HDR Brachytherapy, EBRT and STAD for the Treatment of Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for HDR Brachytherapy, EBRT and STAD for the Treatment of Prostate Cancer (NCT03553602), a na phase 1, phase 2 study. The primary outcome is Genitourinary Toxicity.

2. Clinical Question

3. Trial Design

NCT03553602 is recorded as a phase I/II study of salvage HDR brachytherapy, EBRT, and STAD for node-positive locally recurrent prostate cancer after prior definitive radiotherapy. It is a single-group study with no masking and no randomized comparator. Enrollment was 3, and the registry status is terminated. The record lists a start date of 2017-12-20 and a primary completion date of 2024-07-26. The reason for termination is not reported in the registry record.

The regimen description specifies an HDR brachytherapy implant on day 1, with 2 fractions of 12 Gy to the prostate and proximal seminal vesicles. EBRT is described as 50.4 Gy in 28 fractions to pelvic lymph nodes, with or without para-aortic nodes, and a simultaneous integrated boost up to 70 Gy to PET-positive lesions. Hormonal therapy is described as 6 months of an LHRH agonist and antiandrogen, with the antiandrogen continuing until the end of radiotherapy. The brief description says radiation would start approximately 2 months after hormonal therapy began, and describes an oral medication and an injection.

The study description says participants would be followed at specified intervals to assess treatment side effects and cancer control. However, the specific schedule beyond the month 24 assessment noted for two participants is not reported in the registry record. The record names genitourinary toxicity as the primary outcome and gastrointestinal toxicity as a secondary outcome. It does not report the outcome counts or analysis results. The study’s phase labels do not, by themselves, establish the details of any dose-escalation procedure or phase-specific analysis; those details are 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:

Analysis population for the primary outcome, as defined in the registry: Two participants completed the month 24 assessment

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.

6. Primary Endpoint

The registry lists the primary outcome as Genitourinary Toxicity, measured over 24 months.

The primary endpoint is the number of participants with an acute radiation-related genitourinary toxicity of grade 3 or higher, as described using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. The stated timeframe is 24 months, and the outcome unit is participants. The registry record says that two participants completed the month 24 assessment, but it does not report how many experienced the primary endpoint.

This type of endpoint records whether participants experienced a specified toxicity, rather than measuring an average change in a continuous score. In general, a prespecified toxicity threshold can make the safety question concrete: the outcome is the count meeting the stated severity criterion. The threshold and assessment framework also help define what is being counted. They do not, on their own, establish how often assessments occurred, how events were attributed to radiation, or how missing assessments were handled; those details are not reported in the registry record.

Genitourinary toxicity is relevant to a regimen involving prostate and pelvic radiation, so documenting it addresses a safety question central to the study description. The record also names gastrointestinal toxicity as a secondary outcome. Neither the primary nor secondary toxicity result is reported in the registry record. The endpoint definition should therefore be distinguished from an observed result: a clearly described measure does not show what its value was.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What can a single-group study estimate?

This study assigns all enrolled participants to the same described regimen and does not include a separate control arm. In general, a single-group study can describe outcomes observed among its participants. It cannot directly estimate a between-treatment contrast because there is no concurrent comparison group. Any interpretation of outcomes as caused by treatment would require assumptions beyond the observed counts, and the registry record does not report such an analysis.

The record identifies allocation as not applicable and masking as none. It does not report further details of the study’s statistical plan, including the intended estimand, analysis model, or whether any protocol-defined interim analyses occurred. Those omissions matter because methods determine how observations are summarized and how uncertainty is quantified. No analysis results are listed in the registry record.

How should the primary endpoint be understood?

The primary outcome is a participant count: the number with acute radiation-related genitourinary toxicity at grade 3 or higher under CTCAE version 4.03. A count endpoint represents the number of participants meeting a defined event criterion. General statistical explanation: when an outcome is binary at the participant level, an event count and the number assessed can be used to describe the observed proportion, while an uncertainty interval can indicate how imprecisely that proportion estimates a broader event frequency. The registry record does not report the primary event count, so neither an observed proportion nor its interval is available from the posted results.

The record states that 2 participants completed the month 24 assessment. That assessment count should not be treated as the primary endpoint numerator or as proof that the endpoint was assessed identically for every participant. The event count, detailed assessment schedule, rules for classifying acute toxicity, and missing-outcome handling are not reported in the registry record. The stated endpoint timeframe of 24 months does not by itself fill in those methodological details.

