ALP bouncing and LDH normalization in bone metastatic castration-resistant prostate cancer patients under therapy with Enzalutamide: an exploratory analysis

BackgroundIn bone metastatic castration-resistant prostate cancer (bmCRPC) treated with Enzalutamide commonly used prostate-specific antigen (PSA) can be misleading since initial PSA-flares may occur. In other therapies, bouncing of alkaline phosphatase (ALP-bouncing) was shown to be a promising surrogate for survival outcome. Low lactate dehydrogenase (LDH) is usually associated with better outcome. We evaluated the prognostic ability of ALP-bouncing, LDH, PSA, and the combination of these markers after initiation of Enzalutamide.MethodsEighty-nine patients with bmCRPC and dynamic changes of PSA, LDH and ALP were analyzed. ALP-bouncing, an increase after therapy start followed by a decline below baseline during the first 8 weeks, LDH-normalization and PSA-decline were analyzed regarding their association with survival using Kaplan-Meier analyses and uni- and multivariate (UV and MV) Cox-regression models.ResultsIn Kaplan-Meier analysis a PSA-decline >50%, LDH-normalization and ALP-bouncing were associated with longer median progression-free survival (PFS) with 7 95% confidence interval (CI): 4.2–9.8] vs. 3 (2.3–3.7) months for PSA-decline (log-rank P<0.01), 6 (4.1–8) vs. 2 (1.2–2.8) for LDH-normalization (P<0.01) and 8 (0–16.3) vs. 3 (1.9–4.1) for ALP-bouncing (P=0.01). Analysis of overall survival (OS) showed similar, not for all parameters significant, results with 17 (11.7–22.3) vs. 12 (7.0–17.1) months for PSA (P=0.35), 17 (13.2–20.8) vs. 7 (5.8–8.2) for LDH-normalization (P<0.01) and 19 (7.9–30.1) vs. 12 (7.7–16.3) for ALP-bouncing (P=0.32). In UV analysis, ALP-bouncing hazard ratio (HR): 0.5 (0.3–1.0); P=0.02], PSA-decline >50% HR: 0.5 (0.3–0.7); P<0.01] and LDH-normalization HR: 0.4 (0.2–0.6); P<0.01] were significantly associated with longer PFS. For OS, LDH-normalization significantly prognosticated longer survival HR: 0.4 (0.2–0.6); P<0.01]. In MV analysis, LDH-normalization was associated with a trend towards better OS HR: 0.5 (0.2–1.1); P=0.09]. Comparing ALP-bouncing, LDH-normalization and PSA-decline with a PSA-decline alone, Kaplan-Meier analysis showed significantly longer PFS 11 (0.2–21.8) vs. 4 (0–8.6); P=0.01] and OS 20 (17.7–22.3) vs. 8 (0.3–15.7); P=0.02] in favor of the group presenting with the beneficial dynamics of all three markers. In UV analysis, the presence of favorable changes in the three markers was significantly associated with longer PFS HR: 0.2 (0.1–0.7); P<0.01] and OS HR: 0.3 (0.1–0.8); P=0.02].ConclusionsALP-bouncing and LDH-normalization may add to identification of bmCRPC-patients with favorable prognosis under Enzalutamide.