This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer (NCT02662062), a na phase 2 study. The primary outcome is The Number of Participants Experiencing an Unacceptable Level of Toxicity as Defined Below.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02662062 |
| Phase | Phase 2 |
| Condition | Bladder Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 28 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Australian and New Zealand Urogenital and Prostate Cancer Trials Group |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with non-metastatic muscle invasive bladder cancer after maximal transurethral resection. The registry summary describes eligibility for people seeking bladder preservation or ineligible for cystectomy, with adequate organ function and performance status for cisplatin-based chemoradiotherapy and no contraindication to pembrolizumab. The reported enrollment is 28.
Intervention
The treatment plan combined pembrolizumab with radiation therapy and concurrent cisplatin. Pembrolizumab was planned as an intravenous dose of 200mg every 21 days, starting concurrently with chemoradiotherapy and continuing until the 12 week cystoscopy. The summary describes radiation planned as 64Gy in 32 fractions over 6 weeks and 2 days, and cisplatin 35mg/m2 weekly during radiation for 6 doses.
Comparator
There was no concurrent comparator group: the registry identifies a single-group model, no masking, and allocation as NA. This design describes outcomes in the treated group but cannot, by itself, establish how those outcomes compare with a different treatment or with no pembrolizumab.
Primary question
The primary endpoint asks how many participants experienced an unacceptable level of toxicity during 12 weeks of study treatment. Unacceptable toxicity was defined using specified adverse-event severity and treatment-delivery criteria. The primary endpoint count is not reported in the registry record, so the primary safety question cannot be answered from the posted endpoint information.
3. Trial Design
The registry classifies NCT02662062 as a completed phase 2 study with a single-group model and no masking. Allocation is recorded as NA, consistent with the absence of a randomized treatment comparison. The study’s registered title is Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer. The sponsor is the Australian and New Zealand Urogenital and Prostate Cancer Trials Group.
The recorded enrollment is 28. The brief summary says the study would enrol 30 patients, so the planned enrollment described in the summary and the registry enrollment figure are not the same. The registry record does not explain this difference. The study start date is 2017-07-11, the primary completion date is 2022-05-12, and the status is completed.
The treatment plan combined pembrolizumab, cisplatin, and radiotherapy. The summary describes planned radiotherapy of 64Gy in 32 fractions over 6 weeks and 2 days, with cisplatin 35mg/m2 intravenously each week during radiation for 6 doses. Pembrolizumab was planned at 200mg intravenously every 21 days, beginning concurrently with chemoradiotherapy and continuing until the 12 week cystoscopy and assessment. These are protocol-plan descriptions; the registry record does not report participant-level adherence to each component.
The primary objective was to assess safety and feasibility. The primary endpoint was defined as the number of participants meeting a prespecified unacceptable-toxicity definition during 12 weeks of study treatment. Secondary outcomes included complete response at specified post-treatment assessments, estimated median overall survival, overall survival at 12 months, distant metastasis-free survival at 12 months, and local disease-free survival at 12 months. Numerical results for those outcomes are not reported in the registry record presented for this analysis.
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
| Stage | Pembrolizumab |
|---|---|
| STARTED | 28 |
| COMPLETED | 27 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Pembrolizumab |
|---|---|
| Withdrawal by Subject | 1 |
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.
| Characteristic | Unit | Pembrolizumab |
|---|---|---|
| Participants analysed | 28 | |
| Age, Continuous | years | 72 (58 to 86) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 26 |
| Race and Ethnicity Not Collected | Participants | — |
| Region of Enrollment: Australia | participants | 28 |
| ECOG: ECOG 0 | Participants | 18 |
| ECOG: ECOG 1 | Participants | 10 |
| Histology: Transitional cell/ Urothelial | Participants | 25 |
| Histology: Mixed Transitional/ nontransitional | Participants | 3 |
| Histology: Associated carcinoma in situ | Participants | 9 |
| T stage: T2 | Participants | 26 |
| T stage: T3 | Participants | 2 |
| Prior BCG (Bacillis Calmette-Guerin vaccine) treatment | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as The Number of Participants Experiencing an Unacceptable Level of Toxicity as Defined Below, measured over 12 weeks of study treatment.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the count of participants experiencing an unacceptable level of toxicity during 12 weeks of study treatment. The registry definition includes a grade 3 or worse adverse event under CTCAE V 5.0, with specified exceptions for urinary adverse events; specified withholding or reduction of cisplatin; radiation extending beyond 7 weeks; or a pembrolizumab dose delayed for more than 6 weeks. These criteria combine clinical severity with disruptions to planned treatment delivery.
