A Phase II Neoadjuvant Study of Apalutamide, Abiraterone Acetate, Prednisone, Degarelix and Indomethacin in Men With Localized Prostate Cancer Pre-prostatectomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II Neoadjuvant Study of Apalutamide, Abiraterone Acetate, Prednisone, Degarelix and Indomethacin in Men With Localized Prostate Cancer Pre-prostatectomy (NCT02849990), a na phase 2 study. The primary outcome is Pathologic Complete Response Rate as Assessed From Prostatectomy Specimens Following Neoadjuvant Treatment.

2. Clinical Question

3. Trial Design

This was a phase II, completed, single-group study sponsored by the University of Washington. The registry records enrollment of 22 participants, a start date of 2017-03-09 and primary completion on 2018-12-10. It describes treatment before prostatectomy for men with prostate cancer. Registry conditions include Stage III and Stage IV prostate cancer and adenocarcinoma under AJCC v7.

The treatment arm combined apalutamide, abiraterone acetate, prednisone, degarelix and indomethacin. The record describes oral daily administration of apalutamide and abiraterone acetate, oral prednisone twice daily and oral indomethacin three times daily. Degarelix was administered subcutaneously on day 1 and every 4 weeks for 3 doses. The planned treatment duration was up to 12 weeks, subject to disease progression or unacceptable toxicity. The registry does not report further detail about treatment exposure or adherence.

There was no random allocation or masking, and the study is classified as a single-group model. Consequently, the design describes outcomes within the treated group; it does not establish a randomized treatment contrast. The registry does not report a control arm or a concurrent comparator.

The primary endpoint was pathologic complete response assessed from prostatectomy specimens at 3 months. Listed secondary outcomes include pathologic findings, margin and nodal status, overall survival, biochemical failure at 2 years, apoptotic index and receipt of adjuvant radiation therapy. The record lists 9 outcome measures in total, but does not report results for the primary endpoint or statistical analyses. The primary endpoint denominator and analysis population are also not reported in the registry record.

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:

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 Pathologic Complete Response Rate as Assessed From Prostatectomy Specimens Following Neoadjuvant Treatment, measured over At 3 months.

The primary endpoint is the count of participants with a pathologic complete response in prostatectomy specimens at 3 months. The registry defines pathologic complete response as no evidence of cancer on fully submitted prostatectomy specimens under standard surgical pathology assessment, using H&E assessment for this definition.

This endpoint uses a tissue assessment after surgery to characterize whether cancer is detected in the submitted specimen. A count can describe the observed number of participants meeting the definition; interpretation of that count as a rate also requires knowing the relevant denominator. The registry record does not report either the observed count or the number assessed, so it does not support an estimate of the response rate or its precision.

Pathologic findings are used in this setting because they directly describe the surgical specimen after neoadjuvant treatment. They are distinct from outcomes such as survival or biochemical failure, which concern events over time. The endpoint definition specifies an assessment at 3 months, but the record does not report the pathology results, how incomplete or unevaluable specimens were handled, or whether any further rules were applied to determine the endpoint.

The endpoint is a measure of the observed pathological response in this study. On its own, it cannot establish that the regimen caused a response or indicate how the result would differ under another treatment, because the design has no concurrent comparison group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a participant count as the primary endpoint. In general, a count endpoint records how many participants meet a prespecified definition. To interpret a count as a proportion, the denominator must also be clear: it should be the relevant set of participants whose outcomes could be assessed under the analysis definition. A percentage or rate should not be inferred from a count when the denominator is unreported. In this record, neither the primary endpoint count nor its denominator is reported.

What does the pathology definition mean?

The endpoint uses a pathological assessment of prostatectomy specimens. The registry definition requires no evidence of cancer on fully submitted specimens assessed using standard surgical pathology, with H&E assessment specified for the purpose of defining pathologic complete response. A prespecified definition is important because it determines which findings count as an endpoint event. Without reported specimen results and an analysis population, the endpoint definition alone does not tell readers how many participants met it.

The endpoint is assessed at 3 months. A fixed assessment time helps define when the status is evaluated, while the endpoint itself is a specimen finding rather than a time-to-event measure. The record does not describe how assessments outside the stated time, missing specimens or unevaluable findings were handled. Those details can affect which participants contribute to an observed count and how that count should be interpreted.

How would uncertainty normally be described?

In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical method. It communicates uncertainty around an estimate; it does not make an estimate causal and does not correct for limitations in study design. For a response proportion, the estimated proportion and the number assessed are needed to calculate an interval. The registry record reports no primary response estimate or confidence interval, so no precision estimate can be discussed for this endpoint.

