Trial of Mitomycin C During Nephroureterectomy for Urothelial Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial of Mitomycin C During Nephroureterectomy for Urothelial Carcinoma (NCT03658304), a na phase 2 study. The primary outcome is Bladder Tumor Recurrence Rate.

2. Clinical Question

In general, a single-group endpoint can describe how often an event was observed among the participants who received the intervention. Without a comparator, that description alone cannot establish how the event rate would differ under another treatment strategy or under a different timing of administration. The one-year recurrence result itself is not reported in the registry record, so even the descriptive event rate cannot be assessed from the posted results.

3. Trial Design

This was a phase II, single-group study sponsored by the University of Florida. The registry lists 29 participants as enrolled, with urothelial carcinoma as the condition. The intervention was mitomycin C, described in the study summary as an intraoperative intravesical instillation during nephroureterectomy. The record gives a start date of 2018-12-05, a primary completion date of 2021-11-10, and a status of completed.

Allocation is recorded as not applicable, masking as none, and the study model as single group. These design features mean the registry does not describe randomized assignment, masking, or a concurrent control arm. The outcome is therefore intended as a description of recurrence in the treated study group, rather than a direct randomized comparison between treatment strategies. A separate comparison group or an external benchmark is not reported in the registry record.

The primary outcome was the one-year bladder tumor recurrence rate, expressed as the percentage of subjects with biopsy-confirmed recurrence after nephroureterectomy. The outcome population description states that all 29 enrolled subjects had reached the one-year post-surgery timepoint. The record also lists time to bladder tumor recurrence and the percentage with recurrence at 3 years post-operatively as secondary outcomes, but does not report their observed results.

The study summary says the research addressed whether the timing of intravesical mitomycin C may matter for bladder recurrence. However, the listed design is single group, and no different-timing arm is described. The registry record does not report further design details, such as eligibility criteria, the mitomycin C dose, the planned follow-up schedule beyond the listed outcome timeframes, or a statistical analysis plan. The absence of these details limits how fully the study procedures can be reconstructed.

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: all 29 subjects enrolled have reached the 1 year post-surgery timepoint.

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 Bladder Tumor Recurrence Rate, measured over 1 year.

The primary endpoint is the bladder tumor recurrence rate at 1 year, measured as the percentage of subjects with urothelial carcinoma in the bladder confirmed by bladder biopsy following nephroureterectomy. The registry describes all 29 enrolled subjects as having reached the one-year post-surgery timepoint. However, it does not report the number with recurrence or the resulting percentage in the registry record.

This endpoint is a binary event outcome at a defined timeframe: each participant is classified according to whether a qualifying recurrence was observed within the endpoint definition. In general, binary outcomes can be summarized as the proportion experiencing the event, with the denominator and event count needed to interpret that proportion. Biopsy confirmation gives the endpoint a specified diagnostic basis, rather than relying only on symptoms or an unspecified clinical judgment. The record does not give further details about biopsy timing or adjudication.

A fixed-time recurrence proportion describes the frequency of recurrence by that timepoint, but does not by itself describe when recurrence occurred. The listed secondary outcome, time to bladder tumor recurrence, addresses timing as a separate question. The one-year endpoint is relevant to the study’s stated focus on bladder recurrence after surgery, but the absent event count means the posted results do not support a numerical estimate of that frequency or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: a participant either had a biopsy-confirmed bladder recurrence within the one-year endpoint definition or did not. In general, a binary outcome is summarized by counting events and dividing by the relevant number of participants assessed. For a recurrence rate expressed as a percentage, both the event count and the analysis denominator are needed to identify the estimate. The registry states that all 29 enrolled participants reached the one-year timepoint, but it does not report the event count or a calculated percentage. No recurrence estimate can therefore be reconstructed from the posted results.

In general, uncertainty around a binary proportion can be expressed using a confidence interval. It communicates how much statistical uncertainty remains about the underlying event frequency, given the observed data and the chosen method. The interval is not a guarantee that the true value lies within its bounds, and it does not resolve limitations such as a single-group design or incomplete outcome reporting. The registry record does not report a confidence interval, a standard error, or another uncertainty measure for the primary endpoint.

The design also governs which statistical questions can be answered. This study is listed as single group, with allocation not applicable and no masking. In general, an intervention-versus-comparator analysis requires outcome data for both groups and a defined comparison. A single-group proportion can describe the observed group, but it cannot, on its own, estimate a randomized contrast or separate the intervention’s association from other factors. The registry does not report a concurrent control group or a prespecified comparison value.

The record includes a planning illustration based on an observed effect, with two-sided significance level 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 a planning exercise, not a report of the study’s original design rationale or observed treatment effect. The record does not report the trial’s own sample-size justification. The illustration’s hypothetical two-arm allocation should not be mistaken for the actual single-group design, and planning quantities are not observed power or evidence that an effect was found.

