over PSA was observed in each population. Adding a prostate cancer polygenic risk score slightly improved upon the discriminative ability of the 4K panel.ConclusionsThe superior discriminative ability of the 4K panel over PSA for overall and aggressive prostate cancer across multiethnic populations indicates the broad clinical applicability of the 4K panel.ImpactOur multiethnic investigation suggests potential for the 4K panel to improve current prostate cancer screening practices.
| S-EPMC7334056 | biostudies-literature
Project description:BackgroundThe overdiagnosis of prostate cancer (PCa) caused by unnecessary prostate biopsy has become a worldwide problem that urgently requires a solution. We aimed to reduce the unnecessary prostate biopsies and increase the detection rate of clinically significant PCa (csPCa) by creating a novel multiparametric magnetic resonance imaging (mpMRI)-based strategy.MethodsA total of 1,194 eligible patients who underwent transperineal prostate biopsies from January 2018 to December 2022 were included in this retrospective study. Of these patients, 1,080 who received prostate biopsies from January 2018 to July 2022 were regarded as cohort 1 for primary analysis, and 114 patients who received prostate biopsies from August 2022 to December 2022 were collected in cohort 2 for validation. All the mpMRI images were quantitatively evaluated by the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v. 2.1). The diagnostic performances were assessed through the receiver operating characteristic (ROC) curve and area under the curve (AUC) and were compared with the DeLong test. Cancer diagnosis-free survival analysis was performed using the Kaplan-Meier method and log-rank test. The primary endpoint of this study was clinically significant PCa with an International Society of Urological Pathology (ISUP) grade ≥2.ResultsIn cohort 1, the results of ROC curves demonstrated that the PI-RADS score had a higher diagnostic accuracy (AUC =0.898 for any-grade PCa; AUC =0.917 for csPCa) than did the other clinical variables (P<0.001). Under the novel mpMRI-based biopsy strategy, all patients with PI-RADS 1 can safely avoid prostate biopsy. For patients with PI-RADS 2, prostate biopsy should be considered for patients with prostate-specific antigen density (PSAD) ≥0.3 ng/mL2 and prostate volume <65 mL. As for patients with PI-RADS 3, structured surveillance programs can be a viable option if PSAD <0.3 ng/mL2 and prostate volume ≥65 mL. Finally, patients with a PI-RADS score of 4 and 5 should undergo prostate biopsy due to the high probability of clinically significant PCa. In the validation analysis of cohort 2, 48 patients were placed into a biopsy-spared group with no csPCa cases, while 66 patients were placed in a biopsy-needed group, with an csPCa detection rate of 50.0%. Overall, the novel strategy demonstrated a sensitivity, specificity, positive predictive value, and negative predictive value of 98.9%, 57.5%, 50.5%, and 99.2%, respectively, for diagnosing csPCa.ConclusionsAn mpMRI-based biopsy strategy can effectively avoid about 40% of prostate biopsies and maintain a high detection rate for clinically significant PCa. It can further provide valuable guidance for patients and physicians in considering the necessity of prostate biopsy.
| S-EPMC10895118 | biostudies-literature
Project description:ObjectiveTo assess whether adding prostate volume to the kallikrein panel improves discrimination for ISUP Grade Group 2 or higher (GG2+) disease, as some men may have volume measurements available at the time of blood draw. While prostate volume predicts biopsy outcome, it requires an imaging procedure for measurement. The four kallikrein panel - commercially available as the 4Kscore - predicts risk of GG2+ disease and requires only a blood draw.Materials and methodsA total of 9131 patients with available prostate volume and total PSA ≤25 ng/ml from 5 historical (sextant biopsy, pre-ISUP 2005 grading) and 4 contemporary cohorts (10+ cores, ISUP 2005 grading). Previously published kallikrein panel models were used to predict risk of GG2+. Volume was added to the model in each cohort and change in discrimination was meta-analyzed.ResultsIncreased prostate volume was associated with decreased risk of GG2+ disease after controlling for the kallikrein panel in 7/9 cohorts. However, kallikrein panel discrimination (0.817, 95% CI 0.802, 0.831) was not improved after including volume (AUC difference 0.002, 95% CI -0.003, 0.006). Heterogeneity (P <.0001) was driven by an AUC increase in 1 cohort of academic cancer centers (0.044, 95% CI 0.025, 0.064), with no evidence of heterogeneity after excluding this cohort (P = .15).ConclusionThe kallikrein panel provides a non-invasive approach to assess the risk of high-grade prostate cancer. Our results do not justify the inclusion of prostate volume in the four kallikrein panel. There is some evidence that the predictive value of prostate volume is provider dependent: further research is needed to address this question.