A hypothesis test or p-value would address a specified statistical question under a stated model. For a single-group outcome, that question might concern comparison with a specified benchmark, but no such benchmark or primary statistical test is reported in the registry record. There is no reported p-value or analysis result for the primary endpoint. A p-value cannot be reconstructed from the endpoint definition or enrollment alone.

What can a single-group design estimate?

In general, a single-group study can describe outcomes in participants who received the study regimen. It does not create the like-for-like contrast that random allocation is intended to support. Without a concurrent comparator, an observed outcome cannot be separated from other explanations such as participant characteristics, underlying disease course, co-interventions or assessment practices. This is why an outcome count, even if reported, would not by itself demonstrate a treatment effect relative to another option.

The registry classifies this study as phase II, single-group, with allocation not applicable and no masking. The record does not describe a statistical analysis plan, planned hypothesis tests, sample-size justification or interim analyses. These elements should not be inferred from the phase designation or from the fact that enrollment was recorded.

Sample-size planning is distinct from observed precision and from evidence of an effect. In general, a planning calculation uses assumptions about the effect of interest, variability or event frequency, the significance level and desired power. Any planning illustration based on a hypothetical two-arm comparison would not change the actual single-group design. It would also not be observed power, which is not an appropriate substitute for interpreting the estimated effect and its uncertainty. The registry record does not report the study's own sample-size justification.

How should secondary outcomes be read?

The registry lists secondary outcomes that use different kinds of measurements, including counts, pathology findings and outcomes assessed over time. Each requires its own definition, denominator or follow-up information, and analysis method. Overall survival and biochemical failure, for example, concern time until an event or a specified follow-up status, whereas margin and nodal outcomes are pathological findings. The record does not report statistical analyses or results for these secondary outcomes, so their estimates and precision cannot be evaluated.

In general, over-dispersion matters when count data vary more than a chosen statistical model expects; ignoring it can make uncertainty estimates too narrow. That concept does not establish that over-dispersion occurred in this study. The registry record does not report a count model, a dispersion assessment or an analysis that would permit such a conclusion.

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("Treatment (Neoadjuvant Chemotherapy)")
n      <- c(20)
events <- c(1)
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  Treatment (Neoadjuvant Chemotherapy)  20  1  5.0  0.1  24.9  0.9  23.6  1.2  23.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary outcomes, with 9 outcome measures in total. When a study examines multiple outcomes, multiplicity is a general statistical concern: repeated testing can increase the chance of at least one apparently notable result if each outcome is assessed separately. Statistical plans may address this through prespecified outcome hierarchies or adjustments, but the registry record does not report whether any multiplicity strategy was planned or applied. No outcome analyses are posted, so the effect of any such strategy cannot be assessed.

Missing-data handling is also not reported in the registry record. The available information does not state how participants without a prostatectomy specimen, participants with unevaluable pathology, or other missing endpoint observations were handled. The record does not report whether missingness occurred. These are unknowns, not evidence that data were missing or that a particular method was used.

The analysis populations are not reported. Enrollment of 22 does not, by itself, identify how many participants were included in the primary endpoint analysis or in the secondary outcome analyses. The registry record does not specify an intention-to-treat population, a per-protocol population, or another analysis set.

The registry record also does not report a statistical analysis plan, sample-size justification or interim-analysis approach. These omissions mean that readers cannot determine from the posted record which tests, analysis populations, missing-data rules or multiplicity procedures governed the reported outcomes. Since outcome analyses are not reported, there is no basis for evaluating whether the analyses followed a prespecified plan.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry safety summary records 22 participants at risk for serious adverse events and 0 affected by serious adverse events. It records 22 participants at risk for other adverse events and 22 affected by other adverse events. Deaths are recorded as 0. The summary lists no serious adverse event terms.

These are counts in the posted registry summary, not a comparison between treatment groups. Because this was a single-group study, the figures do not provide a comparative safety estimate. The count for other adverse events does not describe the number of distinct events per participant or their individual characteristics. The record does not provide event-level detail, timing, duration, severity for other adverse events, or information about how events were collected and classified.

A count of 0 serious adverse events in the registry summary should be read as a descriptive entry for this study, not as proof that serious harms are impossible or that the regimen has no safety risks. The available figures also do not establish how completely participants were followed for adverse events. Interpretation is limited to the counts and categories reported in the registry record.

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

The registry record establishes that a phase II, single-group study enrolled 22 participants and evaluated a neoadjuvant regimen before prostatectomy. It defines pathologic complete response as no evidence of cancer in fully submitted prostatectomy specimens under standard surgical pathology assessment using H&E assessment, with the primary endpoint assessed at 3 months. It also gives descriptive adverse-event counts.

