Enzalutamide for Bladder Cancer Chemoprevention: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Enzalutamide for Bladder Cancer Chemoprevention (NCT02605863), a non-randomized phase 2 study. The primary outcome is Number of Participants With Recurrent Disease.

2. Clinical Question

The clinical question is therefore about whether enzalutamide could be associated with fewer recurrences in this population, but the posted information does not permit an effect estimate. The study is listed as terminated. The reason for termination, the intended comparison, and details of the planned analysis are not reported in the registry record. In particular, the two risk categories should not be interpreted as treatment and control groups: both descriptions name the same intervention, while the record identifies no participants in the high-risk group. The available information establishes the study’s topic and registered endpoint, but not whether recurrence occurred or whether the intervention changed recurrence risk.

3. Trial Design

The registry identifies NCT02605863 as a Phase 2, parallel-design study of enzalutamide for bladder cancer chemoprevention. Allocation is listed as non-randomized, and masking is listed as none. Enrollment is 1. The study began in 2016-01, has a primary completion date of 2018-02, and its status is terminated. The reason for termination is not reported in the registry record.

The two listed groups are Intermediate Risk NMIBC and High Risk NMIBC. Both descriptions specify enzalutamide 160mg by mouth daily for 12 months. The primary outcome description explicitly states that there were no participants enrolled in the high-risk arm. The record does not describe a separate control arm, and the groups are risk categories rather than randomized alternatives. Because allocation was non-randomized and the groups differ by risk classification, they cannot be treated as a like-for-like comparison of enzalutamide against no enzalutamide.

The record does not give further information about eligibility criteria, recruitment procedures, adherence, treatment discontinuation, or follow-up beyond the primary outcome timeframe of 1 year. It also does not report a protocol-level sample-size justification or the detailed statistical analysis plan. These absences matter when interpreting a very small enrollment: the recorded enrollment alone does not establish why recruitment stopped, what analyses were intended, or whether follow-up was complete. The registry information describes a study design and intervention, but it does not contain an outcome analysis that can estimate a treatment effect.

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

Analysis population for the primary outcome, as defined in the registry: There were no participants enrolled in the high risk arm.

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: no participants were enrolled in the high risk NMIBC arm

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Recurrent Disease, measured over 1 year.

The registered primary endpoint is the number of participants with recurrent disease, measured at 1 year. It is a participant-level event count: the outcome concerns whether a participant had recurrence during the assessment period, rather than the number of separate recurrence episodes. The registry names bladder cystoscopy, urine cytology, and a pathology report as the basis for assessing recurrence.

Recurrence is relevant to the study’s stated chemoprevention question because the aim was to examine prevention of bladder cancer recurrences in patients with non-muscle invasive bladder cancer. A clearly defined clinical event can be easier to interpret than a surrogate measurement when the question concerns whether disease returns. However, the registry does not provide an observed count of participants with recurrent disease, a denominator for the analyzed primary endpoint, or a comparison estimate. It therefore does not show how often recurrence occurred in the enrolled population.

The endpoint description also states that no participants were enrolled in the high-risk arm. That means the registered outcome cannot inform recurrence in that risk group. Details such as the precise recurrence definition, assessment schedule within the 1-year timeframe, adjudication procedures, and handling of missing assessments are not reported in the registry record. Without those details and the outcome result, the endpoint’s clinical meaning can be described, but its observed frequency and precision cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome was registered?

The primary outcome is the number of participants with recurrent disease at 1 year. This is a binary participant-level outcome represented as a count: each participant either meets the recurrence definition during the specified assessment period or does not. The registry names bladder cystoscopy, urine cytology, and a pathology report as assessment sources. It does not provide the observed count or an analysis of that outcome.

For a binary outcome, an analysis commonly describes the event count alongside the number of participants assessed. A proportion can then communicate how frequent the event was in the analyzed population. A comparison may estimate a difference or another relative measure between appropriately defined groups. These are general statistical approaches, not results reported for this study. No event proportion or comparative estimate can be reconstructed from the registry information because the primary outcome result and analyzed denominator are not reported.

Why does the design affect interpretation?

Random allocation, when used and implemented appropriately, helps make treatment groups comparable on average with respect to measured and unmeasured baseline characteristics. This study is listed as non-randomized. Its two listed arms represent intermediate-risk and high-risk disease categories, and both descriptions specify enzalutamide. They are therefore not randomized treatment and control groups. Differences between risk categories would not, by themselves, isolate the effect of enzalutamide.

The record also states that the high-risk arm had no participants. Consequently, that group supplies no enrolled participant outcomes for a comparison. The fact that the study is described as parallel does not create a valid comparator when one risk group is empty and the listed groups are not treatment alternatives. No adjusted or unadjusted analysis is reported in the registry record.

What does a confidence interval contribute?

