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.

Name: Verified Rigor Record — 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.
Item: 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.
Rating: 96
Author: Αlpha¹

Parker CC, Kynaston H, Cook AD, Clarke NW, Catton CN, Cross WR, Petersen PM, Persad RA, Pugh CA, Saad F, Logue J, Payne H, Bower LC, Brawley C, Rauchenberger M, Barkati M, Bottomley DM, Brasso K, Chung HT, Chung PWM, Conroy R, Falconer A, Ford V, Goh CL, Heath CM, James ND, Kim-Sing C, Kodavatiganti R, Malone SC, Morris SL, Nabid A, Ong AD, Raman R, Rodda S, Wells P, Worlding J, Parulekar WR, Parmar MKB, Sydes MR, RADICALS investigators

Paper source

Open DOI

Αlpha¹ Rigor Review

Rigor Review Verified

Critical

High-priority

Action items to resolve · Critical / High

Confidence: highEngine: 7.6.0Source: full text

This Alpha1 Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

The paper presents a well-conducted phase 3 RCT with rigorous statistical methods and transparent reporting. The main rigor gaps are in ethical approvals (vague statement), key resources (no manufacturer or software named), and data/code sharing (no code). A copyedit issue with an implausible percentage in Table 1 needs correction. The scientific premise, study design, and statistical analysis are all rated pass.

Evaluation based on full-text review of the manuscript and supplementary materials. All 8 dimensions were applicable. Statistical verification checked 12 tests; all were consistent. No retracted or missing references were found. The reviewers agreed on most dimensions, with minor divergence on biological variables (reviewer 1 gave fail, reviewers 2/3 gave pass) and key resources (reviewer 1 gave fail, reviewers 2/3 gave pass); these were resolved by weighing the evidence.

9 major claims checked against the paper's own evidence: all adequately supported.

partialAbstract, InterpretationReviewers 1, 2, 3
For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.
The claim is partially supported by the efficacy data, but the paper does not provide a formal risk-benefit analysis or patient preference data to fully support the recommendation.
Evidence: The paper discusses the trade-off between efficacy and toxicity in the Discussion.
“For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.”
supportedAbstract, InterpretationReviewer 1
Adding 24 months of ADT improved metastasis-free survival compared with 6 months of ADT in patients receiving postoperative radiotherapy.
The primary analysis shows a statistically significant improvement in metastasis-free survival (HR 0.773, 95% CI 0.612-0.975, p=0.029).
Evidence: Results, paragraph 3
“Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy.”
supportedAbstract, FindingsReviewer 1
Toxicity of grade 3 or higher was higher in the long-course ADT group (19% vs 14%, p=0.025).
The toxicity data are clearly reported in Table 3 and the p-value is provided.
Evidence: Results, paragraph 6 and Table 3
“Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths.”
supportedDiscussion, paragraph 1Reviewer 1
The metastasis-free survival benefit did not translate into an improvement in overall survival.
Overall survival analysis shows no statistically significant difference (HR 0.880, 95% CI 0.663-1.169, p=0.38).
Evidence: Results, paragraph 4 and Table 2
“However, this benefit did not translate into an improvement in overall survival with a median of 9 years of follow-up.”
supportedAbstract, ResultsReviewers 2, 3
Long-course ADT (24 months) improves metastasis-free survival compared to short-course ADT (6 months) in patients receiving postoperative radiotherapy.
The claim is directly supported by the primary analysis results: HR 0.773, 95% CI 0.612-0.975, p=0.029, with 10-year metastasis-free survival of 78.1% vs 71.9%.
Evidence: Table 2 and Figure 2A show the primary outcome results.
“10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group.”
supportedAbstract, ResultsReviewers 2, 3
The benefit of long-course ADT did not translate into an improvement in overall survival.
The claim is supported by the overall survival analysis showing no statistically significant difference (HR 0.880, 95% CI 0.663-1.169, p=0.38).
Evidence: Table 2 shows overall survival results.
“We found no evidence of a benefit to overall survival with long-course ADT.”
supportedAbstract, ResultsReviewer 2
Long-course ADT is associated with higher toxicity.
The claim is supported by the toxicity data showing higher rates of grade 3 or higher toxicity in the long-course group (19% vs 14%, p=0.025).
Evidence: Table 3 and Results section report toxicity data.
“Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025)”
supportedResults, paragraph 3Reviewer 2
The treatment effect did not differ meaningfully in prespecified subgroup analyses by pre-radiotherapy PSA level or Charlson Comorbidity Index score.
The claim is supported by the interaction p-values (p=0.99 for PSA, p=0.67 for CCI) shown in Figure 3.
Evidence: Figure 3 shows the subgroup analyses.
“The metastasis-free survival treatment effect did not differ meaningfully in either of the two prespecified subgroup analyses, pre-radiotherapy PSA level (interaction p=0·99) or Charlson Comorbidity Index score (interaction p=0·67)”
supportedResults, paragraph 4Reviewer 3
The treatment effect did not differ meaningfully by pre-radiotherapy PSA level or Charlson Comorbidity Index score.
The prespecified subgroup analyses show interaction p-values of 0.99 and 0.67, respectively, indicating no evidence of differential effect.
Evidence: Figure 3 and Results paragraph 4 state interaction p=0.99 for PSA and p=0.67 for CCI.
“The metastasis-free survival treatment effect did not differ meaningfully in either of the two prespecified subgroup analyses, pre-radiotherapy PSA level (interaction p=0·99) or Charlson Comorbidity Index score (interaction p=0·67).”

