Absolute Benefit of Androgen Deprivation Therapy With Radiotherapy for Localized Prostate Cancer
- 1Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
Abstract
ObjectivesTo estimate the absolute benefit of adding and prolonging androgen deprivation therapy (ADT) to radiation therapy (RT) for men with localized prostate cancer by integrating cancer-specific risk, other-cause mortality (OCM) risk, and relative treatment efficacy.
Subjects and MethodsIndividualized risks were estimated by integrating cause-specific hazard estimates from a validated staging system (STAR-CAP) with those from a validated non-cancer mortality model (OCCAM). ADT treatment efficacy was then incorporated using published hazard ratio estimates from the MARCAP meta-analysis. Model utility was illustrated using the Prostate, Lung, Colon, and Ovarian (PLCO) cancer screening trial cohort (n=5468 prostate cancer patients with complete covariates). The primary outcome was the estimated 10-year absolute risk reduction (ARR) in distant metastasis (DM) from adding short-term ADT (STADT) to RT or extending STADT to long term ADT (LTADT).
ResultsWithin PLCO, model estimated risk of DM at 10 years ranged from <1% to 56% under guideline concordant care and OCM risk ranged from 3% to 80% independent of treatment. For patients with NCCN unfavorable intermediate-risk (n=1814), adding STADT to RT reduced estimated 10 year DM risk by a median of 4%, but the ARR estimates for individuals ranged from <1% to almost 15%. Similar variation was seen within NCCN high-risk patients (n=1289) with a median ARR of 9% [Range: 0.4%-17.2%] when prolonging ADT treatment. Moreover, 25% of NCCN unfavorable intermediate-risk patients have less than a 2.4% ARR while 25% of NCCN high-risk patients experience less than a 5% ARR.
ConclusionAn integrated model accounting for both prostate cancer aggressiveness and comorbidities demonstrates substantial heterogeneity in the estimated absolute benefit of ADT within conventional risk groups. This approach provides individualized estimates to support treatment discussions; external validation is needed before clinical implementation.
Related
- Comparative outcomes of radical prostatectomy, radiotherapy, and radiotherapy plus androgen deprivation therapy for high-risk and very high-risk prostate cancer: a narrative review
- Metastasis-directed radiotherapy (MDRT) for men with de novo, oligometastatic prostate cancer treated with long-term androgen deprivation therapy in the STAMPEDE trial (METANOVA): protocol for a multicentre, phase II randomised controlled trial in the USA
- Effects of androgen deprivation therapy on cerebral glucose metabolism in prostate cancer.
- Fracture and Vertebral Augmentation Utilization Following Androgen Deprivation Therapy in Men With Prostate Cancer: A Propensity Score–matched Cohort Study
- Trial-reported arthralgia of androgen deprivation therapy plus androgen receptor signaling inhibitors in prostate cancer: evidence from phase III randomized trials
BibTeX
@misc{aldous2026absolute,
title = {{Absolute Benefit of Androgen Deprivation Therapy With Radiotherapy for Localized Prostate Cancer}},
author = {J. Aldous and W. C. Jackson and E. Chase and E. Covert and J. Tang and U. Singhal and T. M. Morgan and D. E. Spratt and R. T. Dess and M. J. Schipper},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.26362669},
url = {https://www.medrxiv.org/content/10.64898/2026.09.10.26362669v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Absolute Benefit of Androgen Deprivation Therapy With Radiotherapy for Localized Prostate Cancer
AU - J. Aldous
AU - W. C. Jackson
AU - E. Chase
AU - E. Covert
AU - J. Tang
AU - U. Singhal
AU - T. M. Morgan
AU - D. E. Spratt
AU - R. T. Dess
AU - M. J. Schipper
PY - 2026
DA - 2026/09/10
PB - medRxiv
DO - 10.64898/2026.09.10.26362669
UR - https://www.medrxiv.org/content/10.64898/2026.09.10.26362669v1
AB - ObjectivesTo estimate the absolute benefit of adding and prolonging androgen deprivation therapy (ADT) to radiation therapy (RT) for men with localized prostate cancer by integrating cancer-specific risk, other-cause mortality (OCM) risk, and relative treatment efficacy. Subjects and MethodsIndividualized risks were estimated by integrating cause-specific hazard estimates from a validated staging system (STAR-CAP) with those from a validated non-cancer mortality model (OCCAM). ADT treatment efficacy was then incorporated using published hazard ratio estimates from the MARCAP meta-analysis. Model utility was illustrated using the Prostate, Lung, Colon, and Ovarian (PLCO) cancer screening trial cohort (n=5468 prostate cancer patients with complete covariates). The primary outcome was the estimated 10-year absolute risk reduction (ARR) in distant metastasis (DM) from adding short-term ADT (STADT) to RT or extending STADT to long term ADT (LTADT). ResultsWithin PLCO, model estimated risk of DM at 10 years ranged from <1% to 56% under guideline concordant care and OCM risk ranged from 3% to 80% independent of treatment. For patients with NCCN unfavorable intermediate-risk (n=1814), adding STADT to RT reduced estimated 10 year DM risk by a median of 4%, but the ARR estimates for individuals ranged from <1% to almost 15%. Similar variation was seen within NCCN high-risk patients (n=1289) with a median ARR of 9% [Range: 0.4%-17.2%] when prolonging ADT treatment. Moreover, 25% of NCCN unfavorable intermediate-risk patients have less than a 2.4% ARR while 25% of NCCN high-risk patients experience less than a 5% ARR. ConclusionAn integrated model accounting for both prostate cancer aggressiveness and comorbidities demonstrates substantial heterogeneity in the estimated absolute benefit of ADT within conventional risk groups. This approach provides individualized estimates to support treatment discussions; external validation is needed before clinical implementation.
ER -