Hypofractionated Radiation Therapy for Treating Prostate Cancer High-Risk Features Following Radical Prostatectomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Hypofractionated Radiation Therapy for Treating Prostate Cancer High-Risk Features Following Radical Prostatectomy (NCT03570827), a non-randomized phase 2 study. The primary outcome is Freedom From Failure (FFF).

2. Clinical Question

Statistically, the study asks how the specified treatment approaches relate to freedom from failure in this post-prostatectomy population. Because treatment allocation is non-randomized, differences between groups could reflect differences in participant characteristics, clinical decisions, or other factors, as well as treatment. The registry record does not report the information needed to assess those factors or adjust for them.

3. Trial Design

This is a phase II, non-randomized, parallel-group trial sponsored by Mayo Clinic. The registry reports enrollment of 53 and a completed status. The recorded start date is 2018-05-14, and the primary completion date is 2025-05-15. Masking is listed as none. The registry record does not report a randomized allocation process, and the three groups should not be treated as randomized arms with baseline comparability assured.

Group I receives hypofractionated radiation therapy over 15-30 minutes every other day over 2 weeks, for 5 treatments. Group II begins androgen suppression 8-10 weeks before radiation therapy and receives it for up to 6 months at the treating physician’s discretion, followed by radiation as described for Group I. Group III receives androgen suppression as described for Group II, for up to 18 months at the treating physician’s discretion, followed by hypofractionated radiation over 15-30 minutes every other day over 1-2 weeks, for 1-5 treatments.

The intervention listings also include quality-of-life assessment and questionnaire administration. The registry record does not report how these measures were analyzed or which group comparisons, if any, were planned. It lists 18 outcome measures and zero analyses. The primary outcome is freedom from failure with a five-year timeframe, but no primary outcome result is reported in the registry record.

The group descriptions include treatment decisions at the discretion of the treating physician. That discretion is relevant to interpretation: treatment assignment may be related to clinical circumstances, and the record does not establish that participants in different groups had comparable prognoses or other characteristics. The trial therefore describes several treatment approaches but does not, on the recorded design information, provide a randomized estimate of their comparative effects.

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: All treated patients

6. Primary Endpoint

The registry lists the primary outcome as Freedom From Failure (FFF), measured over 5 years.

The primary endpoint, freedom from failure (FFF), is defined over five years. The registry defines failure as the first occurrence of clinical failure, including local recurrence, regional recurrence, or distant metastasis; the start or restart of salvage therapy, including androgen suppression; or biochemical failure, defined using PSA >= 0.5 ng/ml. The registry says that the count and percentage of participants free from failure will be reported.

This composite endpoint brings together clinical events, treatment decisions, and a biochemical criterion. A composite can capture several ways that a participant may meet the trial’s definition of failure, but its interpretation depends on the specific components and their occurrence. A participant can meet the endpoint definition through any listed component; the components are not interchangeable in clinical meaning. The registry record does not report how often each component occurred, or whether one component accounted for most failures.

Freedom from failure is used to describe whether participants remain without a qualifying event during the stated timeframe. A five-year timeframe gives the endpoint a defined period of interest, but the record does not report the analysis method, follow-up completeness, or primary outcome results. Without those results, the endpoint definition alone cannot establish the observed frequency of failure or freedom from failure in any group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a non-randomized design imply?

In a randomized trial, chance allocation is used to make treatment groups comparable on average with respect to measured and unmeasured characteristics. Here, allocation is listed as non-randomized. That means comparability cannot be presumed from the design. Clinical choices, participant features, or other circumstances may be associated with which group a person enters. If group outcomes were compared, those associations could complicate attribution of differences to treatment.

Statistical adjustment can sometimes account for measured differences, but it cannot automatically correct for factors that were not measured or not included in an analysis. The registry record does not report baseline group characteristics or an adjusted primary outcome analysis. It therefore does not allow readers to assess whether adjustment was performed or whether important differences between groups remain.

What does a composite endpoint mean?

FFF combines several types of first failure: clinical recurrence or distant metastasis, starting or restarting salvage therapy including androgen suppression, and biochemical failure defined by PSA >= 0.5 ng/ml. This is a composite because any one of these events can satisfy the endpoint definition. A composite can make an outcome definition cover multiple ways that the trial considers failure, but the individual components can differ in clinical importance and frequency. Component-specific results help clarify what is driving a composite; they are not reported in the registry record.

The phrase “first occurrence” also matters: the endpoint is defined by the earliest qualifying event, rather than by a count of every event a participant may experience. However, the registry record does not report the analysis details, such as how time to the first event was handled or how participants without a recorded event were treated statistically. The endpoint definition and the analysis method are distinct pieces of information.

How should uncertainty be assessed?

In general, a confidence interval describes the range of estimates compatible with the data and the method used, under its assumptions. A narrow interval indicates greater statistical precision than a wide interval, while an interval that spans effects in different directions may leave substantial uncertainty about the direction or size of an association. A p-value, in general, measures how unusual data at least as extreme as those observed would be under a specified null model; it does not measure the probability that a treatment works or the probability that the null hypothesis is true.

