What is the efficacy of neoadjuvant Androgen Deprivation Therapy (ADT) combined with radiation therapy for the treatment of prostate cancer?

From the Guidelines

Neoadjuvant androgen deprivation therapy (ADT) is recommended for 4-6 months before and during radiation therapy for intermediate and high-risk prostate cancer, as it has been shown to improve overall mortality and prostate cancer-specific mortality 1. The standard regimen includes a GnRH agonist (such as leuprolide 7.5 mg monthly, 22.5 mg every 3 months, or goserelin 10.8 mg every 3 months) often with an anti-androgen (such as bicalutamide 50 mg daily) for the first 2-4 weeks to prevent testosterone flare. For high-risk disease, ADT should be continued for 18-36 months after radiation completion, while for intermediate-risk disease, 4-6 months of total ADT duration is typically sufficient. This approach works by reducing testosterone levels, which suppresses prostate cancer cell growth and increases radiation sensitivity. Some key points to consider when using ADT include:

• The use of ADT before, during, and after radiation therapy has been shown to improve survival in selected patients 1.
• The addition of an antiandrogen to ADT may not be necessary, and its use should be individualized based on patient factors 1.
• Castrate levels of serum testosterone (<50 ng/dL; <1.7 nmol/L) should be achieved with ADT, as low nadir serum testosterone levels have been associated with improved cause-specific survival 1.
• Patients should be monitored for ADT side effects, including hot flashes, fatigue, sexual dysfunction, bone density loss, metabolic changes, and cardiovascular effects.
• Baseline and periodic assessments of bone density, lipid profiles, and blood glucose are important, and calcium and vitamin D supplementation should be considered to help preserve bone health 1.

From the FDA Drug Label

The effects of hormonal treatment combined with radiation were studied in 466 patients (231 ZOLADEX + flutamide + radiation, 235 radiation alone) with bulky primary tumors confined to the prostate (stage B2) or extending beyond the capsule (stage C), with or without pelvic node involvement. In this multicentered, controlled trial, administration of ZOLADEX (3. 6 mg depot) and flutamide capsules (250 mg t.i.d.) prior to and during radiation was associated with a significantly lower rate of local failure compared to radiation alone (16% vs 33% at 4 years, P<0.001). The combination therapy also resulted in a trend toward reduction in the incidence of distant metastases (27% vs 36% at 4 years, P=0. 058). Median disease-free survival was significantly increased in patients who received complete hormonal therapy combined with radiation as compared to those patients who received radiation alone (4.4 vs 2.6 years, P<0. 001).

The efficacy of neoadjuvant Androgen Deprivation Therapy (ADT) combined with radiation therapy for the treatment of prostate cancer is supported by the study, which showed:

• A significantly lower rate of local failure (16% vs 33% at 4 years, P<0.001)
• A trend toward reduction in the incidence of distant metastases (27% vs 36% at 4 years, P=0.058)
• Significantly increased median disease-free survival (4.4 vs 2.6 years, P<0.001) 2 2

From the Research

Efficacy of Neoadjuvant Androgen Deprivation Therapy (ADT) Combined with Radiation Therapy

• The efficacy of neoadjuvant ADT combined with radiation therapy for the treatment of prostate cancer has been evaluated in several studies 3, 4, 5, 6, 7.
• A phase 3 trial found that intermittent adjuvant ADT after external-beam radiation therapy (EBRT) with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy for locally advanced prostate cancer 3.
• Patient-reported outcomes were significantly better in patients receiving intermittent ADT compared to continuous ADT at 20 and 38 months after treatment 4.
• A randomized phase III trial found that the addition of 4 months of ADT to EBRT significantly improved disease-specific mortality, distant metastasis, disease-free survival, and biochemical failure in men with locally advanced disease 5.
• Current trends suggest that ADT is a well-established standard of care in combination with definitive radiotherapy for patients with unfavorable intermediate-risk to high-risk locally advanced prostate cancer 6.
• A randomized phase II neoadjuvant study found that intense androgen-deprivation therapy with abiraterone acetate plus leuprolide acetate suppresses tissue androgens more effectively than leuprolide acetate alone in patients with localized high-risk prostate cancer 7.

Key Findings

• Neoadjuvant ADT combined with radiation therapy improves oncological outcomes for patients with locally advanced prostate cancer 3, 5.
• Intermittent ADT may be a promising treatment strategy for patients with locally advanced prostate cancer 3, 4.
• The addition of ADT to EBRT improves disease-specific mortality, distant metastasis, disease-free survival, and biochemical failure in men with locally advanced disease 5.
• Intense androgen-deprivation therapy with abiraterone acetate plus leuprolide acetate may reduce tumor burden in patients with localized high-risk prostate cancer 7.

Treatment Outcomes

• The 5-year modified biochemical relapse-free survival rates were 84.8% and 82.8% in patients receiving continuous and intermittent ADT, respectively 3.
• Patient-reported outcomes were significantly better in patients receiving intermittent ADT compared to continuous ADT at 20 and 38 months after treatment 4.
• The 10-year overall survival estimates were 43% and 34% in patients receiving ADT and EBRT, and EBRT alone, respectively 5.