RAdium-223 and SABR Versus SABR for Oligometastatic Prostate Cancers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for RAdium-223 and SABR Versus SABR for Oligometastatic Prostate Cancers (NCT04037358), a randomized phase 2 study. The primary outcome is Progression-free Survival.

2. Clinical Question

3. Trial Design

This is a randomized, parallel-group Phase II trial, listed as completed. The registry reports 64 participants enrolled, with a start date of 2019-08-09 and a primary completion date of 2025-07-15. The condition is prostate cancer. The study is non-blinded, and the brief summary describes assignment in a 1:1 ratio to SABR alone or SABR plus Radium-223.

In the combination group, the first Radium-223 infusion is specified to occur within two weeks of SABR. The SABR-only arm description states that SABR will be administered in 1-5 fractions for all men. The registry lists Radium-223 as a drug intervention and SABR as a radiation intervention.

The primary outcome is median progression-free survival in months, with a 95% confidence interval and a timeframe of up to 24 months. The primary outcome’s analysis counts differ by arm: 30 for Radium-223 and SABR, and 33 for SABR. The safety record gives different at-risk counts for the combination group, so those safety denominators should not be substituted for the primary outcome counts.

The registry lists additional outcomes involving toxicity, local and distant progression, metastasis-free survival, ADT-free survival, and pain-related quality of life. The record reports 11 outcome measures and 10 posted secondary outcomes. Detailed statistical design information, including the trial’s sample-size justification and any interim-analysis plan, is not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Participants who completed the study

6. Primary Endpoint

The registry lists the primary outcome as Progression-free Survival, measured over Up to 24 months.

Progression-free survival is the time from therapy to the first qualifying progression event. The registry defines progression using PCWG2 criteria: a PSA increase of at least 25% from nadir and at least 2 ng/mL, clinical or radiographic progression, initiation of ADT, or death from any cause, whichever occurs first. Clinical progression is described as symptomatic worsening or new cancer-related complications. Radiographic progression may be based on RECIST 1.1 enlargement of soft-tissue target lesions on CT or new bone lesions on a bone scan.

The outcome is reported as a median in months, with a 95% confidence interval, and a timeframe of up to 24 months. In general, a time-to-event endpoint incorporates both the timing of an event and whether an event has occurred during observed follow-up. The median marks the estimated time by which half of the relevant event-time distribution has occurred; it is not an average and does not describe every participant’s experience.

Progression-free survival is used to capture several forms of worsening or treatment escalation within one endpoint. The registry’s definition is broad, combining biochemical, clinical, imaging, treatment-initiation, and mortality events. The specific handling of censoring and the analysis method used to estimate the median are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a time-to-event outcome reported as median progression-free survival. This format is different from a simple proportion measured at a single visit: it uses the timing of the first qualifying event, as defined in the registry. The reported medians are 10.5 months for Radium-223 and SABR and 11.8 months for SABR. The corresponding 95% confidence intervals are 7.3 to 12.4 months and 6.67 to 21.2 months.

What does the median describe?

In general, a median time-to-event estimate is the estimated time by which half of the event-time distribution has reached the event. It is not the mean time, and it does not say that each participant experienced an event at or near that time. For a time-to-event endpoint, some participants may not have had the event by the end of their observed follow-up. Common analyses account for incomplete event observation through censoring, but the censoring rules and the estimator used for these medians are not reported in the registry record.

How should the confidence intervals be read?

In general, a confidence interval expresses statistical uncertainty in an estimate under the assumptions of the method used to construct it. It should be read as a range of values compatible with the observed data and that method, rather than as a guarantee about the true value. The registry reports a 95% confidence interval for each arm’s median. It does not report the method used to construct those intervals, nor a confidence interval for a contrast between the arms.

Arm-specific intervals do not replace a direct comparison. A comparison might be expressed through a hazard ratio or another effect measure, accompanied by its uncertainty. The registry record does not report a hazard ratio, a comparative confidence interval, or a p-value for progression-free survival. A statement about whether the arms differ statistically would therefore go beyond the posted result. The record indicates that recalculated comparisons were not estimable for this median time endpoint, and no recalculated comparative result is available to interpret.

What does randomization contribute?

