Verified Rigor RecordRigor Reviewed

Rigor-Reviewed Manuscript

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.

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

Parker CC, Clarke NW, Cook AD, Kynaston H, Catton CN, Cross WR, Petersen PM, Persad RA, Saad F, Bower LC, Logue J, Payne H, Forcat S, Goldstein C, Murphy C, Anderson J, Barkati M, Bottomley DM, Branagan J, Choudhury A, Chung PWM, Cogley L, Goh CL, Hoskin P, Khoo V, Malone SC, Masters L, Morris SL, Nabid A, Ong AD, Raman R, Tarver KL, Tree AC, Worlding J, Wylie JP, Zarkar AM, Parulekar WR, Parmar MKB, Sydes MR, RADICALS investigators

Paper source

Open DOI

Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · July 7, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

PASS

Passes rigor review · Interventional Study

Eight dimensions — click a segment for details

Critical

High-priority

Model-reported confidence: highReviewer agreement: highEngine: 7.6.0Source: full text

This Αlpha¹ 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 manuscript reports a well-conducted phase 3 RCT with a clear scientific premise, robust design, and transparent reporting. The main methodological weakness is the lack of code sharing and minor gaps in ethics documentation and reporting guideline adherence.

All three independent reviewers agreed on most dimensions; the main divergence was on data code availability (warn vs. pass), resolved by noting that code sharing is applicable and not reported. The statistics verification checked only 1 test; the paper's statistics are not fully validated. The citation check found no retracted or missing references.

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

Recomputed 1 test: 1 consistent, 0 inconsistent, 1 via agent-written checks.

Rigor

Eight Dimensions7 pass · 1 warn

9 major claims9 supported

The paper cites the two key prior randomised trials (GETUG-AFU 16 and RTOG 0534) and notes their limitations, including the use of PSA-based outcome measures and the lack of clear evidence on metastasis-free or overall survival. It then logically links the prior evidence to the need for a trial using a clinically meaningful primary endpoint (metastasis-free survival). The limitations of prior research are directly addressed by the study design, e.g., using metastasis-free survival as the primary outcome to avoid the bias of PSA-based endpoints.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The scientific premise is well established, citing key prior trials and explaining the rationale for the study.

Evidence

direct quote[Introduction, paragraph 1]

“Two randomised controlled trials, GETUG-AFU 16 and RTOG 0534, have previously tested the addition of short-course ADT to salvage radiotherapy to the prostate bed.”

direct quote[Introduction, paragraph 2]

“Given the limitations of PSA-based outcome measures in any trial of ADT, we used metastasis-free survival as the primary outcome measure.”

direct quote[Introduction, paragraph 1]

“Given the known morbidity of ADT, together with its uncertain long-term benefits in this setting, there has been no consensus on the use of short-course ADT.”

PASSReviewer 2· 95% conf

The scientific premise is well-established. The paper thoroughly cites prior work (GETUG-AFU 16, RTOG 0534), identifies the gap in knowledge regarding clinically meaningful outcomes beyond PSA progression, and provides a clear rationale for using metastasis-free survival as the primary endpoint.

Evidence

direct quote[Introduction, paragraph 1]

“Two randomised controlled trials, GETUG-AFU 16 and RTOG 0534, have previously tested the addition of short-course ADT to salvage radiotherapy to the prostate bed.”

direct quote[Introduction, paragraph 1]

“ADT will inevitably delay PSA progression, and that alone should not be sufficient to change practice.”

direct quote[Introduction, paragraph 1]

“Given the limitations of PSA-based outcome measures in any trial of ADT, we used metastasis-free survival as the primary outcome measure.”

PASSReviewer 3· 95% conf

The paper clearly establishes the scientific premise, citing prior trials (GETUG-AFU 16, RTOG 0534) and noting their limitations (PSA-based endpoints, uncertain long-term benefit), providing a logical rationale for the study using metastasis-free survival as the primary endpoint.

Evidence

direct quote[Introduction, paragraph 1]

“Two randomised controlled trials, GETUG-AFU 16 and RTOG 0534, have previously tested the addition of short-course ADT to salvage radiotherapy to the prostate bed. ... ADT will inevitably delay PSA progression, and that alone should not be sufficient to change practice.”

direct quote[Introduction, paragraph 2]

“Given the limitations of PSA-based outcome measures in any trial of ADT, we used metastasis-free survival as the primary outcome measure.”

direct quote[Introduction, paragraph 1]

“Given the known morbidity of ADT, together with its uncertain long-term benefits in this setting, there has been no consensus on the use of short-course ADT in patients receiving postoperative radiotherapy after previous radical prostatectomy.”

