Two and Three Dimensional Contrast-enhanced Ultrasound for Screening of Renal Cell Carcinoma Recurrence Following Cryoablation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Two and Three Dimensional Contrast-enhanced Ultrasound for Screening of Renal Cell Carcinoma Recurrence Following Cryoablation (NCT02440334), a na phase 2 study. The primary outcome is The Sensitivity of Detecting RCC Recurrence (Using Contrast-enhanced MRI as a Reference Standard) on a Single Contrast-enhanced Ultrasound Exam..

2. Clinical Question

This is a diagnostic-imaging question, not a comparison of treatments intended to change cancer outcomes. The study asks whether ultrasound findings can identify recurrence in patients already scheduled for follow-up imaging after cryoablation. Contrast enhancement is intended to help assess vascularity, and the study description says ultrasound is performed with two- and three-dimensional curvilinear transducers.

The clinical comparison needs careful wording. The study description says that ultrasound examinations are compared with clinically scheduled MRI or CT. The primary endpoint, however, names MRI as its reference standard. The registry record does not clarify how CT examinations relate to the primary endpoint's MRI reference, or how discordant findings would be handled. It also does not report a sensitivity estimate, the number of recurrences, or the corresponding reference-standard results. Consequently, the clinical question is defined, but the posted registry information does not state the observed diagnostic performance.

3. Trial Design

The registry describes a completed Phase 2, single-group study with enrollment of 53. Its purpose was to assess contrast-enhanced ultrasound for screening renal cell carcinoma recurrence following cryoablation, in comparison with standard evaluation using contrast-enhanced CT or MRI. Each participant was scheduled for follow-up imaging after prior cryoablation and would also undergo a one-time contrast-enhanced ultrasound examination. Ultrasound findings were to be compared with the clinically scheduled MRI or CT examination.

The intervention is listed as Optison, a contrast agent described in the study summary as an FDA-approved ultrasound contrast agent used off-label in this study. The imaging procedure used a state-of-the-art ultrasound scanner with two- and three-dimensional curvilinear transducers. The planned assessment concerned post-cryoablation vascularity changes as a way to screen for recurrent disease.

This design is not a randomized comparison. The registry lists allocation as not applicable, masking as none, and the model as single group. There is no separate control group described. Thus, the comparison is between imaging assessments, not between two groups assigned to different treatments. The CT or MRI assessment is part of the clinical follow-up and functions as the comparator or reference, rather than as a randomized study arm.

The primary endpoint is described as sensitivity for detecting recurrence using contrast-enhanced MRI as the reference standard, with a timeframe of 8 months post cryoblation. The registry record is marked completed, with primary completion listed as 2017-12. It does not report the recruitment dates beyond the listed study start of 2015-04-23, nor does it give the number of participants who completed ultrasound, had an interpretable reference examination, or were included in the endpoint analysis. Those details are 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

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 The Sensitivity of Detecting RCC Recurrence (Using Contrast-enhanced MRI as a Reference Standard) on a Single Contrast-enhanced Ultrasound Exam., measured over 8 months post cryoblation.

The primary endpoint is the sensitivity of a single contrast-enhanced ultrasound examination for detecting renal cell carcinoma recurrence, using contrast-enhanced MRI as the reference standard. Sensitivity is a measure of how often a test identifies the condition among cases classified as having it by the chosen reference standard. For this endpoint, recurrence classification by MRI is the stated basis for judging whether ultrasound detected recurrence.

Sensitivity is relevant to a screening question because it focuses on detection among reference-standard-positive cases. It does not, by itself, describe how often ultrasound findings are positive among people without recurrence. Nor does sensitivity alone give the probability that a person with a positive ultrasound has recurrence; that interpretation also depends on other test characteristics and on how common recurrence is in the population being assessed. These are general properties of diagnostic measures, not additional findings from this study.

