Revealing Prognostic Value of Skeletal-Related Parameters in Metastatic Castration-Resistant Prostate Cancer on Overall Survival: A Systematic Review and Meta-Analysis of Randomized Controlled Trial

BACKGROUND: The skeleton is a preferred site for prostate cancer metastasis, and once metastases occur, the disease becomes incurable. Increasing evidence indicates the prognostic value of skeletal-related parameters, but remains controversial. OBJECTIVE: To perform a systematic review of the existing literature on assessing the prognostic value of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BSAP), urinary N-telopeptide (uNTx), bone scan index (BSI), and Brief Pain Inventory Short Form (BPI-SF) score in castration-resistant prostate cancer (CRPC) patients with skeleton metastasis. EVIDENCE ACQUISITION: PubMed, Web of Science, Cochrane Library, Medline, OVID, and Embase between 2010 and 2019 were reviewed. Key terms included randomized trials, prostate cancer, alkaline phosphatase, bone-specific alkaline phosphatase, urinary N-telopeptide, bone scan index, and Brief Pain Inventory Short Form. Data were collected, checked, and analyzed from December 2019 to March 2020. Hazard ratios (HRs) and overall survival (OS) were extracted to estimate the relationship between the above parameters and OS in patients with metastatic prostate cancer (mPCa). EVIDENCE SYNTHESIS: A total of 1,055 studies were identified via initial screening, including 1,032 from database research and 23 from other sources. After deduplication, 164 records were further excluded according to titles and abstracts. The remaining 36 potential articles were carefully screened. In the end, 15 eligible studies syntheses, which were published between 2010 and 2019, comprised data for a total of 11,378 patients, whose mean age ranged from 66 to 72 years. The sample size ranged from 82 to 1,901 patients. And the median follow-up time ranged from 24 to 55 months. Based on 15 randomized controlled trials published between 2010 and 2019, higher ALP levels (HR = 1.60, 95% CI: 1.38–1.87 P < 0.001), higher BSAP levels (HR = 1.31, 95% CI: 1.11–1.54 P = 0.001), higher uNTx levels (HR = 1.40, 95% CI: 1.29–1.52 P < 0.001), BSI progression (HR = 1.18, 95% CI: 1.08–1.29 P < 0.001), and higher BPI-SF score (HR = 1.47, 95% CI: 1.35–1.61 P < 0.001) had an association with inferior OS. CONCLUSIONS: Higher levels of ALP/BSAP and uNTx, a higher BPI-SF score, and progression of BSI predict inferior OS in patients with mCRPC. More randomized control trials are needed to investigate the promising value of these parameters.