Development of castration resistance in prostate cancer patients treated with luteinizing hormone-releasing hormone analogues (LHRHa): results of the ANARESISTANCE study

World J Urol. 2022 Oct;40(10):2459-2466. doi: 10.1007/s00345-022-04108-x. Epub 2022 Sep 4.


Purpose: Evaluate the percentage of patients with prostate cancer treated with luteinizing hormone-releasing hormone analogues (LHRHa) that develop castration resistance after a follow-up period of 3 years. The secondary objective is to evaluate the variables potentially related to the progression to castration resistant prostate cancer (CRPC).

Methods: A post-authorization, nation-wide, multicenter, prospective, observational, and longitudinal study that included 416 patients treated with LHRHa between 2012 and 2017 is presented. Patients were followed for 3 years or until development of CRPC, thus completing a per-protocol population of 350 patients. A Cox regression analysis was carried out to evaluate factors involved in progression to CRPC.

Results: After 3 years of treatment with LHRHa 18.2% of patients developed CRPC. In contrast, in the subgroup analysis, 39.6% of the metastatic patients developed CRPC, compared with 8.8% of the non-metastatic patients. The patients with the highest risk of developing CRPC were those with a nadir prostate-specific antigen (PSA) > 2 ng/ml (HR 21.6; 95% CI 11.7-39.8; p < 0.001) and those receiving concomitant medication, most commonly bicalutamide (HR 1.8; 95% CI 1-3.1, p = 0.0431).

Conclusions: The proportion of metastatic patients developing CRPC after 3 years of treatment with LHRHa is consistent with what has been previously described in the literature. In addition, this study provides new findings on CRPC in non-metastatic patients. Concomitant medication and nadir PSA are statistically significant predictive factors for the time to diagnosis of CRPC, the nadir PSA being the strongest predictor.

Keywords: Castration-resistant prostatic neoplasms; Gonadotropin-releasing hormone; Observational study; Prospective study.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Androgen Antagonists / therapeutic use
  • Castration
  • Gonadotropin-Releasing Hormone
  • Humans
  • Longitudinal Studies
  • Male
  • Prospective Studies
  • Prostate-Specific Antigen
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / diagnosis
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy


  • Androgen Antagonists
  • Gonadotropin-Releasing Hormone
  • Prostate-Specific Antigen