A composite safety endpoint can capture more than one way a regimen might prove difficult to deliver. It may be useful in a feasibility study because treatment completion and tolerability are relevant alongside the occurrence of serious symptoms or complications. The criteria also make interpretation dependent on the precise definitions and how each event was assessed.
The endpoint is a participant count, not a measure of average severity or duration. A participant meeting more than one criterion would still contribute to a count of participants, rather than necessarily representing multiple participants. The registry record does not report the observed primary endpoint count or explain how overlapping criteria were handled in the analysis.
Because no primary endpoint result is reported in the registry record, the endpoint definition alone does not show how often unacceptable toxicity occurred. Nor does it establish a comparison with another treatment. The registered outcome is safety-focused; it does not by itself quantify complete response or survival.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a study designed to assess safety and feasibility, but the primary endpoint result is not reported in the registry record. The definition of unacceptable toxicity is available, while the number of participants meeting that definition is not. Accordingly, the principal registered safety question cannot be evaluated from that endpoint entry alone.
The adverse-event information does report 13 participants with serious adverse events among 28 at risk in the pembrolizumab group. It also reports 27 participants with other adverse events among 28 at risk, and 8 deaths. These are distinct registry categories. The record does not state whether the same participants appear in more than one category, give a causal assessment for deaths, or explain the relationship between these categories and the primary composite endpoint. They should not be added together or treated as mutually exclusive groups.
The listed serious adverse-event terms include urinary tract infection, haematuria, and fever, each reported as 7.1%. Other listed terms are reported as 3.6% each: Renal and urinary discorders (other), Musculoskeletal and Conncective tissue disorder (other), and Hypetension. The registry’s spelling is retained for these terms. These entries describe the listed event terms and their reported percentages; they do not establish whether events occurred in separate participants or whether each participant had only one event.
The study has no concurrent control group and no masking. The posted outcomes therefore describe the registered study group, not a randomized comparison. Differences between this group’s outcomes and outcomes in another population cannot be attributed to pembrolizumab from this design alone. The registry record also does not report an adjusted comparison or a treatment-effect estimate.
Several secondary outcomes concern response and survival, but their numerical results are not reported in the registry record. The existence of registered outcome names does not constitute evidence about their observed values. The record also does not report confidence intervals for the primary endpoint. Without a reported estimate and its uncertainty, the precision of the primary safety result cannot be assessed. The available safety counts should be read as descriptive registry information, not as proof of a causal treatment effect or as a complete account of the primary analysis.
9. Statistical Methods Explained
In a single-group study, outcomes are recorded for participants receiving the study regimen without a concurrent comparison group. This design can describe what was observed during the study, including adverse events and treatment delivery. It cannot separate the effect of the regimen from other explanations for an outcome, such as the underlying disease or differences among participants. General statistical interpretation therefore distinguishes a descriptive count from evidence of a comparative effect.
What does a participant count represent?
The primary endpoint is defined as a count of participants meeting an unacceptable-toxicity criterion. A count is a direct summary of how many participants met the definition, but it does not, by itself, show how precisely the underlying event frequency is known. Statistical precision depends on the amount of information and the observed result. The registry record does not report the primary count, an interval estimate, or an analysis of that endpoint, so its magnitude and precision cannot be assessed.
