Strategies for Testosterone Therapy in Men with Metastatic Prostate Cancer in Clinical Practice: Introducing Modified Bipolar Androgen Therapy

Abraham Morgentaler

doi:10.1089/andro.2020.0009

Abstract

Purpose: To investigate prostate-specific antigen (PSA) and clinical responses to a variety of treatment strategies involving testosterone therapy (TTh) in men with metastatic prostate cancer (mPCa). Materials and Methods: Case records were reviewed for three men with advanced PCa treated with TTh for improved quality of life. Two had bone metastases and nephrostomies at baseline. The third had biochemical recurrence, and continued TTh after developing bone metastases. All rejected androgen deprivation therapy, desired improved quality of life with TTh, and accepted the risk of rapid PCa progression and death. Results: All men experienced substantial symptomatic and health benefits during TTh, including improved strength, vigor, and sexuality. Two reversed substantial weight loss. A 94-year-old man with baseline PSA of 546 ng/mL survived 11 months with continuous TTh, with last PSA of 2493 ng/mL. Two men in their 60s received some form of TTh for 3.5 and 8 years, respectively, and are still alive. None experienced sudden major adverse events. Continuous TTh resulted in progressive rise in PSA to high values. The combination of TTh and enzalutamide provided moderate protection against weakness and fatigue with PSA <10ng/mL for 6 months. PSA values fluctuated from <1.0 to >100 ng/mL within 1–2 months depending on recent androgen status. The most promising strategy appears to be a modified bipolar androgen therapy consisting of repeating cycles of 8 weeks of high-dose TTh followed by 4 weeks of enzalutamide, allowing for prolonged periods of vigor while maintaining PSA control. Conclusions: These pilot results support explorations of new hormonal strategies involving TTh for men with mPCa.

Highlights

Over the last two decades there has been a major reevaluation of the biology of androgens and prostate cancer (PCa).[1]
The most promising strategy appears to be a modified bipolar androgen therapy consisting of repeating cycles of 8 weeks of high-dose testosterone therapy (TTh) followed by 4 weeks of enzalutamide, allowing for prolonged periods of vigor while maintaining prostate-specific antigen (PSA) control
Whereas it has been long believed that offering testosterone therapy (TTh) to a man with PCa was like ‘‘pouring gasoline on a fire,’’2 numerous case series and observational studies have failed to demonstrate increased risk of disease recurrence or progression with TTh after radical prostatectomy,[3] radiation therapy,[4] and even in men on active surveillance.[5,6]

Summary

Introduction

Over the last two decades there has been a major reevaluation of the biology of androgens and prostate cancer (PCa).[1] Whereas it has been long believed that offering testosterone therapy (TTh) to a man with PCa was like ‘‘pouring gasoline on a fire,’’2 numerous case series and observational studies have failed to demonstrate increased risk of disease recurrence or progression with TTh after radical prostatectomy,[3] radiation therapy,[4] and even in men on active surveillance.[5,6] This lack of progression may be attributed to saturation, namely, the finite ability of androgens to stimulate PCa growth, with a maximum achieved at a relatively low serum testosterone concentration of *250 ng/mL.[7] It is commonplace for health care providers to offer TTh to men after definitive treatment for localized PCa at low risk for recurrence. The most promising of these strategies appears to be a modified BAT (mBAT) protocol to maximize duration of TTh and its associated benefits followed by a shorter period of androgen blockade

Materials and Methods

Findings

Discussion