In this study, we did not observe differences in clinical outcomes based on alternative sequencing of AA and DP in mCRPC patients. The ability to tolerate side effects and patient preference may be used to determine the treatment sequencing. In addition, high pretreatment SII level is a negative independent prognosticator of survival outcomes in mCRPC with sequential therapy using DP followed by AA or vice versa, which might guide clinicians select the best treatment.

Objective To determine the prognostic utility of serum chromogranin A (CgA) and neurone‐specific enolase (NSE) variations during the first 3 months of abiraterone acetate (AA) treatment in patients with metastatic castration‐resistant prostate cancer (mCRPC). Patients and Methods The serum levels of CgA, NSE were measured at baseline and after 3 months of AA treatment in 40 patients with mCRPC. Outcome measures were prostate‐specific antigen progression‐free survival (PSA‐PFS), radiographic PFS (rPFS), and overall survival (OS). Results CgA levels were not correlated with NSE levels (P = 0.296). In multivariate analysis the combination of CgA and NSE (≥1 marker positive vs both markers negative) and the combination of CgA and NSE elevation during the first 3 months of AA treatment (≥1 marker positive vs both markers negative) remained significant predictors of OS, rPFS, and PSA‐PFS. Conclusion We found that CgA and NSE elevation during the first 3 months of AA treatment and elevated baseline CgA and NSE levels were independent prognostic factors for OS, rPFS and PSA‐PFS in patients with mCRPC treated with AA. This suggests that serial CgA and NSE evaluation may help clinicians in distinguishing patients with mCRPC who would obtain the best survival benefit from AA treatment.

Background: This study aimed to describe the aberrations of DNA damage repair genes and other important driving genes in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC) using circulating tumor (ctDNA) sequencing and to evaluate the associations between the clinical outcomes of multiple therapies and key genomic alterations in mCRPC, especially DNA damage repair genes. Patients and Methods: A total of 292 Chinese patients with mCRPC enrolled from 8 centers. Multigene targeted sequencing was performed on 306 ctDNA samples and 23 matched tumor biopsies. The frequency of genomic alterations were compared with the Stand Up to Cancer–Prostate Cancer Foundation (SU2C-PCF) cohort. The Kaplan-Meier method was used to evaluate progression-free survival (PFS) following standard systemic treatments for mCRPC. Cox regression analyses were performed to determine prognostic factors associated with PFS resulting from treatments for mCRPC. Results: In total, 33 of 36 (91.7%) mutations were found consistently between ctDNA and paired biopsy samples. The most common recurrent genomic alterations were found in AR (34.6%), TP53 (19.5%), CDK12 (15.4%), BRCA2 (13%), and RB1 (5.8%). The frequency of CDK12 alterations (15.4%) in our cohort was significantly higher than that in Western populations (5%–7%). AR amplification and TP53 and/or RB1 alterations were associated with resistance to abiraterone or docetaxel. Patients with a CDK12 defect showed rapid disease progression after abiraterone treatment. However, the clinical outcome after docetaxel treatment was similar between patients with and without CDK12 defects. In multivariate Cox regression analysis, a CDK12 defect was significantly associated with inferior PFS after abiraterone treatment. Patients with a BRCA2 defect showed marked response to both PARP inhibitors and platinum-based chemotherapy. Conclusions: Our study explored the genomic landscape of Chinese patients with mCRPC at different treatment stages using minimally invasive methods and evaluated the clinical implications of the driver genomic alterations on patients’ response to the most widely used therapies for mCRPC. We observed a significantly higher alteration frequency of CDK12 in our cohort compared with the SU2C-PCF cohort.