Prognostic Value of Lactate Dehydrogenase in Metastatic Prostate Cancer: A Systematic Review and Meta-analysis

Mori, Keiichiro; Kimura, Shoji; Parizi, Mehdi Kardoust; Enikeev, Dmitry; Glybochko, Petr; Seebacher, Veronika; Fajković, Harun; Mostafaei, Hadi; Лысенко, И. М.; Janisch, Florian; Egawa, Shin; Shariat, Shahrokh F.

doi:10.1016/j.clgc.2019.07.009

Cited by 32 publications

(31 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While ALP did not show any differences between AR-V7 positive and negative patients, we found higher PSA levels in AR-V7 positive patients and a trend for higher LDH in AR-V7 pos patients with low NED gene expression. Higher LDH serum levels have been reported for active tumor metastatic activity and association with shorter OS 48 , 49 . In our study, elevated levels of the NED genes SYP and ENO2 presented with a significant effect on OS which seemed to function independent from both canonical AR as well as AR-V7 expression.…”

Section: Discussionmentioning

confidence: 95%

Molecular analysis of circulating tumor cells of metastatic castration-resistant Prostate Cancer Patients receiving ¹⁷⁷Lu-PSMA-617 Radioligand Therapy

Kessel¹,

Seifert²,

Weckesser³

et al. 2020

Theranostics

View full text Add to dashboard Cite

Rationale: Lu-177-PSMA-617 radioligand therapy (RLT) is currently under approval for treatment of metastatic castration resistant prostate cancer (mCRPC) patients with late stage disease. However, previous studies demonstrated both heterogeneity of prostate specific membrane antigen (PSMA) expression, as well as response to PSMA treatment among mCRPC patients. Thus, there is an unmet need for identifying predictive parametres prior or under PSMA-RLT treatment. We therefore aimed to correlate several clinical and molecular parameters with response to PSMA treatment in a cohort of mCRPC patients undergoing PSMA RLT followed by a detailed analysis of promising candidates. Methods: Nineteen patients, median age 68.8 years (range: 56.9 - 83.3) with mCRPC were included in this study. We performed baseline analysis of clinical parameters based on PSMA PET/CT, (metabolic tumor volume (MTV), total tumor volume (TTV)), serum PSA, ALP, LDH and gene expression analysis of circulating tumor cells (expression of AR full length (AR-FL), AR splice variant 7 (AR-V7), PSA and PSMA) as well as common markers for neuroendocrine differentiation (NED). Results: Patients presented with bone, lymph node, and visceral metastases (89%, 68%, and 21%, respectively). All patients were pretreated with docetaxel, either abiraterone or enzalutamide, or both. Biochemical response in terms of PSA decline ≥50 or ≥30% was observed in 42% and 63%, respectively. There were significant correlations between PSA and PSMA mRNA expression, as well as tumor volumes (both MTV and TTV), AR-FL and AR-V7 mRNA expression. However, there was no correlation with response to PSMA treatment. Furthermore, none of these parameters was significantly correlated with baseline serum PSA values. Common NED markers were shown to be specifically high expressed and revealed impact on OS independent from AR-V7 gene expression. Conclusion: We demonstrate that AR-FL and its splice variant AR-V7 might serve as prognostic biomarkers displaying high tumor burden in mCRPC patient prior to PSMA-RLT. Contrary, PSMA, which has been discussed as a biomarker for PSMA targeted treatment, does not display strong prognostic ability - at least on the mRNA level. Surprisingly, none of these parameters correlates to response to PSMA treatment. In contrast, commom NED markers such as SYP and ENO2 as well as FOXA1 expression level seem to predict OS, but not PFS, more reliably. We admit that a limitation of our study is the focus on mRNA expression of potential biomarkers only. Further investigations analyzing the potential role of protein expression of these markers are therefore warranted.

show abstract

Section: Discussionmentioning

confidence: 95%

Molecular analysis of circulating tumor cells of metastatic castration-resistant Prostate Cancer Patients receiving ¹⁷⁷Lu-PSMA-617 Radioligand Therapy

Kessel¹,

Seifert²,

Weckesser³

et al. 2020

Theranostics

View full text Add to dashboard Cite

show abstract

“…In addition, as a result of clinical analyses, mounting evidence has shown that an elevated serum LDH was observed in various types of cancers and could be a predictive marker of treatment response 17,34‐36 . A meta‐analysis has indicated that an increased serum LDH was an independent prognostic factor of OS in both patients with CRPC and those with hormone‐sensitive PCa 37 …”

Section: Discussionmentioning

confidence: 99%

“…17,[34][35][36] A meta-analysis has indicated that an increased serum LDH was an independent prognostic factor of OS in both patients with CRPC and those with hormone-sensitive PCa. 37 The combination of inflammatory markers has been shown to be a significant predictive parameter not only for patients who received ICI, but also chemotherapy, in NSCLC. 20 Patients with mCRPC may have a chance to undergo a wide range of treatment sequences, and the combination inflammatory index will be a useful biomarker.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of an inflammatory index for patients with metastatic castration‐resistant prostate cancer

