A Phase II Trial Evaluating an Organ-conserving Strategy by Radiochemotherapy for Muscle-infiltrative Bladder Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II Trial Evaluating an Organ-conserving Strategy by Radiochemotherapy for Muscle-infiltrative Bladder Cancer (NCT01495676), a randomized na study. The primary outcome is Disease-free Survival.

2. Clinical Question

The study title frames the comparison as an organ-conserving approach for muscle-infiltrative bladder cancer. Its brief summary explains the rationale as evaluating another chemotherapy agent in a radiochemotherapy regimen, with disease-free survival as the main outcome. The trial is titled a Phase II trial, although the registry phase field is listed as NA. Enrollment is recorded as 69, and the study status is terminated. The record does not state why the trial was terminated or whether termination affected the planned comparison.

3. Trial Design

The registry describes a randomized, parallel-group trial with no masking. Participants were assigned to radiotherapy plus cisplatin or to radiotherapy plus cisplatin and gemcitabine. The study title identifies it as a Phase II trial, while the phase entry in the registry is NA. These descriptions should be kept distinct: the title supplies the phase wording, but the registry’s phase field does not give a phase classification.

The registry records enrollment of 69. That total does not by itself establish how many participants were randomized, treated, or included in the primary outcome analysis. The record does not provide those analysis-population details. The safety information separately lists 24 participants at risk in the radiotherapy plus cisplatin group and 45 in the group receiving radiotherapy, cisplatin, and gemcitabine. Those group figures should not be treated as proof of the allocation process or of the primary endpoint denominators.

The listed interventions are radiotherapy plus cisplatin, and radiotherapy plus cisplatin and gemcitabine. Detailed arm descriptions are blank in the registry. Apart from the study summary’s mention of a recommended gemcitabine dose of 25 mg/m² in an earlier phase I study, the record does not describe the treatment schedules, doses used in this trial, treatment duration, or adherence. The earlier study information is background rationale, not a description of what each participant received in this randomized trial.

The study start is recorded as 2011-07-06 and primary completion as 2022-07-25. Its status is terminated. The reason for termination, the timing of that decision, and whether recruitment or follow-up stopped early are not reported in the registry record. The record also does not report the randomization sequence, allocation concealment, or whether any stratification factors were used. Because masking is listed as none, treatment assignment was not masked according to the registry; blinding of outcome assessors is not separately described.

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

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 Disease-free Survival, measured over Two years after the end of the complete therapeutic sequence.

The primary endpoint is titled disease-free survival and is specified at two years after the end of the complete therapeutic sequence. The registry describes time to relapse as beginning on the date of randomization and ending at the first event. Events include local, regional, or distant events, as well as death. For participants without an event, the time is censored at the date of the latest information.

The registry then gives a two-year success definition: participants who have no relapse and are alive at two years are considered successes. This combines information about recurrence and survival at the stated assessment point. A time-to-event definition can make use of follow-up information from participants whose event status is not observed through the full follow-up period, provided censoring is handled appropriately. Censoring means that the event time is known only to exceed the last observed time; it does not mean that an event occurred at that date.

The endpoint is relevant to the stated treatment question because it reflects remaining alive without a recorded relapse after treatment. However, the registry record does not report the number of successes, event counts, follow-up distribution, or an estimated treatment contrast. It also does not specify how the two-year success definition was connected to the primary statistical analysis. Therefore, the endpoint definition can be described, but the comparative disease-free survival result and its precision cannot be assessed from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

Randomization assigns participants to treatment strategies by chance. In general, this reduces systematic differences between groups in factors that may affect outcomes, including factors that are not measured. It supports a comparison of outcomes by assigned group, provided the randomization and subsequent analysis are appropriately conducted. Randomization does not ensure that groups are identical, particularly in a trial with a limited enrollment, and it does not correct problems arising after assignment, such as incomplete outcome follow-up.

The registry identifies the design as randomized and parallel. It does not describe how the random sequence was generated, how assignments were concealed before enrollment, or whether allocation used any stratification. Those details are important for assessing the safeguards against predictable or influenced assignment, but they are not reported in the registry record.

What does an unmasked design mean?

The registry lists masking as none. In an unmasked study, participants and clinical staff may know which strategy was assigned. In general, knowledge of assignment can influence treatment delivery, additional care, reporting of symptoms, or judgments about outcomes. The risk depends on the outcome and on procedures used to assess it. The registry does not say whether disease-free survival events were reviewed by assessors unaware of treatment assignment, or whether any independent adjudication was used. No particular bias can be assumed, but the absence of masking makes those assessment details relevant.

How should the disease-free survival endpoint be understood?

The endpoint is described through both event timing and a two-year success definition. Time begins at randomization, and the first local, regional, or distant event, or death, is the event time. Participants with no event are censored at their latest information date. In general, a time-to-event analysis uses the timing of events as well as the information available for participants whose event has not been observed by the end of follow-up. Censoring is informative only if its handling and assumptions are suitable; the record does not specify the analysis method or its assumptions.

