Androgen deprivation therapy in prostate cancer: are rising concerns leading to falling use?

Abstract

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Androgen deprivation therapy was originally used for metastatic prostate cancer but is now used to treat all stages of the disease. Once considered to be relatively harmless, androgen deprivation therapy was associated with impaired cognitive function, anemia, loss of muscle strength, osteoporotic fractures, diabetes, and cardiovascular disease by the year 2000. In a large, population‐based sample of prostate cancer patients, the numbers initiating androgen deprivation therapy increased from 1995 to 2001 and then sharply declined to 2005, but the rate of initiation among eligible prevalent cases steadily decreased over that period. Monotherapy with luteinizing hormone‐releasing hormone agonists became the dominant type of androgen deprivation therapy. Changes may be related to fewer cases of late stage disease, potential adverse effects, and new evidence for selected indications and regimens. OBJECTIVE • To describe patterns of initiation of androgen deprivation therapy (ADT) in a population‐based cohort of patients with prostate cancer. PATIENTS AND METHODS • All patients with prostate cancer in Ontario, Canada, who started ≥90 days of ADT at age ≥66 years in 1995–2005 were classified by ADT regimen: medical castration [oestrogen and/or luteinizing hormone‐releasing hormone (LHRH) agonist); orchidectomy; antiandrogen monotherapy; combined androgen blockade (CAB) medical (medical castration plus antiandrogen); CAB surgical (orchidectomy plus antiandrogen). • Indications for ADT were as follows: neoadjuvant (short‐term before prostatectomy or radiation therapy); adjuvant (long‐term with prostatectomy or radiation therapy); metastatic disease; biochemical recurrence; primary (localized disease); other. • We examined trends in ADT regimen and indication over time. RESULTS • The number of patients initiating ADT increased from 1995 to 2001 (2106–2916 per year) and declined thereafter to 2200–2300 annually (total n= 26 809). • However, prostate cancer prevalence doubled over these years, and the rate of ADT initiation decreased from 16 to 7 per 100 person‐years. • Patterns varied by regimen and indication. Medical castration increased from 12% of all ADT in 1995 to 47% in 2005; orchidectomy decreased from 17 to 4%. Use for metastatic disease remained stable, but adjuvant therapy increased from <3% of all ADT in 1995 to 13% in 2005. Primary therapy was the most common indication, but decreased over time. CONCLUSIONS • ADT initiation has fallen and marked changes occurred in treatment patterns for prostate cancer. • Changes might be driven by increasing awareness of potential harms and costs, and by new evidence supporting ADT for specific indications.

Current role of neoadjuvant and adjuvant systemic therapy for high-risk localized prostate cancer

“…3,4 A SEER analysis found that use of ADT increased throughout the 1990’s followed by decline leading up to 2005 5 . A population-based study in Canada found similar patterns 6 . These declines in ADT usage may be related to toxicity concerns.…”

Long-Term Health Care Costs for Prostate Cancer Patients on Androgen Deprivation Therapy

“…Treatment with orchiectomy has declined in recent years 3,6 , and the indications for which it is relevant are few. We therefore included only patients who received orchiectomy for metastatic disease or as primary therapy, and those who received cab-surgical for metastatic disease.…”

Health Care Costs for Prostate Cancer Patients Receiving Androgen Deprivation Therapy: Treatment and Adverse Events

“…Many patients receive androgen deprivation therapy (adt) as primary therapy for all stages of disease or in addition to primary surgery or radiotherapy [2][3][4][5] . Luteinizing hormone-releasing hormone (lhrh) agonists and anti-androgens are now the main types of adt; bilateral orchiectomy and estrogen are less popular [5][6][7] .…”