In general, sample-size calculations depend on assumptions about the effect to detect, variability or event frequency, significance level, allocation, and statistical method. Changing those assumptions changes the planning result. A calculation based on an observed effect is especially dependent on that effect estimate, and the registry record does not report the primary recurrence estimate needed to evaluate it. No additional planning values or calculation outputs are reported in the record. Accordingly, the illustration should be read as a hypothetical planning analysis, not as a description of how many participants the trial enrolled or why that enrollment was chosen.

The registry lists time to bladder tumor recurrence as a secondary outcome. In general, time-to-event methods use both whether an event occurred and the time until the event, and can account for participants whose event time is not observed during follow-up through censoring. Their interpretation depends on adequate follow-up and clear handling of censoring. The record does not report a time-to-event estimate, an analysis method, or details about censoring. It also does not provide the result for recurrence at 3 years post-operatively.

The outcome definition specifies biopsy confirmation, which clarifies what counts as an event. In general, endpoint definitions should also be considered alongside the observation window, the method of assessment, and the population included in analysis. The registry describes the primary endpoint timeframe as 1 year and says all 29 enrolled subjects had reached that timepoint. It does not report whether all had evaluable biopsy or recurrence-status data, how missing outcome information was handled, or whether any participants were excluded from an analysis.

The record reports no analysis results for the primary or secondary outcomes. It does not describe a statistical analysis plan, a model for adjustment, a method for calculating uncertainty, or a prespecified hypothesis test. These omissions prevent assessment of whether the analysis followed a planned procedure, whether any adjustment was made, or how any reported estimate would have been generated. General statistical concepts can clarify what such methods would mean, but they cannot substitute for the unreported analyses or outcomes.

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("Mitomycin C")
n      <- c(29)
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  Mitomycin C  29  12  41.4  23.5  61.1  25.5  59.3  25.5  59.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary outcomes: one-year bladder tumor recurrence rate, time to bladder tumor recurrence, and the percentage of subjects with recurrence 3 years post-operatively. Their results are not reported in the registry record. The record also does not describe a multiplicity strategy, such as prioritizing tests, adjusting significance thresholds, or distinguishing confirmatory from exploratory analyses.

In general, multiplicity arises when several outcomes or statistical tests are considered. The more opportunities there are to identify a nominally notable result, the more important it is to understand whether analyses were prespecified and how the overall chance of false-positive findings was addressed. This general concern cannot be resolved for this study because the statistical plan and outcome analyses are not reported. No claims about the number of tests actually conducted should be inferred from the list of outcomes.

The primary outcome population description states that all 29 enrolled participants reached the one-year post-surgery timepoint. This indicates that the timepoint was reached, but does not establish that complete recurrence-status data were available for every participant or identify the denominator used for an analysis. The record does not report missing outcome data, exclusions, imputation, or sensitivity analyses. It also does not name an analysis population, such as an intention-to-treat or per-protocol population.

In general, missing data can affect an event proportion if participants without an observed outcome are handled differently from participants with known outcomes. Transparent reporting would identify the number assessed, the number with missing status, and the method used to address missingness. Those details are not reported in the registry record. As a result, the stated one-year follow-up status should not be treated as a substitute for a reported analysis denominator or a complete account of outcome data.

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: fever (3.4%).

The registry lists 1 participant affected by a serious adverse event among 29 at risk. It lists 27 participants affected by other adverse events among 29 at risk and records 4 deaths. The top serious adverse event term is Fever, listed as 3.4%. These figures describe what the registry reports for the study group; they are not comparative risks against a control group.

In general, an adverse-event count indicates that an event was recorded during the reporting period, but a count alone does not show that the study intervention caused it. The registry record does not report causal attribution for the serious events, other events, or deaths. It also does not provide event timing, duration, severity details beyond the serious-event classification, or participant-level information. The fever percentage should be read as the value recorded for that serious-event term, not as evidence about causation.

Because the study is single group, the safety figures do not quantify how event frequency differed from another treatment or from no treatment. The counts also do not describe whether events overlapped within participants. The record therefore supports a limited descriptive reading of the listed safety information, not a comparative safety conclusion.

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

The registry record establishes that a completed phase II, single-group study enrolled 29 participants and evaluated intraoperative intravesical mitomycin C during nephroureterectomy for upper urinary tract urothelial carcinoma. Its primary outcome was biopsy-confirmed bladder tumor recurrence at 1 year. The outcome population description says all 29 enrolled participants reached that timepoint.

What the record does not establish is the observed one-year recurrence rate. The recurrence count, percentage, and uncertainty interval are not reported in the registry record. The listed secondary outcome results are also absent. Without those results, there is no numerical basis for describing the frequency or timing of recurrence in the study group, or the precision of an estimate.

