Toxicities of Androgen Deprivation

Abstract & Commentary

Synopsis: Asymptomatic men at risk for clinical recurrence of prostate cancer who elect androgen deprivation therapy experience fatigue, increased sexual problems, and a decline in overall quality of life.

Source: Herr H, O’Sullivan M. J Urol 2000;163:1743-1746.

Quality of life in asymptomatic men at risk for clinical progression of prostate cancer was observed following a decision between immediate and deferred androgen deprivation. Subjects either had extracapsular extension (T3) or an increased or rising prostrate-specific antigen (PSA) following surgery or radiation. Subjects were recruited from a support group conducted by Herr and O’Sullivan, and were predominantly well educated, active, married, white men in their late sixties. Seventy-nine men (31 without prior local therapy) chose immediate treatment, and 65 men (29 without prior local therapy) deferred treatment. Among men choosing immediate treatment, 16 underwent orchiectomy, 41 received leuprolide alone, and 22 received leuprolide and flutamide. Quality of life was evaluated three times over one year using three previously validated quality-of-life instruments. Multiple comparisons were made and conservative statistical criteria for significance were applied (P < 0.007 was considered significant; P < 0.05, a trend). There were no significant differences in demographics or baseline quality-of-life scores between men who chose immediate or deferred treatment.

Men choosing immediate androgen deprivation reported significantly worse status with regard to fatigue, sexual problems, and the quality of life uniscale, and trends toward worse status with regard to physical function and psychological distress. Among men choosing treatment, men choosing orchiectomy reported significantly less fatigue than men choosing leuprolide with or without flutamide.

Comment by John D. Roberts, MD

This report reminds us that in asymptomatic men androgen deprivation has an adverse effect upon quality of life. Post-treatment PSA surveillance labels increasing numbers of asymptomatic men as harboring incurable prostate cancer. These men must make decisions concerning the timing of androgen deprivation in the absence of definitive information concerning survival, or disease-related morbidity differences between immediate vs. delayed treatment. There also has been little information concerning treatment-related morbidity. This report indicates that treatment-related morbidity is multi-dimensional, but the structure of the report does not provide any clinical "feel" for the magnitude of the problems. Clinicians skeptical of the benefits of early androgen deprivation will find further support in a previous report in which six of 16 men surviving for longer than 60 months after orchiectomy experienced osteoporotic fractures.1

Reference

1. Daniel H. J Urol 1997;157:439-444.