Highly Conformal, Hypofractionated, Focally Dose Escalated Post-Prostatectomy Radiotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Highly Conformal, Hypofractionated, Focally Dose Escalated Post-Prostatectomy Radiotherapy (NCT03388619), a non-randomized phase 1 study. The primary outcome is Maximum Tolerated Dose (MTD) of Radiation Dose to Prostate Bed and Dose to Tumor Reported in Gray (Gy).

2. Clinical Question

3. Trial Design

This was a Phase I, non-randomized trial with no masking and a sequential model. The registry record lists the study as completed and reports enrollment of 30 participants. The study start date is 2018-01-17, and the primary completion date is 2023-12-29. Those dates describe the registry record and do not provide information about the timing of individual dose decisions.

The treatment approach depended on whether a recurrent tumor was visible. The visible-tumor groups received prostate-bed radiotherapy with an integrated boost, while the groups without a visible recurrent tumor received prostate-bed irradiation only. The group descriptions list dose levels with 20, 15, and 10 fractions. The brief summary says radiotherapy was delivered each weekday and could last 2, 3, or 4 weeks. The exact dose delivered at each level is not reported in the registry record.

The sequential design and the MTD definition indicate that dose tolerance was central to the trial question. Under the registry’s definition, the MTD is the dose level at which no more than 1 of up to 6 participants experiences a dose-limiting toxicity during the DLT period, and the dose below the level at which at least 2 of up to 6 participants have a treatment-related DLT. The listed DLT period is 3 weeks after radiation. The registry record does not describe the full dose-escalation algorithm or the decisions made at each step.

The trial also lists secondary outcomes covering biochemical progression-free survival, changes in sexual health and urinary and broader quality-of-life measures, and adverse events. The record lists 9 outcome measures, but no analysis results are reported for those secondary outcomes. With no random allocation, differences between the treatment groups cannot be interpreted as randomized treatment effects.

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: 12/30 expansion group participants (6 in Recurrent Tumor Visible: Level 3 Cohort 1, and Recurrent Tumor NOT Visible: Level 3 Cohort 2) were not assessed for MTD and included in the analysis.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of Radiation Dose to Prostate Bed and Dose to Tumor Reported in Gray (Gy), measured over 3 weeks after radiation.

The primary endpoint is the maximum tolerated dose (MTD) of radiation dose to the prostate bed and dose to the tumor, reported in Gray (Gy). This endpoint is intended to identify a dose level using a prespecified tolerance rule, rather than to estimate a comparative benefit between randomized treatments. In an early-phase trial, a dose-tolerance endpoint can guide the choice of dose for further study; it does not by itself establish how a treatment compares with another approach.

The registry defines a dose-limiting toxicity as specified grade 3 rectal, small bowel, urinary, or other in-field toxicity attributable to radiation that does not resolve to grade 2 or less within 4 days with appropriate medical management. A delay of more than one week in completing radiotherapy because of toxicity is also a DLT. The endpoint’s DLT period is 3 weeks after radiation. These rules explain what counts toward the endpoint, but the actual dose levels and the resulting MTD are not reported in the registry record.

The record states that 12/30 expansion group participants were not assessed for MTD and were included in the analysis. It does not explain how their inclusion affected the endpoint calculation, or identify a separate assessed population. Consequently, the endpoint definition can be described, but the posted information does not allow the MTD determination to be reconstructed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial’s sequential, non-randomized structure is consistent with an early-phase dose-tolerance question. Rather than assigning participants by chance to otherwise comparable treatments, the record describes groups defined by whether recurrent tumor was visible and by radiotherapy approach and fractionation level. The registry record does not provide the full dose-escalation algorithm, so it is not possible to describe how a particular toxicity count triggered a decision to escalate, hold, or reduce dose.

How an MTD rule works

In general, a maximum tolerated dose rule uses a specified toxicity outcome and a decision threshold to identify a dose level suitable for further investigation. Here, the registry defines the MTD by the number of participants with DLTs among up to 6 participants at a dose level, with a threshold of no more than 1 DLT and a lower dose boundary associated with at least 2 DLTs. The DLT criteria also set a time window and define which toxicities and treatment delays qualify. Applying this rule requires dose-level assignments, DLT assessments, and decisions across the sequential groups. The posted record does not report the dose values or the resulting decision.