The endpoint title identifies MRI as the reference standard, while the study description says participants were scheduled for contrast-enhanced CT or MRI follow-up. The record does not explain whether every participant had MRI, how the reference standard was selected, or how imaging disagreement was resolved. Although the endpoint timeframe is listed as 8 months post cryoblation, no numerical sensitivity estimate, confidence interval, or underlying recurrence count is reported in the registry record. The endpoint is therefore defined, but its observed value and precision cannot be assessed from the posted registry results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is a binary diagnostic classification: an ultrasound examination either identifies recurrence or does not. The registry describes the primary endpoint as sensitivity, expressed as a percentage of patients, with contrast-enhanced MRI serving as the reference standard. The percentage format is appropriate for a proportion, but the registry record does not give the observed percentage or its underlying counts.

What does sensitivity describe?

In general, sensitivity is the proportion of reference-standard-positive cases that the test classifies as positive. The reference standard supplies the comparison classification used to evaluate the test. A positive ultrasound result that agrees with a positive MRI contributes to detection; a negative ultrasound result in a case classified as positive by MRI represents a missed case for this measure. Sensitivity is therefore conditional on the reference-standard classification, not on the ultrasound result.

This definition does not make the reference standard infallible. If the reference procedure misclassifies disease status, test-performance estimates can be affected. This is a general limitation of diagnostic-accuracy research. The registry names MRI as the reference standard for the primary endpoint, but does not report how MRI findings were interpreted, whether interpretation was blinded to ultrasound, or how disagreements were adjudicated. Masking is listed as none, so the record does not describe a masked study.

Why is the denominator important?

The sensitivity denominator consists of cases classified as having recurrence by the reference standard. It is not necessarily the full enrollment. The registry lists 53 enrolled participants, but does not report how many had an evaluable ultrasound, an evaluable reference examination, or a positive reference-standard result. Without those counts, a reader cannot reconstruct the endpoint or determine how much information supports it.

In general, a confidence interval describes uncertainty around an estimate under specified assumptions. For a diagnostic proportion, its width depends substantially on the number of relevant cases and on the observed proportion. A narrow interval indicates greater precision than a wide interval, but neither alone establishes whether a result is clinically useful. No confidence interval or interval method is reported for this endpoint in the registry record, and no numerical sensitivity result is listed.

How does this design differ from a treatment comparison?

The study is listed as single group, with allocation not applicable. Participants were to receive ultrasound as well as their clinically scheduled MRI or CT follow-up. This is a paired diagnostic comparison in concept: two imaging assessments concern the same participant. It is not a randomized trial comparing outcomes between assigned treatment groups. Consequently, methods for estimating a randomized treatment contrast are not the primary framework for interpreting the stated sensitivity endpoint.

For paired diagnostic assessments, complete and correctly linked results matter. The registry record does not state whether all ultrasound and reference examinations were performed close enough in time for the intended comparison, how missing or uninterpretable scans were treated, or whether every participant was assessed against MRI rather than CT. These details affect which observations enter a diagnostic-accuracy analysis. They are not reported in the registry record.

What can be inferred from the planning illustration?

The registry's planning illustration is described as a recalculation based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. Those assumptions describe an illustration, not the actual single-group imaging design. The record does not report the trial's own sample-size justification, so the illustration should not be treated as the original enrollment rationale.

Such sample-size calculations are planning exercises: they ask how many participants per arm would be needed under specified assumptions for a chosen power target. They do not show the probability that the completed study has detected an effect, and they are not observed power. Here, the illustrative equal-allocation, two-arm setup does not match the registry's single-group design. The observed endpoint estimate on which the illustration is said to be based is not reported in the registry record, so the illustration's numerical implications cannot be independently interpreted from the posted information.

More generally, the analysis plan can determine which participants count, how uncertain estimates are calculated, and whether multiple outcomes or comparisons are addressed. The registry record does not report a detailed statistical analysis plan, confidence-interval method, handling of repeated or indeterminate assessments, or interim analyses. None should be inferred from the endpoint description alone.

