Evaluation of Gallium-68-HBED-CC-PSMA Imaging in Prostate Cancer Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Gallium-68-HBED-CC-PSMA Imaging in Prostate Cancer Patients (NCT02611882), a non-randomized phase 2 study. The primary outcome is Sensitivity of Ga-68 HBED-CC PSMA for Detection of Nodal Metastases.

2. Clinical Question

3. Trial Design

This is a phase 2, non-randomized, parallel study of Ga-68-HBED-CC-PSMA imaging in prostate cancer. The registry lists enrollment as 225 and the study status as completed. The recorded start date is 2015-12-18, and the primary completion date is 2016-10-24. These dates describe the study record; they do not provide the timing of each participant's imaging or pathology assessment.

Three populations are described: high-risk prostate cancer before prostatectomy (preRP), biochemical recurrence (BCR), and castrate resistant prostate cancer (CRCP). Each population received the imaging agent and underwent PET/CT or PET/MRI. The descriptions specify imaging approximately 55-70 minutes after administration. The registry does not report how the imaging modality was chosen, whether the same modality was used for all participants in a group, or whether any participant received both modalities.

There is no randomized allocation and no masking. The populations represent different clinical settings rather than randomized treatment arms, so comparisons among them would not have the interpretation of a controlled comparison. Their underlying clinical characteristics and reasons for imaging may differ. The registry record does not report details of recruitment, eligibility criteria, exclusions, protocol deviations, or the numbers imaged and evaluated for each outcome.

The primary outcome is sensitivity for detection of nodal metastases, assessed using pathology to classify imaging findings. Its stated timeframe is 1 day. The record also names secondary outcomes concerning detection rates by PSA levels in the BCR group and reported changes in medical management in that group. Numerical findings for those outcomes are not reported in the registry record. The record lists six outcome measures but no analyses.

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.

Population: No participants were enrolled in the CRCP arm of this protocol

6. Primary Endpoint

The registry lists the primary outcome as Sensitivity of Ga-68 HBED-CC PSMA for Detection of Nodal Metastases, measured over 1 day.

The primary endpoint is the sensitivity of Ga-68 HBED-CC PSMA imaging for detection of nodal metastases. Sensitivity is the proportion of participants with pathology-positive nodal disease whose imaging result is positive. In the registry definition, positive imaging with positive pathology is a true positive, while positive pathology with negative imaging is a false negative. These classifications determine the true-positive rate.

Pathology serves as the reference classification in this endpoint. The registry also defines true negatives and false positives, although those classifications are not themselves the named primary endpoint. Sensitivity answers a focused question about detection among cases that pathology identifies as positive; it does not, on its own, describe how often a positive scan is correct among all positive scans. That latter question involves a different measure.

The endpoint is useful for describing detection performance against the specified reference, but its interpretation depends on who underwent imaging and pathology and how those assessments were conducted. The registry lists a 1-day timeframe and says the point estimate is to be reported with a 95% confidence interval. The sensitivity estimate, interval, and underlying classification counts are not reported in the registry record. As a result, neither the estimated detection rate nor its precision can be evaluated from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does sensitivity measure?

Sensitivity is a conditional proportion: among cases classified as positive by the reference method, it is the share that the test under study also classifies as positive. In this study, the registry identifies pathology as the reference for nodal status and imaging as the test being assessed. A pathology-positive case with positive imaging contributes to the true-positive count. A pathology-positive case with negative imaging contributes to the false-negative count. Sensitivity is based on those two categories. It is not the same as the fraction of all participants with a positive scan, and it does not by itself indicate how likely a positive scan is to be correct.

The registry also describes true negatives and false positives. These categories concern participants whose pathology is negative and distinguish those with negative from those with positive imaging. They are relevant to other measures of diagnostic performance, but the stated primary outcome is sensitivity. The record does not report the category counts or additional diagnostic performance estimates.

Why report a confidence interval?

A point estimate gives a single summary of the observed data. A confidence interval adds information about statistical uncertainty around that estimate. In general, estimates based on fewer reference-positive cases tend to be less precise, while more information can support greater precision. The interval is not a guarantee that the true value lies within its endpoints, nor does it remove limitations in how participants were selected or how measurements were made.

The registry says that sensitivity would be reported with a 95% confidence interval. It does not report the estimate, interval, or the number of pathology-positive cases used in the calculation. This means the precision cannot be judged. Without the underlying counts, readers also cannot check how the estimate relates to the observed true-positive and false-negative classifications.

What does the study structure permit?