Why the sequential design matters

General statistical context: sequential dose-finding designs use accumulating information to guide which dose is studied next. Their estimates and conclusions depend on the prespecified decision rules and on accurate classification of outcomes within the relevant period. Because groups are not randomized here, descriptive differences across dose levels do not have the same interpretation as differences in a randomized trial. Participant characteristics, tumor visibility, and treatment approach may differ across groups; the registry does not provide data to assess those factors or adjust for them.

Precision and sparse events

General statistical context: estimates based on small groups can be imprecise, particularly when outcomes are uncommon. Confidence intervals can communicate that uncertainty, but no primary endpoint estimate or confidence interval is reported in the registry record. The safety results give affected-participant counts by group; they do not include intervals or an inferential comparison. A count of 0 serious adverse events in a group is a descriptive observation, not proof that the underlying risk is zero.

Over-dispersion is a general concern when count outcomes vary more than a simple statistical model expects. It may matter for analyses of event counts, but the registry record does not report a count model or an over-dispersion assessment. The safety entries describe participants affected, and do not report the total number of events per participant or a model for repeated events. It would therefore be inappropriate to infer that such a model was used.

Planning illustrations

General statistical context: a sample-size calculation for a future comparison depends on assumptions about the effect to detect, the significance level, allocation, and analysis method. The record’s planning illustration is described as based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration concerns total events; for other outcomes, it concerns participants per arm. Such illustrations are planning aids, not observed power and not evidence that the original trial was designed with those assumptions. The numerical illustration results and an observed effect are not reported in the registry record.

There is no analysis detail for the reported secondary outcomes. The registry lists biochemical progression-free survival, changes in several quality-of-life measures, and attributable adverse events, but does not give statistical models, estimands, analysis populations, or numerical results. Those methods should not be inferred from the outcome names alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures, including a primary MTD endpoint and secondary measures for biochemical progression-free survival, quality of life, and adverse events. It does not report a multiplicity strategy for interpreting several outcomes, such as a hierarchy, adjustment procedure, or designation of secondary outcomes as descriptive. The record lists 0 analyses, so there are no posted analysis outputs from which to determine how multiple outcomes were handled.

Missing-data procedures are also not reported in the registry record. In particular, no imputation method, censoring rule, or approach to incomplete quality-of-life assessments is described. The MTD entry states that 12/30 expansion group participants were not assessed for MTD and were included in the analysis. The reason for this, the contribution of those participants to the endpoint analysis, and the handling of other participants without an assessment are not explained.

Analysis populations are not fully specified. The record does not identify an intention-to-treat population or a separate safety population, nor does it provide outcome-specific denominators for the secondary outcomes. Enrollment of 30 should therefore not be assumed to be the denominator for every result. For the adverse-event entries, the record gives group-specific counts at risk and affected; those figures do not resolve the analysis populations for other endpoints.

General statistical context: when outcomes or assessments are missing, the interpretation can depend on why they are missing and how the analysis handles them. When multiple outcomes are tested, the chance of at least one apparently unusual result can depend on the testing strategy. Without a reported missing-data or multiplicity plan, the registry results cannot be used to assess either issue.

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: back pain (33.3%).

The adverse-event results are organized by treatment group and dose level. For serious adverse events, the registry reports 0 affected participants in five groups and 1 affected participant among 3 at risk in Level 1/Cohort 2. The record reports 0 deaths in all six groups. These are observed counts; they do not establish that serious events cannot occur in a group with a recorded count of 0.

The separate other-adverse-event counts range from 3 to 9 affected participants across groups, with the corresponding at-risk counts listed as 3 or 9. These results should not be confused with the serious-event counts. The registry’s serious-event listing identifies back pain at 33.3%, but does not report further context for that term. No event-level narrative or comparative statistical analysis is included in the record.

Because this trial was non-randomized and the groups differ in tumor visibility and treatment approach, the counts should be read descriptively rather than as evidence that one treatment caused more or fewer events than another. The record does not provide confidence intervals or adjusted comparisons for these safety outcomes.

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

The trial addresses whether a shortened schedule of post-prostatectomy radiotherapy, including a focal boost for visible recurrent tumor, can be evaluated using a defined dose-limiting-toxicity rule. Its primary endpoint is a dose-tolerance measure, not a direct comparison of clinical benefit between randomized treatments. The registry record documents the endpoint definition and reports safety counts, but it does not report the resulting maximum tolerated dose.

