Association of free-prostate specific antigen subfractions and human glandular kallikrein 2 with volume of benign and malignant prostatic tissue

Steuber, Thomas; Niemelä, Pauliina; Haese, Alexander; Pettersson, Kim; Erbersdobler, Andreas; Chun, K.-H. Felix; Graefen, Markus; Kattan, Michael W.; Huland, Hartwig; Lilja, Hans

doi:10.1002/pros.20156

Cited by 34 publications

(20 citation statements)

References 21 publications

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“…Increasing hK2 was significantly associated with cancer volume, presence of ECE, and high-grade PCa (12)(13)(14).…”

Section: Discussionmentioning

confidence: 95%

“…It is, however, unclear whether protein concentrations in tissue correlate with those in circulation; PSA and hK2 concentrations are up to 10 6 -fold higher in tissue than in blood (11 ). Nevertheless, recent studies have demonstrated that hK2 concentrations in serum are significantly associated with extracapsular extension (ECE) of PCa and with the volume of PCa in prostatectomy specimens (12)(13)(14). Although these studies have provided indications that serum hK2 may be a predictor of advanced PCa, definitive evidence is lacking.…”

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confidence: 99%

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Comparison of Free and Total Forms of Serum Human Kallikrein 2 and Prostate-Specific Antigen for Prediction of Locally Advanced and Recurrent Prostate Cancer

et al. 2007

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Background:We evaluated the association of total and free forms of serum human kallikrein 2 (hK2) and prostate-specific antigen (PSA) with prostate cancers of unfavorable prognosis. Methods: We retrospectively measured total PSA (tPSA), free PSA (fPSA), and total hK2 (thK2) in preoperative serum samples from 867 men [and assessed free hK2 (fhK2) measured in 577 of these men] treated with radical prostatectomy for clinically localized prostate cancer. Associations between biomarker concentrations and extracapsular extension, seminal vesicle invasion, and biochemical recurrence (BCR) were evaluated. A subset of patients with PSA <10 g/L, the group most commonly seen in clinical practice in the US, was analyzed. Results: thK2 was the strongest predictor of extracapsular extension and seminal vesicle invasion (areas under the ROC curve [AUC], 0.662 and 0.719, respectively), followed by tPSA (AUC, 0.654 and 0.663). All biomarkers were significant predictors of BCR. hK2 forms, but not PSA forms, remained highly significant for predicting BCR in the low-PSA group. Combining tPSA, fPSA,

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“…Increasing hK2 was significantly associated with cancer volume, presence of ECE, and high-grade PCa (12)(13)(14).…”

Section: Discussionmentioning

confidence: 95%

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confidence: 99%

Comparison of Free and Total Forms of Serum Human Kallikrein 2 and Prostate-Specific Antigen for Prediction of Locally Advanced and Recurrent Prostate Cancer

et al. 2007

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“…15,16 Similarly, free and complexed PSA (cPSA) have been shown to be differentially associated with benign and malignant prostate tissue. 13,14 We therefore hypothesize that %fPSA and hK2 add greater predictive value closer to diagnosis.In our previous paper, 9 we reported associations between cancer and biomarkers measured in blood taken from men aged 50 or less who participated in a cardiovascular prevention project (MPM) in Malm€ o, Sweden. The project enrolled participants (74% acceptance rate) during 1974 -1986 .…”

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confidence: 98%

The predictive value of prostate cancer biomarkers depends on age and time to diagnosis: Towards a biologically‐based screening strategy

