Abstract

Approximately 15% of men with hormone naïve metastatic prostate cancer primarily fail to respond to androgen deprivation treatment (ADT). The reason why the response to ADT differs in this subgroup of men with prostate cancer remains unclear. The aim of this study was to describe the characteristics of these men and to thereby define predictors of early ADT failure in prostate cancer patients with bone metastases. The study was based on 915 men from the prospective randomized multicenter trial (no. 5) conducted by the Scandinavian Prostate Cancer Group comparing parenteral estrogen with total androgen blockade. Early ADT failure was defined as death from metastatic prostate cancer within 12 months after the start of ADT. Multivariate logistic regression models were applied to identify clinical predictors of early ADT failure. Ninety‐four (10.3%) men were primarily nonresponders to ADT. Independent predictors of early ADT failure were poor Eastern Cooperative Oncology Group performance status (PS), analgesic consumption, low hemoglobin, and high Soloway score (extent of disease observed on the scan), in where patients with poor PS and/or high analgesic consumption had a threefold risk of early ADT failure. Not significantly factors related to early ADT failure were age, treatment, cardiovascular comorbidity, T category, grade of malignancy, serum estrogen level, and SHBG at enrolment. We analyzed characteristics of a subgroup of patients who primarily failed to respond to ADT. Four independent clinical predictors of early ADT failure could be defined, and men exhibiting these features should be considered for an alternative treatment.

Highlights

  • Androgen deprivation treatment (ADT) has been the gold standard in treatment of prostate cancer with distant metastases for more than half a century [1,2,3]

  • A total of 94 of 915 (10.4%) patients died of progressive metastatic prostate cancer within 12 months after start of ADT and fulfilled the criteria for early ADT failure

  • The early ADT failure group had a statistically significant higher burden of cancer-r­elated pain, a poorer performance status (PS), analgesic consumption, and a higher Soloway score compared to the remaining cohort

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Summary

Introduction

Androgen deprivation treatment (ADT) has been the gold standard in treatment of prostate cancer with distant metastases for more than half a century [1,2,3]. Did Huggins and coworkers describe the significant improvement in the clinical condition of patients with metastatic prostate cancer treated with ADT, they defined a new disease state of early ADT-­refractory prostate cancer, that is, early ADT failure [1]. In their series of 21 consecutive patients “a noticeable improvement occurred in the clinical status for all but three patients.”. The disease ceases to respond to hormone manipulation, becomes castration resistant, and the patient eventually dies of cancer progression unless death due to an unrelated cause intervenes

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