In general, random allocation is intended to make treatment groups comparable on average with respect to both measured and unmeasured characteristics. It does not guarantee identical groups in a particular trial, especially when group sizes are limited. This study is described as randomized, with a 1:1 allocation ratio, and as non-blinded. The registry does not report the sequence-generation procedure, allocation concealment, stratification factors, or other randomization details. Those methods should not be inferred from the allocation label alone.

Non-blinding means that treatment assignment was not masked. In general, knowledge of assignment can influence care, reporting, or outcome assessment, depending on the outcome and how it is measured. Progression in this trial can include PSA change, clinical symptoms, imaging findings, ADT initiation, and death. The registry does not report whether outcome assessment was independently reviewed or otherwise protected from knowledge of treatment assignment.

How should planning calculations be interpreted?

The planning illustrations use the observed effect as a reference and consider fractions of that effect under a two-sided significance level of 0.05, equal allocation, and a normal approximation. For time-to-event outcomes, the planning quantities refer to total events; other planning quantities refer to participants per arm. These are planning illustrations, not observed power and not evidence that the trial was designed around those assumptions. The trial’s own sample-size justification is not reported in the registry record.

In general, a planning calculation estimates the amount of information a future study might need under specified assumptions. It does not establish what the current study was powered to detect, and it does not change the uncertainty in the observed result. An illustration based on an observed effect can also depend strongly on that estimate. The registry does not report a prespecified target effect, the assumptions used in the trial’s original design, or whether the design included provisions for interim analyses.

The trial record reports no analysis entries. That absence means the registry record does not provide a fuller account of model choice, adjustment, handling of missing data, or checks of model assumptions. It does not justify assuming that a particular survival model was used. In general, methods such as Kaplan-Meier estimation and proportional-hazards models are common for time-to-event outcomes, but their use in this trial is not reported in the registry record. The interpretation should therefore stay with the posted medians and confidence intervals rather than attributing unreported methods to the investigators.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists secondary outcomes covering adverse events, local control, locoregional and distant progression, metastasis-free survival, ADT-free survival, and pain-related quality of life. It reports 10 posted secondary outcomes and 11 outcome measures. These outcomes involve different event definitions, timeframes, and measurement approaches, so results across them would not automatically represent a single confirmatory test.

When a study evaluates multiple outcomes or makes multiple comparisons, the chance of at least one apparently positive finding can increase. In general, a prespecified multiplicity strategy can address this issue by defining which tests are confirmatory and how inference is controlled. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a statistical analysis plan describing how the primary and secondary outcomes were to be interpreted together.

The record reports no analysis entries. Methods for handling missing outcome data, incomplete follow-up, or withdrawals are not reported in the registry record. The analysis populations are also not reported: it is not stated whether the primary analysis followed intention-to-treat principles, used an evaluable population, or applied another rule. The arm-specific primary outcome counts are 30 and 33, while the safety counts differ for the combination arm; the reasons for these denominators are not explained. These reporting gaps limit assessment of whether outcome availability could affect the comparison.

Interim-analysis procedures and any stopping rules are not reported in the registry record. They should not be inferred from the Phase II designation or from the completed status.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety record reports serious adverse events for the two groups separately. In the Radium-223 and SABR group, 31 participants were at risk and 0 were recorded as affected by a serious adverse event. In the SABR group, 33 were at risk and 0 were recorded as affected. The record lists 0 deaths in each group. No top serious-event terms are listed.

For all other adverse events, the registry reports 30 affected among 31 at risk in the combination group, and 33 affected among 33 at risk in the SABR group. These are counts from the safety record, not the primary progression-free survival analysis counts. The registry also lists a secondary toxicity outcome defined as the number of participants experiencing adverse events of grade 3 or greater under CTCAE v4.0. The posted safety counts should not be assumed to be that grade-specific outcome; the record does not provide grade-specific counts in these figures.

In general, a count of participants with at least one event does not convey the number of events per participant, event duration, severity distribution, or relationship to treatment. The registry figures also do not establish that no unrecorded events occurred. They describe the adverse-event information posted in the registry, with the stated at-risk denominators.

12. What the Result Does, and Does Not, Mean

The registry result supports a narrow descriptive statement: median progression-free survival was reported as 10.5 months with Radium-223 and SABR and 11.8 months with SABR alone, with arm-specific 95% confidence intervals. The registry also supplies the outcome definition, including biochemical, clinical, radiographic, treatment-initiation, and mortality events. These details help clarify what counted as progression in this trial.

