| Backgroud:Prostate specific antigen is widely used as screening tool for prostate cancer, and free to total prostate specific antigen (f/tPSA), PSA density (PSAD) and PSA velocity (PSAV) are the related parameters that can be used to improve the ability of PSA in predicting prostate cancer. There are still a few limits for PSA:1. There are geographical and racial difference for PSA, the cut-off values of PSA and its related parameters for prostate biopsy in China are almost all refer to the values abroad; 2. The level of serum PSA can be affected by many factors, such as catheterization, digital rectal examination and body mass index and so on; 3. As a single index, the positive rate of prostate biopsy with PSA is higher than DRE and transrectal ultrasonography, but the sensitivity and specificity are still not high,which may result in missed diagnosis and misdiagnosis. Now we need more accurate method to predict prostate cancer to increase the positive rate of prostate cancer. Objective:We preliminarily establish the warning system for early diagnosis of prostate cancer based on PSA and its related parameters according the data of patients who have ever visited our hospital for prostate disease:firstly, determine the effect of obesity on PSA, and develop a new PSA related parameter that can eliminate the effect of obesity; secondly, we calculate PSAD according to the different prostate volume which are measured by transrectal ultrasound and transabdominal ultrasound respectively, and analyze the diagnostic value of the two PSAD; thirdly, we establish the cut-off value of PSA, f/tPSA and PSAD for screening prostate cancer; finally, we develop a nomogram for predicting the risk of prostate cancer based on clinic indexes of Chinese patients. Methods:The study was divided into four parts, in which patients were enrolled according to strict inclusion and exclusion criteria.1. We reviewed clinical data of men with pathologic BPH and prostate cancer in our hospital, such as height, weight, prostate volume and so on. We established two novel PSA related parameters, PSA mass (total circulating PSA protein) and PSA mass ratio (total circulation PSA protein per prostate volume), and calculated PSA mass and PSA mass ratio respectively. Finally, we analyzed the association between BMI and PSA, PSA mass, PSA mass ratio. Then we evaluate the diagnostic value of PSAM and PSAMR for predicting prostate cancer, and compare the predictive value of PSAM, PSAMR, total PSA (tPSA), percent free PSA (f/tPSA), and PSA density with receiver operating characteristic (ROC) curve.2. We retrospectively analyzed the clinical data of patients who underwent prostate volume examination by transrectal ultrasound and transabdominal ultrasound within a week. Variables including free PSA, total PSA, prostate volume and pathological result. We compared the difference between prostate volumes measured by two ultrasound methods and PSAD with paired t-test, and Receiver operating characteristic (ROC) analysis was performed to analyze the accuracy of two PSADs3.. We have analyzed the pathological and clinical data of patients who were submitted to systematic 12 (12+X) needle biopsy in General Hospital of Chinese PL A. To analyze the detection rate of prostate cancer according to different PSA ranges, and evaluate the diagnostic value and the cut-off value of percent free PSA (f/tPSA) and PSA density (PSAD) in different PSA values4. We retrospectively analyzed the clinical data of patients who underwent prostate biopsy for prostate cancer in our hospital. Variables including age, prostate volume, free PSA (fPSA) and total PSA (tPSA) were collected. Of these patients, we randomly selected 20% as validation group, and the other 80% as development group. We performed logistic regression analysis to identify the independent risk factors related to positive prostate biopsy in development group. Then we constructed a prediction model according to regression equation to predict the result of prostate biopsy. Receiver operating characteristic (ROC) analysis was performed to verify the diagnostic value of the novel prediction model, which was furtherly compared with the diagnostic values of PSA alone, f/t PSA, PSAD respectively. Results:1.1268 patients, with 706 benign prostatic hyperplasia and 562 prostate