| S-EPMC8671182 | biostudies-literature
Project description:Many men with elevated prostate-specific antigen (PSA) levels in serum do not have aggressive prostate cancer and undergo unnecessary biopsy. Retrospective studies using cryopreserved serum suggest that four kallikrein markers can predict biopsy outcome. Free, intact and total PSA, and kallikrein-related peptidase 2 were measured in cryopreserved blood from 6129 men with elevated PSA (≥3.0ng/mL) participating in the prospective, randomized trial Prostate Testing for Cancer and Treatment. Marker levels from 4765 men providing anticoagulated plasma were incorporated into statistical models to predict any-grade and high-grade (Gleason score ≥7) prostate cancer at 10-core biopsy. The models were corrected for optimism by 10-fold cross validation and independently validated using markers measured in serum from 1364 men. All statistical tests were two-sided. The four kallikreins enhanced prostate cancer detection compared with PSA and age alone. Area under the curve (AUC) for the four kallikreins was 0.719 (95% confidence interval [CI] = 0.704 to 0.734) vs 0.634 (95% CI = 0.617 to 0.651, P < .001) for PSA and age alone for any-grade cancer, and 0.820 (95% CI = 0.802 to 0.838) vs 0.738 (95% CI = 0.716 to 0.761) for high-grade cancer. Using a 6% risk of high-grade cancer as an illustrative cutoff, for 1000 biopsied men with PSA levels of 3.0ng/mL or higher, the model would reduce the need for biopsy in 428 men, detect 119 high-grade cancers, and delay diagnosis of 14 of 133 high-grade cancers. Models exhibited excellent discrimination on independent validation among men with only serum samples available for analysis. A statistical model based on kallikrein markers was validated in a large prospective study and reduces unnecessary biopsies while delaying diagnosis of high-grade cancers in few men.
| S-EPMC4554254 | biostudies-literature
Project description:BackgroundDiagnosis of Gleason 6 prostate cancer can leave uncertainty about the presence of undetected aggressive disease.ObjectiveTo evaluate the utility of a four kallikrein (4K) panel in predicting the presence of high-grade cancer in men on active surveillance.Design, setting, and participantsPlasma collected before the first and subsequent surveillance biopsies was assessed for 718 men prospectively enrolled in the multi-institutional Canary PASS trial. Biopsy data were split 2:1 into training and test sets. We developed statistical models that included clinical information and either the 4Kpanel or serum prostate-specific antigen (PSA).Outcome measurements and statistical analysisThe endpoint was reclassification to Gleason ≥7. We used receiver operating characteristic (ROC) curve analyses and area under the curve (AUC) to assess discriminatory capacity, and decision curve analysis (DCA) to report clinical net benefit.Results and limitationsSignificant predictors for reclassification were 4Kpanel (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.31-1.81) or PSA (OR 2.11, 95% CI 1.53-2.91), ≥20% cores positive (OR 2.10, 95% CI 1.33-3.32), two or more prior negative biopsies (OR 0.19, 95% CI 0.04-0.85), prostate volume (OR 0.47, 95% CI 0.31-0.70), and body mass index (OR 1.09, 95% CI 1.04-1.14). ROC curve analysis comparing 4K and base models indicated that the 4Kpanel improved accuracy for predicting reclassification (AUC 0.78 vs 0.74) at the first surveillance biopsy. Both models performed comparably for prediction of reclassification at subsequent biopsies (AUC 0.75 vs 0.76). In DCA, both models showed higher net benefit compared to biopsy-all and biopsy-none strategies. Limitations include the single cohort nature of the study and the small numbers; results should be validated in another cohort before clinical use.ConclusionsThe 4Kpanel provided incremental value over routine clinical information in predicting high-grade cancer in the first biopsy after diagnosis. The 4Kpanel did not add predictive value to the base model at subsequent surveillance biopsies.Patient summaryActive surveillance is a management strategy for many low-grade prostate cancers. Repeat biopsies monitor for previously undetected high-grade cancer. We show that a model with clinical variables, including a panel of four kallikreins, indicates the presence of high-grade cancer before a biopsy is performed.
| S-EPMC7327706 | biostudies-literature
Project description:A key challenge in melanoma diagnosis is the large number of unnecessary biopsies on benign nevi, which requires significant amounts of time and money. To reduce unnecessary biopsies while still accurately detecting melanoma lesions, we propose using Raman spectroscopy as a non-invasive, fast, and inexpensive method for generating a "second opinion" for lesions being considered for biopsy. We collected in vivo Raman spectral data in the clinical skin screening setting from 52 patients, including 53 pigmented lesions and 7 melanomas. All lesions underwent biopsies based on clinical evaluation. Principal component analysis and logistic regression models with leave one lesion out cross validation were applied to classify melanoma and pigmented lesions for biopsy recommendations. Our model achieved an area under the receiver operating characteristic (ROC) curve (AUROC) of 0.903 and a specificity of 58.5% at perfect sensitivity. The number needed to treat for melanoma could have been decreased from 8.6 (60/7) to 4.1 (29/7). This study in a clinical skin screening setting shows the potential of Raman spectroscopy for reducing unnecessary skin biopsies with in vivo Raman data and is a significant step toward the application of Raman spectroscopy for melanoma screening in the clinic.
