Predictors of early androgen deprivation treatment failure in prostate cancer with bone metastases

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.

The Clinical Efficacy of Radium-223 for Bone Metastasis in Patients with Castration-Resistant Prostate Cancer: An Italian Clinical Experience

“…In fact, scores obtained with the SF-36 suggested a better perception of own health state after treatment, and these results were consistent with the findings reported in literature [22,23]. Nevertheless, patients who received radium-223 before treatment with docetaxel [24] experienced less hematologic toxicity and hospitalization compared to placebo group, whereas patients who received radium-223 after docetaxel [25] showed a higher rate of hematologic toxicity. However, although our results were consistent with those in the literature, we realized that some limitations, such as the response evaluation and the small sample size, needed to be considered.…”

Predictive factor of androgen deprivation therapy for patients with advanced stage prostate cancer

“…These results correspond with the study from Ross et al 8 which reported that in the locally advanced group the PSA nadir was the only independent factor with a shorter TTP. In contrast, Varenhorst et al 19 reported the level of pretreatment PSA or the Gleason score at diagnosis could not predict patients likely to be unresponsive to ADT. They mentioned that patients with a low Eastern Cooperative Oncology Group performance status, analgesic consumption, high Soloway score, and a low hemoglobin level were found to be predictive of early ADT failure 19 …”

Clinical and prognostic significance of changes in haemoglobin concentration during 1 year of androgen‐deprivation therapy for hormone‐naïve bone‐metastatic prostate cancer

“…This study was based on the Scandinavian Prostate Cancer Group (SPCG) Trial number 5, a Phase III study in which 915 men with hormone‐naive M1b prostate cancer were included from 61 centres in Denmark, Finland, Iceland, Norway and Sweden between December 1992 and June 1997 . The SPCG‐5 was designed as a non‐inferiority trial.…”

“…Inclusion criteria were skeletal metastases (M1b) and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–2, where: 0 = fully active; 1 = restriction in strenuous activity but ambulatory; and 2 = ambulatory and capable of self‐care but unable to work. The primary objective of the trial was to determine whether survival after high‐dose parenteral oestrogen therapy was not inferior to that after total androgen blockade (TAB) . The secondary objective was to provide information on cardiovascular side‐effects and health‐related quality of life (QoL) before and during ADT .…”

“…PSA, alkaline phosphatase (ALP), testosterone and Hb levels were determined by routine laboratory testing before the start of treatment . Skeletal involvement was assessed using bone scans supplemented by X‐ray in selected cases . The extent of bone metastases was quantified according to a modified three‐grade Soloway Score where: 1 = the total area of hot spots <3 lumbar vertebral bodies; 2 = the total area of hot spots larger than Score 1, but <75% of the total scan; and 3 = ≥75% of the total scan or super scan.…”