Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer (NCT03570476), a na phase 2 study. The primary outcome is Pathologic Complete Response (pCR) Rate.

2. Clinical Question

The clinical question is about a short preoperative treatment course and a tissue-based finding at surgery, not about a comparison of long-term outcomes between treatment groups. The registry describes a phase II, open-label pilot study sponsored by the University of Washington. Its stated rationale is that olaparib may interfere with PARP activity inside cells and may affect tumor growth. That rationale is not itself evidence of an observed response in this study. The record gives the planned regimen and the endpoint definition, but not a reported pCR count or rate. It also does not report whether all enrolled participants received the full course or underwent the planned surgery.

3. Trial Design

The registry describes an open-label, phase II pilot study of olaparib as neoadjuvant therapy for participants with localized prostate cancer undergoing prostatectomy. Its model is single-group, with allocation recorded as NA and masking as none. Thus, the treatment experience is not compared with a concurrent control arm in this study. Enrollment was 2, and the status is terminated. The registry dates the study start to 2018-09-11 and primary completion to 2019-05-31.

Participants in the treatment group were to receive olaparib orally twice daily for 90 days in the absence of unacceptable toxicity. Radical prostatectomy was to begin 1 day after the last olaparib dose. The primary endpoint was assessed at the time of prostatectomy, specified as at 12 weeks. This sequence makes the surgical specimen the basis for the main tissue-response assessment. The registry lists rate of positive surgical margins and stage of disease as secondary outcomes, and states that there are 4 outcome measures overall.

The record does not report a control condition, randomization, masking, or a between-group treatment estimate. It also does not report the reason for termination, the number who completed olaparib, whether surgery took place for each participant, or the number with an evaluable specimen. Those details are not reported in the registry record. The distinction matters: the treatment plan is described, but it should not be mistaken for a completed exposure history or an outcome result. The registry records 0 analyses. Consequently, the available results do not include a statistical analysis of the primary endpoint or the secondary outcomes.

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 Pathologic Complete Response (pCR) Rate, measured over At time of prostatectomy (at 12 weeks).

The primary endpoint is the pathologic complete response (pCR) rate at prostatectomy, with assessment specified at 12 weeks. A pCR is defined in the registry as absence of morphologically identifiable carcinoma in the prostatectomy specimen, assessed according to recommendations of the International Society of Urological Pathology. The endpoint is expressed as a participant count and a percent in its description.

As a general statistical concept, a pathology-based endpoint can provide a direct assessment of tumor presence in tissue removed during surgery. It differs from a symptom measure or a time-to-event endpoint: it is based on examination of the surgical specimen at a defined assessment point. The endpoint can only be interpreted for participants with an evaluable specimen, and the denominator used to calculate a rate is important. The registry record does not report an evaluable-participant count, a pCR count, or a pCR rate. It therefore does not establish how many participants met the endpoint or what denominator would apply to a rate calculation.

The endpoint definition describes what would count as pCR; it does not establish that pCR occurred. Nor does a pathology finding by itself provide a comparison with outcomes under another treatment. With a single-group design and no posted pCR result, the registry record does not permit an estimate of treatment effect or a comparative conclusion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry records a single-group study with no allocation and no masking. It reports 0 analyses. No statistical analysis method for the primary or secondary outcomes is reported in the registry record. The endpoint is described as a participant count, while the primary outcome description refers to a percent. Because the posted results do not give a pCR count or analysis denominator, no observed response rate or estimate of uncertainty can be interpreted from this record.

What a response rate would describe

As a general statistical concept, a response rate is the number of participants meeting a defined response criterion divided by the relevant analysis population. The response criterion is the absence of morphologically identifiable carcinoma in the prostatectomy specimen. The analysis population and denominator matter: participants who did not undergo surgery or did not have an evaluable specimen may affect how a rate is defined. The registry does not report how such cases were handled, or whether any participants lacked an evaluable specimen. Without both the response count and the denominator, the rate cannot be determined.

A confidence interval is a range of values compatible with the data under a stated statistical method. It communicates sampling uncertainty around an estimate; it is not a guarantee that the true value lies in the interval. General statistical principle: a small amount of information tends to produce substantial uncertainty. For this study, there is no posted pCR estimate or confidence interval to interpret. No interval should be inferred from enrollment alone, because the outcome count and analysis population are not reported.

Why a control group matters

As a general statistical concept, a comparison group helps distinguish outcomes associated with an intervention from outcomes that might also occur without it or under another treatment. This registry record describes a single group receiving olaparib before prostatectomy. It therefore cannot yield a randomized between-group contrast. Even if a pCR result had been posted, the design would support a descriptive account of the participants in the study, rather than a direct estimate of the difference between olaparib and a control condition.