The study is non-randomized, unmasked, and described as parallel. It includes distinct clinical settings: high-risk disease before prostatectomy, biochemical recurrence, and castrate resistant prostate cancer. These are not randomized control arms. In general, randomization can help make groups comparable for a treatment comparison; it does not apply to this study's recorded allocation. Differences across the populations should therefore not be read as causal effects of one imaging approach or population versus another.

The record names PET/CT and PET/MRI but does not state how participants were assigned to a modality, whether modality selection followed a consistent rule, or whether the modality-specific results were evaluated separately. It also does not report masking of image readers or pathology assessors. These omissions limit assessment of potential differences in measurement or interpretation. The registry describes imaging approximately 55-70 minutes after administration, but does not give additional acquisition or reading procedures.

What can be inferred from a missing result?

The absence of a reported estimate is not evidence that the estimate was high, low, or otherwise favorable or unfavorable. It means the registry record does not provide the numerical result needed to characterize performance. The record lists six outcome measures and zero analyses. No numerical primary result or confidence interval is reported. General statistical interpretation cannot substitute for those missing observations.

Similarly, a listed enrollment figure does not establish how many participants contributed to each endpoint. Participants can be excluded from an analysis or lack a required reference assessment, and the registry does not report outcome-specific analysis populations or missingness. It is not possible to infer the number with both imaging and pathology results from the enrollment entry alone.

The record includes a general sample-size planning description based on an observed effect, two-sided significance level 0.05, equal allocation, and a normal approximation. It does not give numerical sample-size illustrations in the record summarized for this analysis. Such planning calculations, when available, are hypothetical design illustrations rather than observed results or observed power. They cannot answer the primary diagnostic question or replace a confidence interval for the actual endpoint.

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("High-risk Prostate Cancer Pre-prostatectomy (preRP", "Biochemical Recurrence (BCR) Population")
n      <- c(42, 72)
events <- c(0, 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  High-risk Prostate Cancer Pre-prostatectomy (preRP  42  0  0.0  0.0  8.4  -0.0  8.4  0.1  8.2
ARM  Biochemical Recurrence (BCR) Population  72  1  1.4  0.0  7.5  0.2  7.5  0.3  7.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures, including the primary sensitivity endpoint and secondary outcomes concerning BCR detection rates by PSA levels and reported changes in medical management. It lists zero analyses. No multiplicity adjustment, hierarchy among secondary outcomes, or strategy for interpreting multiple tests is reported in the registry record. In general, evaluating multiple outcomes can increase the chance of obtaining at least one apparently notable result by chance; prespecified priorities and adjustment methods can help clarify how such results should be interpreted. The record does not provide enough information to determine whether or how those issues were addressed.

Missing-data methods and analysis populations are not reported in the registry record. The entry does not say how participants with missing imaging, pathology, or follow-up information were handled, whether all enrolled participants were included in each analysis, or whether any sensitivity analyses were conducted. These details matter because the endpoint depends on both imaging and pathology classifications. If either is unavailable, a participant's contribution to the sensitivity calculation may be uncertain or absent.

The enrollment entry is 225, but the number contributing to the primary endpoint is not reported. The record also does not provide group-specific primary outcome denominators, exclusions, or the counts underlying the diagnostic classifications. No interim analyses or statistical analysis plan are reported in the registry record. As a result, the prespecification and handling of incomplete data and multiple outcomes cannot be assessed from the posted information.

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.

The registry's adverse-event entries report zero serious adverse events and zero other adverse events among 75 at risk in the high-risk pre-prostatectomy population. For the BCR population, the record reports zero serious adverse events and zero other adverse events among 150 at risk. Deaths are recorded as zero in both listed populations. A safety group for the CRCP population is not included in these adverse-event entries.

These figures describe what is entered in the registry; they do not establish that no adverse events occurred outside the recorded categories or reporting period. The time period for adverse-event collection, event definitions, ascertainment procedures, and handling of missing safety information are not reported in the registry record. The record does not provide further detail about exposure or safety assessment for the CRCP population.

Zero recorded events should therefore be read as a registry count, not as proof of zero risk. The counts also do not establish a comparative safety advantage: the study is non-randomized and does not include a like-for-like control comparison. These entries are separate from the missing primary diagnostic performance result.

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

The registry record establishes that the study evaluated Ga-68-HBED-CC-PSMA imaging in three prostate cancer populations and specified sensitivity for nodal metastasis detection as its primary outcome. It describes comparison of imaging findings with pathology and specifies that the sensitivity estimate would have a 95% confidence interval. This is enough to identify the diagnostic question the study was designed to address, but not enough to quantify the answer.