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("Contrast Ultrasound Reccurence Screening")
n      <- c(53)
events <- c(53)
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  Contrast Ultrasound Reccurence Screening  53  53  100.0  93.3  100.0  93.2  100.0  93.4  100.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 1 outcome measure, the sensitivity of a single contrast-enhanced ultrasound examination for detecting recurrence using contrast-enhanced MRI as the reference standard. It lists 0 analyses. The record does not report a multiplicity-adjustment method, a hierarchy of outcomes, or a detailed plan for testing more than one endpoint. A single listed outcome does not establish that no additional analyses were conducted; it means the posted registry information does not describe them.

Missing-data handling is also not reported in the registry record. It does not say how participants with absent, incomplete, or uninterpretable ultrasound or reference imaging were handled, whether they were excluded from the endpoint calculation, or whether any sensitivity analyses addressed missing results. These issues matter because sensitivity depends on the number of reference-standard-positive cases with usable paired results.

The analysis population is not defined in the posted record. Enrollment is listed as 53, but the record does not state how many participants completed imaging or contributed to the primary endpoint. It also does not describe an intention-to-diagnose population, a per-protocol population, or other endpoint-specific inclusion rules. The listed enrollment should therefore not be assumed to equal the number analyzed.

No interim analyses or stopping rules are reported in the registry record. Their absence from the entry is not evidence that such procedures did or did not occur; the record does not state them. Without a detailed analysis plan and participant flow, readers cannot determine how missing assessments, exclusions, or additional comparisons may have affected the reported analysis. No primary numerical analysis is posted against which to evaluate those decisions.

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 lists 53 participants at risk for serious adverse events in the contrast ultrasound screening group and 0 affected by a serious adverse event. Deaths are listed as 0. These are the serious-event figures recorded for the group; they do not provide a full description of all adverse events or all possible safety outcomes.

A count of 0 recorded serious adverse events should be read narrowly. It means the registry entry reports no participants affected by a serious adverse event in that category. It does not establish that no symptoms, non-serious events, or other problems occurred, and it does not by itself quantify risk with high precision. The record lists no serious adverse event terms, so it gives no event-specific descriptions.

Safety interpretation also depends on the duration and completeness of monitoring and on how events were defined and collected. Those details are not reported in the registry record. The study involved a one-time contrast-enhanced ultrasound examination and described off-label use of the FDA-approved ultrasound contrast agent Optison, but the posted serious-event counts alone do not characterize the full safety profile of the imaging procedure or agent.

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

The registry record describes a study intended to assess whether contrast-enhanced ultrasound can detect renal cell carcinoma recurrence after cryoablation when compared with follow-up imaging. The primary endpoint focuses on sensitivity, using contrast-enhanced MRI as the reference standard, and the stated timeframe is 8 months post cryoblation. This gives readers the diagnostic question the study was designed to address.

The posted record does not report the sensitivity estimate or its uncertainty. It therefore does not show how often ultrasound detected recurrence among MRI-positive cases, nor how precisely that performance was estimated. The record also does not report the number of recurrence cases, the number of usable paired examinations, specificity, or other diagnostic-accuracy measures. The design and endpoint should not be mistaken for evidence of a particular test-performance result.

Even a reported sensitivity value would answer only a defined part of the diagnostic question. In general, sensitivity alone does not show how often a test is positive when recurrence is absent, how results vary across patients, or what the consequences of false-positive and false-negative findings may be. It also would not establish that using ultrasound in place of another imaging procedure improves outcomes. Those questions require additional measures and, for clinical consequences, evidence beyond a sensitivity estimate.

The single-group design is suited to comparing imaging assessments, not estimating the causal effect of assigning one treatment rather than another. No randomized control group is described. The posted information therefore supports an account of the study's planned imaging comparison, but not a conclusion about comparative treatment benefit or patient outcomes. The registry entry is marked completed, yet the primary numerical result and analysis are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable because it poses a diagnostic-accuracy question within a single-group imaging study. The endpoint is sensitivity against a named reference standard, rather than a difference in clinical outcomes between randomized groups. That distinction determines what the analysis can answer: sensitivity concerns detection among reference-standard-positive cases, while treatment-effect methods address a different kind of comparison.