The study is open-label, with masking recorded as none. In general, knowledge of treatment can affect behavior, assessment, or reporting, depending on the outcome and study procedures. The primary endpoint is based on pathology, but the registry does not describe further safeguards or assessment procedures beyond reference to ISUP recommendations. It would be speculative to characterize how open-label conduct affected assessment in this study.

Planning illustrations and observed evidence

The registry's planning assumptions describe an illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such illustrations are not the trial's design or observed evidence. General statistical principle: a planning calculation asks what sample size might be needed under specified assumptions; it does not show the probability that a completed study has established an effect. A planning illustration is not observed power and should not be read as a result from the participants.

The assumptions specify participants per arm for outcomes other than time-to-event outcomes, and total events for time-to-event outcomes. They also refer to detecting a stated fraction of the observed effect. The current study is single-group, and the registry does not report a primary endpoint effect estimate. Thus, the two-arm planning assumptions do not describe the study's actual allocation, and no observed treatment contrast is available to ground an effect-based calculation. Any such sample-size figures are planning illustrations rather than evidence about the outcome in this study.

Multiplicity and outcome selection

Multiplicity arises when several endpoints or analyses are considered, because repeated testing can increase the chance of at least one apparently positive result. The registry lists the primary pCR endpoint, the secondary outcomes of positive surgical margins and disease stage, and 4 outcome measures overall. It does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or an analysis plan. Nor does it report completed analyses. The statistical handling of multiple endpoints is therefore not reported in the registry record. General statistical principle: the prespecified primary endpoint is usually distinguished from exploratory outcomes, but no further inferential interpretation is possible without the analysis plan and results.

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 (Olaparib, Radical Prostatectomy)")
n      <- c(2)
events <- c(0)
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 (Olaparib, Radical Prostatectomy)  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies pathologic complete response as the primary endpoint and lists rate of positive surgical margins and stage of disease as secondary outcomes. It reports 4 outcome measures overall and 0 analyses. A multiplicity strategy—such as a hierarchy for testing outcomes or an adjustment for multiple comparisons—is not reported in the registry record. Because no analyses are posted, there are no reported p-values or estimates to assess in light of multiple testing. General statistical principle: when several outcomes are tested, interpretation should account for how the testing plan handles the chance of false-positive findings. The record does not permit that assessment.

The handling of missing outcome data is also not reported. In particular, the record does not state whether all enrolled participants received the intended olaparib course, underwent prostatectomy, or had pathology suitable for pCR assessment. It does not describe how participants without an evaluable specimen would be counted in an endpoint denominator. These details affect how a rate would be defined and interpreted.

Analysis populations are not described. The registry does not specify whether the primary endpoint was to use all enrolled participants, only those who received treatment, or only those with evaluable surgery specimens. No participant flow or outcome-specific denominator is reported. General statistical principle: reporting the analysis population and accounting for missing outcomes helps readers understand who contributed to each estimate and the possible effect of incomplete data. With these details absent and no endpoint results posted, the primary outcome cannot be reconstructed or assessed for missing-data sensitivity.

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.

The registry safety fields report 0 participants with serious adverse events among 2 at risk, 0 with other adverse events among 2 at risk, and 0 deaths in the treatment group. The serious and other adverse-event counts are distinct categories in the record; neither category should be treated as a description of a particular symptom or event. No serious adverse event terms are listed.

These figures are counts reported by the registry, not a comparison of risk between olaparib and another treatment. There is no concurrent control group, and the record reports no event-rate analysis. It also does not report detailed exposure duration for each participant, follow-up completeness, or whether all participants completed the planned treatment. Consequently, the counts should not be used to infer a comparative safety profile or to conclude that the treatment caused no adverse effects.

General statistical principle: a zero count means that no event was recorded in the specified category for the recorded group; it does not establish that the underlying event risk is zero. Interpretation also depends on the number of participants observed and the completeness of event collection. Here, enrollment was 2, but the registry does not provide further detail on safety ascertainment or follow-up. The figures are best read narrowly as the posted registry counts.

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

The record establishes that a phase II, open-label, single-group pilot study of olaparib before prostatectomy was registered, with enrollment of 2 and status recorded as terminated. It describes the intended dosing schedule and defines pCR at surgery as the absence of morphologically identifiable carcinoma in the prostatectomy specimen. It also reports the safety counts in the treatment group. These are details about the design and the posted registry fields.

