Study On The Prediction Of Prostate Cancer And Bone Metastasis Of Prostate Cancer By Transrectal Contrast-enhanced Ultrasonography Combined With Clinical Indicators

Background:Prostate cancer(PCa)is a common malignant tumor in males of European and American countries,which has become the number one malignancy among males in the United States with approximately 180,890 new cases in 2016 and 26,120 PCa-related deaths.[1]In recent twenty years,with the rapid development of social economy and the continuous improvement of people's living standards,the incidence of prostate cancer in China showed a clear trend of sustained growth,which not only influenced the health of patients,but also increased family economic burden and socio-economic burden of patients.Transrectal ultrasound-guided prostate biopsy is the key standard for diagnosing prostate cancer in many imaging diagnostic methods for prostate cancer.However,because of the multifocal distribution of prostate cancer,there are certain missed rates and false positives in puncturing and complications increased with increased number of puncture needles.Therefore,improving the diagnostic rate of prostate cancer,reducing complications and providing timely and effective treatments for patients is the direction of doctors.Ultrasound contrast agent microbubbles can enhance the display of microvessels in the visceral parenchyma and lesions.In recent years,it has been used in the diagnosis,targeted puncture,and therapeutic evaluation of benign and malignant prostatic diseases.[[2-4]In this study,we use transrectal prostate imaging parameters and clinical data to establish a predictive adenocarcinoma model that aim to improve the accuracy of predicting prostate cancer and avoid unnecessary biopsy of the needle to reduce complications.Glean score of prostate cancer is a prostate cancer pathological indicator made based on the degree of tumor gland differentiation and structural variation.When the prostate cancer Gleason score reachs 8 points or more,it represents a high-risk cancer,7 points a moderate-risk cancer,and 2-6 points a low-risk cancer.With the Gleason score increases,the degree of differentiation of prostate cancer cells gradually reduces,the degree of malignancy increases and the cancer cells become more aggressive.Because the treatment options for different risks of prostate cancer are different,for this purpose,this study also studied the features of benign and malignant prostate diseases and contrast-enhanced features of prostate cancer with the different degrees of risk,in order to provide guidance for clinical diagnosis?treatments and prognosis of prostate cancer.Prostate cancer metastasis is the major cause of death in patients,and bone is the most common metastatic site of prostate cancer.Due to the occult onset and the lack of typical clinical manifestations at early stage of prostate cancer,most patients diagnosed with advanced prostate cancer are often accompanied by bone metastases[5].The five-year survival rate of patients diagnosed with advanced prostate cancer with bone metastases was 25%and the median of survival time was 40 months[6].Therefore,early diagnosis and prediction of prostate cancer bone metastasis is of great significance for improving patients' quality of life and improving the health of people.Currently the common imaging methods for clinical diagnosis of bone metastases are X-ray plain film,CT,MRM,and SPECT/CT whole body bone imaging.The prediction of bone metastases focuses more on clinical biochemical markers and on the exploration of tumor maxkers[7-11],while the use of contrast-enhanced ultrasound parameters to predict prostate cancer bone metastases is rarely reported in the literature.To this end,this study also studied the role and value of ultrasound contrast parameters,Color Doppler ultrasound blood flow parameters,prostate cancer Gleason score,clinical relevant data and other factors in the prediction of prostate cancer bone metastasis risk to provide valuable information for clinical diagnosis and treatments of prostate cancer bone metastases.PART One Multivariate analysis of prediction prostate cancer based on the contrast-enhanced transrectal ultrasonography and clinical dataObjective To explore the value of transrectal contrast-enhanced ultrasonography(TR-CEUS)and clinical data in prediction prostate cancer(PCa).Methods The clinical and images data of 152 patients who highly suspected with PCa were analyzed retrospectively.All patients were not treated before operation,in addition,TR-CEUS and prostate biopsy were taken.To analyze images with time intensity curves(TIC)analysis software,6 parameters which including arrival time(RT),time-to-peak(TP),peak intensity(PI)and so on were measured.According to the results of pathological findings and images,the patients were classified into PCa and benign prostatic hyperplasia(BPH)group.The pathological result was used as the dependent variable,the P<0.30 variables as independent variables,multivariate analysis was performed using Logistic regression,the statistically significant factors were used to establish a diagnosis model,construct ROC curve and calculate the area under the curve(AUC).Results Of total 152 patients,BPH accounted for54.6%(83/152),PCa accounted for 45.4%(69/152),In the single factor analysis,the RT of TR-CEUS parameter in the PCa group was lower than that in the BPH group(P=0.021),and the PI was higher than that in the BPH group(P=0.005).The single factor analysis of P<0.30 variables including age,volume,PSA,RT,PI,MTT,AUC and TTP eight variables were in Logistic regression,the results showed that PSA,PI and AUC are independent risk factors in prediction PCa(P-=0.05),established a diagnosis model,The area under ROC curve was 0.797(P<0.001),the diagnosis model of boundary value was 0.383,the PCa forecast sensitivity was 77.9%,specificity was 79.5%,Youden index was 57.5%,the positive predictive rate was 65.1%,the negative predictive value was 81.5%.Conclusions In the TR-CEUS parameter,PI and AUC are independent predictors in prediction PCa,and