The registry record does not report a primary endpoint estimate, confidence interval, or p-value. Those concepts therefore explain what would be useful for interpreting a reported comparison, but they cannot be applied to produce a conclusion for this trial from the posted primary outcome information.

Why does allocation matter for inference?

For a non-randomized comparison, statistical uncertainty around an estimate does not capture every source of uncertainty. A confidence interval can quantify sampling variability under an analysis model, but it does not necessarily account for confounding from treatment selection or incomplete measurement. Statistical precision and causal credibility are related but separate questions: a precise comparison may still be biased if groups differ in relevant ways.

The group descriptions also differ in treatment content. Group I is described as radiation alone, whereas Groups II and III include androgen suppression as well as radiation. Group III’s radiation schedule is described differently, and androgen suppression duration is at the treating physician’s discretion. A contrast among groups would therefore concern treatment packages as recorded, rather than isolating the effect of a single component, unless an analysis and design supported such separation. No such analysis is reported in the registry record.

What do the planning calculations represent?

The sample-size calculations are identified as planning illustrations computed from the observed effect, not as the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such calculations illustrate how a hypothetical future study might be planned under particular assumptions. They are not evidence that the current trial had that planned allocation or target, and they are not observed power.

For binary outcomes, sample-size planning depends on the event frequency and the effect a study is intended to detect, as well as the chosen error rate and allocation assumptions. When the event estimate comes from a study with limited or uncertain information, planning values can also be uncertain. The registry record does not report the trial’s own sample-size justification or an analysis plan that connects the illustration to the trial design.

What is not available for evaluating the primary analysis?

The record lists 18 outcome measures and zero analyses, but does not report primary endpoint results or analysis methods. It does not describe the analysis population, handling of missing outcome information, censoring, adjustment variables, or any planned interim analysis. Those details would be needed to understand how the endpoint was estimated, which participants contributed to an analysis, and how uncertainty was calculated. Their absence means the endpoint definition should not be mistaken for a complete statistical analysis.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Group I (Hypofractionated Radiation Therapy)", "Group II (Radiation Therapy, Androgen Suppression ", "Group III (Radiation Therapy, Androgen Suppression")
n      <- c(11, 32, 6)
events <- c(7, 16, 5)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Group I (Hypofractionated Radiation Therapy)  11  7  63.6  30.8  89.1  35.4  84.8  34.9  84.8
ARM  Group II (Radiation Therapy, Androgen Suppression   32  16  50.0  31.9  68.1  33.6  66.4  33.5  66.5
ARM  Group III (Radiation Therapy, Androgen Suppression  6  5  83.3  35.9  99.6  43.6  97.0  42.1  96.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 18 outcome measures, but the record reports zero analyses. It does not identify which outcomes were designated as primary beyond the stated FFF endpoint, explain how other outcomes were prioritized, or report a multiplicity adjustment. When multiple outcomes or comparisons are examined, the chance of finding at least one apparently notable result can increase. In general, a prespecified testing strategy or multiplicity adjustment can address that issue, but the registry record does not report such a strategy. With no posted outcome analyses, the extent of any multiplicity problem cannot be assessed.

The record also does not report how missing data were handled. For the primary endpoint, relevant details would include whether follow-up was complete, how participants without an observed failure were treated, and how incomplete follow-up affected the estimate. These are general considerations for interpreting a time-defined clinical endpoint; the registry does not state which methods, if any, were used.

The analysis population is not reported in the registry record. It is therefore unclear which enrolled participants would be included in an endpoint analysis, or how deviations from the assigned or received treatment, if any, were handled. The registry also does not report an interim analysis plan or statistical analysis plan. These omissions limit assessment of prespecification, data completeness, and the reproducibility of any eventual estimate.

These are reporting gaps, not evidence that particular procedures were or were not used outside the registry record. The absence of a reported method should not be filled by assuming a standard approach.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death nos (16.7%), cardiac arrest (7.1%).

The registry reports safety counts separately for the three groups. For Group I, 14 participants were at risk for serious adverse events and 2 were affected; 14 were at risk for other adverse events and 10 were affected; deaths were 2. For Group II, the corresponding figures are 33 at risk and 0 affected for serious adverse events, 33 at risk and 32 affected for other adverse events, and 0 deaths. For Group III, 6 were at risk and 1 was affected for serious adverse events, 6 were at risk and 6 were affected for other adverse events, and deaths were 1.

These are descriptive counts. The “at risk” values indicate the group denominators reported for each category; affected counts indicate participants recorded with an event. The record does not specify event timing, duration, recurrence, treatment relatedness, or the criteria used to classify seriousness. It also does not describe missing safety observations. The reported counts should not be treated as a controlled comparison, given the non-randomized design and differing treatment approaches.

The record lists “Death NOS” at 16.7% and “Cardiac arrest” at 7.1% among top serious terms. The denominator and method behind those percentages are not explained in the record, so they should not be interpreted as group-specific risks or compared directly with the group counts without that context.