The record does not report the observed primary endpoint count, denominator, response rate, confidence interval or statistical test. It therefore does not show how frequently pathologic complete response occurred in the analyzed participants, nor how precisely that frequency could be estimated. A missing result in the registry record should not be interpreted as a zero response or as evidence for either a favorable or unfavorable outcome.

Even a reported response count from this design would describe the treated group rather than establish what would have happened under a different treatment. With no concurrent comparator and no random allocation, a treatment contrast cannot be estimated directly. General explanations such as changes in disease status, participant selection or other aspects of care cannot be separated from treatment effects by a single-group result alone.

The safety summary reports 0 serious adverse events among 22 at risk, 22 participants with other adverse events among 22 at risk, and 0 deaths. These figures describe the registry entries; they do not show comparative risk, detailed event patterns or the absence of unreported events.

Accordingly, the posted record supports a description of the design, regimen, endpoint definition and summary safety counts. It does not support a conclusion about the size or precision of the primary response, a causal treatment effect, or comparative safety. Results for the listed secondary outcomes are also not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between an endpoint definition and an endpoint result. The registry precisely describes what counted as pathologic complete response, including the specimen assessment and the 3-month timing. However, it does not report the number of participants meeting that definition, the number assessed or an estimate with uncertainty. A clearly defined outcome cannot be interpreted quantitatively without the corresponding observations and denominator.

It also illustrates how design determines the scope of statistical conclusions. The single-group structure can support descriptive reporting of outcomes among participants treated, but it does not provide a randomized comparison. This distinction matters when readers encounter a clinical question framed around how well a regimen works: a study's question and its ability to answer a comparative question are not the same thing.

The record's safety entries offer another statistical lesson. Counts of participants affected are useful descriptive information, but they do not convey the full pattern of events, timing or severity. Nor do they estimate comparative risk without a comparison group. A zero count in one category is a statement about the recorded observations, not a guarantee about risk beyond those observations.

Finally, the absence of posted analyses leaves key interpretive elements unknown. The analysis population, handling of missing endpoint data, multiplicity approach, confidence intervals and statistical testing are not reported. These details determine how estimates are constructed and how uncertainty should be assessed. This case therefore shows why registry design information, endpoint definitions, observed results and analysis methods need to be considered together when interpreting a clinical trial.

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 efficacy is that the registry record does not report the primary endpoint result. It gives no pathologic complete response count, denominator, rate or measure of uncertainty. Although enrollment is 22, the number of participants who underwent prostatectomy or had evaluable specimens is not reported. The endpoint result therefore cannot be reconstructed from the enrollment figure.

The design is single-group and has no concurrent comparator. Any outcome reported for treated participants would be descriptive rather than a direct randomized estimate of a treatment difference. The registry does not report a statistical analysis plan, the analysis population, missing-data methods, multiplicity handling, sample-size justification or interim analyses. Their absence from the record prevents assessment of those analytic choices; it does not establish which choices were made.

The registry describes the regimen and its intended duration as up to 12 weeks, but does not report actual treatment exposure, adherence or reasons for stopping. It also does not report further details about eligibility or the characteristics of the participants included in any endpoint analysis. These omissions limit assessment of who contributed to the outcomes and how representative the analyzed group may have been.

The safety summary is limited to participant counts by broad categories. It gives no listed serious adverse event terms and no event-level descriptions for other adverse events. The record also does not provide comparative safety data. The listed secondary outcomes have no reported results or statistical analyses, limiting interpretation beyond the primary question and the descriptive safety entries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase II Neoadjuvant Study of Apalutamide, Abiraterone Acetate, Prednisone, Degarelix and Indomethacin in Men With Localized Prostate Cancer Pre-prostatectomy — NCT02849990.
• Registry record last updated 2022-01-13; status last verified 2021-12.
• Results first posted 2020-01-18.
• 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.

19. Record Summary

The registry describes a completed phase II, single-group neoadjuvant study sponsored by the University of Washington. Enrollment was 22. The recorded start date is 2017-03-09 and primary completion date is 2018-12-10. Participants received apalutamide, abiraterone acetate, prednisone, degarelix and indomethacin before prostatectomy, with treatment planned for up to 12 weeks subject to disease progression or unacceptable toxicity.

The primary endpoint was pathologic complete response in prostatectomy specimens at 3 months, defined as no evidence of cancer on fully submitted specimens using standard surgical pathology assessment with H&E assessment. The primary endpoint result and its analysis denominator are not reported in the registry record. The registry lists 9 outcome measures and no analyses.

The safety summary records 0 serious adverse events among 22 at risk, 22 participants with other adverse events among 22 at risk, and 0 deaths. The design has no concurrent comparator, so the record does not provide a randomized treatment contrast.