The endpoint combines several criteria: adverse-event severity, cisplatin delivery, radiation duration, and pembrolizumab delay. Composite endpoints are intended to represent a broader concept through multiple qualifying events. Their interpretation depends on the component definitions. A participant may qualify through different routes, and a composite count does not show which component was most common unless component-level results are reported. The registry record does not report the observed component counts or explain overlap among qualifying criteria.
Why does the study design affect interpretation?
Random allocation can support a like-for-like comparison by distributing participant characteristics across treatment groups, on average. This registry record identifies no randomized comparison and describes a single group. As a result, the adverse-event counts do not have a concurrent control rate against which to compare them. They describe the study group as recorded, but do not establish how much of an observed outcome is attributable to the regimen.
Masking concerns whether participants or study personnel are unaware of assigned treatment. The registry records no masking. In a study with no masking, knowledge of treatment can potentially affect reporting or assessment, depending on the outcome and the assessment process. That is a general methodological consideration; the registry record does not describe whether or how this influenced assessment in this study.
What can uncertainty estimates add?
A confidence interval is a statistical range expressing uncertainty around an estimate under a specified method. It helps readers distinguish an estimate that is relatively precise from one that remains compatible with a broad range of values. An interval does not guarantee that the true value lies within its bounds, and it does not correct for bias or limitations in design. No confidence interval for the primary endpoint is reported in the registry record, so the precision of that result cannot be discussed.
For a binary outcome, statistical summaries may report participants with an event and participants at risk. Such summaries need a clearly defined outcome, population, and observation period. The serious and other adverse-event figures in this record are descriptive counts; the registry record does not give a corresponding inferential analysis or explain whether the categories overlap. The serious-event term percentages are listed separately, and should not be combined into a total because the record does not establish that they are mutually exclusive.
How should the sample-size illustrations be read?
General sample-size planning asks how much information a future study might need to detect a specified effect under stated assumptions. The registry record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions describe a hypothetical planning exercise, not the observed design of this single-group study. A planning illustration is not observed power and does not show that the trial was adequately powered for its registered safety endpoint.
The registry record does not report the observed primary endpoint result needed to assess how an effect-based illustration relates to the safety question. The assumptions also refer to a two-arm allocation, whereas the registered study model is single-group. These planning assumptions should therefore be understood as hypothetical rather than as a description of the trial’s actual allocation. The registry record does not report the protocol’s sample-size justification or a statistical analysis plan.
Why can over-dispersion matter?
General statistical models sometimes assume that observations vary around an expected value in a particular way. Over-dispersion occurs when the observed variability is greater than that assumed by the model. If unaccounted for, standard errors and uncertainty intervals can be misleading. This is a general consideration for count-based analyses, not a claim about this study: the registry record does not report a model for the primary endpoint or evidence of over-dispersion.
More broadly, interpreting trial results requires the outcome definition, analysis population, missing-data approach, and analysis method. The registry record does not report enough detail to evaluate those features for the primary endpoint. The absence of those details is a limit on interpretation, not evidence that any particular method was or was not used.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several secondary outcomes, including complete response at Week 19 and Week 31, estimated median overall survival, overall survival at 12 months, distant metastasis-free survival at 12 months, and local disease-free survival at 12 months. When multiple outcomes are assessed, the chance of a seemingly notable result arising by chance can increase if each is tested separately without an appropriate strategy. General methods to address this include prespecifying a primary outcome, adjusting for multiple comparisons, or treating secondary outcomes as exploratory.
The registry record does not report a multiplicity adjustment or explain how inferential claims across secondary outcomes were intended to be controlled. It also does not report numerical results for these secondary outcomes in the information analyzed. Their listing should not be read as evidence that an effect was observed.
The registry record does not report the analysis population for the primary endpoint, the handling of missing outcome information, or how participants who did not complete planned treatment were incorporated in the endpoint analysis. These choices can matter for an endpoint that includes treatment-delivery criteria. The record also does not report how missing cystoscopy assessments or other follow-up information were handled for response and survival outcomes. These details are not reported in the registry record.