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

The registry record establishes that this was a completed phase II trial of hypofractionated radiation therapy for prostate cancer with high-risk features after radical prostatectomy. It documents three non-randomized treatment groups, describes radiation and androgen suppression schedules, and defines freedom from failure over five years. It also reports group-level safety counts.

Those details do not establish the frequency of freedom from failure or show how the groups compared on the primary endpoint. No primary outcome results, estimates, confidence intervals, or statistical tests are reported in the registry record. The endpoint definition is not itself an outcome result. The available safety counts likewise do not show whether events were caused by treatment or whether one treatment approach had a different safety profile.

Even if group outcome estimates were available, non-randomized allocation would require caution. Participants receiving different treatment approaches may differ for reasons related to clinical decisions or other characteristics. Without reported baseline information and a suitable analysis, an observed group difference could not automatically be attributed to the treatment approach.

The study’s treatment descriptions also combine differing approaches. Groups II and III include androgen suppression, while Group I is described as radiation therapy. The androgen suppression durations and radiation schedules are not identical across all groups. A comparison of groups would therefore not necessarily isolate the contribution of any single treatment component.

The statistical planning illustration has a separate purpose: it uses stated assumptions to illustrate planning based on an observed effect. It is not a report of the study’s own design rationale, and it is not observed power. Taken together, the registry supports a description of the trial design and recorded safety information, but not a conclusion about the primary endpoint’s result or the comparative effects of the treatment groups.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why endpoint definitions, design, and results must be read together. The primary endpoint is defined as a five-year composite that includes clinical events, salvage treatment, and a PSA threshold. That definition specifies what counts as failure, but it does not reveal how many participants experienced failure or how precisely an outcome was estimated.

The non-randomized, parallel-group design is also central to interpretation. The groups receive different treatment approaches, and treatment duration is described as being at the treating physician’s discretion in the androgen suppression groups. These features make group comparability an important question rather than an assumption. Statistical methods can help address measured differences, but the registry record does not report the characteristics or analyses needed to evaluate that issue.

The trial also illustrates the difference between safety descriptions and an efficacy analysis. Group-specific event counts can convey what the record reports about adverse events, while leaving unanswered questions about attribution, event timing, and comparison. Neither the safety counts nor the intervention descriptions substitute for the missing primary outcome estimates.

Finally, a planning calculation derived from an observed effect should not be confused with a design justification or with evidence of achieved power. Keeping those concepts separate helps prevent a planning illustration from being read as proof that a trial could detect an effect, or that a treatment effect was demonstrated. The registry record’s value is in defining the intended question and documenting design and safety information; its missing primary analysis limits what can be inferred about the trial’s main endpoint.

15. 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.

Several trial-specific limitations of interpretation follow from the registry information. First, allocation is non-randomized and masking is listed as none. The record does not report baseline characteristics, so it is not possible to assess whether the groups differed before treatment. Any potential group comparison would be vulnerable to confounding, and the record does not report an adjusted analysis.

Second, the treatment approaches are not identical apart from a single component. Group I receives hypofractionated radiation therapy; Groups II and III also receive androgen suppression. The groups differ in the described androgen suppression duration and radiation schedule, including the number of treatments described for Group III. The record therefore does not establish a comparison that isolates the effect of one treatment component.

Third, the primary endpoint is a composite of clinical recurrence or metastasis, salvage therapy, and biochemical failure. Component-specific outcome counts are not reported, nor are the primary endpoint results. The record also does not report analysis methods, follow-up completeness, missing-data handling, analysis populations, or confidence intervals. This prevents assessment of both the endpoint estimate and its precision.

Finally, safety information is presented as counts, without reported treatment relatedness, event timing, or a full description of missing observations. The registry does not report the trial’s own sample-size justification or a statistical analysis plan. These limitations concern what the registry record documents; they do not establish what may have been collected or analyzed outside that record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Hypofractionated Radiation Therapy for Treating Prostate Cancer High-Risk Features Following Radical Prostatectomy — NCT03570827.
• Registry record last updated 2026-05-26; status last verified 2025-08.
• Results first posted 2026-05-26.
• 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.

19. Record Summary

This completed phase II trial, sponsored by Mayo Clinic, enrolled 53 participants and studied hypofractionated radiation therapy for prostate cancer with high-risk features after radical prostatectomy. Its non-randomized, parallel-group design included radiation alone and approaches combining radiation with androgen suppression. The record lists no masking.

The primary endpoint is freedom from failure at five years, defined using clinical recurrence or metastasis, salvage therapy, or biochemical failure based on PSA >= 0.5 ng/ml. The registry record reports no primary endpoint analysis, and lists 18 outcome measures and zero analyses. It does provide group-level serious and other adverse-event counts and deaths, but does not report event attribution or timing.

Because the groups are non-randomized and differ in treatment approach, their outcomes would not constitute a like-for-like randomized comparison. The record supports describing the planned endpoint, treatment groups, and recorded safety counts, but not estimating or comparing primary endpoint outcomes.