The result does not establish that either treatment approach improves progression-free survival relative to the other. The registry record does not report a hazard ratio, a direct confidence interval for the difference, or a p-value for the primary comparison. The two medians are not themselves a comparative test, and they do not describe the entire event-time distributions. Without the analysis method and comparative estimate, the size and precision of any relative treatment effect cannot be assessed from the registry record.

The result also does not provide a complete account of how all enrolled participants contributed to the primary analysis. The record reports 64 enrolled and arm-specific outcome counts of 30 and 33, but does not explain the analysis population or the reason for the differing counts. Follow-up completeness, missing-data handling, and the actual follow-up distribution are not reported in the registry record.

Safety figures should likewise be read within their scope. The registry reports no participants affected by serious adverse events and no deaths in either group in the posted safety record, while other adverse events were recorded for participants in both arms. These counts do not provide a full account of severity, event frequency, or treatment attribution.

Accordingly, these findings describe the posted registry results for this trial; they do not support medical advice or a definitive treatment recommendation.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why arm-level summaries and comparative estimates answer different questions. A median progression-free survival estimate describes the event-time distribution within an arm. A direct treatment comparison requires an effect estimate that contrasts the groups and communicates its uncertainty. The registry reports the former but not the latter for the primary endpoint.

The endpoint definition is also consequential. Progression-free survival includes PSA change, clinical or imaging progression, ADT initiation, or death. Combining several types of events can make an endpoint clinically broad, but it also means interpretation depends on how each component is assessed and how the first event is recorded. The registry specifies criteria for these events, while assessment procedures and analysis details are not reported.

The separate outcome and safety denominators matter for interpretation. The primary outcome counts are 30 and 33; the safety record gives 31 and 33 at risk. These counts should remain tied to their respective outcomes. The registry does not explain why denominators differ, so assumptions about participant inclusion or missing results would be unwarranted.

Finally, planning illustrations based on an observed effect should be distinguished from the original design and from observed power. Their assumptions can help readers understand how sample-size planning works in general, but they do not supply the trial’s unreported design justification. These features make the record a useful reminder to separate descriptive estimates, inferential comparisons, planning calculations, and safety summaries rather than treating them as interchangeable evidence.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpretation is the absence of a reported comparative effect estimate for progression-free survival. The registry provides medians and confidence intervals for each arm, but no hazard ratio, comparative interval, or p-value. The method used to estimate the medians and intervals is not reported in the registry record, so the statistical procedure cannot be evaluated from the posted results.

The registry does not explain the relationship between 64 enrolled participants and the primary outcome counts of 30 and 33. It also does not report the analysis population, how missing endpoint data were handled, or the amount and pattern of follow-up. These omissions prevent assessment of whether the available outcome data represent all randomized participants or a selected subset.

The study is non-blinded. The registry does not describe blinded or independent outcome assessment, and the endpoint includes clinical judgments and decisions such as symptoms, imaging interpretation, and ADT initiation. The extent to which knowledge of assignment could have influenced assessment is not reported.

Other relevant details—including the sample-size justification, interim-analysis plan, multiplicity strategy, and full statistical analysis plan—are not reported in the registry record. The safety summaries do not provide detailed event severity, frequency, or attribution, and the grade 3 or greater toxicity outcome is listed without corresponding grade-specific figures in the posted safety data. These limitations call for a restrained reading of the available descriptive results, rather than a conclusion about comparative efficacy or complete safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: RAdium-223 and SABR Versus SABR for Oligometastatic Prostate Cancers — NCT04037358.
• Registry record last updated 2025-12-19; status last verified 2025-12.
• Results first posted 2025-12-19.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a completed, non-blinded, randomized, parallel-group Phase II study of men with oligometastatic prostate cancer and at least one bone metastasis. It compares SABR plus Radium-223 with SABR alone. The record lists 64 participants enrolled, a start date of 2019-08-09, and a primary completion date of 2025-07-15.

The primary outcome is median progression-free survival in months, assessed up to 24 months. The reported medians are 10.5 months for Radium-223 and SABR and 11.8 months for SABR, with respective 95% confidence intervals of 7.3 to 12.4 months and 6.67 to 21.2 months. A comparative hazard ratio and other formal test results are not reported in the registry record.

The record also lists secondary outcomes and safety counts. Statistical analysis details, the analysis populations, missing-data methods, and sample-size justification are not reported in the registry record.