Prostate Cancer Progression To CRPC After Endocrine Therapy Related Analysis Of Influencing Factors And The Development Of Nomogram Model

Objective:To study the related factors that affect the progression of prostate cancer patients to castration-resistant prostate cancer(CRPC)after endocrine therapy,establish a Nomogram survival prediction model based on the influencing factors,and verify its accuracy.Methods:1.A retrospective analysis was conducted of the clinical data of 109 patients with prostate cancer diagnosed in the urology department of Gansu Provincial People’s Hospital and treated solely with endocrine therapy between 2018 and 2021.2.Patients were divided into non-progression to CRPC group and progression to CRPC group according to whether they progressed to CRPC or not.The cardinality test was used to analyze whether there was any difference between the data of the two groups.One-way and multi-way logistic regressions were used to analyze the correlation between Body Mass Index(BMI),initial prostate specific antigen(PSA)level,time to the nadir of PSA,nadir PSA value,prostate-specific antigen density(PSAD),Gleason score,clinical T-stage,fibrinogen,alkaline phosphatase,hemoglobin,neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and monocyte-to-lymphocyte ratio(MLR).3.Using the ROC curve,calculate the area under the curve(AUC),and establish the cut-off value at the maximum Joden index.Kaplan Meier survival analysis and log-rank test were used to compare the differences in the progression time of CRPC between different groups.4.Based on statistically significant relevant influencing factors,draw a Nomogram survival prediction model,and draw a calibration chart to verify its accuracy.Results:1.Among 109 prostate cancer patients,62 progressed to CRPC and 47 did not progress to CRPC,with a time to progression of 5～31 months and a median time of 18 months.The BMI value is 16.71～31.14 kg/m~2,with an average of(23.27±3.28)kg/m~2;The initial PSA value was 0.28 to 347.72 ng/m L,with a median of 77.20(24.63,100.00)ng/m L;The time to the nadir of PSA is from 2 to 28 months,with a median of 9.00(6.50,15.00)months;The nadir PSA value was 0.02 to 31.14 ng/m L,with a median of 0.26(0.11,1.24)ng/m L;The density of prostate specific antigen ranged from 0.02 to7.53ng/(m L·cm~3),with a median of 1.22(0.50,2.61)ng/(m L·cm~3);Gleason scores ranged from 6.00 to 10.00,with a median of 8.00(8.00,9.00)points;The clinical T stage ranged from T2 to T4,with a median of T3;Fibrinogen ranged from 0.70 to 6.63 g/L,with a median of 3.50(2.89,4.36)g/L;Alkaline phosphatase ranged from 29.00 to 6341.00 U/L,with a median of 85.00(65.00,119.00)U/L;Hemoglobin ranged from 89.00 to 242.00 g/L,with a median of 146.00(129.50,153.00)g/L;NLR ranged from0.32 to 45.31,with a median of 2.44(1.90,3.83);PLR ranged from 1.04 to 163.85,with a median of 7.82(5.59,11.20);MLR ranged from 0.05 to 3.77,with a median of 0.34(0.26,0.43).2.Single factor logistic regression analysis showed that there was no significant difference in BMI,fibrinogen,hemoglobin,NLR,PLR,and MLR(P>0.05),but there was significant difference in initial PSA,time to the nadir of PSA,nadir PSA,PSAD,Gleason score,clinical T stage,and alkaline phosphatase(P<0.05);In a multifactorial logistic regression analysis,the results showed that the time to nadir PSA(P=0.006,OR=1.159,95%CI:1.044～1.287),the nadir PSA(P=0.034,OR=1.153,95%CI:1.011～1.315),and PSAD(P=0.030,OR=1.632,95%CI:1.049～2.536)were independent risk factors for progression to CRPC.3.The time to the nadir of PSA AUC was 0.924(95%CI:0.876～0.972),P<0.001,cut-off value was 11.5 months,sensitivity was 76.60%,and specificity was 93.50%.The nadir PSA AUC was 0.722(95%CI:0.624～0.820),P<0.001,with a cut-off value of 0.155 ng/m L,sensitivity of 82.30%and specificity of 57.40%.PSAD AUC was 0.729(95%CI:0.629～0.828),P<0.001,with a cut-off value of 0.845 ng/(m L·cm~3),with a sensitivity of 77.40%and specificity of 68.10%;The log-rank P<0.001 for the survival curve of time to the nadir of PSA versus CRPC progression time,log-rank P=0.025 for the survival curve of nadir PSA versus CRPC progression time,and log-rank P=0.002 for the survival curve of PSAD versus CRPC progression time.4.A Nomogram survival prediction model was developed,and a C-index of 0.821(95%CI:0.725～0.917)was calculated,and calibration curves were plotted for the 1,2,and 3year models,respectively.Conclusion:1.Compared to other studies,our patients with primary prostate cancer were older,had higher initial PSA values,higher PSAD values,higher Gleason scores,and later clinical T-stage.2.In the single factor logistic regression analysis,initial PSA,time to the nadir of PSA,nadir PSA,PSAD,Gleason score,clinical T stage,and alkaline phosphatase were influential factors for progression to CRPC after endocrine therapy in prostate cancer patients;in the multi-factor logistic regression analysis,time to nadir PSA,nadir PSA,and PSAD were influential factors for progression to CRPC after endocrine therapy in prostate cancer patients.3.The shorter the time to the nadir of PSA,the higher the nadir PSA value,and the higher the PSAD,the more likely the patient was to enter CRPC.4.The Nomogram survival prediction model established by the factors influencing the progression of prostate cancer patients to CRPC after endocrine therapy has good predictive efficacy and has clinical significance in predicting long-term survival of patients and guiding individualized treatment.