The posted safety figures describe the recorded number of participants affected in each group. They show 1 participant with a serious adverse event in Level 1/Cohort 2 and 0 in the other five groups; deaths are recorded as 0 in each group. Other adverse events are also recorded by group. These findings are limited to the registry’s categories and counts. They do not, on their own, establish the likelihood of an event in a broader population or provide a comparison between the radiotherapy approaches.

The absence of a reported MTD value means that the primary question cannot be answered from the posted result information. It is not appropriate to infer a tolerated dose from the group labels, the fractionation schedule, or the adverse-event entries. The record also does not report comparative efficacy estimates for biochemical progression-free survival or the quality-of-life outcomes.

General statistical context: a small early-phase study is generally designed to inform dose and safety questions, while estimates of benefit and harm often require further evaluation. That distinction does not supply a result missing from the record. Here, the trial’s non-randomized design, the differing cohort definitions, and the absence of a reported endpoint analysis limit causal and comparative interpretation. No conclusion about whether a treatment should be used follows from these registry results.

13. Why This Trial Matters Statistically

This trial illustrates how a clinical study can have a clearly defined statistical endpoint without a posted numerical result for that endpoint. The MTD rule specifies the toxicity window, qualifying DLTs, and a participant-count threshold. Those details make the intended decision framework understandable, but they are not a substitute for reporting the actual dose levels, assessments, and final MTD determination.

The sequential structure also highlights the distinction between dose finding and treatment comparison. The groups differ in recurrent-tumor visibility and radiotherapy approach, and allocation was not randomized. As a result, their safety counts are useful as descriptive information about the recorded groups but do not support a like-for-like causal contrast. This distinction matters when readers encounter numerical outcomes arranged by arm or dose level.

The record also emphasizes why denominators and analysis populations matter. It reports enrollment of 30, while noting that 12/30 expansion group participants were not assessed for MTD and were included in the analysis. Without further explanation, readers cannot reconstruct the primary analysis population or determine how those participants entered the endpoint calculation. Clear reporting of who was assessed, who was analyzed, and how missing assessments were handled is essential to interpreting a dose-finding result.

Finally, the listed planning illustration is conceptually separate from the trial’s observed findings. Planning calculations depend on assumptions and can inform future studies, but they do not establish the trial’s achieved precision or observed power. The registry record does not report numerical planning results or the underlying observed effect. Distinguishing design illustrations, outcome definitions, and actual estimates is central to sound interpretation.

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.

Important trial-specific information is not reported in the registry record. The primary MTD result, the dose values for each level, and the final dose-escalation decisions are absent. Although the endpoint definition is detailed, the record does not provide the data needed to reproduce its application. It also notes that 12/30 expansion group participants were not assessed for MTD and were included in the analysis, without explaining how they contributed to the calculation.

The trial was non-randomized and sequential, and the cohorts differed by tumor visibility and radiotherapy approach. The groups therefore do not constitute a like-for-like control comparison. The registry does not report participant-level characteristics or adjusted analyses that could clarify differences among groups. The safety results are counts without confidence intervals or comparative analyses.

The record lists secondary outcomes but does not report their numerical results or analysis methods. Multiplicity handling, missing-data methods, endpoint-specific analysis populations, and the detailed statistical plan are not reported in the registry record. The listed planning illustration does not replace these results, and its numerical outputs are not included. These limitations constrain conclusions about precision, comparative effects, and the generalizability of the observed safety counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Highly Conformal, Hypofractionated, Focally Dose Escalated Post-Prostatectomy Radiotherapy — NCT03388619.
• Registry record last updated 2026-08-28; status last verified 2026-08.
• Results first posted 2024-05-14.
• 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

NCT03388619 is a completed, non-randomized Phase I trial of hypofractionated, focally dose-escalated post-prostatectomy radiotherapy, with enrollment of 30 participants. The primary endpoint is the maximum tolerated dose to the prostate bed and tumor, defined using dose-limiting toxicities during the 3 weeks after radiation. The registry describes groups receiving prostate-bed irradiation with an integrated boost or prostate-bed irradiation only, with fractionation levels of 20, 15, or 10 fractions.

The registry record reports group-level serious and other adverse-event counts and 0 deaths in each group. It does not report the MTD value, dose levels in Gy, or numerical analyses for the primary or secondary outcomes. The record also notes that 12/30 expansion group participants were not assessed for MTD and were included in the analysis, without explaining the analysis in further detail.