Ultrasound-Guided Implant Radiation Therapy in Treating Patients With Locally Recurrent Prostate Cancer Previously Treated With External-Beam Radiation Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ultrasound-Guided Implant Radiation Therapy in Treating Patients With Locally Recurrent Prostate Cancer Previously Treated With External-Beam Radiation Therapy (NCT00450411), a na phase 2 study. The primary outcome is Number of Patients With Late Treatment-related Gastrointestinal (GI) and Genitourinary (GU) Adverse Events (AE).

2. Clinical Question

The study focuses on safety and treatment experience in a specific clinical setting: locally recurrent prostate cancer after prior external-beam radiation therapy. The primary endpoint counts participants with late treatment-related gastrointestinal and genitourinary adverse events. The registry describes adverse-event severity using CTCAE v3.0, which grades events from mild through death related to an adverse event.

The registry also lists outcomes concerning acute adverse events, survival, disease failure, and biochemical failure. These are additional questions, not alternative versions of the primary endpoint. The record names these outcomes but does not report their results in the information available for this analysis.

Because the study is single-group, it can describe outcomes among treated participants but does not provide a like-for-like control group for estimating what would have happened without this treatment. The registry record does not report a comparative treatment effect.

3. Trial Design

This is a prospective phase II trial registered as completed. It evaluates prostate brachytherapy for locally recurrent prostate adenocarcinoma following external-beam radiation therapy. The study began in 2007-05, and its primary completion is recorded as 2016-06. The registered enrollment is 100; that figure is not the number reported as contributing to the primary endpoint.

The trial is listed as a single-group study with allocation not applicable and no masking. The Brachytherapy group received prostate brachytherapy using either 125-iodine or 103-palladium. No randomized or concurrent control group is described. The two radioactive materials are treatment options within the intervention description, not separate comparison arms in the registry record.

The primary endpoint concerns the number of participants with late treatment-related gastrointestinal and genitourinary adverse events. The specified assessment period is between 271 days and 730 days from implantation. The population defined for that endpoint is eligible patients who received protocol treatment and had at least 23 months of follow-up from implantation. This eligibility description should not be confused with the registered enrollment or with the number of participants represented in the adverse-event summaries.

Other registered outcomes address acute gastrointestinal and genitourinary adverse events, overall survival, disease-free survival, disease-specific survival, local failure, distant failure, and biochemical failure. The registry record identifies these outcome topics but does not provide their numerical results in the registry record analyzed. Details of the protocol beyond these design features, including a more extensive statistical plan, 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: Eligible patients who received protocol treatment with at least 23 months follow-up from the date of implantation

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: Eligible patients who received protocol treatment

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Late Treatment-related Gastrointestinal (GI) and Genitourinary (GU) Adverse Events (AE), measured over Between 271 days and 730 days from date of implantation.

The primary endpoint is the number of participants with late treatment-related gastrointestinal and genitourinary adverse events. It is assessed between 271 days and 730 days from implantation, among eligible patients who received protocol treatment and had at least 23 months of follow-up from that date. The registry describes adverse-event severity using CTCAE v3.0: grades range from mild to death related to an adverse event, with intermediate categories for moderate, severe, and life-threatening or disabling events.

A participant count is a direct way to describe how many people in the defined endpoint population experienced an event. It is distinct from an event count: one participant might experience more than one event, but the primary endpoint is explicitly defined in terms of participants. The registry record does not report the primary endpoint count or a denominator for that endpoint, so the result and its precision cannot be assessed from this record.

General: A specified follow-up window helps define which events belong to an endpoint and when they are assessed. A count is most informative when read alongside the endpoint population, follow-up period, and the rules for attributing an event to treatment. The registry gives the follow-up window and population description, but further operational details, such as how treatment-relatedness was determined, are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the study as a prospective phase II trial with a single-group model, allocation not applicable, and no masking. Those design features set limits on the statistical interpretation. The study can describe outcomes in the treated group, but the registry does not describe a concurrent control group or randomized comparison. The record does not report a detailed statistical analysis plan, so the methods used for analyses beyond the outcome definitions are not reported in the registry record.

What does a participant count represent?

The primary endpoint is a count of participants with late treatment-related gastrointestinal and genitourinary adverse events. This is not necessarily the same as counting all event occurrences. If an individual experiences more than one event, a participant-based endpoint still concerns whether that participant is represented as having an event under the endpoint rules. The registry identifies the unit as participants, but does not report the primary endpoint count or the denominator used for its result.

General: Counts are useful for making the number of affected people concrete. To understand how common an event was in the population under study, a count is usually read with a clearly defined denominator. A proportion can describe the share of the population affected, but that proportion cannot be established when the relevant outcome count or endpoint denominator is not reported. The separate adverse-event summary includes its own at-risk and affected figures; those values should not be assumed to supply the missing denominator for the primary endpoint.

Why does the follow-up window matter?

