The prognostic value of serum MMP-7 levels in prostate cancer patients who received docetaxel, abiraterone, or enzalutamide therapy

Urol Oncol. 2021 May;39(5):296.e11-296.e19. doi: 10.1016/j.urolonc.2020.09.005. Epub 2020 Oct 9.

Abstract

Objectives: The rapidly changing treatment landscape in metastatic castration-resistant prostate cancer (mCRPC) calls for biomarkers to guide treatment decisions. We recently identified MMP-7 as a potential serum marker for the prediction of response and survival in mCRPC patients who received docetaxel (DOC) chemotherapy. Here, we aimed to test this finding in an independent patient cohort and in addition to explore the prognostic potential of serum MMP-7 in abiraterone (ABI) or enzalutamide (ENZA) treated patients.

Methods and materials: MMP-7 levels were measured in 836 serum samples from 320 mCRPC patients collected before and during DOC (n = 95), ABI (n = 140), or ENZA (n = 85) treatment by using the ELISA method. Results were correlated with clinical and follow-up data.

Results: MMP-7 baseline levels were similar between the 3 treatment groups. In the ABI and ENZA cohorts, baseline MMP-7 levels were lower in patients with prior radical prostatectomy (P = 0.058 and P = 0.041, respectively). Baseline MMP-7 levels above the median were associated with shorter overall survival for the DOC (P = 0.001) and ENZA (P = 0.006) cohorts. Multivariable analyses in the DOC and ENZA cohorts revealed that high pretreatment MMP-7 level is an independent risk factor for patients' survival. In addition, in DOC-treated patients with high baseline MMP-7 level, marker decrease at the third DOC cycle was associated with improved survival. Patients with high baseline MMP-7 levels had better survival when treated with ABI compared to DOC or ENZA.

Conclusions: We confirmed the prognostic value of pretreatment MMP-7 serum level and its changes as independent predictors of survival in DOC-treated mCRPC patients. In addition, high MMP-7 was a negative predictor in ENZA-treated but not in ABI-treated patients. These results warrant further research to confirm the predictive value of serum MMP-7 and to explore the potential mechanistic involvement of MMP-7 in DOC and ENZA resistance of mCRPC patients.

Keywords: Abiraterone; Docetaxel; Enzalutamide; MMP-7; Prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Androstenes / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Benzamides / therapeutic use*
  • Docetaxel / therapeutic use*
  • Humans
  • Male
  • Matrix Metalloproteinase 7 / blood*
  • Middle Aged
  • Nitriles / therapeutic use*
  • Phenylthiohydantoin / therapeutic use*
  • Prognosis
  • Prostatic Neoplasms, Castration-Resistant / blood*
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Retrospective Studies
  • Survival Rate

Substances

  • Androstenes
  • Antineoplastic Agents
  • Benzamides
  • Nitriles
  • Docetaxel
  • Phenylthiohydantoin
  • enzalutamide
  • Matrix Metalloproteinase 7
  • abiraterone