The registry’s success rule classifies participants without relapse who are alive at two years after completion of the therapeutic sequence as successes. The relationship between this binary classification and the stated time-to-relapse description is not further explained. The record does not identify the primary statistical model, the precise analysis time point for participants with incomplete follow-up, or how missing status was handled. Thus the endpoint can be described, but the analysis implementation cannot be reconstructed.

What can the safety counts say?

Serious adverse event counts are listed with numbers at risk and numbers affected. In general, a count of affected participants is not the same as a count of event episodes: one participant may have more than one event. The record does not state whether the reported counts refer to people with at least one serious event, how seriousness was defined, or how events were attributed. The group-specific counts should therefore be read as posted safety summaries, not as a fully specified comparative safety analysis.

The record also gives a list of serious event terms and percentages, without describing their denominator or assigning them to particular treatment groups. Percentages without a clear denominator and analysis population are difficult to interpret. They cannot establish how frequently an event occurred in each randomized group or whether a difference between strategies is statistically distinguishable from chance.

What do the planning illustrations represent?

The record’s sample-size assumptions describe planning illustrations computed from an observed effect, not the trial’s original design. The stated framework uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. In general, such illustrations show the sample size that might be needed under specified assumptions. They are not evidence that the trial was originally planned around those assumptions, and they are not observed power.

The record does not report the original sample-size justification, the effect size assumed at design, or whether the planned enrollment changed. It also does not report an efficacy estimate from which the planning illustrations’ starting effect can be evaluated. The illustration should therefore be interpreted as conditional planning information, not as a confirmation of the trial’s design adequacy or a substitute for a treatment-effect estimate with uncertainty.

Which analysis details remain unknown?

The registry does not report an intention-to-treat or per-protocol population, a primary analysis model, covariate adjustment, confidence intervals, or a strategy for handling missing data. It does not describe interim analyses, stopping rules, or multiplicity control. These omissions prevent a detailed audit of the statistical analysis. General statistical principles can explain why those choices matter, but they cannot establish which methods were used in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists disease-free survival as the primary outcome and identifies overall survival, acute and late toxicities, and the correlation between lymphocyte apoptosis and severity of late toxicities as secondary outcomes. Considering several outcomes can create a multiplicity issue: when many hypotheses are tested, the chance of at least one apparently unusual result can increase. General approaches include prespecifying a hierarchy, adjusting the significance threshold, or treating secondary analyses as exploratory. The registry record does not report whether any multiplicity strategy was planned or used.

The primary result itself is not reported in the registry record. The record also lists zero analyses, so no information is available about the statistical tests, model, confidence intervals, or p-values used for the outcomes. The study’s termination status does not explain whether analysis plans changed or whether analyses were performed but not entered in the registry.

Missing-data handling is also not reported. For the time-to-relapse definition, participants without an event are censored at the date of latest information. In general, censoring differs from treating a participant as event-free indefinitely: it records that event-free status was known only through a particular observation time. The validity of time-to-event estimates can depend on whether the censoring process is adequately handled and on assumptions about the relationship between loss of observation and event risk. The registry does not provide follow-up completeness, reasons for missing assessments, or sensitivity analyses.

Analysis populations are not described. It is therefore not possible to determine whether the primary outcome was assessed among everyone randomized, only those who began treatment, or another defined group. Nor does the record report exclusions or how participants with incomplete follow-up were classified under the two-year success rule. These gaps limit interpretation of both the efficacy endpoint and the safety summaries.

11. 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: gastroenteritis radiation (8.3%), thrombopenia (6.7%), acute kidney injury (4.4%), hematuria (4.4%), renal failure (4.4%).

The registry lists serious adverse events for two groups. In the radiotherapy plus cisplatin group, 9 of 24 participants at risk were affected by serious adverse events. In the radiotherapy plus cisplatin and gemcitabine group, 23 of 45 participants at risk were affected. Death counts are listed as 7 in the first group and 20 in the second. These are posted counts, not adjusted comparisons.

The record’s top serious event terms include gastroenteritis radiation (8.3%), thrombopenia (6.7%), acute kidney injury (4.4%), hematuria (4.4%), renal failure (4.4%), and atrial flutter (4.4%). The registry does not identify the denominator or treatment-group attribution for these percentages. The percentages should not be treated as arm-specific rates or converted into participant counts.

In general, safety summaries require attention to the event definition, duration of observation, population at risk, and whether counts represent participants or event episodes. The registry does not report these details, nor does it specify event attribution or a statistical comparison between arms. The counts therefore describe what is entered in the record, but they do not by themselves establish a comparative safety effect. Death counts should not be assumed to correspond to deaths from a particular cause or to the primary endpoint without further information.

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

The record supports a clear description of the trial question: a randomized comparison of radiotherapy plus cisplatin with the same strategy plus gemcitabine, using disease-free survival as the primary endpoint. It also documents enrollment of 69 and a terminated status. It does not provide the primary outcome counts or a treatment-effect estimate. Consequently, the comparative efficacy result, its direction, and its precision cannot be stated from the registry entries.