The endpoint covers events between 271 days and 730 days from implantation. This time window defines what counts as a late event for the primary outcome. The registry separately names acute treatment-related adverse events as a secondary outcome, reinforcing that timing distinguishes the outcome categories. The record describes the primary endpoint population as eligible patients who received protocol treatment and had at least 23 months of follow-up from implantation. It does not report how participants with shorter follow-up or incomplete assessments were handled in the analysis.

General: Follow-up definitions help ensure that outcome counts refer to comparable observation periods. If participants are observed for different lengths of time, they may have different opportunities for an event to be detected. Time-to-event methods can account for event timing and follow-up duration, but the registry record does not state which methods were used for the primary endpoint.

How should severity grades be read?

The registry says adverse events are graded using CTCAE v3.0. Its descriptions range from grade 1, mild, to grade 5, death related to an adverse event; the intermediate categories cover moderate, severe, and life-threatening or disabling events. These grades characterize severity. A severity grade is not itself a measure of treatment effect, and it does not establish that treatment caused an event. The primary endpoint description also specifies treatment-related events, but the criteria for assigning that relationship are not reported in the registry record.

What can be learned from the design?

In a single-group study, an observed event count describes what was recorded among participants receiving the study intervention. Without a concurrent control group, the study design does not directly estimate how outcomes would differ under another treatment or no study treatment. General: A comparison requires an estimate for each comparison condition and a method for accounting for uncertainty in their difference. When treatment allocation is not randomized, differences between groups may also reflect differences in who received each treatment. Here, no like-for-like control comparison is described.

How should planning illustrations be understood?

The sample-size planning illustrations are explicitly based on the observed effect and are not the trial's own design. Their stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event outcomes, the illustrations give the total number of events using the Schoenfeld approach; other illustrations give participants per arm.

These assumptions describe hypothetical planning exercises rather than the single-group trial design. They should not be read as observed power or as evidence that the completed trial was planned around those assumptions. General: A sample-size calculation estimates the amount of information a hypothetical study might need under specified assumptions. It does not measure the probability that a completed study's result is correct. The registry record does not report the trial's own sample-size justification, so that rationale is not reported in the registry record.

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("Brachytherapy")
n      <- c(87)
events <- c(12)
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  Brachytherapy  87  12  13.8  7.3  22.9  8.1  22.6  8.1  22.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary adverse-event outcome and additional outcomes concerning acute adverse events, survival, disease failure, and biochemical failure. The record does not report how the analysis handled the possibility of examining multiple outcomes. In particular, any adjustment for multiple statistical tests, prespecified hierarchy among outcomes, or distinction between confirmatory and exploratory analyses is not reported in the registry record.

The primary endpoint population is described as eligible patients who received protocol treatment and had at least 23 months of follow-up from implantation. However, the registry does not report the primary endpoint's analyzed participant count, its outcome denominator, or how missing assessments were handled. No imputation approach, complete-case rule, or sensitivity analysis for missing data is reported in the registry record.

The registry's description of an endpoint population does not establish that every eligible participant contributed complete data. The separate adverse-event summaries have their own at-risk and affected figures, and the record does not explain whether or how those populations correspond to the primary endpoint population. Results for the listed secondary outcomes and their analysis populations are also not reported in the registry record.

General: Multiplicity matters because examining multiple outcomes can increase the chance of finding an apparently notable result by chance. Missing-data methods matter because estimates can be affected when the availability of outcome information differs across participants. Without the analysis plan and reporting of populations, these issues cannot be evaluated for the primary endpoint or the listed secondary outcomes.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diarrhea (1.1%), edema limbs (1.1%), prostate infection [with unknown anc] (1.1%), cystitis (1.1%), hemorrhage urinary tract (1.1%).

The serious adverse-event summary lists 92 participants at risk and 8 affected in the Brachytherapy group. It also lists six serious-event terms, each with a displayed value of 1.1%: diarrhea, edema limbs, prostate infection with unknown ANC, cystitis, hemorrhage urinary tract, and urethral obstruction. These term-specific entries are not a substitute for the primary endpoint result, which is not reported in the registry record.

The separate summary for other adverse events lists 92 at risk and 89 affected. Serious and other adverse-event summaries are distinct categories in the record and should not be combined. The record does not explain how individual participants may appear across terms or categories, so the term entries should not be added to produce a total.

These figures describe recorded events in the treated group. They do not, by themselves, show how the event experience compares with another treatment or establish that treatment caused an event. The registry's primary endpoint is specifically late treatment-related gastrointestinal and genitourinary adverse events assessed between 271 days and 730 days after implantation, and its result is not reported in the registry record.

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

The record establishes that the trial evaluated ultrasound-guided prostate brachytherapy in patients with locally recurrent prostate cancer after external-beam radiation therapy. It specifies a primary safety outcome based on participants with late treatment-related gastrointestinal and genitourinary adverse events, assessed between 271 days and 730 days after implantation. It also supplies selected serious and other adverse-event summaries for the Brachytherapy group.

