Phase II Study of Adenovirus/PSA Vaccine in Men With Recurrent Prostate Cancer After Local Therapy APP21: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Study of Adenovirus/PSA Vaccine in Men With Recurrent Prostate Cancer After Local Therapy APP21 (NCT00583752), a randomized phase 2 study. The primary outcome is Number of Participants Who Develop a Strong or Modest Anti-PSA Immune Response.

2. Clinical Question

3. Trial Design

This was a phase II randomized, parallel-arm study with no masking. The registry record lists an enrollment of 50 participants. Its two treatment arms were adenovirus/PSA vaccine alone and adenovirus/PSA vaccine with androgen deprivation therapy (ADT). Participants on Arm A could begin the three vaccinations immediately. On Arm B, ADT began 14 days before vaccination. The record does not describe how the random allocation sequence was generated or concealed, or whether assignment used any stratification.

The study title specifies men with recurrent prostate cancer after local therapy. Its stated purpose was to determine whether vaccination induced anti-PSA immunity that would result in destruction of remaining prostate cancer cells. That purpose describes the rationale, not a reported finding. The primary outcome focused on an immune response, rather than directly measuring destruction of cancer cells.

The registry record gives a start date of 2007-12, a primary completion date of 2020-12-31, and a status of completed. It does not report the duration of follow-up for each participant, the dates of individual vaccinations, or the timing of the ADT course beyond its start relative to vaccination. It also does not report a planned sample-size justification, the intended statistical analysis plan, or any interim analyses.

Three outcome measures are listed, including the primary immune-response measure and secondary outcomes concerning changes in PSA doubling time (PSADT) and participants alive or deceased following treatment. The registry indicates no analyses. That absence matters: the trial design and endpoint descriptions can be discussed, but they do not provide an estimated treatment effect or a test of a difference between arms.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 21 evaluable participants analyzed on Arm A and included in analysis of outcome measure one. 1 participant was lost to long-term follow-up for outcome measure three.

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 Number of Participants Who Develop a Strong or Modest Anti-PSA Immune Response, measured over 18 months.

The primary endpoint is the number of participants who develop a strong or modest anti-PSA immune response, with an 18-month timeframe. The outcome description defines an anti-immunologic response as an increase of >200% above pre-immunization levels of anti-PSA T cells, measured using ELISPOT analysis. The registry record does not provide the observed number meeting this definition.

As a general statistical point, an immune-response endpoint can measure whether a biological change occurred after treatment. It is not the same as a clinical outcome such as disease progression or survival. The study’s stated rationale connects immune response with destruction of remaining prostate cancer cells, but the primary endpoint alone would not establish that such destruction occurred. That would require relevant outcome data and an analysis designed to address the clinical question.

The endpoint is expressed as a participant count. To compare the randomized arms, readers would need outcome counts for each arm, clear analysis populations, and an appropriate statistical comparison. Those primary results are not reported in the registry record. The population description notes 21 evaluable participants on Arm A included in analysis of the first outcome measure; it does not supply an outcome count or clarify the primary analysis population for Arm B. Consequently, the endpoint’s definition is available, but its observed frequency and comparative result are not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a randomized, parallel-arm phase II design without masking. In general, random assignment is intended to make treatment groups comparable on average at the start of a study. The word “randomized” alone does not describe how the sequence was generated, how assignments were concealed, or whether the allocation process had safeguards against prediction. Those details are not reported in the registry record. No masking means the record does not describe blinded treatment assignment; it does not, by itself, establish how outcome assessment was conducted.

What does a participant-count endpoint mean?

The primary outcome is a count of participants who meet the stated immune-response definition. The definition specifies an increase of >200% above pre-immunization levels of anti-PSA T cells measured by ELISPOT analysis. For an arm-to-arm comparison, the count needs to be interpreted alongside the number of participants assessed in that arm. The registry notes 21 evaluable Arm A participants included for outcome measure one, but does not give the event count or a corresponding Arm B analysis population. Without both arm-specific denominators and event counts, the frequency and comparative effect cannot be determined from the record.

In general, binary-outcome analyses can report each arm’s event frequency and a contrast between arms, such as a difference or ratio, with uncertainty. Such estimates answer different questions and depend on the chosen analysis. No primary-outcome estimate, uncertainty interval, or test is reported. None should be inferred from the endpoint definition or the study’s enrollment figure.

What can be inferred from “no analyses”?

The registry lists zero analyses. This indicates that the record does not present an analysis result for the outcomes listed; it is not evidence that a treatment effect is zero. Without an analysis, there is no reported primary comparison to interpret for magnitude or precision. The registry also does not report the intended statistical plan, so it is not possible to identify from this record which model, test, covariate adjustment, or handling of repeated measurements was planned.