et al. 2020

View full text Add to dashboard Cite

Background The inflammatory process has been reported to be involved in the formation and progression of various types of cancer. Recently, a peripheral inflammatory index, combining the derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and the lactate dehydrogenase (LDH) level, was proposed as a useful prognostic marker in advanced nonsmall cell lung cancer. The prognostic value of inflammatory markers in prostate cancer has not been established. We aimed to validate the prognostic significance of this peripheral inflammatory index in metastatic castration‐resistant prostate cancer (mCRPC). Methods Clinical data of 196 mCRPC patients were retrospectively collected from multiple institutions. Clinical factors and inflammatory markers at the development of CRPC, including white blood cell count, absolute neutrophil count, dNLR, neutrophil‐lymphocyte ratio, platelet‐lymphocyte ratio, C‐reactive protein (CRP), and LDH levels, were evaluated. The patients were classified into three groups based on the inflammatory index: Good (low dNLR and LDH), Intermediate (high dNLR or LDH), and Poor (high dNLR and LDH). Overall survival (OS) and cancer‐specific survival after CRPC were analyzed using Cox proportional hazard models and Kaplan‐Meier methods. Results The median age and baseline prostate‐specific antigen level were 75 years and 397.15 ng/mL, respectively. On multivariate analysis, dNLR (≥1.51; hazard ratio [HR] = 1.624; P = .0173), LDH (≥upper limit of normal; HR = 2.065; P = .0004), alkaline phosphatase (≥310 U/L; HR = 2.546; P < .0001), and positive N stage (HR = 1.621; P = .048) were associated with poor OS after CRPC, whereas other inflammatory markers including the NLR were not. The Good inflammatory index group showed significantly longer OS after CRPC compared to the Intermediate and Poor groups, with median survivals of 46.2, 28.9, and 16.6 months, respectively. Conclusions The novel inflammatory index combining dNLR and LDH was a useful prognostic parameter in patients with mCRPC. Our analysis suggested that dNLR emerged as a more valuable prognostic marker than NLR.

show abstract

“…Lactate dehydrogenase, as a systemic inflammation indicator, has attracted attention. Multiple previous studies in various cancer types indicated that high LDH level is a poor prognostic factor for PFS or OS (30)(31)(32)(33). A meta-analysis of 1136 patients with NSCLC treated with immune checkpoint inhibitors suggested that high LDH levels were related to shorter PFS and OS (30).…”

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes for PD-1 Inhibitor Plus Chemotherapy as Second-Line or Later Therapy Compared to PD-1/PD-L1 Inhibitor Alone in Advanced Non-small-cell Lung Cancer

Zhai

Jing

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Background: Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor monotherapy has been approved as second-line or later therapy in advanced non-small-cell lung cancer (NSCLC). The study aimed to compare the clinical outcomes of PD-1 inhibitor plus chemotherapy with PD-1/PD-L1 inhibitor monotherapy as second-line or later therapy in advanced NSCLC. Methods: The clinical data of patients with advanced NSCLC who received PD-1/PD-L1 inhibitors as second-line or later line therapy was retrospectively collected. Patients were assigned to one of the two groups according to the therapeutic modality used: PD-1/PD-L1 inhibitor monotherapy group or PD-1 inhibitor plus chemotherapy combination therapy group. Disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated between the two groups. The prognostic effect of the derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) on the outcomes was also evaluated. Results: From April 2017 to October 2019, a total of 84 patients were enrolled in the current study. Twenty-six patients (PD-1 inhibitor, n = 25; PD-L1 inhibitor, n = 1) received PD-1/PD-L1 inhibitor monotherapy, and fifty-eight patients received PD-1 inhibitor plus chemotherapy. The chemotherapy regimens used were as follows: liposome paclitaxel (n = 15); nab-paclitaxel (n = 12); docetaxel (n = 9); pemetrexed (n = 6); and others (n = 16). The DCR and OS were not significantly different between the two groups. The PFS of the monotherapy group was longer than that of the combination therapy group (mPFS: 9.6 vs. 4.6 months, P = 0.01). Univariate and multivariate analyses suggested that LDH and sex were independent prognostic factors of PFS. In the second-line therapy subgroup of 38 patients, OS and PFS were not significantly different between the two groups. In the subgroup of 46 patients treated beyond the 2nd line, the monotherapy group had a longer PFS (mPFS: 9.6 vs. 4.2 months,

show abstract

Prognostic Value of Lactate Dehydrogenase in Metastatic Prostate Cancer: A Systematic Review and Meta-analysis

Cited by 32 publications

References 79 publications

Molecular analysis of circulating tumor cells of metastatic castration-resistant Prostate Cancer Patients receiving ¹⁷⁷Lu-PSMA-617 Radioligand Therapy

Molecular analysis of circulating tumor cells of metastatic castration-resistant Prostate Cancer Patients receiving ¹⁷⁷Lu-PSMA-617 Radioligand Therapy

Prognostic value of an inflammatory index for patients with metastatic castration‐resistant prostate cancer

Clinical Outcomes for PD-1 Inhibitor Plus Chemotherapy as Second-Line or Later Therapy Compared to PD-1/PD-L1 Inhibitor Alone in Advanced Non-small-cell Lung Cancer

Contact Info

Product

Resources

About

Prognostic Value of Lactate Dehydrogenase in Metastatic Prostate Cancer: A Systematic Review and Meta-analysis

Cited by 32 publications

References 79 publications

Molecular analysis of circulating tumor cells of metastatic castration-resistant Prostate Cancer Patients receiving 177Lu-PSMA-617 Radioligand Therapy

Molecular analysis of circulating tumor cells of metastatic castration-resistant Prostate Cancer Patients receiving 177Lu-PSMA-617 Radioligand Therapy

Prognostic value of an inflammatory index for patients with metastatic castration‐resistant prostate cancer

Clinical Outcomes for PD-1 Inhibitor Plus Chemotherapy as Second-Line or Later Therapy Compared to PD-1/PD-L1 Inhibitor Alone in Advanced Non-small-cell Lung Cancer

Contact Info

Product

Resources

About

Molecular analysis of circulating tumor cells of metastatic castration-resistant Prostate Cancer Patients receiving ¹⁷⁷Lu-PSMA-617 Radioligand Therapy

Molecular analysis of circulating tumor cells of metastatic castration-resistant Prostate Cancer Patients receiving ¹⁷⁷Lu-PSMA-617 Radioligand Therapy