cancer, with integrity data were enrolled in this study. Higher BMI was not significantly associated with PSA and prostate volume (P>0.05) among patients of prostate cancer; But among BPH patients, higher BMI was significantly associated with higher plasma volume and prostate volume (P<0.05). The adjusted R2 of BMI vs plasma volume was greater than that of BMI vs PSA in linear regression (adjusted R2:0.569 VS 0.027). PSA had positive association with prostate volume, negative association with BMI and plasma volume (P<0.05). PSA mass(PSAM) had positive association with prostate volume (P<0.05), but no association with BMI and plasma volume (P> 0.05). PSA mass ratio(PSAMR) had no association with prostate volume (P>0.05), but had negative association with BMI and plasma volume. The patients was divided into three groups according to BMI:normal (BMI<23kg/m2), overweight (BMI: 23-24.9kg/m2) and obesity (BMI>25kg/m2). Plasma volume and prostate volume were different significantly among BMI groups (P<0.05), and so were PSA and PS AMR (P<0.05). But PSAM kept stable among different BMI groups (P>0.05).In all patients, PSA, f/tPSA, PSAD, PSAM and PSAMR had significant difference between prostate cancer and BPH (P<0.05). The area under the ROC curve (AUC) of PSAM was 0.732, there was no significant difference between tPSA (0.73) and PSAM (P>0.05), the AUC of PSAMR was 0.821, which was greater than tPSA (P<0.05). In patients with PSA 4-10ng/ml, the AUC of PSAMR was greater AUC than f/tPSA (0.856 VS 0.756) (P<0.05), but there was no significant difference between PSAMR and PSAD (0.856 VS 0.85) (P>0.05).2.1437 patients were enrolled in this study. There were no difference between two prostate volume (P>0.05). Comparing area under the ROC curve (AUC), there was no significant difference between two PSADs (P>0.05), whose AUC were 0.733 (transrectal) and 0.699 (transabdominal) respectively.3.1144 patients were enrolled in this study. The positive prostate biopsy rates in tPSA 0-2.5ng/ml,2.6-4ng/ml,4.1-10ng/ml,10.1-20ng/ml and more than 20ng/ml were 17.9%,17.9%,34.7%,44.8% and 78.6% respectively. And the detection rate of high grade prostate cancer (Gleason>7) in all PSA ranges were more than 50%. When tPSA level was 4.1-20ng/ml, f/tPSA and PSAD were significant different between prostate cancer and benign prostatic hyperplasia patients, and at the same higher sensitivity (about 95%), the specificity of f/tPSA and PSAD were 18.9% and 26%, respectively. At the same time, it was suggested that the cut-off value of f/tPSA was 0.25 and PSAD was 0.1.4.958 patients with integrity datas whose PSA was under 100ng/ml were enrolled in this study, of which 767 were randomly selected as development group and 191 as validation group (63 whose PSA is between 4ng/ml-10ng/ml). TPSA, age and prostate volume were independent risk factors by logistic regression analysis. And the nomogram based on all variables was established. The area under the ROC curve of the model was greater than those of tPSA, f/tPSA and PSAD.Conclusions:1. Higher BMI is associated with greater plasma volume in BPH patients, lower PSA concentration may be due to hemodilution which caused by greater plasma volume in obese patients with BPH, and PSAM can eliminate the effect of obesity on PSA. But PSAM has similar ability with PSA, and PSAMR has similar ability with PSAD in diagnosis of prostate cancer.2. The value of prostate volume measured by two ultrasound methods are similar, by which the PSAD calculated had equal ability to diagnose prostate cancer. And then the PSAD can be calculated by transabdominal ultrasound result, in addition to transrectal ultrasound.3. PSA4.0ng/ml can be used as normal reference value for prostate cancer screening, which is similar to other studes keeping high sensitivity. But biopsy-detected prostate cancer is not rare among men with PSA level 4.0ng/ml or less. The higher levels of the tPSA, the higher percentage of positive biopsy. When PSA was 4.1-20ng/ml, f/tPSA (0.25 or less) and PSAD (more than 0.1) could be used ao prostate cancer screening normal reference value.4. The nomogram established in this study has better diagnostic value for prostate cancer compared with PSA and other PSA related parameters, which is a simple and convenient method. |
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