Predictive factors for progression to metastatic castration-resistant prostate cancer

Objective To explore the predictive factors of metastatic prostate cancer progression to castration resistance and establish a risk prediction model. Methods Clinical data of 118 prostate cancer patients with bone metastasis who were diagnosed in our department from January 2010 to July 2020, initially received adjuvant endocrine therapy (AET) and then advanced to metastatic castration-resistant prostate cancer (mCRPC) were collected and retrospectively analyzed. The clinical information, including age, having diabetes or not, taking metformin or not, prostate specific antigen (PSA) level at diagnosis, nadir levels of PSA and testosterone, time to the nadirs, Gleason score, number of bone metastases, and serum levels of alkaline phosphatase, hemoglobin, albumin, lactate dehydrogenase, uric acid and cystatin C were collected and analyzed. Chi-square test was used to compare the differences of factors between groups with rapid and slow onset of CRPC. Kaplan-Meier survival analysis and Cox multivariate risk proportional regression model were used to compare the time difference of progression to CRPC in different groups. Cox risk proportional regression model was used to analyze and evaluate the effect of these factors on the time of CRPC progression, and a risk prediction model was established, and then the receiver operating characteristic (ROC) curve was used to detect the accuracy of the model. Results The median time for progression to CRPC was 17 (9.5~28.0) months. Univariate analysis indicated that the PSA nadir level, time to PSA nadir level, levels of alkaline phosphatase and lactate dehydrogenase, and number of bone metastases were significantly correlated with the time of progression to CRPC (P < 0.05). The results of multivariate analysis showed that the PSA nadir level (HR=2.549, 95%CI: 1.565~4.151, P < 0.001), time to PSA nadir level (HR=0.373, 95%CI: 0.227~0.612, P < 0.001), number of bone metastases (HR=2.393, 95%CI: 1.292~4.43, P=0.006), lactate dehydrogenase level (HR=1.681, 95%CI: 1.045~2.703, P=0.032) were independent risk factors for short-term progression to CRPC. Based on these 4 independent risk factors, a risk prediction model was established. The equation is pi=1.788×(the PSA nadir level)-1.275×(the time to PSA nadir level) +0.441×(lactate dehydrogenase level) +1.114×(number of bone metastases)-1.5. The area under ROC curve was 0.812 (95%CI: 0.731~0.893, P < 0.001, β=0.041). The sensitivity, specificity and Youden index were 0.803, 0.718 and 0.521, respectively. Conclusion The PSA nadir level, time to PSA nadir value, number of bone metastases, lactate dehydrogenase level are independent risk factors for progression to mCRPC after androgen deprivation therapy (ADT) in prostate cancer patients with bone metastasis. Based on these 4 factors, the establishment of CRPC prediction model can improve the accuracy of prediction