The outcome description specifies an 18-month timeframe, but does not explain whether measurements were collected at other times or how multiple observations, if any, were handled. The registry’s note that the primary outcome has several categories or time points and was not reduced to one comparison further limits interpretation of a single primary contrast. The detailed structure of those categories or time points is not reported in the registry record.

How should planning illustrations be read?

General sample-size planning uses assumptions about the target effect, significance level, allocation, and statistical method to estimate the number of participants needed for a specified power. These are planning quantities, not outcomes observed in a trial. The registry’s stated illustration assumptions include a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. The record does not report a trial-specific sample-size justification. Any planning illustration based on an observed effect should not be interpreted as observed power or as evidence that the study had adequate precision for its primary question.

For non-time-to-event outcomes, the planning description refers to participants per arm; for time-to-event outcomes, it refers to a total number of events. Those conventions describe the planning illustration, not the enrollment or results of this trial. No planning estimate is reported in the registry record, and none can be recovered from the assumptions alone without adding an unreported effect value.

Why does missing information matter?

An analysis needs a defined population, outcome rules, and a method for addressing participants without an observed outcome. The registry says one participant was lost to long-term follow-up for outcome measure three. It does not say that this participant was missing the primary endpoint, nor does it report a missing-data method for any outcome. The primary outcome population description gives 21 evaluable participants on Arm A, but does not explain exclusions or missing measurements. Thus, the effect of missingness on the primary analysis cannot be assessed from the registry record.

In general, missing outcomes can affect an estimate if participants with unavailable measurements differ systematically from those assessed. The direction and size of any such effect depend on the missingness pattern and assumptions used in the analysis. Since those details and the primary outcome results are not reported, no sensitivity analysis or adjustment can be evaluated.

What is the role of secondary outcomes?

PSADT categories and alive/deceased status are listed as secondary outcomes. These measures address different questions from an immune-cell response. In general, multiple outcomes and multiple categories can create multiplicity: the more comparisons considered, the greater the chance that an apparently noteworthy finding arises by chance if results are interpreted without an appropriate plan. The registry does not report a multiplicity strategy or secondary-outcome analyses. It is therefore not possible to assess how such results were selected or interpreted.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures: the primary anti-PSA immune-response count and secondary outcomes concerning PSA doubling-time categories and vital status. It also indicates that the primary outcome has several categories or time points and was not reduced to one comparison. The detailed categories, time points, and planned contrasts are not reported in the registry record. A multiplicity plan, such as a prespecified approach for interpreting several outcomes or comparisons, is also not reported.

In general, multiplicity matters when several outcomes, categories, time points, or statistical comparisons are examined. Without a prespecified plan, readers may have difficulty distinguishing the central planned question from exploratory findings. Here, no outcome analyses are listed, so there are no reported primary or secondary comparisons to assess for multiplicity.

The population description states that 21 evaluable participants on Arm A were included in the analysis of outcome measure one. It does not provide the primary endpoint count, the analyzed population for Arm B, or an account of participants excluded from that analysis. One participant was lost to long-term follow-up for outcome measure three; the record does not link that loss to the primary outcome. A method for handling missing values, withdrawals, or incomplete follow-up is not reported in the registry record.

As a general principle, interpretation of missing data depends on how much is missing, why it is missing, and the assumptions made in analysis. Those details are unavailable for the primary endpoint. The record therefore does not support assessment of whether missingness could have changed the estimated treatment comparison.

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 non-serious adverse event terms

The registry lists 25 participants at risk for serious adverse events in each group and reports 0 affected in each group. For other adverse events, it lists 15 affected participants in the ADT-plus-vaccine group and 18 in the vaccine group, with 25 at risk in each. It also lists 17 deaths in the ADT-plus-vaccine group and 10 in the vaccine group.

These are registered counts, not evidence by themselves that treatment caused or prevented an event. The record does not provide the definitions, event terms, severity breakdown, timing, attribution, or follow-up details needed to interpret the “other” category or the death counts. It reports no top serious adverse-event terms. The death counts should not be read as treatment-related deaths: cause and attribution are not reported in the registry record. These safety figures do not replace the missing primary immune-response results or establish the comparative safety of the regimens.

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

The available record establishes the study question and design: a phase II randomized comparison of adenovirus/PSA vaccine alone with the vaccine preceded by ADT. It identifies a primary immune-response endpoint, defines the response using an increase of >200% above pre-immunization anti-PSA T-cell levels measured by ELISPOT, and gives an 18-month timeframe. It also records adverse-event and death counts by group.