The reference standard and analysis population are central to interpreting diagnostic performance. The endpoint title names contrast-enhanced MRI, while the study description refers to clinically scheduled contrast-enhanced CT or MRI. The registry record does not explain how that distinction was handled in the analysis. It also does not state how many participants had complete, interpretable paired examinations or how many had recurrence by the reference standard. These omissions prevent assessment of the denominator and precision for sensitivity.

The record also illustrates why enrollment alone is not enough to assess an endpoint. Although enrollment is 53, the number contributing to the diagnostic analysis is not reported. A sensitivity estimate depends on relevant reference-standard-positive cases, not simply the total enrolled. Without the numerator, denominator, and uncertainty interval, readers cannot judge how stable an estimate would be or how well the study distinguishes among possible performance levels.

Finally, the record marks the study completed but lists 0 analyses and does not report a numerical primary result. The study question and intended comparison can be understood, but the posted registry information does not allow readers to assess the observed diagnostic performance. This separation between a clearly stated endpoint and an unavailable result is important when interpreting trial registries.

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 registry record leaves several trial-specific details unclear. The study description says participants scheduled for contrast-enhanced CT or MRI would also undergo ultrasound, while the primary endpoint specifies MRI as the reference standard. The record does not state whether all participants received MRI, whether CT results were used for any endpoint assessment, or how differing imaging findings were handled. This ambiguity limits understanding of the exact reference-standard procedure.

The record does not report the number of participants with recurrence, the number with complete and interpretable paired imaging, or the number included in the primary endpoint analysis. Although enrollment is listed as 53, that figure cannot be assumed to be the endpoint denominator. The sensitivity estimate, its confidence interval, and the underlying diagnostic classifications are also not reported, preventing evaluation of performance and precision.

Masking is listed as none. The record does not explain whether ultrasound readers knew MRI or CT results, or whether reference imaging readers knew the ultrasound results. It also does not describe how images were interpreted, how recurrence was defined for each modality, or whether indeterminate findings were possible and how they would be handled. These are relevant details for judging diagnostic-accuracy methods, but they are not reported in the registry record.

The trial is single group and does not describe randomized assignment. Its design therefore does not provide a randomized comparison of imaging strategies or a treatment-effect estimate. The registry record also does not report the original sample-size justification, a detailed statistical analysis plan, missing-data procedures, interim analyses, or a definition of the analysis population. The planning illustration described in the record uses a two-arm equal-allocation framework, which is not the stated single-group design and should not be read as the trial's actual design rationale.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Two and Three Dimensional Contrast-enhanced Ultrasound for Screening of Renal Cell Carcinoma Recurrence Following Cryoablation — NCT02440334.
• Registry record last updated 2025-05-04; status last verified 2025-05.
• Results first posted 2019-04-30.
• 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

NCT02440334 is a completed Phase 2, single-group study sponsored by Thomas Jefferson University. It enrolled 53 participants and evaluated a one-time contrast-enhanced ultrasound examination using Optison in patients scheduled for follow-up imaging after renal cell carcinoma cryoablation. The ultrasound used two- and three-dimensional imaging and was intended to assess vascularity changes associated with recurrence.

The primary endpoint was sensitivity for detecting recurrence, with contrast-enhanced MRI named as the reference standard and a timeframe of 8 months post cryoblation. The study description also refers to clinically scheduled contrast-enhanced CT or MRI. Allocation is listed as not applicable, masking as none, and the model as single group.

The registry lists 1 outcome measure and 0 analyses. It reports 0 participants affected by serious adverse events among 53 at risk, and 0 deaths. A numerical primary endpoint result, analysis population, confidence interval, and detailed handling of missing or discordant imaging results are not reported in the registry record.