TOPLINE:

In a pooled analysis, longer duration of androgen deprivation therapy (ADT) was associated with nonlinear improvements in outcomes in men with prostate cancer receiving definitive radiotherapy. Relative benefits were associated with ADT durations up to about 12 months and diminished thereafter, whereas extended ADT was associated with increased other‑cause mortality. Optimal ADT duration varied by risk group and individual patient factors, generally ranging from 0 to 12 months.

METHODOLOGY:

• Multiple randomized trials have shown that adding and prolonging ADT with definitive radiotherapy improves survival in patients with localized prostate cancer; however, the optimal duration of ADT that accounts for benefits and risks and best balances prostate cancer-specific mortality and other-cause mortality is unknown.
• Researchers conducted an individual-patient data meta-analysis including 10,266 men with nonmetastatic prostate cancer receiving definitive radiotherapy (median age, 70 years) from 13 randomized phase 3 clinical trials. Participants had a median follow-up duration of 11.3 years; most patients (72%) had National Comprehensive Cancer Network (NCCN) high-risk or very high-risk disease.
• The primary endpoint was overall survival; secondary endpoints included biochemical recurrence, distant metastasis, prostate cancer-specific mortality, and other-cause mortality.
• Absolute benefits and numbers needed to treat (NNTs) to prevent one 10-year distant metastasis were calculated; an NNT threshold of 35 (2.86% absolute benefit) was used to identify a cutoff of clinical benefit.

TAKEAWAY:

• Compared with no ADT, longer durations of ADT were associated with nonlinear reductions in prostate cancer-specific mortality and improvements in overall survival ꟷ with benefits diminishing beyond 9-12 months. However, each additional month of ADT was associated with a small increase in the hazard of other‑cause mortality. Longer durations of ADT were also associated with lower risks for biochemical recurrence and distant metastasis.
• Compared with 36 months, shorter durations of ADT were associated with worse overall survival (3 vs 36 months: hazard ratio [HR], 1.75; 9 vs 36 months: HR, 1.50), whereas overall survival did not differ significantly between 18 and 36 months (HR, 1.02).
• However, shorter ADT durations were associated with lower risks for other‑cause mortality (3 vs 36 months: HR, 0.60; 6 vs 36 months: HR, 0.77).
• Regarding personalization of ADT duration, the optimal duration based on relative effect size estimates was not affected by radiotherapy dose or risk group. The optimal ADT duration to maintain an NNT of 35 or less to prevent one 10‑year distant metastasis was 0 months for patients with one intermediate‑risk factor, 6 months for patients with two or more intermediate‑risk factors, 12 months for patients with NCCN high‑risk disease, and not defined for patients with NCCN very high‑risk disease.

IN PRACTICE:

“Prolongation of ADT has different associations with prostate-cancer specific mortality vs other-cause mortality,” the authors wrote, noting that “individualized ADT decisions are needed for patients based on prognostic risk, comorbidities, life expectancy, and patient preferences.”

SOURCE:

The study, led by Nicholas G. Zaorsky, MD, MS, University Hospitals Seidman Cancer Center in Cleveland, was published online in JAMA Oncology.

LIMITATIONS:

The analysis pooled trials conducted over multiple decades and across many countries, which introduced heterogeneity. Different trials compared different durations of ADT, making it challenging to isolate specific duration effects. Adherence data for short-term ADT use were incomplete and unavailable for all patients assigned to receive long-term ADT. Additionally, comorbidity, medication, and consistent long-term quality-of-life data were incompletely captured, limiting subgroup and toxicity analyses.

DISCLOSURES:

The study received support through grants from National Institutes of Health. Zaorsky disclosed receiving support from the American Cancer Society via the Tri State CEOs Against Cancer Clinician Scientist Development Grant, the US Department of Defense, and the National Institutes of Health grant. Several authors reported receiving grants or personal fees and having other ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.