Impact of adding hormone therapy to postoperative radiotherapy in prostate cancer
Affiliations & Notes
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Article Info
Publication History:
Published February 26, 2026
DOI: 10.1016/S0140-6736(26)00368-5 External LinkAlso available on ScienceDirect External Link
Copyright: © 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
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OkThe addition of hormone therapy to radiotherapy improves overall survival in men with high-risk prostate cancer, over radiotherapy alone.1 Mechanisms proposed to explain this effect include cytoreduction, the androgen receptor's regulation of key DNA damage response pathways, and suppression of micrometastases.2,3 However, randomised trials evaluating the benefit of adding hormone therapy to postoperative radiotherapy (PORT) have yielded conflicting results.4–9
References
1.
Kishan, AU ∙ Sun, Y ∙ Hartman, H ∙ et al., the MARCAP Consortium group
Androgen deprivation therapy use and duration with definitive radiotherapy for localised prostate cancer: an individual patient data meta-analysis
Lancet Oncol. 2022; 23:304-316
2.
Pilié, PG ∙ Tang, C ∙ Mills, GB ∙ et al.
State-of-the-art strategies for targeting the DNA damage response in cancer
Nat Rev Clin Oncol. 2019; 16:81-104
3.
Shore, ND ∙ Luz, MA ∙ De Giorgi, U ∙ et al.
Improved survival with enzalutamide in biochemically recurrent prostate cancer
N Engl J Med. 2025; 394:563-575
4.
Shipley, WU ∙ Seiferheld, W ∙ Lukka, HR ∙ et al., the NRG Oncology RTOG
Radiation with or without antiandrogen therapy in recurrent prostate cancer
N Engl J Med. 2017; 376:417-428
5.
Carrie, C ∙ Magné, N ∙ Burban-Provost, P ∙ et al.
Short-term androgen deprivation therapy combined with radiotherapy as salvage treatment after radical prostatectomy for prostate cancer (GETUG-AFU 16): a 112-month follow-up of a phase 3, randomised trial
Lancet Oncol. 2019; 20:1740-1749
6.
Pollack, A ∙ Karrison, TG ∙ Balogh, AG ∙ et al.
The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial
Lancet. 2022; 399:1886-1901
7.
Parker, CC ∙ Clarke, NW ∙ Cook, AD ∙ et al., the RADICALS Investigators
Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial
Lancet. 2024; 403:2405-2415
8.
Parker, CC ∙ Clarke, NW ∙ Cook, AD ∙ et al., the RADICALS Investigators
Randomised trial of no, short-term, or long-term androgen deprivation therapy with postoperative radiotherapy after radical prostatectomy: results from the three-way comparison of RADICALS-HD (NCT00541047)
Eur Urol. 2024; 86:422-430
9.
Parker, CC ∙ Kynaston, H ∙ Cook, AD ∙ et al., the RADICALS Investigators
Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial
Lancet. 2024; 403:2416-2425
10.
Kishan, AU ∙ Sun, Y ∙ Parker, CC ∙ et al.
Hormone therapy use and duration with postoperative radiotherapy for recurrent prostate cancer: an individual patient data meta-analysis
Lancet. 2026;
published online Feb 26. https://doi.org/10.1016/S0140-6736(26)00137-6
11.
Stewart, DJ ∙ Bradford, JP ∙ Sehdev, S ∙ et al.
New anticancer drugs: reliably assessing “value” while addressing high prices
Curr Oncol. 2024; 31:2453-2480
12.
Mazzone, E ∙ Thomson, A ∙ Chen, DC ∙ et al.
The role of prostate-specific membrane antigen positron emission tomography for assessment of local recurrence and distant metastases in patients with biochemical recurrence of prostate cancer after definitive treatment: a systematic review and meta-analysis
Eur Urol. 2025; 88:129-141
13.
Spetsieris, N ∙ Boukovala, M ∙ Alafis, I ∙ et al.
Abiraterone acetate plus prednisone in non-metastatic biochemically recurrent castration-naïve prostate cancer
Eur J Cancer. 2021; 157:259-267
14.
Raychaudhuri, R ∙ Lin, DW ∙ Montgomery, RB
Prostate cancer: a review
JAMA. 2025; 333:1433-1446
15.
Ong, WL ∙ Romero, T ∙ Roy, S ∙ et al., the MARCAP Consortium Investigators
Testosterone recovery following androgen suppression and prostate radiotherapy (TRANSPORT): a pooled analysis of five randomized trials from the Meta-Analysis of Randomized Trials in Cancer of the Prostate (MARCAP) Consortium
Eur Urol. 2025; 87:49-57
16.
Tang, C ∙ Sherry, AD ∙ Hwang, H ∙ et al.