Even if a single-group recurrence proportion were available, in general it would describe the study participants rather than provide a direct estimate of what would happen under a different strategy. The registry describes no comparator group and no separate arm assigned to a different timing of administration. Therefore, the design cannot directly quantify a relative effect between timing strategies or attribute an observed difference to mitomycin C. The study summary identifies timing as a motivating question, but the listed design does not provide a concurrent timing comparison.

The safety record provides counts of serious adverse events, other adverse events, and deaths, along with a serious-event term and percentage. Those entries are descriptive and do not establish whether the intervention caused any event. The record does not provide a comparator that would support relative safety estimates.

In general, a registry entry can document the planned question and selected study characteristics without providing enough outcome information to judge an observed effect. Here, the intervention, endpoint, enrollment, follow-up milestone, and safety counts are reported, while the central recurrence result is not. No medical or treatment conclusion follows from the unavailable outcome estimate, and the posted information does not establish benefit, lack of benefit, or comparative safety.

14. Why This Trial Matters Statistically

This trial illustrates the difference between defining an endpoint and reporting its result. The registry gives a clear primary outcome concept: the percentage of subjects with bladder recurrence confirmed by biopsy at 1 year after nephroureterectomy. It also states that all 29 enrolled subjects had reached the one-year timepoint. But the recurrence count and percentage are not reported in the registry record. Without them, the endpoint cannot be interpreted quantitatively.

The design makes this distinction especially important. A single-group study can provide a descriptive account of outcomes among participants receiving the intervention. In general, it does not furnish the same comparative evidence as a design with a concurrent control group. The summary presents timing as the motivating issue, while the listed design has no separate group receiving mitomycin C at another time. Thus the question of whether timing changes recurrence cannot be directly separated from other influences using the listed design alone.

Statistical precision is also central. In general, an estimate needs an uncertainty measure to show how much information the data provide about plausible event frequencies. Neither the primary estimate nor its precision measure appears in the registry record. Enrollment and reaching a follow-up timepoint are not substitutes for an outcome estimate; they describe participation and observation status, not the observed recurrence frequency.

The planning illustration provides a separate educational point: sample-size calculations depend on stated assumptions and should not be mistaken for the trial’s actual design or evidence of an observed effect. The registry’s planning assumptions describe a hypothetical two-arm calculation, whereas the trial itself is listed as single group. Keeping planning, design, and observed results distinct is necessary for sound interpretation.

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 consequential limitation in the registry record is that the primary recurrence result is not reported. Although the endpoint is defined and all 29 enrolled participants are described as having reached the one-year timepoint, the event count, percentage, and uncertainty measure are absent. The registry also does not report results for either listed secondary outcome.

The single-group design limits comparative interpretation. No concurrent comparator or different-timing group is described, so the study record does not support a direct estimate of the relative effect of intraoperative administration versus another strategy. The registry identifies timing as a motivation, but the design details do not show a direct comparison of timing approaches.

Additional details needed to assess conduct and analysis are not reported in the registry record. These include eligibility criteria, dose and administration specifics, the statistical analysis plan, analysis population, treatment of missing outcome data, and methods for estimating uncertainty. The record says all participants reached the one-year timepoint, but does not state whether outcome status was available for all of them or what denominator an analysis would have used.

Safety interpretation is limited to the recorded counts and the listed serious-event term. Causal attribution, event timing, participant-level overlap, and a comparator safety profile are not reported. The study’s completed status does not fill these reporting gaps. These limitations concern what can be concluded from the registry record; they do not establish that additional information is unavailable elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Trial of Mitomycin C During Nephroureterectomy for Urothelial Carcinoma — NCT03658304.
• Registry record last updated 2024-11-05; status last verified 2024-11.
• Results first posted 2022-11-02.
• 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

The registry describes NCT03658304, a phase II, single-group study sponsored by the University of Florida. It enrolled 29 participants with urothelial carcinoma and evaluated mitomycin C administered intravesically during nephroureterectomy. The record lists no masking and no allocation to separate study arms. The study status is completed; the listed start date is 2018-12-05 and primary completion date is 2021-11-10.

The primary outcome was the percentage of subjects with biopsy-confirmed bladder tumor recurrence at 1 year. The record states that all 29 enrolled subjects had reached that timepoint, but does not report the recurrence result. Secondary outcomes were time to recurrence and recurrence percentage at 3 years post-operatively; their results are not reported in the registry record.

Safety entries include 1 participant with a serious adverse event among 29 at risk, 27 with other adverse events among 29 at risk, 4 deaths, and Fever listed as the top serious adverse event term at 3.4%. These are descriptive entries and do not establish causation or a comparative safety effect.