What does a small enrollment mean for precision?

General statistical explanation: with a small number of observations, a single participant’s outcome can materially change a descriptive estimate. Confidence intervals are therefore important when interpreting event rates, because they show uncertainty around an estimate rather than presenting a point estimate as exact. A small study may be useful for collecting early safety information, but its counts generally cannot support precise estimates of uncommon outcomes. This general principle does not supply an estimate for this study: the primary toxicity result and its uncertainty are not reported.

The enrollment of 3 and the 2 participants completing the month 24 assessment also limit what can be said about follow-up. The record does not state why the assessment was not completed for the remaining participant, whether that participant had earlier assessments, or how the missing assessment was treated. Different approaches to missing outcomes can lead to different estimates; the approach used is not reported in the registry record.

How should planning calculations be read?

The planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes, the stated planning convention is a total number of events using the Schoenfeld method; other outcomes are expressed as participants per arm. These are planning assumptions, not a report of the trial’s design rationale. The record does not report the original sample-size justification.

Those assumptions describe a two-arm planning framework, whereas this study is recorded as single-group. Any resulting sample-size illustrations should therefore be read as hypothetical planning exercises, not as a description of the study’s actual allocation or as evidence about its statistical power. In general, planned power is a design-stage quantity; it is not a measure of how likely an observed result is to be true. The illustrations are explicitly based on the observed effect, but the primary outcome result is not reported in the registry record. Such calculations do not replace a reported endpoint estimate, its uncertainty, or a prespecified design justification.

General statistical explanation: over-dispersion occurs when variability is greater than a chosen model expects. If present, it can make standard errors and confidence intervals from a simple model too small. Whether over-dispersion was assessed, or whether a model requiring that assessment was used, is not reported in the registry record. More broadly, the record does not describe a statistical model for the primary outcome, covariate adjustment, or a method for handling repeated assessments.

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("HDR Brachytherapy + EBRT + STAD")
n      <- c(2)
events <- c(0)
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  HDR Brachytherapy + EBRT + STAD  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record names genitourinary toxicity as the primary outcome and gastrointestinal toxicity as a secondary outcome. It does not report an outcome-analysis plan, the number of planned comparisons, or any adjustment for multiple testing. Multiplicity refers, in general, to the increased chance of at least one false-positive finding when several hypotheses are tested. Whether that issue was addressed in the study’s protocol or analysis is not reported in the registry record. No analysis results are listed.

The record states that 2 participants completed the month 24 assessment, while enrollment was 3. It does not report the reason for the missing assessment, the availability of other follow-up measurements, the analysis population for the primary endpoint, or the method used to handle missing data. General statistical point: missing outcomes can affect an estimate if the participants with missing measurements differ in relevant ways from those assessed. That possibility cannot be evaluated from the reported completion count alone.

The record does not state whether analyses followed an intention-to-treat principle, included only participants who completed treatment, or used another population definition. Such distinctions can affect which participants contribute to an estimate. No imputation method, sensitivity analysis, or missing-data assumption is reported in the registry record. It is therefore not possible to determine from the posted information whether the available assessment count was the denominator used for the primary outcome or how any unavailable outcome was treated.

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.

The serious adverse event entry lists 3 participants at risk and 0 affected. The other adverse event entry likewise lists 3 at risk and 0 affected. The record separately lists 1 death. These are distinct entries: the death count should not be silently reclassified as a serious adverse event, nor should it be assumed to be unrelated to treatment. Its cause, timing, and relationship to the regimen are not reported in the registry record.

These safety counts are descriptive. They do not establish that the primary genitourinary toxicity endpoint was absent, because that endpoint’s result is not reported. The adverse event record also does not provide event terms for serious events. A zero affected count means no affected participants are recorded for that category in the posted entry; it does not explain how events were collected, adjudicated, or followed, and it does not establish the absence of risk in a larger population.

General statistical point: when few participants are observed, zero recorded events can still leave substantial uncertainty about the event frequency beyond the study. The registry record’s small enrollment limits how broadly these counts can be applied. No inference about comparative safety is possible without a comparator group.

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

The posted record describes a study of salvage HDR brachytherapy, EBRT, and STAD for node-positive locally recurrent prostate cancer after prior definitive radiotherapy. It documents a single-group design, enrollment of 3 participants, and completion of the month 24 assessment by 2 participants. It also records 0 participants affected by serious adverse events, 0 affected by other adverse events, and 1 death. These figures describe what the registry entry reports; they do not provide a complete account of the primary outcome.