In general, a confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval spanning a broad range of effects may leave substantial uncertainty. Confidence intervals do not correct for bias from non-randomized allocation, incomplete outcome ascertainment, or a poorly defined comparison. They also cannot be interpreted without an estimate and an analysis population.

No confidence interval or primary effect estimate is reported in the registry record. With the outcome result absent, there is no posted estimate whose precision can be assessed. The low enrollment also means that any estimate based on the enrolled population would need particularly careful attention to uncertainty, but no inferential result is available to quantify it.

How should sample-size illustrations be read?

The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. These are assumptions for planning calculations, not evidence that the actual trial was designed with those assumptions. The registry does not report its own sample-size justification.

A planning sample size estimates how many participants per arm might be needed under specified assumptions. It is not a count of participants actually analyzed, and a calculation based on a hypothetical effect does not establish that an effect was observed. Such calculations are not observed power. Their relevance depends on the validity of the assumed effect and design, and the registry does not provide an observed primary effect to interpret. The record describes binary outcomes as participants with an event, so the applicable planning convention is participants per arm rather than a total event count for a time-to-event analysis.

Why can over-dispersion matter in other settings?

As a general statistical concept, over-dispersion occurs when observed variability is greater than a model assumes. It can make standard errors too small and confidence intervals too narrow if the model does not allow for that extra variability. The registered primary outcome is a binary participant-level event count, and no outcome model or analysis is reported. The registry does not identify over-dispersion as an issue in this study; the concept is relevant as general background, not as a finding about this trial.

More broadly, valid interpretation depends on transparent reporting of the outcome definition, analyzed population, missing observations, comparison, and analysis method. The registry names the endpoint and its timeframe but does not report the primary outcome result, analysis population, missing-data handling, or inferential method. Those omissions prevent independent assessment of an effect estimate, its uncertainty, and the assumptions behind it.

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("Intermediate Risk NMIBC")
n      <- c(1)
events <- c(1)
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  Intermediate Risk NMIBC  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 1 outcome measure and no analysis results. A single listed primary outcome does not establish that no other outcomes or analyses were planned or conducted; the record does not give enough information to determine the full analysis family. A multiplicity adjustment or strategy for handling multiple comparisons is not reported in the registry record. Without an analysis plan and reported tests, it is not possible to assess whether multiplicity arose or how it was addressed.

Missing-data handling is also not reported. The registry does not state how participants with absent cystoscopy, urine cytology, or pathology information would be classified, whether incomplete follow-up was expected, or how missing primary outcomes would be handled. These choices matter because excluding participants without complete assessment can affect the event estimate if missingness is related to recurrence or treatment experience. That is a general concern, not evidence that missing outcomes occurred in this study.

The analysis population is not reported. The record does not state whether the primary endpoint was to be analyzed among all enrolled participants, those who began treatment, those who completed treatment, or another defined population. With enrollment of 1 and no participants in the high-risk arm, the absence of an analysis population and endpoint result leaves no basis for reconstructing who contributed to a primary estimate. The reason for termination and the disposition of participants are not reported in the registry record. These gaps limit assessment of both the analysis and the possibility of selective reporting.

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 non-serious adverse event terms

The registry reports serious adverse events by group. In the intermediate-risk group, 1 participant was listed as at risk, 0 as affected by a serious event, and 0 deaths were recorded. The high-risk group had 0 listed as at risk, 0 affected by a serious event, and 0 deaths. Because the high-risk group had no participants, its zero event figures do not provide information about the frequency of events in treated high-risk participants.

For other adverse events, the intermediate-risk group lists 1 at risk and 1 affected; the high-risk group lists 0 at risk and 0 affected. The registry does not provide terms for the reported other event in the information recorded here, and it lists no top serious-event terms. These categories should not be conflated: the figures for other adverse events are separate from the serious-event figures.

Adverse-event counts are descriptive, not a comparison of enzalutamide with a control treatment. With enrollment of 1 and no comparator group, the figures cannot establish a rate difference or characterize uncommon harms. A zero serious-event count in the recorded intermediate-risk group does not show that serious events are impossible, while zero events in a group with no participants provide no safety evidence for that group. The registry does not report further detail on event type, timing, severity beyond the serious classification, or relationship to treatment.

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

The record supports a limited description: a Phase 2, non-randomized, parallel study of enzalutamide was registered for bladder cancer chemoprevention; both listed risk groups were assigned the same described regimen; enrollment was 1; the high-risk group had no participants; and the study is terminated. The primary endpoint was the number of participants with recurrent disease at 1 year, assessed using cystoscopy, urine cytology, and pathology information.