Metastasis-directed therapy and standard of care versus standard of care for oligometastatic prostate cancer (WOLVERINE): a systematic review and individual patient data meta-analysis from the X-MET collaboration
Lancet Oncol. 2026; 27:181-190
17.
Morgan, TM ∙ Boorjian, SA ∙ Buyyounouski, MK ∙ et al.
Salvage therapy for prostate cancer: AUA/ASTRO/SUO guideline part i: introduction and treatment decision-making at the time of suspected biochemical recurrence after radical prostatectomy
J Urol. 2024; 211:509-517
18.
Freedland, SJ ∙ de Almeida Luz, M ∙ De Giorgi, U ∙ et al., the EMBARK Study
Improved outcomes with enzalutamide in biochemically recurrent prostate cancer
N Engl J Med. 2023; 389:1453-1465
19.
National Comprehensive Cancer Network
Prostate cancer, version 5
https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf
Date: 2026
Date accessed: February 16, 2026
Facts Only
The addition of hormone therapy to radiotherapy improves overall survival in high-risk prostate cancer compared to radiotherapy alone.
Proposed mechanisms include cytoreduction, androgen receptor regulation of DNA damage response, and micrometastasis suppression.
Randomized trials evaluating hormone therapy with postoperative radiotherapy (PORT) have yielded conflicting results.
The RADICALS-HD trial compared short-course (6 months) versus no ADT with PORT, showing potential benefits of short-term therapy.
The GETUG-AFU 16 trial found improved outcomes with short-term ADT combined with radiotherapy as salvage treatment after prostatectomy.
The NRG Oncology/RTOG 0534 trial evaluated adding ADT and pelvic lymph node treatment to prostate bed salvage radiotherapy.
The MARCAP Consortium conducted meta-analyses on hormone therapy use and duration with radiotherapy for prostate cancer.
Studies published between 2017 and 2026 in journals like *The Lancet*, *New England Journal of Medicine*, and *European Urology* inform current guidelines.
The National Comprehensive Cancer Network (NCCN) provides clinical guidelines for prostate cancer treatment, last updated in 2026.
Research institutions involved include MD Anderson Cancer Center, NRG Oncology, and the MARCAP Consortium.
Key researchers include Kishan, Parker, Shipley, and Carrie, among others.
The debate continues over optimal duration and necessity of ADT in conjunction with PORT.
Executive Summary
Full Take
**Steelman:** The strongest version of this narrative acknowledges that while hormone therapy combined with radiotherapy demonstrates survival benefits in high-risk prostate cancer, the evidence for postoperative settings remains inconsistent. The article credibly presents multiple trials, highlighting both supportive and conflicting data, and avoids overstating conclusions. It frames the debate as an ongoing scientific inquiry rather than a settled matter, which is intellectually honest.
**Pattern Scan:** The discussion avoids overt manipulation patterns, but there is a subtle tension between the optimism of mechanistic explanations (e.g., DNA damage response regulation) and the ambiguity of clinical trial results. This could reflect a common "hope vs. evidence" dynamic in medical reporting, where promising biological rationales outpace definitive outcomes. No clear distortion or bad faith is detected, though the emphasis on certain trials over others might hint at selection bias in synthesis.
**Root Cause:** The paradigm here is the tension between personalized medicine and population-level evidence. The assumption that more aggressive therapy (longer ADT) equals better outcomes is being challenged by trials suggesting shorter courses may suffice. This echoes historical shifts in oncology, where treatment intensity is increasingly balanced against quality of life.
**Implications:** For patients, the uncertainty means navigating trade-offs between survival benefits and hormone therapy’s side effects (e.g., fatigue, osteoporosis). For clinicians, it underscores the need for shared decision-making. The financial and systemic costs of prolonged ADT—both to healthcare systems and patients—are underdiscussed here, as are the psychological burdens of extended treatment.
**Bridge Questions:**
1. How might emerging biomarkers (e.g., PSMA-PET) refine patient selection for ADT + PORT, reducing reliance on broad trial averages?
2. What role do industry incentives play in promoting longer ADT courses, and how might this bias trial design or interpretation?
3. If short-term ADT proves non-inferior, how should guidelines adapt to prioritize minimal effective dosing?
**Counterstrike Scan:** A coordinated influence campaign might cherry-pick trials to push a specific drug or duration, downplaying conflicting data. This article, however, presents a balanced range of studies and acknowledges uncertainty, aligning more with genuine scientific discourse than advocacy. No structural alignment with manipulation tactics is detected.
Patterns detected: none
Sentinel — Human
This article shows strong indicators of human authorship, with the stylistic complexity, domain expertise, and citation rigor characteristic of academic medical research.