the establishment of a diagnostic model combined with serum PSA has a certain clinical value in predicting PCa and by using this diagnostic model,the positive rate of prostate cancer can be increased and unnecessary biopsy can be decreased.Part Two:Diagnostic Value of Transrectal contrast-enhanced Ultrasound in Prostate Cancer with Benign and Malignant Lesions and Different Risk DegreeObjective To study the diagnostic value of transcrectal contrast-enhanced ultrasound in prostate cancer with benign and malignant lesions and different risk degree.Methods From the clinical data and imaging data of 257 highly suspected patients with prostate cancer from March 2013to January 2018,all patients were untreated preoperatively,and underwent transrectal contrast-enhanced ultrasound and prostate biopsy.By applying quantitative analysis of RT,peak intensity(PI),mean transit time(MTT),area under the curve(AUC),half-intensity reduction time(IHT),rising branch slope(WIS)and peak time(TTP),and in according to the results of puncture pathology,divided them into prostate cancer group(PCa)and benign prostatic hyperplasia gproup(BPH),and statistically analyzed the difference of contrast group in different groups.According to the pathological Gleason score,8 point or more for high-risk cancer,7 point for moderate-risk cancer,2-6 point is divided into low-risk cancer,we statistically analyzed the difference between high-risk cancer group and moderate-low risk cancer group in contrast ultrasound.Results Among 257 patients,benign hyperplasia accounted for 54.47%(140/257),prostate cancer accounted for 45.53%(117/257),of which 47.87%were high-risk cancers(56/117),56.13%were moderate-low risk cancers(61/117).By comparing contrast parameter of group BPH and group PCa we found the parameters in BPH group were higher than those in PCa group(P<0.05),while those in BPH group and BPH group were lower than those in PCa group(P<0.05);MTT,HT,TTP in the two groups showed no significant difference(p>0.05).By drawing the ROC curves of two groups of different indicators we found that the area under the prostate-cancer-diagnosis ROC curve(AUC)of RT,WIS,AUC and PI were 0.616,0.612,0.544 and 0.561 respectively.The sensitivity(TRP),specificity(TNP),positive predictive value(PPV)and negative predictive value(NPV)were 40.17%,82.14%,65.28%,62.16%,73.50%,46.43%,53.42%,67.71%,82.91%,26.43%,48.50%,64.91%,57.26%,53.37%,50.76%,53.57%.The contrast ultrasound parameters of high-risk cancer group PI and AUC were higher than those of low-and medium-risk cancer group(p<0.05);no significant difference was found between the two groups in RT,MTT,TTP,HT and WIS(p>0.05).Constructing the ROC curve for diagnosing different degrees of risk of prostate cancer,we found the AUC of diagnostic parameters of AUC and PI in series and parallel diagnosis of high-risk prostate cancer were 0.647,0.647,0.659,0.625,respectively.The levels of TRP,TNP,PPV and NPV were 64.29%,65.57%,63.16%,66.67%and 50.00%,77.50%,66.67%,62.67%,48.21%,83.61%,72.97%,63.75%,66.07%,59.02%,59.68%,65.45%.Conclusions Transrectal contrast-enhanced Ultrasound can dynamically display the microvascular perfusion information of prostate lesions and indirectly reflect the perfusion characteristics of prostate cancer with different risk levels.The contrast parameters RT and WIS have certain value in the differential diagnosis of benign and malignant prostatic diseases.Contrast ultrasound parameters AUC and PI are significant predictors of high-risk prostate cancer,and their accuracy can be improved to a certain extent by tandem diagnosis.Part Three Prediction Bone Metastasis of Prostate Cancer by transrectal contrast-enhanced Ultrasonography Combined with Clinical IndicatorsObjective To explore the value of prediction of the prostate cancer bone metastasis by transcrectal contrast-enhanced ultrasound combined with related clinical data and other factorsMethods The imaging data and clinical data of 117 patients with prostate cancer diagnosed by transrectal ultrasound guided biopsy in our hospital from March 2013 to January 2018 were retrospectively analyzed.All patients underwent transrectal contrast-enhanced ultrasound(TR-CEUS)an examination.The process was quantitatively analyzed by QLAB software using the time intensity curve(TIC),Rise time(RT),peak intensity(PIa),mean transit time(MTT),Area under curve(AUC),Itensity-half time(IHT),wash in slope(WIS),time to peak(TTP)all 7 parameters.Color Doppler:flow parameters PSV,EDV,RI,Plb,end systolic blood flow velocity/end diastolic flood flow velocity(S\D)and clinical data were measured,including age,prostate volume,Total prostate specific antigen(TPSA),free prostate specific antigen(fPSA),Gleason score of prostate cancer.According to whether there is bone metastasis of prostate cancer divided into prostate cancer non-bone metastasis(NBM)group of 70 cases and prostate cancer with bone metastasis(BM)group of 47 cases.Results TPSA,fPSA and Gleason scores in BM group were higher than those in NBM group,the difference was statistically significant(P<0.05).The difference of contrast-enhanced ultrasound PIa and AUC between BM and NBM group was statistically significant(P<0.05).The difference of Color Doppler parameter RI,PIb,S/D between NMB group and BM group was statistically significant(P<0.05).TPSA,fPSA,Gleason score,PI.,AUC,RI,PIb and S/D were all positively correlated with bone metastasis of prostate cancer(P<0.05).Univariate Logistic analysis showed that fPSA,Gleason score,PIa AUC,RI and PIb were risk factors for predicting prostate cancer(P<0.05).Multivariate Logistic analysis showed that fPSA and AUC were independent risk factors for predicting prostate cancer.0.038-fold increase in the risk of prostate cancer bone metastases with one unit increase in fPSA(ng/ml);0.002-fold increase in the risk of prostate cancer bone metastases for each additional dBs of AUC.Conclusions The TR-CEUS parameter AUC and serum fPSA are independent risk factors of bone metastasis in prostate cancer and have a certain clinical value in predicting bone metastasis of prostate cancer.