Redefining Clinically Significant Castration Levels in Patients With Prostate Cancer Receiving Continuous Androgen Deprivation Therapy

Abstract

In the current report the lowest testosterone castration level with clinical relevance in medically castrated patients with prostate cancer was 32 ng/dl. Breakthrough increases greater than this threshold predicted a lower survival free of androgen independent progression. Maximal androgen blockade might benefit medically castrated cases of prostate cancer with breakthrough increases of more than 50 ng/dl.

Testosterone monitoring for men with advanced prostate cancer: Review of current practices and a survey of Canadian physicians

“…24 Several studies have shown a correlation between adequate testosterone suppression and freedom from progression to castrate-resistant disease. 13,28 Among 73 patients with non-metastatic prostate cancer receiving three-month depots of LHRH agonist, 41 patients had progressed to castrate-resistant prostate cancer (CRPC) after a median followup of 51 months. 13 Testosterone breakthroughs above 1.7 nmol/L and 1.1 nmol/L were found to be predictors of progression to CRPC.…”

“…13,28 Among 73 patients with non-metastatic prostate cancer receiving three-month depots of LHRH agonist, 41 patients had progressed to castrate-resistant prostate cancer (CRPC) after a median followup of 51 months. 13 Testosterone breakthroughs above 1.7 nmol/L and 1.1 nmol/L were found to be predictors of progression to CRPC. Mean survival free of androgen-independent progression was 88 months in patients with testosterone breakthroughs above 1.1 nmol/L, compared with 137 months in those without breakthrough increases (p<0.03).…”

“…Mean survival free of androgen-independent progression was 88 months in patients with testosterone breakthroughs above 1.1 nmol/L, compared with 137 months in those without breakthrough increases (p<0.03). 13 In a prospective cohort series of 32 patients undergoing ADT with LHRH agonist or antagonist at a tertiary centre from 2006-2011, patients with a nine-month serum testosterone level of less than 1.1 nmol/L had a significantly increased time to CRPC compared with patients with testosterone levels between 1.1 and 1.7 nmol/L (p=0.001; median progression-free survival [PFS] 33.1 months). 28 Patients with first-year mean testosterone levels below 1.1 nmol/L also had a significantly longer time to CRPC than those with levels between 1.1 and 1.7 nmol/L (p=0.05, median PFS 33.1 months).…”

“…4,[7][8][9][10][11] Several studies since the early 1990s have therefore challenged the outdated benchmark of 1.7 nmol/L and recommended revisiting the definition, with many suggesting a new benchmark of 0.7 nmol/L. 4,[12][13][14] In light of conflicting opinion on the ideal goal for suppression of serum testosterone in men with advanced cancer, we conducted a survey of Canadian urologists, uro-oncologists, and radiation oncologists to gain a better understanding of their testosterone monitoring practices when managing men with hormone-sensitive prostate cancer. Survey participants were selected from a private database of Canadian healthcare providers who have participated in educational, advisory, and editorial activities related to the treatment of prostate cancer.…”

Current trends for the use of androgen deprivation therapy in conjunction with radiotherapy for patients with unfavorable intermediate‐risk, high‐risk, localized, and locally advanced prostate cancer

“…In a 6-month study, > 30% of patients receiving an LHRH agonist with or without bicalutamide recorded a testosterone breakthrough of 0.2 ng/ mL to 0.5 ng/mL, whereas 25% recorded breakthroughs of > 0.5 ng/mL. 53 It remains to be determined whether "mini" testosterone; surges adversely impact the outcomes of men with localized androgen-sensitive disease receiving short-term ADT.…”