INTRODUCTION & OBJECTIVES: Obesity is becoming highly prevalent all around the world. Its link with prostate cancer (PCa) is controversial, although it seems associated with increased risk of high-grade Gleason Score (GS) at biopsy. Even if PSA accuracy is not affected by BMI, it remains low. In this study, we tested the hypothesis that [-2]proPSA (p2PSA) and derivatives (%p2PSA and PHI) are more accurate than tPSAin predicting PCa in obese men (BMI ≥ 30). MATERIAL & METHODS: The analysis consisted of a nested case-control study from the PRO-psa Multicentric European Study (PROMEtheuS) project (ISRCTN04707454). The primary outcome was to test sensitivity, specificity and accuracy of serum p2PSA, %p2PSA ([(p2PSA pg/ml)/(fPSA ng/ml · 1000)] · 100) and Beckman Coulter PHI ((p2PSA/fPSA) · √PSA), in identifying PCa in obese (BMI ≥ 30) men (clinical validity), and the number of un-necessary biopsies, which could be avoided (clinical utility). Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis. RESULTS: Over 965 subjects, 383 (39.7%) were normal-weight (BMI < 25), 440 (45.6%) were overweight (BMI 25-29.9) and 142 (14.7%) were obese patients (BMI ≥ 30). Within obese group, PCa was found in 65 subjects (45.8%), 21 with GS 6 (32.3%), 26 with GS 7 (40.0%), and 6, 10 and 2 with GS 8, 9 and 10 (9.2, 15.4 and 3.1%) respectively. PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly lower in patients with PCa (p<0.001). At univariable accuracy analysis, %p2PSA and PHI were the most accurate predictors of PCa at biopsy. In patients with a BMI ≥30, %p2PSA and PHI significantly outperformed tPSA (p<0.001 vs PHI), fPSA (p<0.001) and %fPSA (p=0.008 vs PHI). At 90% sensitivity, the cut-off of %p2PSA and PHI were, respectively, 1.22 and 35.7 with a specificity of 32.5 and 52.3%. At a %p2PSA cut-off of 1.22 a total of 29 (20.4%) biopsies could have been avoided, but 5 (7.7%) cancers would have been missed: 3 with GS 6 (3+3) and 2 cancers with a GS of 7 (3+4). At a PHI cut-off of 35.7 a total of 46 (32.4%) biopsies could have been avoided but 6 (9.2%) cancers would have been missed: 4 with GS 6 (3+3) and 2 cancers with a GS of 7 (3+4). In multivariable logistic regression models, %p2PSA and PHI achieved independent predictor status, significantly increasing the accuracy, by 9.9 (p=0.005) and 8.8% (p=0.007), respectively, of the multivariable base model consisting of patient age, prostate volume, tPSA, fPSA and %fPSA. CONCLUSIONS: In obese patients, %p2PSA and PHI values are significantly and even more accurate than the currently used tests in determining the presence of PCa and could avoid unnecessary biopsies without missing significant PCa.

Accuracy of p2PSA and derivatives (%p2PSA and PHI) in predicting prostate cancer in obese men from a multicenter European study

Buffi N;Lughezzani G;Guazzoni G
2014

Abstract

INTRODUCTION & OBJECTIVES: Obesity is becoming highly prevalent all around the world. Its link with prostate cancer (PCa) is controversial, although it seems associated with increased risk of high-grade Gleason Score (GS) at biopsy. Even if PSA accuracy is not affected by BMI, it remains low. In this study, we tested the hypothesis that [-2]proPSA (p2PSA) and derivatives (%p2PSA and PHI) are more accurate than tPSAin predicting PCa in obese men (BMI ≥ 30). MATERIAL & METHODS: The analysis consisted of a nested case-control study from the PRO-psa Multicentric European Study (PROMEtheuS) project (ISRCTN04707454). The primary outcome was to test sensitivity, specificity and accuracy of serum p2PSA, %p2PSA ([(p2PSA pg/ml)/(fPSA ng/ml · 1000)] · 100) and Beckman Coulter PHI ((p2PSA/fPSA) · √PSA), in identifying PCa in obese (BMI ≥ 30) men (clinical validity), and the number of un-necessary biopsies, which could be avoided (clinical utility). Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis. RESULTS: Over 965 subjects, 383 (39.7%) were normal-weight (BMI < 25), 440 (45.6%) were overweight (BMI 25-29.9) and 142 (14.7%) were obese patients (BMI ≥ 30). Within obese group, PCa was found in 65 subjects (45.8%), 21 with GS 6 (32.3%), 26 with GS 7 (40.0%), and 6, 10 and 2 with GS 8, 9 and 10 (9.2, 15.4 and 3.1%) respectively. PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly lower in patients with PCa (p<0.001). At univariable accuracy analysis, %p2PSA and PHI were the most accurate predictors of PCa at biopsy. In patients with a BMI ≥30, %p2PSA and PHI significantly outperformed tPSA (p<0.001 vs PHI), fPSA (p<0.001) and %fPSA (p=0.008 vs PHI). At 90% sensitivity, the cut-off of %p2PSA and PHI were, respectively, 1.22 and 35.7 with a specificity of 32.5 and 52.3%. At a %p2PSA cut-off of 1.22 a total of 29 (20.4%) biopsies could have been avoided, but 5 (7.7%) cancers would have been missed: 3 with GS 6 (3+3) and 2 cancers with a GS of 7 (3+4). At a PHI cut-off of 35.7 a total of 46 (32.4%) biopsies could have been avoided but 6 (9.2%) cancers would have been missed: 4 with GS 6 (3+3) and 2 cancers with a GS of 7 (3+4). In multivariable logistic regression models, %p2PSA and PHI achieved independent predictor status, significantly increasing the accuracy, by 9.9 (p=0.005) and 8.8% (p=0.007), respectively, of the multivariable base model consisting of patient age, prostate volume, tPSA, fPSA and %fPSA. CONCLUSIONS: In obese patients, %p2PSA and PHI values are significantly and even more accurate than the currently used tests in determining the presence of PCa and could avoid unnecessary biopsies without missing significant PCa.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11699/10104
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