Anti-PD(L)1 and SBRT in the Treatment of Advanced, Platinum-Refractory Urothelial Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Anti-PD(L)1 and SBRT in the Treatment of Advanced, Platinum-Refractory Urothelial Carcinoma (NCT03287050), a na phase 2 study. The primary outcome is The Percentage of Subjects Who Receive 4 Doses of Pembrolizumab and at Least One Session of Treatment of SBRT.

2. Clinical Question

3. Trial Design

This was a Phase 2 feasibility trial of pembrolizumab and stereotactic body radiation therapy (SBRT) in advanced, platinum-refractory urothelial carcinoma. The registry record identifies the design as single-group, with allocation listed as not applicable and masking listed as none. It records a Pembrolizumab + SBRT group and no separate comparator group. The design therefore describes experience with the combined intervention, rather than a randomized, like-for-like treatment comparison.

Enrollment was 6. The recorded start date was 2018-01-24, and primary completion was recorded as 2019-03-13. The status is terminated. The reason for termination is not reported in the registry record; the status alone does not establish why the study ended or what happened to individual participants.

The primary endpoint was the percentage of participants who received 4 doses of pembrolizumab and at least one SBRT session within 15 weeks from the first pembrolizumab dose. The registry record also lists secondary outcomes concerning Grades 3-5 drug-related adverse events, the percentage of patients who respond to treatment, and progression-free survival time. It records 4 outcome measures, but does not report analyses for them. The primary endpoint result, response results, and progression-free survival results are not reported in the registry record.

The listed interventions are pembrolizumab and SBRT. The record identifies the University of Michigan Rogel Cancer Center as sponsor. Additional details about treatment delivery beyond the stated endpoint are not reported in the registry record. In particular, the record does not specify the planned SBRT schedule or provide a fuller treatment protocol in the arm description. The trial's feasibility focus makes the recorded primary endpoint a measure of whether participants received the specified components within the stated period, not a direct measure of tumor response or comparative benefit.

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 The Percentage of Subjects Who Receive 4 Doses of Pembrolizumab and at Least One Session of Treatment of SBRT, measured over 15 weeks.

The primary endpoint is the percentage of participants who received 4 doses of pembrolizumab and at least one session of SBRT within 15 weeks from the first pembrolizumab dose. It combines a drug-delivery requirement with a radiation-treatment requirement and a time window. A participant would meet the endpoint only if the recorded treatment exposure satisfied both components within that window.

Feasibility endpoints are used to describe whether a planned intervention can be delivered as specified in a study population. In general, a percentage expresses how common the defined event was among the participants counted in the analysis. Its interpretation depends on a clear definition of who is included in the denominator and how missing or incomplete treatment information is handled. Those analysis details are not reported in the registry record.

This endpoint does not itself measure tumor response, progression-free survival, or adverse events. Those topics appear among the listed secondary outcomes, but their results are not reported in the registry record. The primary endpoint result is also not reported, so the record does not establish what percentage met the feasibility definition. Without that result and the analysis population, the endpoint cannot be interpreted as a quantitative estimate of treatment delivery.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either meets the stated treatment-delivery definition within the specified period or does not. The registry describes the endpoint as a percentage of participants. In general, a percentage for a binary outcome is the number meeting the definition divided by the number included in the analysis, expressed on a percentage scale. The record does not report the endpoint count, percentage, or analysis denominator, so no observed feasibility proportion can be interpreted.

What does a confidence interval describe?

In general, a confidence interval expresses the statistical uncertainty around an estimate, such as a proportion. It is not a guarantee that the true value lies within the reported interval, and it does not address every source of uncertainty. For a small study, the interval around a proportion can be broad because relatively few participant outcomes contribute information. The registry record does not report a confidence interval for the primary endpoint or an estimate to which one could be applied.

For a binary outcome, the precision of an estimate depends on the number of participants and on how many meet the event definition. A percentage without its count and denominator can conceal how much information supports it. Here, enrollment was 6, but the record does not report how many participants were included in the primary endpoint analysis, whether all enrolled participants were assessed, or how unavailable endpoint information was treated. Enrollment alone cannot substitute for those analysis details.

Why does the single-group design matter?

In general, a single-group study can describe what occurred among participants receiving the intervention, but it does not directly estimate a contrast against a concurrent control group. Differences between treated and untreated outcomes cannot be calculated when a suitable comparison group is absent. This trial is recorded as single-group, with allocation not applicable and masking none. Accordingly, its stated primary purpose is feasibility, not a randomized test of comparative efficacy.

Masking concerns whether participants or study personnel are unaware of assigned treatment. The registry records masking as none. That design description does not tell whether endpoint assessment was standardized or independently reviewed; those details are not reported in the registry record. The record also does not report an analysis plan describing how the endpoint was assessed or how deviations from the treatment schedule were classified.

What do the planning assumptions mean?