The brief summary describes follow-up assessments, but the analysis populations and missing-data methods are not reported in the registry record. No assumptions about those methods should be inferred from the schedule alone. Without these details and the primary endpoint result, the completeness and robustness of the primary safety analysis cannot be assessed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Pembrolizumab | 13 | 28 | 46.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Pembrolizumab | 8 of 28 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 3.5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Pembrolizumab | 27 of 28 |
Most frequent serious adverse event terms
| Event term | Organ system | Pembrolizumab |
|---|---|---|
| Urinary tract infection | Infections and infestations | 2 of 28 |
| Haematuria | Renal and urinary disorders | 2 of 28 |
| Fever | General disorders | 2 of 28 |
| Renal and urinary discorders (other) | Renal and urinary disorders | 1 of 28 |
| Musculoskeletal and Conncective tissue disorder (other) | Musculoskeletal and connective tissue disorders | 1 of 28 |
| Hypetension | Vascular disorders | 1 of 28 |
| Cystitis noninfective | Renal and urinary disorders | 1 of 28 |
| Infusion related reaction | Product Issues | 1 of 28 |
| Metabolism and nutritional disorder (other) | Metabolism and nutrition disorders | 1 of 28 |
| Delusions | Psychiatric disorders | 1 of 28 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pembrolizumab |
|---|---|---|
| Fatigue | General disorders | 19 of 28 |
| Urinary frequency | Renal and urinary disorders | 16 of 28 |
| Diarrhoea | Gastrointestinal disorders | 14 of 28 |
| Constipation | Gastrointestinal disorders | 10 of 28 |
| Haematuria | Renal and urinary disorders | 9 of 28 |
| Rash Maculopapular | Skin and subcutaneous tissue disorders | 9 of 28 |
| Cystitis Noninfective | Renal and urinary disorders | 6 of 28 |
| Nausea | Gastrointestinal disorders | 6 of 28 |
| Anaemia | Blood and lymphatic system disorders | 4 of 28 |
| Hypothyroidism | Endocrine disorders | 4 of 28 |
Serious events with the highest arm-level rate: urinary tract infection (7.1%), haematuria (7.1%), fever (7.1%), renal and urinary discorders (other) (3.6%), musculoskeletal and conncective tissue disorder (other) (3.6%).
The registry reports 13 participants with serious adverse events among 28 at risk in the pembrolizumab group. It separately reports 27 with other adverse events among 28 at risk and 8 deaths. The record does not establish whether the categories overlap, whether the deaths were related to treatment, or whether the reported adverse events meet the primary composite definition of unacceptable toxicity.
The serious-event terms listed include urinary tract infection, haematuria, and fever, each at 7.1%. Renal and urinary discorders (other), Musculoskeletal and Conncective tissue disorder (other), and Hypetension are each listed at 3.6%. These percentages are event-term entries in the registry. They should not be summed: the record does not say that the terms occurred in different participants, and one participant may have contributed more than one event term.
These figures are descriptive. They do not provide a comparison with another treatment, establish causation, or replace the primary endpoint result. The number meeting the predefined unacceptable-toxicity endpoint is not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this completed phase 2 study evaluated a planned combination of pembrolizumab, cisplatin, and radiotherapy in a single group of people with muscle invasive bladder cancer. It describes the intended treatment schedule, the safety-focused primary endpoint, and several secondary outcomes. It also records adverse-event information for the pembrolizumab group, including serious events, other events, listed serious-event terms, and deaths.
The posted safety counts can be read as descriptions of the study group. They do not determine whether the regimen caused a particular event, how the counts compare with another treatment, or whether participants would have had different outcomes under another approach. The study has no concurrent randomized comparator, and the registry reports no masking.
The primary endpoint result is not reported in the registry record. As a result, the observed number meeting the predefined unacceptable-toxicity criteria cannot be stated, and neither the size nor precision of that primary safety result can be assessed. Numerical results for the registered response and survival outcomes are also not reported in the registry record.