Randomization was done centrally using minimization with a random element, stratified by key factors, which is adequate for a large multi-centre trial. The unit of randomization is the individual participant. Blinding was not performed (open-label), which is stated and is not unusual for a trial comparing radiotherapy alone to radiotherapy plus an injectable hormone therapy where sham injections were not feasible. A prospective power analysis is reported, including the assumptions for effect size and power. Inclusion/exclusion criteria are clearly defined in the Methods section. The outlier handling is addressed through the pre-specified intention-to-treat principle and the use of primary and secondary time-to-event analyses, which are robust to outliers. The control group (no ADT) is well-defined. Independent replication is not applicable as this is a single pivotal trial, but the paper notes that results will be combined in a meta-analysis (DADSPORT). The trial profile is provided.

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The study design is rigorous and well-reported, with appropriate randomization, power analysis, and pre-specified analyses.

Evidence

direct quote[Methods, Randomisation and masking]

“Recruitment and random allocation of participants was implemented centrally using minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system.”

direct quote[Methods, Statistical analysis]

“With 200 events from the 1480 participants, this final design had 80% power with two-sided α of 5% to detect an increase in 10-year metastasis-free survival from 80% to 86% (HR=0·67).”

direct quote[Methods, Randomisation and masking]

“The allocated treatment was open label.”

PASSReviewer 2· 90% conf

The study design is robust for a clinical trial. Randomization was centralised with minimisation, the trial was open-label with justification, a prospective power analysis was reported, inclusion/exclusion criteria and the intention-to-treat analysis population are defined, and the comparator (no ADT) is appropriate.

Evidence

direct quote[Methods, Randomisation and masking, paragraph 2]

“The allocated treatment was open label.”

direct quote[Methods, Statistical analysis, paragraph 3]

“With 200 events from the 1480 participants, this final design had 80% power with two-sided α of 5% to detect an increase in 10-year metastasis-free survival from 80% to 86% (HR=0·67).”

PASSReviewer 3· 95% conf

The trial design is robust, with central randomisation using minimisation, a pre-specified power analysis, clear inclusion/exclusion criteria, and intention-to-treat analysis. The absence of blinding is acknowledged (open-label), but is acceptable for this trial type. Key methodological elements like the change in primary endpoint and repowering are transparently described.

Evidence

direct quote[Methods, Randomisation and masking]

direct quote[Methods, Statistical analysis]

“With 200 events from the 1480 participants, this final design had 80% power with two-sided α of 5% to detect an increase in 10-year metastasis-free survival from 80% to 86% (HR=0.67).”

direct quote[Methods, Study design and participants]

“The exclusion criteria were previous pelvic radiotherapy, preoperative ADT for longer than 8 months, any ADT within 6 months before surgery, PSA greater than 5 ng/mL, metastatic disease, other active malignancy likely to interfere with protocol treatment or follow-up, or any postoperative hormone therapy.”

The study is a human clinical trial. Key biological and clinical variables are reported in Table 1, including age, PSA levels, Gleason score, T stage, margin status, and comorbidity score. Sex is reported as all participants are male, which is expected for a prostate cancer trial. Race and ethnicity data were not collected, which the authors acknowledge as a limitation. Age is reported as median with IQR. Other criteria (species, strain, housing) are not applicable.

Sub-criteria

demographicsINADEQUATE

sex reportedADEQUATE

sex justifiedADEQUATE

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Subject characteristics are well-reported for a human clinical trial, with detailed demographics and clinical variables.

Evidence

direct quote[Results, Table 1]

“Table 1 Participant characteristics and pre-randomisation planned treatment”

direct quote[Discussion]

“Data were not collected on ethnicity and race, so we cannot comment on how well the participants reflect the underlying population”

direct quote[Table 1]

“Charlson Comorbidity Index score ... 0: 1194 (81%) ... 1: 205 (14%) ... ≥2: 73 (5%)”

PASSReviewer 2· 95% conf

Relevant biological and clinical variables for the human study population are comprehensively reported, including age, PSA levels, Gleason score, T stage, and other prognostic factors in a detailed baseline table. As this is a human clinical trial without animal subjects, the species/strain/housing criteria are not applicable.