| S-EPMC7355922 | biostudies-literature
Project description:PurposeWe sought to develop diagnostic models incorporating mpMRI examination to identify PCa (Gleason score≥3+3) and CSPCa (Gleason score≥3+4) to reduce overdiagnosis and overtreatment.MethodsWe retrospectively identified 784 patients according to inclusion criteria between 2016 and 2020. The cohort was split into a training cohort of 548 (70%) patients and a validation cohort of 236 (30%) patients. Age, PSA derivatives, prostate volume, and mpMRI parameters were assessed as predictors for PCa and CSPCa. The multivariable models based on clinical parameters were evaluated using area under the curve (AUC), calibration plots, and decision curve analysis (DCA).ResultsUnivariate analysis showed that age, tPSA, PSAD, prostate volume, MRI-PCa, MRI-seminal vesicle invasion, and MRI-lymph node invasion were significant predictors for both PCa and CSPCa (each p≤0.001). PSAD has the highest diagnostic accuracy in predicting PCa (AUC=0.79) and CSPCa (AUC=0.79). The multivariable models for PCa (AUC=0.92, 95% CI: 0.88-0.96) and CSPCa (AUC=0.95, 95% CI: 0.92-0.97) were significantly higher than the combination of derivatives for PSA (p=0.041 and 0.009 for PCa and CSPCa, respectively) or mpMRI (each p<0.001) in diagnostic accuracy. And the multivariable models for PCa and CSPCa illustrated better calibration and substantial improvement in DCA at threshold above 10%, compared with PSA or mpMRI derivatives. The PCa model with a 30% cutoff or CSPCa model with a 20% cutoff could spare the number of biopsies by 53%, and avoid the number of benign biopsies over 80%, while keeping a 95% sensitivity for detecting CSPCa.ConclusionOur multivariable models could reduce unnecessary biopsy without comprising the ability to diagnose CSPCa. Further prospective validation is required.
| S-EPMC7688051 | biostudies-literature
Project description:A disadvantage of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) is that many men must be screened, biopsied, and diagnosed to prevent one death.To increase the specificity of screening for lethal PCa at an early stage.We conducted a case-control study nested within a population-based cohort. PSA and three additional kallikreins were measured in cryopreserved blood from a population-based cohort in Västerbotten, Sweden. Of 40379 men providing blood at ages 40, 50, and 60 yr from 1986 to 2009, 12542 men were followed for >15 yr. From this cohort, the Swedish Cancer Registry identified 1423 incident PCa cases, 235 with distant metastasis.Risk of distant metastasis for different PSA levels and a prespecified statistical model based on the four kallikrein markers.Most metastatic cases occurred in men with PSA in the top quartile at age 50 yr (69%) or 60 yr (74%), whereas 20-yr risk of metastasis for men with PSA below median was low (?0.6%). Among men with PSA >2 ng/ml, a prespecified model based on four kallikrein markers significantly enhanced the prediction of metastasis compared with PSA alone. About half of all men with PSA >2 ng/ml were defined as low risk by this model and had a ?1% 15-yr risk of metastasis.Screening at ages 50-60 yr should focus on men with PSA in the top quartile. A marker panel can aid biopsy decision making.For men in their fifties, screening should focus on those in the top 10% to 25% of PSA values because the majority of subsequent cases of distant metastasis are found among these men. Testing of four kallikrein markers in men with an elevated PSA could aid biopsy decision making.
| S-EPMC4496315 | biostudies-literature
Project description:PURPOSE:The human kallikrein-2 (hK2) protein and two single nucleotide polymorphism (SNPs) (rs2664155, rs198977) of the gene are associated with prostate cancer risk. We examined whether hK2 protein and gene SNPs predict prostate cancer at the time of repeat biopsy. METHODS:We prospectively offered a repeat biopsy to men with a negative prostate biopsy performed for a PSA >4.0 ng/mL or abnormal Digital Rectal Exam (DRE) between 2001-2005. We genotyped and measured serum hK2 levels in 941 men who underwent a repeat prostate biopsy. Logistic regression analyses were conducted to determine the significance of KLK2 SNPs and hK2 levels for predicting cancer at repeat biopsy. RESULTS:Of the 941 patients, 180 (19.1%) were found to have cancer. The rs198977 SNP was positively associated with cancer at repeat biopsy (OR variant T allele?=?1.8, 95% CI: 1.04-3.13, p?=?0.049). When combined, the odds ratio for prostate cancer for patients with high hK2 levels and the variant T-allele of rs198977 was 3.77 (95% CI: 1.94-7.32, p?<?0.0001), compared to patients with low hK2 levels and the C-allele. The addition of hK2 levels and KLK2 rs198977 to the baseline predictive model did not significantly increase the area under the curve from a baseline model of 0.67 to 0.69 (p?=?0.6). CONCLUSIONS:The KLK2 SNP rs198977 was positively associated with hK2 levels and predicts prostate cancer at the time of repeat prostate biopsy. Further characterization of the KLK2 gene will be needed to determine its clinical utility.
| S-EPMC4162525 | biostudies-literature