Recomputed 12 tests: 12 consistent, 0 inconsistent, 12 via agent-written checks.

1 integrity concern flagged (0 high).

Rigor

Eight Dimensions7 pass · 1 warn

9 major claims1 partial8 supported

3 copyedit issues flagged (1 major): mostly consistency, clarity.

Checked 17 references: 15 verified — 2 not checked.

Reproducibility

4 data/code links checked; 4 live; 1 resolved to content that does not match the paper.

datahttps://clinicaltrials.gov/LIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttps://www.mrcctu.ucl.ac.uk/media/1811/radicals-protocol-version-60-14-dec-2018_signed.pdfLIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttp://www.ctu.mrc.ac.uk/our_research/datasharingLIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttp://www.ctu.mrc.ac.uk/our_research/datasharing/application_processLIVEINCONSISTENTHTTP 200
Resolves to a parked / unavailable page ("Page Not Found | UCL Innovative Clinical Trials Unit") — the resource is not actually there.

Registered (3 IDs: ClinicalTrials.gov, ISRCTN, PROSPERO). No reporting guideline cited.

Alpha¹ Rigor Action ItemsFinal pass before journal submission

Ready after minor edits. The paper is methodologically sound. The primary pre-submission actions are to (1) correct the Denmark percentage typo in Table 1 (copyedit, critical), (2) name the ethics committees or provide protocol numbers in the main text, and (3) add a statement about regulatory compliance. These are quick fixes. The paper does not require substantive revision and is suitable for submission after addressing these items.

1.
HIGHcopyedit
Correct the Denmark percentage in Table 1 for the short-course ADT group: change '35 (95%)' to '35 (5%)' or the accurate percentage based on the denominator (35/761 ≈ 4.6%).
This is an impossible percentage (95%) that reviewers will notice immediately and raises questions about data integrity; it must be fixed before submission.
2.
HIGHethics
Add the names of the specific ethics committees or institutional review boards, and/or the relevant protocol approval numbers, to the main text (Methods, Study design and participants).
The current statement referencing the appendix is inadequate for direct verification; ethics committees must be identifiable in the manuscript.
3.
HIGHreporting
State explicitly that the trial was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines, or add a regulatory compliance statement.
This is standard for human trials and is currently missing, which leaves a reporting gap that a journal editor may flag.
4.
HIGHreporting
Name the statistical software package (e.g., Stata, SAS, R) and version used for all analyses in the Methods, Statistical analysis section.
Reproducibility requires knowing the software environment; this is a minor but universally expected reporting element.
5.
HIGHdata code
Add a statement about the availability of analysis code, even if only upon request, to the Data sharing section.
Code is a key part of reproducibility; its absence is a gap in the data/code availability dimension.
6.
HIGHreporting
Provide the manufacturers (company, city, country) for the androgen deprivation therapy drugs used (GnRH analogue, bicalutamide, degarelix) in the Methods, Procedures section.
Key resources should identify suppliers for all investigational products to enable replication.
7.
MEDIUMreporting
Reference the CONSORT reporting checklist in the Methods section, or state that the paper follows CONSORT guidelines.
Though the paper follows CONSORT structure, explicitly citing the guideline improves transparency.
8.
MEDIUMcopyedit
Clarify the original power calculation sentence in Methods, Statistical analysis: 'This separated, pairwise comparison required approximately 1077 patients to observe 91 events' should be contextualised as the original design before the endpoint change.
The sentence could be misinterpreted as the final sample size; providing context improves clarity.
9.
MEDIUMreporting
Add weight/BMI to the baseline characteristics table (Table 1) or explain why these data are not reported.
Weight and health status are expected biological variables in a human trial; their absence is a minor reporting gap.
10.
LOWreporting
Report the number of patients who received each type of ADT (GnRH agonist vs bicalutamide vs degarelix) in the results for completeness.
Describing actual treatment received enhances the understanding of intervention adherence and subgroup analysis context.

Full text (54,205 chars)Analyzed: Jul 7, 2026

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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.

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DOI

10.1016/S0140-6736(24)00549-X

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Issued Jul 7, 2026Engine 7.6.0

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