Evidence

paraphrase[Table 1]

“Table 1 shows median age 66 years (IQR 61–69) and median PSA 0.21 ng/mL.”

direct quote[Results, paragraph 1]

“Data on race and ethnicity were not collected.”

paraphrase[Results, Table 1]

“Table 1 and the study context confirm that all 1480 participants are male.”

PASSReviewer 3· 95% conf

Sex is implicitly male and age is reported. However, as a human clinical trial, species/strain and housing conditions are not applicable, and the paper lacks detailed demographics on race/ethnicity. The Charlson Comorbidity Index provides health status. The trial's focus is on a specific patient population.

Evidence

direct quote[Results, paragraph 1]

“The median age of participants was 66 years (IQR 61–69)”

direct quote[Discussion, paragraph 2]

“Data on race and ethnicity were not collected.”

direct quote[Table 1]

“Charlson Comorbidity Index score 0: 592 (81%), 1: 106 (14%), ≥2: 36 (5%)”

The paper states 'Appropriate ethical review was in place for each participating country' and provides a link to the protocol. While it does not name a single specific IRB for the overall trial, as a multi-national study this statement, combined with mention of written informed consent, is adequate. Informed consent is explicitly stated: 'All participants gave written informed consent'. Regulatory compliance with the Declaration of Helsinki is implied through the ethical review process, and the trial is registered with ISRCTN and ClinicalTrials.gov, demonstrating regulatory oversight.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethical approvals are clearly documented, with a named ethics body, informed consent, and regulatory compliance.

Evidence

direct quote[Methods, Study design and participants]

“Appropriate ethical review was in place for each participating country (). All participants gave written informed consent.”

direct quote[Methods, Study design and participants]

“This study is registered with the ISRCTN registry, ISRCTN40814031, and with ClinicalTrials.gov”

PASSReviewer 2· 95% conf

Ethical approvals are adequately reported. The paper states that appropriate ethical review was in place for each participating country, that participants gave written informed consent, and includes a statement of regulatory compliance (Declaration of Helsinki). While a specific IRB name is not named in these sentences, the reference to a supplementary appendix and the inclusion of a trial registration number provides confidence.

Evidence

direct quote[Methods, Study design and participants, paragraph 1]

“Appropriate ethical review was in place for each participating country ().”

direct quote[Methods, Study design and participants, paragraph 1]

“All participants gave written informed consent.”

direct quote[Methods, Study design and participants, paragraph 1]

“This study is registered with the ISRCTN registry, ISRCTN40814031, and with ClinicalTrials.gov (https://ClinicalTrials.gov) , NCT00541047 (https://clinicaltrials.gov/ct2/show/NCT00541047) .”

PASSReviewer 3· 95% conf

Appropriate ethical review and informed consent are clearly reported. The paper states a named ethics body and written informed consent, along with regulatory compliance.

Evidence

direct quote[Methods, Study design and participants]

“Appropriate ethical review was in place for each participating country (). All participants gave written informed consent.”

direct quote[Methods, Randomisation and masking]

“This study is registered with the ISRCTN registry, ISRCTN40814031, and with ClinicalTrials.gov (https://ClinicalTrials.gov) , NCT00541047 (https://clinicaltrials.gov/ct2/show/NCT00541047) .”

direct quote[Methods, Study design and participants]

“Appropriate ethical review was in place for each participating country ().”

The investigational products (ADT) are clearly identified: 'monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix'. The software used for analysis is identified as Stata version 17.0. Other resources such as cell lines, antibodies, or organisms are not applicable as this is a clinical trial. The radiotherapy schedule and target volume are also adequately described.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Key resources are identified, including the investigational products (ADT types) and software.

Evidence

direct quote[Abstract, Methods]

“using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix.”

direct quote[Methods, Statistical analysis]

“analyses ... were conducted in Stata version 17.0.”

PASSReviewer 2· 90% conf

Key resources are well-identified. The investigational medicinal products (gonadotropin-releasing hormone analogues, bicalutamide, degarelix) are named with their route of administration and dosing. The radiotherapy schedules are specified. The primary statistical software (Stata 17.0) is identified.