The primary endpoint is defined as acute radiation-related genitourinary toxicity of grade 3 or higher, but its event count is not reported in the registry record. The gastrointestinal toxicity outcome is named as secondary, but its result is also not reported. The study description refers to cancer control, yet a cancer-control result is not reported in the registry record. Without those results, there is no basis for estimating the regimen’s observed toxicity rate or cancer-control outcome from the posted information.

The study’s single-group design also limits interpretation. It can describe outcomes among participants who received the regimen, but it cannot show how those outcomes compare with an alternative treatment. The record does not report an adjusted analysis, an uncertainty interval, or a statistical comparison. Small enrollment further limits precision and generalizability. These limitations do not negate the value of recording experience in a specific clinical setting, but they constrain what conclusions can be drawn.

The terminated status is a registry status, not an explanation of why the study ended. The reason is not reported in the registry record. In particular, termination alone does not establish that treatment was unsafe, ineffective, or successful. The appropriate interpretation is bounded: the record gives the study design and some safety counts, while leaving the primary outcome result and other key clinical results unreported.

14. Why This Trial Matters Statistically

This study raises statistical questions common to small early-phase investigations: what can a participant count tell readers, how should incomplete follow-up be described, and how much confidence is justified when only a few people are observed? Its primary outcome is a clinically defined toxicity count, but the registry record does not report the count. That contrast between a specified endpoint and an unavailable result is important. An endpoint definition explains what investigators intended to measure; it is not evidence of the outcome.

The design also highlights the distinction between describing experience and comparing treatments. A single-group study may record safety events in a specific population receiving a defined regimen, but it lacks a concurrent control group for estimating comparative effects. Readers should not treat descriptive safety counts as a treatment contrast. The listed death also illustrates why event categories need context: the registry gives a death count, but not its cause or relationship to treatment.

Finally, the record makes clear why completion information and analysis details matter. Two participants completed the month 24 assessment, but the reason for the other participant’s non-completion and the handling of missing outcomes are not reported. The record lists no analyses. Without endpoint results, denominators, and an analysis approach, statistical precision cannot be assessed. These are not merely technical omissions: they determine whether a count can be interpreted as a reliable estimate, how much uncertainty surrounds it, and how far it can be generalized.

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.

The most direct limitation is that the primary endpoint result is not reported in the registry record. Although the outcome is defined and two participants are identified as completing the month 24 assessment, no count of participants with grade 3 or higher genitourinary toxicity is posted. The secondary gastrointestinal toxicity result is also not reported. A statistical interpretation of treatment-related toxicity therefore cannot be based on these outcomes.

Enrollment was 3, and the study had no comparator group. These features limit precision and prevent a direct comparative estimate. Only 2 participants are reported as completing the month 24 assessment; the reason for the remaining participant’s non-completion and the handling of missing data are not reported. The record also lists 1 death without its cause, timing, or treatment relationship.

Other details needed to assess the findings are not reported in the registry record, including the statistical analysis plan, analysis population, endpoint analysis method, multiplicity strategy, and original sample-size justification. The study is marked terminated, but the reason for termination is not reported. The record’s planning assumptions describe a two-arm framework, which differs from the study’s single-group design; those assumptions should not be mistaken for the study’s actual design rationale. These limits mean that the posted information supports a narrow description of enrollment, follow-up, and recorded adverse event counts, rather than a precise assessment of toxicity or cancer control.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: HDR Brachytherapy, EBRT and STAD for the Treatment of Prostate Cancer — NCT03553602.
• Registry record last updated 2026-01-29; status last verified 2026-01.
• Results first posted 2026-01-29.
• 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

NCT03553602 is a terminated phase I/II, single-group study of salvage HDR brachytherapy, EBRT, and STAD for node-positive locally recurrent prostate cancer after prior definitive radiotherapy. Enrollment was 3. The record identifies genitourinary toxicity as the primary outcome, defined as acute radiation-related toxicity of grade 3 or higher using CTCAE version 4.03, with a 24-month timeframe. Two participants completed the month 24 assessment, but the primary endpoint count is not reported in the registry record.

The safety entry lists 0 of 3 participants affected by serious adverse events, 0 of 3 affected by other adverse events, and 1 death. The death’s cause and relationship to treatment are not reported. No analyses are listed, and the gastrointestinal toxicity result and cancer-control result are not reported. The reason for termination, analysis methods, and missing-data handling are also not reported in the registry record.