The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe participants per arm for outcomes other than time-to-event outcomes; time-to-event illustrations describe a total number of events using the Schoenfeld approach. The illustrations are based on a stated fraction of an observed effect. They are planning illustrations, not observed power, and they are not a description of this trial's single-group design.

These assumptions describe a hypothetical planning framework. They do not establish that the trial itself was designed with two arms, that equal allocation was used in the trial, or that the trial had a sample-size justification based on those assumptions. The registry record does not report the trial's sample-size justification. It also does not report a numerical planning estimate in the registry entries. Because the primary endpoint result is not reported, the basis for any observed-effect planning illustration cannot be assessed from the registry record.

In general, a significance level is a prespecified threshold used in a statistical testing procedure. A two-sided procedure considers departures in either direction. A normal approximation uses a mathematical distribution to approximate the sampling behavior of an estimate or test statistic. The quality of an approximation depends on the setting and the data; an assumption listed for planning does not establish that an analysis was performed or that its conditions were met.

Why can over-dispersion matter?

In general, over-dispersion describes variation greater than a statistical model expects. It can make model-based standard errors too small if the extra variation is ignored, which can make intervals appear more precise than warranted. This concept is relevant to some count and rate models, but the registry record does not identify such a model for the primary binary feasibility endpoint. It does not report model details or an over-dispersion assessment. Therefore, over-dispersion should not be presumed to have been present or assessed in this trial.

For time-to-event outcomes, general methods account for both event timing and censoring, which occurs when a participant's event time is not observed during the available follow-up. The registry lists progression-free survival time as a secondary outcome but does not report its analysis, follow-up details, event definition, or censoring approach. The Schoenfeld reference in the planning assumptions concerns event-count planning illustrations; it does not demonstrate that a time-to-event analysis was conducted or provide a progression-free survival result.

The registry records 0 analyses. This indicates that the registry record does not include posted analyses for the outcomes; it does not reveal what analyses may have been conducted outside the registry. In general, statistical interpretation depends on the outcome definition, analysis population, missing-data rules, and prespecified methods, as well as the estimate and its uncertainty. Those elements are not reported for the primary endpoint. Consequently, the design and planning assumptions can be described, but an estimate, significance test, or precision assessment for the primary outcome cannot be evaluated from the record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Pembrolizumab + SBRT")
n      <- c(6)
events <- c(5)
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  Pembrolizumab + SBRT  6  5  83.3  35.9  99.6  43.6  97.0  42.1  96.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures, including the primary feasibility endpoint and secondary outcomes concerning Grades 3-5 drug-related adverse events, response, and progression-free survival. When multiple outcomes are assessed, multiplicity is a general statistical concern: testing many hypotheses can increase the chance of at least one apparently notable result arising by chance. Researchers may address this through prespecified outcome hierarchies or adjusted testing procedures, but the registry record does not report whether any multiplicity approach was planned or used.

The primary endpoint result and secondary outcome analyses are not reported in the registry record. It records 0 analyses. Therefore, no reported hypothesis tests, estimates, confidence intervals, or multiplicity adjustments can be evaluated. This lack of posted analyses should not be interpreted as evidence that investigators performed no analyses outside the registry.

The analysis population is also not reported in the registry record. Enrollment was 6, but the record does not state whether the primary endpoint denominator included every enrolled participant or how participants with incomplete treatment or follow-up information were handled. Missing-data methods and reasons for missing data are not reported. In general, missingness can affect both the estimate and its interpretation, particularly when the outcome depends on completing specified treatment within a defined period. Without the relevant rules and participant-level accounting, the degree of any such effect cannot be assessed.

Details of interim analyses, protocol-defined analysis sets, and statistical stopping rules are not reported in the registry record. The terminated status alone does not establish that a statistical stopping rule was used or explain the study's completion. Interpretation should therefore remain limited to the registry's design and recorded results, without assuming unreported analysis procedures.

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: spinal fracture (16.7%), bone pain (16.7%).

For the Pembrolizumab + SBRT group, the registry records 6 participants at risk and 1 affected in the serious adverse-event category. It records 6 participants at risk and 6 affected in the other adverse-event category, and 3 deaths. The listed serious-event terms are spinal fracture and bone pain, each recorded as 16.7%. These are registry-recorded figures for this group; the record does not provide a comparison group.

“At risk” identifies the recorded group denominator for the adverse-event entries, while “affected” is the number recorded with the corresponding category. These summaries do not show the timing, duration, recurrence, or severity details of individual events. The registry record does not report whether the deaths were related to treatment, nor does the presence of an event term establish causation. The serious-event terms should be read as recorded event information, not as proof that the combination caused those events.

The small enrollment means the safety counts describe a limited group of participants and cannot establish how frequently events would occur in a broader population. No inferential safety analysis or uncertainty interval is reported in the registry record. The figures are descriptive and should not be interpreted as a comparative estimate of risk.