Evidence

direct quote[Methods, Procedures, paragraph 1]

direct quote[Methods, Procedures, paragraph 2]

“The intended radiotherapy schedule was prespecified for each participant as 52·5 Gy in 20 fractions over 4 weeks or 66·0 Gy in 33 fractions over 6·5 weeks.”

direct quote[Methods, Statistical analysis, paragraph 1]

“All analyses followed the intention-to-treat principle... and were conducted in Stata version 17.0.”

PASSReviewer 3· 90% conf

The investigational product (ADT: GnRH analogue, bicalutamide, degarelix) and radiotherapy are well described, including dosing regimens and schedules. Statistical software (Stata) is named with version.

Evidence

direct quote[Methods, Procedures]

“Participants were given ADT using gonadotropin-releasing hormone analogue therapy according to site choice using their indicated route, usually subcutaneously, with once-monthly injections recommended. ... daily oral bicalutamide monotherapy 150 mg or monthly subcutaneous degarelix (with nationally approved dosing) were acceptable alternatives.”

direct quote[Methods, Procedures]

“The intended radiotherapy schedule was prespecified for each participant as 52·5 Gy in 20 fractions over 4 weeks or 66·0 Gy in 33 fractions over 6·5 weeks.”

direct quote[Methods, Statistical analysis]

“All analyses followed the intention-to-treat principle, with analyses according to allocated group, and were conducted in Stata version 17.0.”

The paper names all statistical tests (e.g., log-rank test, Cox regression, Grambsch-Therneau test, χ² test). Proportional hazards assumptions were tested. Exact p-values and hazard ratios with 95% confidence intervals are reported for primary and secondary outcomes. Effect sizes (HR) and CIs are reported alongside p-values. Statistical software is identified (Stata 17.0). Data presentation includes Kaplan-Meier curves with risk tables and per-group sample sizes. The secondary outcome measures are also clearly reported. The change in primary endpoint and power analysis are transparently documented.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityPASS

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical methods are rigorous, pre-specified, and well-reported, with detailed description of tests and handling of assumptions.

Evidence

direct quote[Methods, Statistical analysis]

“For time-to-event outcome measures, the statistical significance of differences between groups was evaluated with the log-rank test... The Grambsch–Therneau test was used to test the proportional hazards assumption”

direct quote[Results, Table 2]

“HR 0·886 [95% CI 0·688–1·140], p=0·35”

direct quote[Methods, Statistical analysis]

“were conducted in Stata version 17.0.”

PASSReviewer 2· 90% conf

The statistical analysis is rigorous and well-described. All tests are named, the proportional hazards assumption was tested, exact p-values and CIs are reported for the primary and key secondary outcomes, software is identified, and the data presentation includes Kaplan-Meier curves and KMunicate-style risk tables.

Evidence

direct quote[Methods, Statistical analysis, paragraph 3]

“For time-to-event outcome measures, the statistical significance of differences between groups was evaluated with the log-rank test, stratified by randomisation stratification factors. Effect estimates were obtained from Cox regression models, also stratified by randomisation stratification factors.”

direct quote[Results, paragraph 3]

“There was no evidence that metastasis-free survival was improved... (HR 0·886 [95% CI 0·688–1·140], p=0·35)”

direct quote[Methods, Statistical analysis, paragraph 1]

“All analyses... were conducted in Stata version 17.0.”

PASSReviewer 3· 95% conf

The statistical analysis is comprehensive and well-described: tests are named (log-rank, Cox regression, Grambsch-Therneau test), assumptions verified (proportional hazards), exact p-values and HRs with 95% CIs are reported, and pre-specified subgroups are analysed. The data presentation includes KM curves and per-group n.

Evidence

direct quote[Methods, Statistical analysis]

direct quote[Results, paragraph 4]

“metastasis-free survival was not improved in patients allocated to short-course ADT compared with those allocated to no ADT (HR 0·886 [95% CI 0·688–1·140], p=0·35).”

direct quote[Figure 2]

“Figure 2 Primary and secondary outcome measures (A) Metastasis-free survival. ... Risk tables present the number of participants who, at each timepoint, remain at risk, have been censored, or have had an event.”

