Urologic Oncology: Seminars and Original Investigations
Original articleAlkaline phosphatase velocity predicts overall survival and bone metastasis in patients with castration-resistant prostate cancer
Introduction
Despite recent controversy, prostate-specific antigen (PSA) remains the primary screening parameter for all stages of prostate cancer (CaP). Since its clinical application nearly 3 decades ago, patients present at an earlier stage with predominantly low-grade, organ-confined disease at younger age [1]. However, despite increased screening with PSA-based strategies, almost 4% of patients continue to be diagnosed with advanced-stage disease at the time of initial presentation [2], [3], [4]. More importantly, approximately 12% of the patients with organ-confined CaP at the time of initial presentation ultimately go on to develop bone metastases (BM) and less than 1% of those patients with BM have survival of 5 or more years [3], [4], [5].
Currently, metrics such as PSA doubling time (PSADT) and PSA velocity are the only relevant measures commonly used to evaluate the risk for disease progression and BM in men diagnosed with CaP [6]. Nevertheless, the efficacy of PSADT in predicting the onset of BM in patients with rising PSA is limited [7].
Alkaline phosphatase (AP) has been shown to be a nonspecific bone turnover marker that has been used to evaluate efficacy of treatment and to predict overall survival (OS) in men with castration-resistant prostate cancer (CRPC) [7], [8], [9], [10]. Historically, the clinical use of AP has been limited to detecting values above the upper limit of the reference range; only recently have AP kinetics been evaluated for clinical predictive value. A recently published study of a cohort of patients with CRPC demonstrated that alkaline phosphatase velocity (APV) has been shown to predict OS and bone metastasis–free survival (BMFS) [11].
It is well known that men who progress to metastatic CRPC have the highest probability of CaP-specific death compared with other stages of this disease. Furthermore, health care costs are significantly higher for patients who are diagnosed with this stage of disease [12], [13]. Subsequently, from the clinical perspective of improved patient care as well as from an economic perspective, better tools are needed to identify and treat patients at risk for metastatic CRPC. The primary aim of this study was to confirm a prior observation that APV is a useful predictor of PCa progression in the interval between achievement of CRPC status and metastasis.
Section snippets
Study population
Subjects of interest included those with biopsied-detected CaP between January 1, 1989 and December 31, 2010, who underwent androgen deprivation therapy (ADT) as primary CaP treatment or secondary to radical prostatectomy (RP) and provided written informed consent for study enrollment at Memorial Sloan Kettering Cancer Center (MSKCC). Patients with radiographic evidence of metastasis before or at the time of ADT initiation or within the first 12 months after ADT initiation were excluded from
Results
In total, 89 patients were identified who had 2 or more AP values, permitting an APV calculation. A flow diagram of patient selection and inclusion criteria is depicted in Fig. 1. Demographic and clinical characteristics are described in Table 1. Of the main cohort (n = 89), 17 developed BM (19.1%). Death was confirmed in 26 patients (29.2%); among the deceased, 9 (34.6%) patients had documented BM. Across kinetics measure categories, 60 patients (70%) had a PSADT≥10 months, whereas 26 patients
Discussion
In clinical practice, PSA is the most commonly accepted parameter used to evaluate patients with CaP for their risk of metastatic disease, CRPC, and PCSM [18]. This includes PSA kinetics, such as PSADT, PSA nadir, and PSA velocity [19]. The use of various biomarkers for bone turnover have long been used in conjunction with PSA kinetics. However, the clinical usage of biomarkers for bone turnover in patients with advanced CaP has not been established. Traditionally, single cut points of these
Conclusion
AP kinetics, specifically APV, appear to be predictive of BMFS and OS in a second cohort of patients with CRPC treated in a tertiary cancer center. PSADT is also strongly predictive of BMFS and OS. These data are additional evidence of the potential value of AP kinetics in an unique subset of patients with highly advanced CaP. Further, prospective data are needed to confirm these findings in geographically and racially diverse groups. APV should also be examined in larger study cohorts as a
Conflict of interest
The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed
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2020, Biochimica et Biophysica Acta - Molecular Basis of DiseaseCitation Excerpt :AP velocity (ie. The increase of AP in patients' sera over time) is an excellent predictor of cancer progression and metastasis [57,58], consistent with higher AP expression in metastatic PCa cells than in healthy cells which is linked to the EMT and migration. We could only find this osteogenic capacity in exosomes derived from C4-2B bone metastatic cell line, since the non-tumor cell line WPMY-1 could not induce any osteoblastic response in MC3T3-E1.
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2018, Journal of Bone OncologyCitation Excerpt :Biologically this is in line with worse overall bone turnover given that NTX is a cleavage product generated by bone degradation and BSP is usually involved in bone mineralization, so smaller drops in NTX would be associated with continued degradation, while larger drops in BSP would be consistent with failure to promote bone formation. These differential changes over time are reminiscent of measures of rates of change or velocity, and indeed it has recently been shown that BSAP velocity is associated with worse overall survival in prostate cancer patients [23,41], however its association with SRE were not evaluated in these studies. It would be interesting to evaluate these two markers in particular in extended time courses of analysis, and perhaps develop a composite score of their velocities over time to determine if an association with SRE exists.
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