The study’s treatment plan and its outcome definitions describe what investigators intended to evaluate; they do not, by themselves, show treatment completion or response. The registry’s adverse-event figures should not be treated as a substitute for those missing outcome results. Overall, the record supports a limited descriptive account of design and adverse-event reporting, but does not permit a complete statistical assessment of the primary endpoint or a comparative conclusion about treatment effects.
13. Why This Trial Matters Statistically
This study raises several important statistical distinctions for clinical researchers. Its objective combines safety and feasibility, while its primary endpoint turns those concepts into a participant-level toxicity definition. That definition includes both adverse-event severity and interruptions or extensions to planned treatment. Such composite endpoints can capture multiple forms of difficulty, but readers need component-level results to understand what drove the overall finding. Those primary and component results are not reported in the registry record.
The single-group design also matters. Descriptive safety information can be useful for understanding what was recorded during treatment, but without a concurrent comparator it cannot establish whether event rates differ from another treatment strategy. No masking is recorded, which is relevant to interpretation of outcome assessment as a general design consideration. Neither point can be resolved by the adverse-event counts alone.
The record also illustrates why outcome names, endpoint definitions, and observed results are not interchangeable. Response and survival outcomes are listed, but their numerical results are not reported in the registry record. Likewise, the primary endpoint is carefully defined, but its observed count is absent. Statistical conclusions require estimates, and their uncertainty, in addition to a protocol-level description of what was to be measured.
Finally, the registry includes planning assumptions for sample-size illustrations that refer to a hypothetical two-arm allocation, while the study itself is registered as single-group. Recognizing the difference between planning assumptions and the actual design prevents a hypothetical calculation from being mistaken for a trial result or observed power. These features make the record a useful example of why design, endpoint reporting, and analysis details all shape what can be concluded.
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 registry record does not report the primary endpoint count, its uncertainty, or the component results underlying the unacceptable-toxicity definition. This omission prevents direct evaluation of the primary safety question. Numerical results for the listed response and survival outcomes are also not reported in the registry record, so those outcomes cannot be interpreted from the information available.
The study is registered as a single-group, unmasked phase 2 study with allocation recorded as NA. It therefore offers no concurrent randomized comparison for estimating a relative treatment effect. The record does not report a statistical analysis plan, the analysis population, handling of missing data, or methods for any endpoint analysis. These are limits on assessing the analysis, not grounds for assuming a particular method.
The recorded enrollment is 28, while the brief summary says the study would enrol 30 patients. The registry record does not explain the difference. It also does not report participant-level treatment completion or adherence to the planned cisplatin, radiation, and pembrolizumab schedules. Therefore, the planned regimen should not be treated as confirmation that every participant received every component as intended.
The adverse-event information does not explain overlap among serious events, other events, event terms, and deaths, or provide a causal assessment of deaths. The reported serious-event percentages cannot be summed or interpreted as mutually exclusive participant groups. These limitations restrict interpretation to the descriptive information recorded and prevent broader causal or comparative conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer — NCT02662062.
- Registry record last updated 2025-01-27; status last verified 2024-05.
- Results first posted 2025-01-27.
- 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.
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18. Record Summary
NCT02662062 is a completed phase 2, single-group study titled Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer. The sponsor is the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. The study began on 2017-07-11, reached primary completion on 2022-05-12, and has recorded enrollment of 28. The brief summary describes planned enrollment of 30, a difference the registry record does not explain.
The intended regimen combined pembrolizumab with cisplatin and radiotherapy. The primary endpoint counted participants experiencing unacceptable toxicity during 12 weeks of study treatment. Although the endpoint definition is recorded, its observed count is not reported in the registry record. The adverse-event entry reports 13 participants with serious adverse events, 27 with other adverse events, and 8 deaths in the pembrolizumab group; it does not establish category overlap or causation. Numerical results for the registered response and survival outcomes are not reported in the registry record.