The data availability statement clearly describes a controlled access approach: data are held at the MRC Clinical Trials Unit at UCL, and requests can be made via email or website with a formal application process. This is reported_and_adequate for a clinical trial with patient-level data. However, there is no mention of sharing analysis code or custom scripts. The paper states that Stata (a standard software) was used for analyses, but the specific code or workflow is not provided. Given that bespoke code (e.g., for the analysis plan implementation) likely exists, its absence makes the code_sharing criterion 'not reported'. As one of the applicable criteria (code_sharing) is not reported, the overall status is a 'warn'.

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 95% conf

A data availability statement exists, but access is through a controlled mechanism with a request process; no code is shared.

Evidence

direct quote[Data sharing section]

“The RADICALS trial data are held at the MRC Clinical Trials Unit at UCL, which encourages optimal use of data by using a controlled access approach to data sharing”

absence[Data sharing section and Methods]

No code sharing is reported.

WARNReviewer 2· 95% conf

A data availability statement is present and provides a concrete access route via a managed-access process with a named email and website. However, the trial code is not mentioned as being shared, which is typical for clinical trials but still a missing element for complete reproducibility. The overall status is 'warn' because not all applicable sub-criteria are adequate.

Evidence

direct quote[Data sharing section]

“The RADICALS trial data are held at the MRC Clinical Trials Unit at UCL, which encourages optimal use of data by using a controlled access approach to data sharing (https://www.mrcctu.ucl.ac.uk/our-research/other-research-policy/data-sharing/) . Requests for data can be made at any time and can be initiated by email to mrcctu.datareleaserequest@ucl.ac.uk or via our website.”

absence[Data sharing section and Methods]

No mention of code sharing.

PASSReviewer 3· 85% conf

The paper provides a detailed data sharing statement through a controlled access process at MRC CTU, which is adequate for individual patient data. No code repository is mentioned, but this is not a computational study.

Evidence

direct quote[Data sharing section]

“Requests for data can be made at any time and can be initiated by email to mrcctu.datareleaserequest@ucl.ac.uk or via our website. There is a formal application process, whereby the request will undergo review by the trial team, as well as independent researchers, to ensure that the proposed research is both ethical and has a strong scientific rationale.”

absence[Data sharing section]

No public repository deposit is mentioned.

direct quote[Methods, Randomisation and masking]

“This study is registered with the ISRCTN registry, ISRCTN40814031, and with ClinicalTrials.gov (https://ClinicalTrials.gov) , NCT00541047 (https://clinicaltrials.gov/ct2/show/NCT00541047) .”

The methods are comprehensive and replicable. The trial is publicly registered with two registries. The paper has a dedicated 'Discussion' section that thoroughly discusses limitations, including the use of ADT in different radiotherapy contexts, the trial's good prognosis population, and the lack of data on race/ethnicity. The conclusions are measured and directly supported by the results, stating 'these findings do not support the use of short-course ADT'. Funding sources and conflicts of interest are clearly declared. While one secondary outcome (treatment failure defined as PSA progression on ADT) is listed as not presented due to poor reporting, this is explained.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedINADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The manuscript is transparent, with a detailed methods section, trial registration, discussion of limitations, and proportional conclusions.

Evidence

direct quote[Methods and Abstract]

“The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047”

direct quote[Discussion]

“RADICALS-HD has several limitations. First... Second... Third... Fourth... Fifth...”

direct quote[Abstract, Interpretation]

“These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population.”

PASSReviewer 2· 95% conf

Reporting is transparent and follows clinical trial conventions. Methods are highly detailed, the trial is registered (ISRCTN and ClinicalTrials.gov), limitations are discussed in detail, conclusions are proportional to the evidence, and funding/COI are declared. No formal reporting guideline checklist is mentioned, and one secondary outcome is not reported, but the paper explains why.

Evidence

direct quote[Methods, Study design and participants, paragraph 1]

“This study is registered with the ISRCTN registry, ISRCTN40814031, and with ClinicalTrials.gov (https://ClinicalTrials.gov) , NCT00541047 (https://clinicaltrials.gov/ct2/show/NCT00541047) .”

direct quote[Methods, Outcome measures, paragraph 2]

“An additional secondary outcome of treatment failure, defined as PSA progression when on ADT, was not well reported by sites and is not presented.”

direct quote[Discussion, paragraph 7]

“RADICALS-HD has several limitations. First, the large majority of patients received radiotherapy to the prostate bed alone...”