It does not report the number of participants meeting the primary response definition, an arm-to-arm effect estimate, a confidence interval, or a statistical test. As a result, the registry record does not show whether the endpoint was more or less frequent in either arm, or how precisely any difference was estimated. A completed trial status does not fill that gap.

The primary endpoint is an immunologic measure. In general, a biological response can be relevant to a treatment’s proposed mechanism, but it is not interchangeable with a clinical outcome. The stated study purpose connects anti-PSA immunity with destruction of remaining cancer cells; the primary endpoint definition alone does not establish that cancer cells were destroyed or that participants experienced a clinical benefit. The record’s secondary-outcome titles refer to PSADT and vital status, but their results are not reported in the registry record.

The adverse-event counts should also be interpreted narrowly. They report numbers in specified categories and groups, but do not include enough detail to determine event attribution, timing, or comparative risk. In particular, the deaths listed by group should not be taken as caused by either regimen. Overall, the registry provides descriptive trial and endpoint information, but not the efficacy analysis needed to answer the primary comparative question.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly named endpoint and a completed study status are not enough to interpret a clinical comparison. The record specifies a biological response definition and randomized treatment arms, yet it does not report the primary event counts or an analysis. Without those, readers cannot assess the observed response frequency, the estimated difference between groups, or the uncertainty around that difference.

It also highlights the distinction between an endpoint’s biological rationale and the outcome actually measured. The stated purpose concerns immune induction and destruction of remaining cancer cells, while the primary endpoint counts participants meeting an anti-PSA T-cell response definition. Such an endpoint may address a mechanistic question, but it does not by itself demonstrate a downstream clinical effect.

The population description also demonstrates why analysis denominators matter. The registry identifies 21 evaluable participants on Arm A for the first outcome measure, while enrollment was 50. Those figures refer to different populations and cannot be treated as interchangeable. Clear arm-specific denominators, event counts, missing-data explanations, and analysis methods are needed to make a comparative result interpretable.

Finally, the safety record separates serious events, other events, and deaths, but offers limited context for those counts. Statistical interpretation requires attention to definitions and follow-up as well as the numbers themselves. In this record, the design and endpoint can be understood, but the absent primary analysis and limited outcome detail prevent a complete assessment of the trial’s statistical findings.

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 primary-outcome results are not reported in the registry record. Although the endpoint definition and timeframe are given, the number meeting the response definition, arm-specific denominators, between-arm estimate, and uncertainty are unavailable. The record’s analysis count is zero, so there is no reported statistical test or model to interpret.

The population statement identifies 21 evaluable participants on Arm A for outcome measure one, but does not explain how that population was formed or give the corresponding Arm B population. The enrollment of 50 does not resolve this missing information. One participant is described as lost to long-term follow-up for outcome measure three; the record does not specify whether any primary outcome data were missing or how missing observations were handled.

Although the trial is described as randomized, the sequence-generation and allocation-concealment procedures are not reported. The study is unmasked, and the record does not describe how the immune response was assessed in relation to treatment knowledge. The detailed vaccination schedule, ADT regimen, follow-up procedures, and analysis plan are also not reported in the registry record.

The primary outcome is an immune-response measure, whereas the stated purpose refers to destruction of remaining cancer cells. The record does not report results for the listed secondary outcomes on PSADT or vital status. Its safety counts lack event definitions, timing, attribution, and follow-up detail, limiting interpretation of the serious and other adverse-event categories and deaths. These gaps mean the registry supports a description of the trial, but not a full assessment of its primary comparative result.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase II Study of Adenovirus/PSA Vaccine in Men With Recurrent Prostate Cancer After Local Therapy APP21 — NCT00583752.
• Registry record last updated 2023-05-18; status last verified 2023-04.
• Results first posted 2023-05-18.
• 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

This completed phase II study was randomized, parallel-arm, and unmasked, with an enrollment of 50. It compared adenovirus/PSA vaccine alone with vaccine preceded by ADT, which began 14 days before vaccination in the combination arm. The primary outcome was the number of participants developing a strong or modest anti-PSA immune response at 18 months, defined in the record as an increase of >200% above pre-immunization anti-PSA T-cell levels measured by ELISPOT.

The registry describes 21 evaluable Arm A participants in the analysis population for outcome measure one, but does not report primary outcome counts or an arm-to-arm analysis. It lists secondary outcomes for PSADT and vital status, as well as safety counts by group. The record does not report the statistical analysis plan, missing-data methods, or the detail needed to attribute adverse events or deaths.