How Long Should Hormone Suppression Continue After Radiotherapy for Prostate Cancer?
In this article
1. The Clinical Question: How Long Should ADT Continue?
For localized or locally advanced prostate cancer, ADT given with definitive radiotherapy has long been part of standard care. Yet a crucial question in clinical practice remained unresolved:
Should ADT continue for 3–6 months, 12–18 months or 36 months ? Does the optimal duration differ between risk groups?
This systematic review and individual-patient-data meta-analysis in JAMA Oncology addresses the question using a dataset of 10,266 patients , examining how ADT duration affects both death from prostate cancer and death from other causes.
2. Study Design and Patient Profile
Methodology Summary
- Multicenter studies published between 1980–2020 were screened: randomized Phase III trials.
- Men with localized or locally advanced, nonmetastatic prostate cancer were included.
- All patients received definitive radiotherapy ; ADT use and duration were specified in the protocols.
- Studies had to report metastasis, overall survival and other survival endpoints.
Patient Data
- Total Patients: 10,266
- Median Age: 70 years
- High / Very High Risk: 72% (NCCN definition)
- Radiotherapy dose < 74 Gy: 81% (moderate dose)
- Received at least 6 months of ADT: 55%
- Received 36 months of ADT: 10%
3. ADT Duration and Overall Survival: A Critical Threshold of 12–18 Months
The study shows that ADT duration has a nonlinear effect on overall survival (OS) , rather than a linear relationship . Short regimens of 3 and 9 months were associated with substantially worse outcomes than a long, 36-month regimen:
3 Months of ADT vs 36 Months of ADT
75% worse overall survival
95% CI: 1.37 – 2.24
9 Months of ADT vs 36 Months of ADT
50% worse overall survival
95% CI: 1.07 – 2.10
18 Months of ADT vs 36 Months of ADT
No difference (not statistically significant)
95% CI: 0.83 – 1.26
4. Longer ADT Increases the Risk of Death from Other Causes
One of the study's most important observations was that longer ADT was associated with increased noncancer mortality :
- 3 months of ADT: HR 0.60 for other-cause mortality compared with 36 months (lower risk)
- 9 months of ADT: HR 0.77 compared with 36 months
- As ADT duration increases: The HR for other-cause mortality rises each month; 28 months of ADT was associated with other-cause mortality reaching HR 1.28 compared with no ADT (p=0.002).
5. A Nonlinear Relationship: When Does ADT Begin to Help?
When the benefit of ADT versus no ADT is examined, the curve is nonlinear :
- Overall Survival: A clear OS advantage from ADT begins to emerge around months 9–12 of treatment.
- Prostate Cancer-Specific Mortality: The benefit is stronger, but still nonlinear: insufficient with short durations and tending to plateau after 12 months.
- Death from Other Causes: Each additional month brings a slow but steady increase.
6. Optimal ADT Duration by Risk: Who Benefits, and by How Much?
The researchers calculated absolute differences in 10-year distant metastasis rates and the number needed to treat (NNT) to prevent 1 metastasis , offering a practical framework for each risk group. The aim was for the NNT to prevent one distant metastasis not to exceed 35.
| Risk Group (NCCN) | Risk Profile | Recommended ADT Duration for NNT ≤ 35 |
|---|---|---|
| Intermediate (1 risk factor) | One intermediate-risk criterion (e.g. PSA 10–20 alone) | 0 months of ADT (limited additional benefit) |
| Intermediate (≥2 risk factors) | At least two intermediate-risk criteria | ≈ 6 months of ADT |
| High Risk | High Gleason score, elevated PSA or T3 | ≈ 12 months of ADT |
| Very High Risk | Locally advanced disease, highly aggressive biology | An optimal duration cannot be clearly defined statistically; longer ADT may be considered, but must be balanced against toxicity. |
7. Key Messages for Clinical Practice
1) ADT Duration Is No Longer a Copy-and-Paste Decision
The study's overall findings support individualizing ADT duration according to risk group, comorbidities, life expectancy and patient preference .
2) Limited Gains Beyond 18 Months
The absence of a significant overall survival difference between 18 and 36 months supports a rational approach, particularly in older patients with substantial comorbidity: shorter but adequate regimens.
3) Cardiometabolic Burden Must Not Be Overlooked
Long-term ADT can increase noncancer mortality through weight gain, diabetes, hypertension and cardiovascular events. This risk becomes particularly evident with 28 months or more of treatment.
Conclusion: The Longer-Is-Better Era Is Ending
ADT combined with radiotherapy remains a crucial component of localized prostate cancer treatment. However, this meta-analysis shows that regimens lasting beyond 12–18 months do not always extend life further, while potentially increasing side effects and noncancer death risk . ADT duration should now be a genuinely individualized decision based on tumor biology, cardiovascular health, age and life expectancy .
Zaorsky NG, Sun Y, Nabid A, et al. Optimal duration of androgen deprivation therapy with definitive radiotherapy for localized prostate cancer: A meta-analysis. JAMA Oncology. Published online: 20 November 2025. doi:10.1001/jamaoncol.2025.4800
```
Was this article helpful?
Your feedback helps us improve our content.
Reader comments
Share your comment
Your name and comment are published only after administrator approval. Your email address is never shown to visitors.
Be the first to comment.