However, the primary endpoint result is not reported in the registry record. The serious and other adverse-event figures do not fill that gap, because they are separate summaries and the record does not establish that their definitions, populations, or follow-up windows match the primary endpoint. The registry also lists survival and disease-failure outcomes without reporting their numerical results in the registry record analyzed.

The single-group design matters. The observed summaries can describe events among treated participants, but there is no concurrent control group for a like-for-like comparison. Consequently, the registry information does not estimate a comparative benefit or harm, and it cannot establish what would have occurred under another treatment or without the study intervention.

General: Statistical uncertainty is part of interpreting an estimate. A count without a reported endpoint denominator, and without an interval or other precision measure, offers limited information about how precisely the underlying event frequency is estimated. Likewise, an event recorded after treatment is not automatically caused by treatment; attribution requires a defined approach, and a control comparison can help assess differences in event experience. The registry record does not report enough detail to make those assessments for the primary endpoint.

The appropriate reading is therefore narrow: the record describes the design, planned outcome topics, endpoint timing, and selected adverse-event summaries. It does not provide a complete numerical answer to the primary safety question or support a claim of comparative treatment effect.

14. Why This Trial Matters Statistically

This trial raises several important statistical issues for clinical research. First, the population and timing used to define an endpoint are essential to interpreting a result. The primary outcome concerns eligible, treated participants with at least 23 months of follow-up and focuses on late adverse events between 271 days and 730 days from implantation. Those criteria define the intended setting for the endpoint, but the result and its denominator are not reported in the registry record.

Second, the study's single-group design distinguishes descriptive safety reporting from comparative evidence. Counts in a treated group can document what was observed, but without a concurrent control group they cannot establish how outcomes differ from an alternative. This is especially relevant when interpreting events in a population with prior radiation therapy and recurrent disease: the registry information does not separate treatment-associated events from other possible causes through a comparison.

Third, endpoint reporting needs enough detail to connect an outcome definition to its estimate. The registry describes CTCAE v3.0 severity grading and names the primary endpoint as a participant count, yet the primary endpoint result is not reported in the registry record. The adverse-event summaries offer selected information, but they do not replace a reported result for the defined primary endpoint.

Finally, statistical transparency includes analysis populations, missing-data handling, multiplicity, and the rationale for study size. The registry record does not report these details. General: These elements help readers judge whether estimates are precise, whether outcomes were analyzed as planned, and how much confidence to place in findings. Their absence limits assessment even when the clinical question and endpoint timing are clearly described.

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 main trial-specific limitation for interpreting the primary outcome is that its result is not reported in the registry record. The record identifies the endpoint population and assessment period, but it does not report the primary endpoint count, denominator, or a precision estimate. The serious and other adverse-event summaries are separate and do not establish the missing primary endpoint result.

The single-group design provides no like-for-like control comparison. Therefore, the reported adverse-event summaries cannot establish how event experience differs from another treatment or from no study intervention. The record also does not report the criteria used to determine whether an event was treatment-related, beyond defining the endpoint in those terms.

The registry describes a primary endpoint population requiring at least 23 months of follow-up, but does not report the number contributing to that endpoint or how incomplete follow-up and missing assessments were handled. The analysis populations for the listed secondary outcomes are not reported in the registry record.

Statistical details that would support fuller evaluation, including the trial's own sample-size justification, analysis methods, multiplicity approach, and missing-data procedures, are not reported in the registry record. The sample-size illustrations are planning exercises based on the observed effect, not evidence of observed power or a description of the trial's own design.

The registered enrollment is not identified as the number analyzed for the primary endpoint. The record's other adverse-event figures should therefore be read only within their stated summary categories, not treated as a substitute for a complete endpoint analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ultrasound-Guided Implant Radiation Therapy in Treating Patients With Locally Recurrent Prostate Cancer Previously Treated With External-Beam Radiation Therapy — NCT00450411.
• Registry record last updated 2022-06-21; status last verified 2022-05.
• Results first posted 2017-11-07.
• 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

NCT00450411 is a completed prospective phase II, single-group study of transperineal ultrasound-guided prostate brachytherapy for locally recurrent prostate adenocarcinoma following external-beam radiation therapy. The intervention used either 125-iodine or 103-palladium. The registered enrollment is 100, and the primary completion is recorded as 2016-06.

The primary endpoint counts participants with late treatment-related gastrointestinal and genitourinary adverse events between 271 days and 730 days after implantation. The defined endpoint population is eligible treated patients with at least 23 months of follow-up. The primary endpoint result is not reported in the registry record.

The record lists serious-event figures of 92 at risk and 8 affected, and other-event figures of 92 at risk and 89 affected. It also names secondary outcomes concerning acute adverse events, survival, and disease failure, but their numerical results are not reported in the registry record.