What is intermittent Androgen Deprivation Therapy (ADT)?

From the Guidelines

Intermittent Androgen Deprivation Therapy (ADT) is a treatment approach for prostate cancer where ADT is given in cycles, with periods of treatment followed by periods without treatment.

Key Points

• The goal of intermittent ADT is to delay the development of castration resistance and reduce toxicity, improving quality of life and reducing treatment costs 1.
• Intermittent ADT has been evaluated in several trials, with mixed results, but a systematic review of 9 studies with 5508 patients found evidence to recommend its use, with a combined hazard ratio for overall survival of 1.02 1.
• The optimal PSA threshold to initiate intermittent ADT remains unclear, and the eligibility threshold of PSA level greater than 3 ng/mL was chosen mainly to aid accrual 1.
• Close monitoring of PSA and testosterone levels, and possibly imaging, is required when using intermittent ADT, especially during off-treatment periods 1.
• The 2018 NCCN Guidelines recommend intermittent ADT for patients with asymptomatic, castration-naïve, metastatic prostate cancer, with a possible small trade-off in overall survival for improved quality of life during the off cycle 1.

Treatment Details

• ADT can be given by means of orchiectomy, GnRH agonists, or antagonists, with medical castration being the most commonly used option in economically well-developed countries 1.
• The SWOG 9346 trial compared continuous ADT to intermittent ADT in metastatic patients, with a median follow-up of 9.8 years, and found that median survival was 5.1 years for the intermittent ADT arm and 5.8 years for the continuous ADT arm 1.
• Quality of life measures, such as erectile function and mental health, were better in the intermittent ADT arm after 3 months off ADT compared with the continuous ADT arm 1.
• Patients who do not achieve adequate suppression of serum testosterone with medical or surgical castration can be considered for additional hormonal manipulations, although the clinical benefit remains uncertain 1.

From the Research

Definition of Intermittent Androgen Deprivation Therapy (ADT)

• Intermittent Androgen Deprivation Therapy (IADT) involves cycles of androgen deprivation therapy (ADT) with a period between cycles where testosterone is allowed to rise above castrate levels 2.
• IADT is an alternative to continuous androgen deprivation therapy (ADT) in prostate cancer patients with nonmetastatic disease 3.

Purpose of IADT

• The purpose of IADT is to improve the quality of life and to delay progression of prostate cancer to castration resistance 3.
• IADT aims to mitigate the side effects of ADT while retaining the oncological benefits 4.

Comparison with Continuous ADT

• IADT was found to be non-inferior in the primary setting for non-metastatic prostate cancer as well as in treatment of biochemical recurrence following radiotherapy 2.
• In the metastatic prostate cancer setting, IADT was not found to be non-inferior to continuous ADT 2.
• A systematic review and meta-analysis found no significant difference between intermittent and continuous therapy for overall survival, cancer-specific survival, and progression-free survival 5.

Benefits and Side Effects

• IADT has been shown to improve quality of life with fewer side effects, including improved physical and sexual functioning 5.
• However, the long-term complications of ADT, such as osteoporosis and metabolic abnormalities, are not well-studied in the context of IADT 2.
• IADT may also reduce the cost of treatment compared to continuous ADT 4.

Patient Selection and Monitoring

• Patient selection is important to maintain good oncologic results with IADT 6.
• Monitoring of prostate-specific androgen response and duration of off-treatment intervals allow for stratification of patients by risk of progression 6.