The record does not establish the pCR result. No pCR count, rate, or analysis is reported. It also does not report how many participants completed treatment, had surgery, or contributed evaluable pathology. Thus, the outcome the study set out to measure cannot be assessed from the posted results. The absence of a reported endpoint is not evidence that the endpoint was absent; it means the result is not reported in the registry record.

The study also cannot provide a treatment-versus-control estimate because it has no concurrent comparator. General statistical principle: a result observed in a single group does not, on its own, show what would have happened to comparable participants under another approach. This record provides no comparative estimate, and no treatment effect should be inferred from the design description or stated rationale.

The safety fields show zero recorded serious adverse events, other adverse events, and deaths among the reported group counts. Those figures do not demonstrate that there was no risk, and they do not indicate how safety compares with another treatment. The reason the study was terminated, the completeness of follow-up, and the handling of missing data are not reported in the registry record. The appropriate interpretation is therefore limited: the registry describes a planned preoperative regimen and endpoints, but the posted results do not answer the primary efficacy question or support a comparative safety conclusion.

14. Why This Trial Matters Statistically

This study is statistically instructive because it separates a clearly described endpoint from an endpoint result. The registry defines pCR in terms of pathology at prostatectomy and specifies the assessment timing. That makes the intended outcome recognizable, but a definition alone is not an estimate. Without the pCR count, denominator, or analysis, the primary result cannot be quantified or evaluated for precision.

The single-group design also shows why design information matters when reading outcome claims. There is no randomized control comparison in the registry record, so the study cannot estimate a difference between olaparib and another treatment. General statistical principle: a comparison is needed to directly describe how outcomes differ between treatment conditions. A single-group observation, even when fully reported, has a narrower interpretation.

Enrollment of 2 highlights the importance of sample size and uncertainty, while the record's lack of outcome reporting prevents a numerical assessment of precision. The registry's sample-size assumptions are planning illustrations based on an observed effect, not evidence that the trial had a particular probability of detecting an effect. They use equal allocation between two arms, whereas the trial design is single-group. Keeping planning assumptions distinct from observed study results is essential for avoiding misleading interpretation.

Finally, the terminated status and the reported zero safety counts should be read in context. The reason for termination and details of outcome completeness are not reported in the registry record. The safety counts are descriptive registry entries, not proof of absence of risk. Together, these features make the record a useful example of why trial status, design, endpoint definition, analysis population, and posted results must be considered separately.

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 main limitation for interpretation is that the registry does not report the primary endpoint result or any analysis. The pCR count, rate, analysis denominator, and uncertainty estimate are absent. The record also does not report results for the listed secondary outcomes. Although 4 outcome measures are recorded, their result details are not available in the posted results.

Enrollment was 2, and the study is single-group. The small enrollment constrains the amount of information available, while the lack of a comparator prevents a direct treatment contrast. No statistical analysis is posted to address uncertainty or adjust for other factors. The registry does not report the sample-size justification or an analysis plan for this study. The generic planning assumptions do not substitute for those details and do not establish an observed effect.

The record does not report the reason for termination, whether each participant received the intended course, whether surgery occurred for each participant, or whether each specimen was evaluable. It also does not describe the analysis populations, handling of missing data, or completeness of follow-up. Those omissions limit interpretation of both efficacy and safety counts.

The safety results are confined to the registry counts for serious adverse events, other adverse events, and deaths. No serious-event terms are listed, but further event descriptions and ascertainment details are not reported. Finally, the open-label design has no masking, and no further pathology-assessment procedures are described beyond the stated ISUP recommendations. These limitations should not be filled in by assumption.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer — NCT03570476.
• Registry record last updated 2020-09-21; status last verified 2020-07.
• Results first posted 2020-09-21.
• 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 University of Washington sponsored this phase II, open-label pilot study of olaparib before radical prostatectomy for localized prostate cancer. The registry records a single-group design, no allocation, no masking, enrollment of 2, and terminated status. The study start is listed as 2018-09-11 and primary completion as 2019-05-31.

The intended regimen was oral olaparib twice daily for 90 days unless unacceptable toxicity occurred, followed by radical prostatectomy beginning 1 day after the last dose. The primary endpoint was pCR at prostatectomy, at 12 weeks, defined as absence of morphologically identifiable carcinoma in the specimen. Positive surgical margins and disease stage were listed as secondary outcomes.

The registry reports 0 serious adverse events among 2 at risk, 0 other adverse events among 2 at risk, and 0 deaths. It reports 0 analyses. The primary outcome result, reason for termination, analysis populations, and handling of missing data are not reported in the registry record.