This absence should not be read as evidence of no difference, as evidence that the treatments are equivalent, or as proof that the study failed to detect an effect. Those interpretations require results and an analysis, neither of which is reported in the registry record. Similarly, the safety counts should not be treated as a formal test of whether one strategy caused more serious events. Definitions, observation periods, and comparison methods are not posted by the record.

The word “randomized” describes an important design feature, but it does not answer questions about how assignments were generated, whether concealment was adequate, or who was included in analyses. The unmasked designation indicates that masking was not used, but the record does not explain how outcomes were assessed. These details matter when judging the reliability of a result; they cannot be resolved using the available entries.

The study’s terminated status also has a limited interpretation. It means that the registry marks the trial as terminated, but the reason and implications are not reported. It is not possible to tell whether the planned follow-up was completed, whether the outcome was analyzed, or whether termination changed the study’s intended statistical approach.

Overall, the registry is informative about the intervention comparison, endpoint definition, enrollment, status, and selected safety counts. It is not sufficient to determine whether the added gemcitabine strategy changed disease-free survival, how large any change might have been, or how uncertain an estimate would be. Those conclusions would require the outcome results and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its endpoint combines a time-to-event description with a fixed-time success definition. The registry defines the event as the first local, regional, or distant event, or death, and describes censoring for participants without an event. It also classifies as successes participants alive and without relapse at two years after the complete therapeutic sequence. Such definitions show why a statistical endpoint is more than a label: the event, time origin, censoring rule, and assessment point determine what comparison is being made.

The design also makes the interpretation of the treatment contrast important. The randomized groups differ by the addition of gemcitabine to radiotherapy and cisplatin. A comparative estimate would address the strategies as assigned, while details such as adherence, analysis population, and post-randomization treatment are relevant to understanding what that estimate represents. The registry does not report those details or the primary analysis result.

From an education perspective, the record illustrates the distinction between a trial’s scientific question and the evidence needed to answer it. A primary outcome can be precisely defined without its result being available. Safety counts can be recorded without providing a comparative safety analysis. A terminated status can be known without revealing why the trial ended or what happened to follow-up. Each piece of information answers a different question.

The registry also identifies planning illustrations based on an observed effect, using specified assumptions. General interpretation requires keeping such planning scenarios separate from the original trial design and from observed statistical power. A planning illustration is conditional on its assumptions and does not replace reporting the observed effect, uncertainty, and analysis population. Here, the primary outcome estimate is not reported, so the illustrations cannot establish what the trial found.

The value of this record for statistical reading is therefore primarily methodological: it invites careful separation of design, endpoint definition, safety reporting, and comparative results. It documents a randomized research question but leaves the efficacy analysis unavailable in the registry record.

14. 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 interpretation is the absence of reported primary outcome results. No disease-free survival success counts, event counts, treatment-effect estimate, confidence interval, or primary comparison p-value are listed. Without those results, the central comparison cannot be quantified or judged for precision.

The registry does not give the reason for termination. It also does not state whether participants completed the intended follow-up, whether outcome assessment was complete, or whether the primary analysis was performed. These omissions make it impossible to assess whether the reported enrollment and study status correspond to a completed efficacy evaluation.

Although the record identifies randomization, details of sequence generation and allocation concealment are not reported. Masking is listed as none, but the record does not say whether outcome assessment was blinded or independently reviewed. The arm descriptions are blank, and treatment schedules, doses used in this trial, and adherence are not described. These gaps limit assessment of how closely the assigned interventions were implemented.

The registry does not define the analysis population or provide baseline characteristics. It also omits the primary statistical model, missing-data procedures, and any sensitivity analyses. The endpoint description refers to both censoring and a two-year success classification, but the analysis connecting those descriptions is not given. This restricts assessment of how incomplete follow-up may have affected the primary comparison.

Safety interpretation is limited by missing definitions, observation periods, and attribution details. The record does not clarify the denominator or arm allocation for the listed serious-event percentages. The counts should therefore be treated as descriptive registry entries rather than as a complete comparative safety analysis. These limitations do not establish a particular bias or result; they define what cannot be resolved from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase II Trial Evaluating an Organ-conserving Strategy by Radiochemotherapy for Muscle-infiltrative Bladder Cancer — NCT01495676.
• Registry record last updated 2025-10-10; status last verified 2025-07.
• Results first posted 2025-10-10.
• 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.

18. Record Summary

The registry describes a randomized, parallel-group, unmasked study titled as a Phase II trial comparing radiotherapy plus cisplatin with radiotherapy plus cisplatin and gemcitabine for muscle-infiltrative bladder cancer. The phase field is NA. Enrollment is 69, the status is terminated, the study start is 2011-07-06, and primary completion is 2022-07-25.

Disease-free survival is the primary endpoint, with success defined as being alive and without relapse at two years after the complete therapeutic sequence. Overall survival and toxicities are listed among the secondary outcomes. Serious adverse event and death counts are recorded by group, along with selected serious event terms and percentages.

The registry does not report the primary outcome results, the reason for termination, the analysis population, or the statistical analysis details. The record therefore describes the design and endpoint but does not permit an interpretation of the comparative disease-free survival result.