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

The registry record defines a feasibility question: whether participants received 4 doses of pembrolizumab and at least one SBRT session within 15 weeks from the first pembrolizumab dose. However, the percentage meeting that definition is not reported. The record therefore does not show whether the treatment-delivery objective was met, how often it was met, or how much uncertainty surrounds an estimate.

The record does establish that the study was a Phase 2, single-group trial with enrollment of 6 and a terminated status. It also records adverse-event information for the Pembrolizumab + SBRT group. These details describe the study and its posted safety entries, but they do not answer the primary feasibility question or provide comparative evidence about treatment outcomes.

The listed secondary outcomes include response and progression-free survival, but their results are not reported in the registry record. It is therefore not possible to infer tumor response or time to progression from the outcome descriptions. Similarly, the recorded deaths cannot be attributed to treatment based on the information in the registry. The record does not report a separate control group that could support a comparative estimate.

In general, a study's estimate is distinct from a conclusion about treatment effect. A feasibility proportion would describe treatment delivery in the analyzed participants; it would not by itself show that a treatment improves health outcomes. A single-group study also cannot directly distinguish intervention effects from other explanations for observed outcomes. Here, the primary proportion and its uncertainty are absent, and the relevant efficacy results are not reported. The appropriate interpretation is consequently limited: the registry outlines a feasibility study and records certain safety counts, but it does not provide the outcome results needed to judge feasibility or efficacy.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary question is about feasibility rather than a comparative treatment effect. The endpoint is defined around delivering a particular combination of pembrolizumab and SBRT within a fixed period. That kind of question is distinct from asking whether one treatment produces better outcomes than another. The registry's single-group design is consistent with describing intervention delivery, but it does not create a randomized comparison.

The endpoint also illustrates why definitions and analysis denominators matter. A treatment-delivery percentage depends on which participants are counted and whether incomplete or unavailable treatment information is classified consistently. Enrollment was 6, while the primary endpoint count, denominator, and percentage are not reported. Without those details, the central feasibility estimate cannot be reconstructed or assessed for precision.

The registry also illustrates the difference between recording an outcome and reporting its analysis. Secondary outcomes are listed, and adverse-event counts are recorded, but the record reports 0 analyses. Statistical conclusions require more than outcome labels: they depend on estimates, uncertainty, analysis populations, and methods. The absence of those elements limits what can be concluded without implying that no research analyses were performed outside the registry.

Finally, the planning assumptions describe a hypothetical two-arm framework, while the trial itself is recorded as single-group. Keeping planning illustrations separate from trial design is important: such illustrations are neither observed power nor evidence that the trial used those assumptions. The record does not report the trial's sample-size justification. These distinctions help prevent a feasibility study's limited descriptive information from being mistaken for a randomized efficacy result.

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 primary limitation for interpreting this trial is that the registry record does not report the primary endpoint result. The record defines the treatment-delivery criterion and its 15-week timeframe, but gives no participant count or percentage meeting it. It also does not report an analysis denominator or uncertainty interval. Thus, the central feasibility outcome cannot be quantified from the registry record.

Enrollment was 6, and the design was single-group. These features limit the amount of information available for describing outcomes and preclude a randomized comparison with a control group. The absence of a comparator means that observed outcomes cannot be used to estimate a treatment contrast. This is particularly important for interpreting safety counts and any outcomes that might otherwise be treated as evidence of efficacy.

The status is terminated, but the reason for termination is not reported in the registry record. The record does not report whether enrollment ended as planned, whether all participants completed the intended treatment, or whether termination related to feasibility, safety, logistics, or another reason. None of these explanations should be inferred from status alone.

Further details relevant to interpretation are also not reported: the primary analysis population, handling of missing endpoint information, protocol deviations, outcome assessment procedures, interim analyses, and the statistical analysis plan. The listed secondary outcomes lack reported analyses, including response and progression-free survival results. The safety information provides recorded counts and terms but not detailed event timing, participant-level context, or a treatment-causality assessment for deaths. These omissions restrict interpretation to the design and available registry entries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Anti-PD(L)1 and SBRT in the Treatment of Advanced, Platinum-Refractory Urothelial Carcinoma — NCT03287050.
• Registry record last updated 2021-12-15; status last verified 2021-12.
• Results first posted 2021-12-15.
• 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

NCT03287050 is a Phase 2 feasibility trial of pembrolizumab and SBRT in advanced, platinum-refractory urothelial carcinoma, sponsored by the University of Michigan Rogel Cancer Center. The registry records a single-group, unmasked design, enrollment of 6, a start date of 2018-01-24, primary completion on 2019-03-13, and status terminated.

The primary endpoint was the percentage receiving 4 pembrolizumab doses and at least one SBRT session within 15 weeks from the first dose. That result is not reported in the registry record. The registry lists secondary outcomes on adverse events, response, and progression-free survival, and records 0 analyses. It also records adverse-event information for the Pembrolizumab + SBRT group, including 3 deaths. The reason for termination, primary analysis population, and statistical analysis plan are not reported in the registry record.