The value of tumor markers in men with metastatic prostate cancer undergoing [¹⁷⁷Lu]Lu‐PSMA therapy

Abstract

Background Currently, prostate‐specific membrane antigen‐radioligand therapy (PSMA‐RLT) is considered a last‐line treatment option in advanced castration‐resistant prostate cancer. Despite these patients' poor prognosis, accurate estimation of their overall survival (OS) is essential to determine whether benefits exist from the treatment and whether the loss of valuable time and unnecessary side effects can be avoided. The aim of the present study is to evaluate whether various biochemical markers can predict OS in men undergoing PSMA‐RLT and whether the changes assessed after PSMA‐RLT correlate with the OS. Methods The tested tumor markers in this retrospective analysis were alkaline phosphatase (ALP), bone‐specific alkaline phosphatase (BAP), prostate‐specific antigen (PSA), lactate dehydrogenase (LDH), chromogranin A, and pro‐gastrin‐releasing peptide (pro‐GRP). For the evaluation, we performed blood tests before each PSMA‐RLT cycle and during follow‐up visits (which were 2‐3 months apart). All patients were followed up until their deaths. To test the correlations between the tumor markers and survival, we conducted the logrank tests and the multivariate Cox proportional‐hazards regression model. The significance level was set at P < .05. Results The study included 137 patients who received a total of 487 PSMA‐RLT cycles between January 2015 and November 2017. Of the tested biochemical tumor markers, baseline ALP (120 U/L cut‐off), LDH (248 U/L cut‐off), and PSA (first quartile cut‐off) correlated significantly with survival post‐PSMA‐RLT (P < .001 for ALP and LDH, and P = .007 for PSA). Stable and/or decreased values in most of the initially abnormal parameters were associated with significantly better OS; these parameters were ALP (P = .009), LDH (P = .005), PSA (P < .001), and pro‐GRP (P = .013). The BAP and ALP responses also correlated significantly with survival in patients with bone metastases (P = .002 and P < .001, respectively). Furthermore, there was a strong correlation of the kinetic patterns of PSA, ALP, BAP, and LDH with the survival, showing that patients with steadily increasing markers had the shortest OS. Conclusion Along with the established tumor marker PSA, ALP, LDH, BAP, and pro‐GRP were correlated with the OS post‐PSMA‐RLT in the univariate and multivariate analyses.

Factors predicting biochemical response and survival benefits following radioligand therapy with [177Lu]Lu-PSMA in metastatic castrate-resistant prostate cancer: a review

“…On the contrary, PSA level measured 1 day before [ 177 Lu]Lu-PSMA RLT did not show a negative impact on the response to [ 177 Lu]Lu-PSMA RLT, in a study by Ferdinandus et al [24]. The same results were reported by other authors who did not show any significant association between baseline PSA level and patients' OS after [ 177 Lu]Lu-PSMA RLT [31,32,35,36]. Gafita et al [37] found no association between PSA level and either PFS or OS, in a cohort with the median PSA baseline of 126 ng/ml (IQR: 37-368).…”

“…LDH ≥ 225 mg/L was prognostic of shorter OS in a study by Ahmadzadehfar et al, in the univariate analysis [35]. Also, the same research group reported that a baseline LDH level of < 248 mg/L and any change after the first cycle could predict better survival [32]. However, others did not find a correlation between higher LDH and response to therapy or OS [24,38,39,63].…”

“…Yordanova et al [32] outlined that baseline PSA level significantly correlates with survival following [ 177 Lu]Lu-PSMA RLT, as patients with PSA values lower than 47 ng/mL at baseline achieved a longer OS than patients with higher PSA levels (20 vs. 11 months). In another study, Gafita et al [33] delineated that baseline PSA level significantly associates with OS in the multivariable analysis (HR: 1.63, P = 0.007) but not with the imaging-based PFS.…”

“…Also, pre-treatment ALP level < 120 U/L and any change after the first cycle have been addressed in a study by Ahmadzadehfar et al [32], which predicted longer survival. Additionally, Yordanova et al [32] evaluated the Bonespecific Alkaline Phosphatase (BAP) and showed that the decreasing BAP after the treatment is predictive of longer OS. Nevertheless, Grubmüller et al and Gafita et al did not find a correlation between ALP and outcome following [ 177 Lu]Lu-PSMA RLT [33,36].…”

Neuron-specific enolase has potential value as a biomarker for [18F]FDG/[68Ga]Ga-PSMA-11 PET mismatch findings in advanced mCRPC patients

“…As another point of criticism, no quantitative SUV threshold defining low PSMA expression on [ 68 Ga]Ga-PSMA-11 PET/CT was set, which is also a global problem in literature suffering from defined cut-offs for adequate PSMA expression. Furthermore, additional serum parameters, which were recently reported as prognostic markers in the mCRPC setting for PSMA-RLT, such as the neuroendocrine marker chromogranin A or the lactate dehydrogenase (LDH) [48][49][50], were not available for testing in this study. Serum chromogranin A values might also be higher in patients with mismatch findings similar to NSE.…”