Abstract
Aim: Metastatic prostate cancer (mPCa) has a poor outcome with median survival of two to five years. The use of androgen deprivation therapy (ADT) is a gold standard in management of this stage. Aim of this study is to analyze the prognostic value of PSA kinetics of patient treated with hormonal therapy related to survival from several published studies Method: Systematic review and meta-analysis was performed using literature searching in the electronic databases of MEDLINE, Science Direct, and Cochrane Library. Inclusion criteria were mPCa receiving ADT, a study analyzing Progression Free Survival (PFS), Overall Survival (OS), or Cancer Specific Survival (CSS) and prognostic factor of survival related to PSA kinetics (initial PSA, PSA nadir, and time to achieve nadir (TTN)). The exclusion criteria were metastatic castration resistant of prostate cancer (mCRPC) and non-metastatic disease. Generic inverse variance method was used to combine hazard ratio (HR) within the studies. Meta-analysis was performed using Review Manager 5.2 and a p-value <0.05 was considered statistically significant. Results: We found 873 citations throughout database searching with 17 studies were consistent with inclusion criteria. However, just 10 studies were analyzed in the quantitative analysis. Most of the studies had a good methodological quality based on Ottawa Scale. No significant association between initial PSA and PFS. In addition, there was no association between initial PSA and CSS/ OS. We found association of reduced PFS (HR 2.22; 95% CI 1.82 to 2.70) and OS/ CSS (HR 3.31; 95% CI 2.01-5.43) of patient with high PSA nadir. Shorter TTN was correlated with poor result of survival either PFS (HR 2.41; 95% CI 1.19 - 4.86) or CSS/ OS (HR 1.80; 95%CI 1.42 - 2.30) Conclusion: Initial PSA before starting ADT do not associated with survival in mPCa. There is association of PSA nadir and TTN with survival.
Highlights
Prostate cancer (PCa) is the second most common cancer in men, and the fourth most common cancer worldwide
The inclusion criteria were that (i) the participant of the study had metastatic PCa; (ii) patients were treated with Androgen deprivation therapy (ADT) either using orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist with or without anti-androgen (AA); (iii) the studies outcome were either progresion free survival (PFS), overall survival (OS) or cancer specific survival (CSS); (iv) the studies had to analyze Prostate specific antigen (PSA) kinetics (intial PSA prior to initiation of ADT, PSA nadir, and time to reach nadir (TTN) PSA)
Seventeen studies were found to be consistent to the inclusion criteria of the study, but seven studies could not be evaluated the in meta-analysis (Figure 1)
Summary
Prostate cancer (PCa) is the second most common cancer in men, and the fourth most common cancer worldwide. More than one million men worldwide were diagnosed with PCa in 20121. The incidence of local-regional PCa has increased since the introduction of prostate specific antigen (PSA). This circumstance reduces the incidence of metastatic PCa2. PCa patient treated at early stages have a good prognosis with 5-year overall survival (OS) reaching 99%. Metastatic PCa patients generally experience a poor outcome. Androgen deprivation therapy (ADT) becomes the standard treatment of patients with advanced PCa6,7, and with the first use reported by Huggins and Hodges in 19418
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