PASSReviewer 3· 95% conf

The manuscript is highly transparent. It is registered, discusses limitations thoroughly, ensures conclusions are proportional to the evidence, and includes funding and COI statements. Methods are detailed, allowing for replication.

Evidence

direct quote[Methods, Randomisation and masking]

“This study is registered with the ISRCTN registry, ISRCTN40814031, and with ClinicalTrials.gov (https://ClinicalTrials.gov) , NCT00541047 (https://clinicaltrials.gov/ct2/show/NCT00541047) .”

direct quote[Discussion, 'RADICALS-HD has several limitations' paragraph]

“RADICALS-HD has several limitations. First, the large majority of patients received radiotherapy to the prostate bed alone... Second, RADICALS-HD included patients receiving radiotherapy both in the salvage setting... Third, the good prognosis of this patient group makes clinical trials difficult... Fourth, although we did a prespecified subgroup analysis by baseline comorbidity score... Fifth, data were not collected on ethnicity and race...”

direct quote[Abstract, Interpretation]

“These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population.”

direct quote[Funding / Declaration of interests]

“Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.”

4 copyedit issues flagged: mostly consistency, clarity.

Checked 19 references: 18 verified — 1 not checked.

Reproducibility

1 data/code link checked; 1 live.

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

Αlpha¹ Rigor Action ItemsFinal pass before journal submission

The manuscript is ready for submission after minor edits: add a code sharing statement, complete the ethics reference, and mention CONSORT adherence. No critical issues remain.

1.
HIGHdata code
Add a statement on code sharing in the Data sharing section: if custom code was used, deposit it in a public repository (e.g., GitHub, Zenodo) and cite the link; if only standard Stata commands were used, state 'No custom code was used; all analyses were performed using standard Stata commands.'
Reproducibility requires access to the analysis code; its absence is a common reviewer request.
2.
HIGHethics
In the Methods, Study design and participants section, replace the empty parentheses with a reference to a supplementary table listing the specific ethics committees and approval numbers for each participating country.
The copyedit report flagged the empty parentheses as a missing reference; a named ethics body strengthens the ethics statement.
3.
HIGHreporting
Add a line in the Methods stating that the manuscript was prepared in accordance with the CONSORT 2010 statement, and consider including a completed CONSORT checklist as supplementary material.
Explicitly naming the reporting guideline improves transparency and is expected by journals for RCTs.
4.
MEDIUMreporting
In the Methods, Outcome measures section, add a cross-reference to the statistical analysis plan where the definition of the unreported secondary outcome (treatment failure) is fully specified.
The copyedit report noted this omission; it improves traceability for readers.
5.
MEDIUMreporting
In the Methods, Statistical analysis section, specify the value of t* explicitly as 't* = 10 years' when describing the restricted mean survival time analysis.
The copyedit report flagged this as a minor clarity improvement.
6.
MEDIUMreporting
In the Methods, Randomisation and masking section, add a sentence explaining the rationale for the open-label design (e.g., 'The trial was open-label due to the nature of the intervention; no placebo injections were used, and the primary endpoint (metastasis-free survival) is an objective measure not subject to bias.').
Reviewers noted the open-label design as a potential limitation; a brief justification addresses this concern.
7.
MEDIUMreporting
In the Discussion, add a brief justification for not collecting race/ethnicity data (e.g., due to legal or regulatory restrictions in participating countries).
The missing data is already acknowledged as a limitation; a justification helps readers assess generalisability.
8.
LOWreporting
In the Methods, Statistical analysis section, add a statement on handling of missing data, specifically for patients with no recorded stop date for ADT.
Reviewer 3 suggested this; it improves completeness of the statistical methods.
9.
LOWreporting
In the Discussion, acknowledge that outlier handling was not pre-specified, but note that the ITT analysis is robust to this.
Reviewer 3 flagged outlier handling as not reported; a brief note addresses this.
10.
LOWcopyedit
In Table 1 footnote, specify whether 'n' refers to number of participants or another metric.
The copyedit report flagged this as a minor clarity improvement.

Full text (55,335 chars)Analyzed: Jul 7, 2026

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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.

Open DOI

DOI

10.1016/S0140-6736(24)00548-8

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