The primary estimate and its confidence interval are not reported in the registry record. Nor are the true-positive and false-negative counts or the number of participants contributing to the endpoint. Consequently, the posted results do not show how often imaging detected pathology-positive nodal disease or how precise such an estimate was. The record's completed status does not supply that missing evidence.

The registry also names secondary outcomes related to BCR detection rates by PSA levels and reported changes in medical management. Numerical results for those outcomes are not reported. A recorded management change, even if available, would describe a change in care rather than demonstrate its effect on subsequent health outcomes. No inference about that effect can be made from the outcome name alone.

The adverse-event entries report zero events in the two listed populations, but do not provide enough information to establish the completeness or timing of safety ascertainment. They should not be interpreted as proof of no risk. The record offers no randomized control comparison, so it cannot support causal conclusions based on differences among its clinical populations.

In general, a diagnostic performance claim requires the observed results and adequate detail about how the test and reference standard were assessed. Those numerical results and several relevant analysis details are not reported. The registry description therefore characterizes the study question and design, but does not permit a conclusion about the magnitude or precision of the primary diagnostic performance.

14. Why This Trial Matters Statistically

This study is statistically relevant because it frames imaging performance against a pathology reference rather than treating a positive scan as self-validating. Its primary endpoint is sensitivity for nodal metastases, which focuses on detection among pathology-positive cases. The endpoint definition distinguishes true positives and false negatives, making clear what information would be needed to estimate the true-positive rate.

The record also illustrates why an endpoint definition and an endpoint result are different kinds of information. It names the estimate and a 95% confidence interval as intended summaries, but neither is reported. Without the numerical estimate, interval, and contributing classification counts, readers cannot judge either detection performance or statistical precision. The record's listing of six outcome measures alongside zero analyses reinforces the distinction between outcomes named in a registry and analyses reported there.

The three clinical populations also make interpretation important. They represent different disease settings and are not randomized comparison groups. Even if population-specific results were reported, differences could not automatically be attributed to imaging modality or to a treatment effect. The record does not provide such primary endpoint results.

Finally, the study connects diagnostic imaging with a secondary question about reported management changes in BCR. This distinction matters: evidence that a scan changes decisions is not itself evidence about the consequences of those decisions. The registry record identifies the question but does not report its numerical answer. Thus, the record is useful for understanding the planned diagnostic focus and the limits of the available results, while leaving the central performance estimate unresolved.

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 record is that the numerical result for the named primary endpoint is not reported. The sensitivity estimate, its 95% confidence interval, and the underlying true-positive and false-negative counts are absent. The number of participants contributing to the endpoint and any population-specific estimates are also not reported. This prevents assessment of the magnitude and precision of diagnostic performance.

The registry describes pathology as the reference method but does not report detailed procedures for pathology assessment, image interpretation, or adjudication of discordant findings. Masking is listed as none, but the record does not specify which study personnel, if any, knew the results of other assessments. Imaging could be performed with PET/CT or PET/MRI; the method for selecting the modality and separate results by modality are not reported.

The non-randomized design and distinct clinical populations preclude treating the groups as comparable control arms. The record does not give detailed eligibility criteria, baseline characteristics, or population-specific endpoint denominators. It also does not report missing-data handling, analysis populations, interim analyses, or a statistical analysis plan. These gaps make it difficult to assess selection, measurement, and analysis risks.

Secondary outcome values are not reported, and no analyses are listed. Safety entries cover the preRP and BCR populations but do not list a safety group for CRCP; adverse-event collection timing and methods are also not reported. These omissions limit interpretation of both outcome completeness and safety reporting.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Gallium-68-HBED-CC-PSMA Imaging in Prostate Cancer Patients — NCT02611882.
• Registry record last updated 2020-12-22; status last verified 2020-11.
• Results first posted 2020-12-22.
• 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 record describes a completed phase 2, non-randomized, unmasked, parallel imaging study with enrollment listed as 225. It evaluated Ga-68-HBED-CC-PSMA with PET/CT or PET/MRI in high-risk prostate cancer before prostatectomy, biochemical recurrence, and castrate resistant prostate cancer. Imaging was described as occurring approximately 55-70 minutes after administration.

The primary outcome is sensitivity for nodal metastasis detection using pathology as the reference, with a stated timeframe of 1 day. The registry describes a point estimate and 95% confidence interval, but the result and interval are not reported. The record lists six outcome measures and zero analyses. It also names secondary BCR outcomes concerning detection by PSA levels and reported changes in medical management, without numerical findings.

Adverse-event entries report zero serious and zero other events in the preRP and BCR populations, and zero deaths in both listed groups. The record does not provide the timing and methods of safety assessment or a CRCP safety entry.