Vickers

Ulmert

Serio

et al. 2007

Intl Journal of Cancer

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Both benign and malignant prostate diseases elevate total prostatespecific antigen (tPSA), and the incidence of benign disease increases markedly with age. There is evidence, however, that freeto-total PSA ratio (%fPSA) and human kallikrein 2 (hK2) more closely reflect the malignant process. We tested the hypothesis that tPSA levels are more strongly predictive of cancer in younger when compared to older men, whereas %fPSA and hK2 are more strongly predictive in men tested closer to diagnosis. The study included 13,676 men age 44 in Sweden, where PSA screening was uncommon during the study period. fPSA, tPSA and hK2 were measured in archived plasma collected during 1974-1986 in 501 men subsequently diagnosed with prostate cancer up to 1999 and in 1,292 matched controls. The predictive value of tPSA was lower in older men (p 5 0.003) but was not strongly affected by time to diagnosis (p 5 0.3); the predictive value of hK2 was higher closer to diagnosis (p < 0.0005) but was not modified by age (p 5 0.7). A model including tPSA, fPSA and hK2 was superior (p 5 0.02) to tPSA alone in older (AUC 0.819 vs. 0.794), but not in younger men (0.758 vs. 0.759). Total PSA can be used as a single marker at early middle age to predict long-term risk of prostate cancer and thus to determine intensity of subsequent screening. In contrast, %fPSA and hK2 add important predictive value in older men and much closer to diagnosis. Strategies for prostate cancer screening should be based on thorough understanding of the interaction of kallikreinrelated biomarkers with prostate pathobiology. ' 2007 Wiley-Liss, Inc.Key words: prostate cancer; prediction; detection; prostate specific antigen Screening for prostate cancer with prostate-specific antigen (PSA) testing is controversial.1,2 The controversy is partly due to a lack of appropriate randomized evidence, 3 but the diagnostic characteristics of PSA testing also remain a key concern.3 For example, in their analysis of the Prostate Cancer Prevention Trial, Thompson and colleagues reported sensitivity and specificity of 20 and 95% for the commonly used 4 ng/ml threshold for biopsy. Lowering the threshold to improve sensitivity to 30 or 50% decreased specificity to 85 and 75%, respectively. The modest diagnostic accuracy of PSA testing has led investigators to evaluate additional biomarkers, such as ratio of free-tototal PSA (%fPSA) 5,6 and human kallikrein 2 (hK2). 7,8 Population-based studies have generally shown that these biomarkers aid in cancer detection.We have previously shown that a single PSA test taken at age 44-50 is a strong predictor of prostate cancer diagnosed up to 25 years later. 9 In some contrast to the prior literature, we reported that although %fPSA and hK2 univariately predicted subsequent prostate cancer, a multivariable model including these markers alongside PSA was not superior to a model with PSA alone. The men in our cohort were generally younger than those in typical studies in the literature and we considered whether the explanation for the disparate findin...

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“…Moreover, some investigators have reported that free PSA (fPSA) and percent-fPSA (%fPSA) outperform PSA as predictors of prostate enlargement without PCa. [7][8][9] Previous studies have consistently shown that increased adiposity, as determined by various anthropometric measures, such as body weight (BW), 10 body mass index (BMI) [10][11][12] and waist circumference, 10,11 is positively associated with transrectal ultrasound-and with magnetic resonance imaging-measured TPV.…”

Section: Introductionmentioning

confidence: 99%

“…Although there are several predictive models estimating clinical prostatic enlargement based on levels of PSA or PSA derivatives, [6][7][8][9][10][11][12][13] Jacobson et al 13 recently reported that age and weight can be incorporated into models based on serum PSA levels to achieve greater accuracy when estimating TPV. However, predictive models including anthropometric measurements have never been investigated in Asia.…”

Section: Introductionmentioning

confidence: 99%

A novel equation and nomogram including body weight for estimating prostate volumes in men with biopsy-proven benign prostatic hyperplasia

Nakanishi

Masuda²,

Kawakami³

et al. 2012

Asian J Androl

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Anthropometric measurements, e.g., body weight (BW), body mass index (BMI), as well as serum prostate-specific antigen (PSA) and percent-free PSA (%fPSA) have been shown to have positive correlations with total prostate volume (TPV). We developed an equation and nomogram for estimating TPV, incorporating these predictors in men with benign prostatic hyperplasia (BPH). A total of 1852 men, including 1113 at Tokyo Medical and Dental University (TMDU) Hospital as a training set and 739 at Cancer Institute Hospital (CIH) as a validation set, with PSA levels of up to 20 ng ml 21 , who underwent extended prostate biopsy and were proved to have BPH, were enrolled in this study. We developed an equation for continuously coded TPV and a logistic regression-based nomogram for estimating a TPV greater than 40 ml. Predictive accuracy and performance characteristics were assessed using an area under the receiver operating characteristics curve (AUC) and calibration plots. The final linear regression model indicated age, PSA, %fPSA and BW as independent predictors of continuously coded TPV. For predictions in the training set, the multiple correlation coefficient was increased from 0.38 for PSA alone to 0.60 in the final model. We developed a novel nomogram incorporating age, PSA, %fPSA and BW for estimating TPV greater than 40 ml. External validation confirmed its predictive accuracy, with AUC value of 0.764. Calibration plots showed good agreement between predicted probability and observed proportion. In conclusion, TPV can be easily estimated using these four independent predictors.

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Association of free-prostate specific antigen subfractions and human glandular kallikrein 2 with volume of benign and malignant prostatic tissue

Abstract: The multi-chain fPSA-N subfractions of fPSA may be a valuable predictor of both benign prostate hyperplasia (BPH) and CaVol that is likely to be more useful in predicting tz volumes than CaVols. fPSA-I may provide information on cancer without being influenced by the presence of BPH.

Cited by 34 publications

References 21 publications

Comparison of Free and Total Forms of Serum Human Kallikrein 2 and Prostate-Specific Antigen for Prediction of Locally Advanced and Recurrent Prostate Cancer

Comparison of Free and Total Forms of Serum Human Kallikrein 2 and Prostate-Specific Antigen for Prediction of Locally Advanced and Recurrent Prostate Cancer

The predictive value of prostate cancer biomarkers depends on age and time to diagnosis: Towards a biologically‐based screening strategy

A novel equation and nomogram including body weight for estimating prostate volumes in men with biopsy-proven benign prostatic hyperplasia

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