The record does not report the primary recurrence result, a comparison estimate, a confidence interval, or an analysis. It therefore cannot establish whether recurrence occurred among the enrolled participant or whether enzalutamide changed recurrence risk. The absence of an outcome result is not the same as a finding of no recurrence, and it is not evidence that the treatment prevented recurrence. No reason for study termination is reported, so termination should not be interpreted as proof of benefit, lack of benefit, a safety problem, or a feasibility problem.

The study also cannot provide a meaningful comparison between intermediate-risk and high-risk participants. They are risk categories, not randomized treatment groups; both intervention descriptions specify enzalutamide, and the high-risk arm had no participants. Even a reported outcome in the intermediate-risk group would describe a very limited experience rather than establish a causal treatment effect. Non-randomized designs can be affected by differences in participant characteristics and other factors, and this record contains no adjusted comparison to address them.

The adverse-event figures are similarly descriptive and limited. They do not estimate comparative safety, and the absence of serious events in the recorded intermediate-risk group cannot establish safety in a broader population. The figures for the empty high-risk group do not characterize risk for people in that group. Overall, the posted data document the trial’s registration and sparse safety counts, but they do not provide an efficacy result or a reliable estimate of treatment effects.

14. Why This Trial Matters Statistically

This study is statistically instructive because its registered question is clinically understandable while its posted results do not permit an answer. Recurrence at 1 year is a direct event-oriented endpoint for a chemoprevention question. Yet an endpoint definition alone is not an analysis: interpretation also requires observed outcomes, a denominator, a clearly described analysis population, and a comparison suited to the question.

The design illustrates why labels such as parallel study should not be mistaken for evidence of a controlled comparison. Allocation is non-randomized, and the listed groups differ by disease-risk category rather than by intervention. Both descriptions specify enzalutamide, and no participants were enrolled in the high-risk arm. Consequently, there is no reported basis for comparing enzalutamide against no enzalutamide or another treatment. A contrast between risk categories would not isolate the intervention effect.

Enrollment of 1 also highlights the distinction between feasibility information and evidence of effectiveness. A small enrolled population can document that a study was attempted, but it does not by itself establish whether an outcome occurred or how precisely an effect can be estimated. Here, the registry supplies no primary outcome value or analysis result, so neither the direction nor the magnitude of an effect is available. It is not appropriate to substitute planning calculations for observed evidence.

Finally, the terminated status demonstrates the importance of complete reporting. Without the reason for termination, participant disposition, missing-data approach, and planned analysis, readers cannot distinguish among possible explanations for the incomplete record. These are general lessons about interpreting clinical-trial registries: transparent design, outcome, and analysis reporting are necessary for conclusions that are both statistically sound and appropriately limited.

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 limitations are specific to the information recorded for this study. Enrollment is 1, and the primary outcome value is not reported in the registry record. As a result, there is no recurrence count or analyzed denominator from which to describe the observed endpoint. The high-risk arm had no participants, so the registered outcome provides no information about recurrence in that group.

The non-randomized allocation and risk-based arm descriptions prevent a like-for-like treatment comparison. Both groups are described as receiving enzalutamide, and the registry does not identify a separate control group. Any comparison across the risk categories would be difficult to interpret as an intervention effect because risk category is not treatment assignment. No adjusted analysis is reported.

The study is listed as terminated, but the reason is not reported. The record also does not state the participant disposition, whether treatment was started or completed, whether follow-up reached the 1-year endpoint, or whether any outcome observations were missing. Details of eligibility, recurrence adjudication, and the statistical analysis plan are not reported in the registry record. Without these details, it is not possible to assess deviations from the intended design or the handling of incomplete information.

Safety information is sparse and descriptive. The record lists no serious events in the intermediate-risk group and no participants at risk in the high-risk group, but it does not provide event terms for the other adverse event or a comparative safety analysis. These limitations mean that neither recurrence effects nor broader safety conclusions can be drawn from the posted information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Enzalutamide for Bladder Cancer Chemoprevention — NCT02605863.
• Registry record last updated 2018-10-03; status last verified 2018-09.
• Results first posted 2018-05-07.
• 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

NCT02605863 is a Phase 2, non-randomized, parallel study sponsored by the University of Rochester. It concerns enzalutamide for bladder cancer chemoprevention in patients with non-muscle invasive bladder cancer. The record lists enrollment of 1, a start date of 2016-01, primary completion in 2018-02, and terminated status. The reason for termination is not reported in the registry record.

The intermediate-risk and high-risk group descriptions each specify enzalutamide 160mg by mouth daily for 12 months. The record states that no participants were enrolled in the high-risk arm. The primary outcome is the number of participants with recurrent disease at 1 year, assessed by bladder cystoscopy, urine cytology, and pathology report. The primary outcome result and an analysis are not reported. Serious adverse-event figures list 0 affected in the intermediate-risk group and 0 participants at risk in the high-risk group; other adverse-event figures list 1 affected in the intermediate-risk group. The registry does not provide a treatment-effect estimate or a control-group comparison.