Detection of SLN in Patients With Endometrial Cancer Undergoing Robotic Assisted Staging: Comparison of ISB and ICG: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Detection of SLN in Patients With Endometrial Cancer Undergoing Robotic Assisted Staging: Comparison of ISB and ICG (NCT02068820), a randomized na study. The primary outcome is Number of Pelvic Sentinel Lymph Nodes (SLN) in Endometrial Cancer Patients Detected by Either ICG and/or ISB Dyes..

2. Clinical Question

The clinical question is about the number of pelvic sentinel lymph nodes (SLNs) detected during robotic-assisted staging. The registry describes a randomized, parallel-group comparison, with 20 participants in the ISB-only group and 180 in the ICG group. The ICG group received ISB and standard white-light imaging first, then ICG and FireFly fluorescence imaging. Thus, the comparison concerns the addition of a fluorescence-imaging approach in that group, while the other group used ISB with standard white light.

The primary outcome is a count of detected pelvic SLNs, summarized as a mean. It is not itself a measure of diagnostic sensitivity, specificity, negative predictive value, cancer recurrence, or survival. The study summary discusses the potential relevance of SLN biopsy to those diagnostic and surgical questions, and one secondary outcome is named as negative predictive value in relation to the number of nodes with metastasis. However, the registry record does not report results for that secondary outcome. The posted primary results therefore address lymph-node counts, not whether the approaches identify metastatic disease more accurately or change clinical outcomes.

3. Trial Design

The registry describes NCT02068820 as a completed, randomized, parallel-group trial of SLN mapping during robotic-assisted staging for endometrial cancer. Enrollment is recorded as 200. The trial began in 2012-09, and primary completion is recorded as 2015-01. The phase is listed as not applicable. Masking is listed as none, so the record does not describe a blinded trial.

The two intervention descriptions distinguish ISB dye with standard white-light imaging from ICG dye with FireFly fluorescence imaging. The ICG group description says mapping used the da Vinci surgical system with ISB and standard white light first, followed by ICG and FireFly imaging. The other group description says mapping used the da Vinci surgical system with ISB and standard white light. The record reports 20 participants in the ISB-only group and 180 in the ICG group.

There is an important qualification to how the primary outcome groups are described. The primary outcome population note says the ISB-only group (n=20) and the ICG group (n=180) are combined because both groups received ISB. Yet the posted primary outcome results list an ISB, standard-white-light group with n=200 and an ICG, FireFly group with n=180. The registry record does not explain this difference in group labeling. The reported comparison should therefore be read alongside that population note rather than assumed to represent a simple comparison of two independent randomized arms.

The registry does not report the randomization procedure, concealment method, eligibility details, trial sites, or a fuller protocol description. These details are not reported in the registry record. The sponsor is AdventHealth.

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

Analysis population for the primary outcome, as defined in the registry: The ISB dye alone group (n=20) and the ICG group (n=180) are combined, because both groups received the ISB dye.

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 Pelvic Sentinel Lymph Nodes (SLN) in Endometrial Cancer Patients Detected by Either ICG and/or ISB Dyes., measured over through 6 weeks post-operative.

The primary endpoint is the number of pelvic sentinel lymph nodes detected, expressed as a mean count in nodes. The stated timeframe is through 6 weeks post-operative. A sentinel lymph node is the node or nodes mapped as the first drainage point from a tumor region. Counting detected nodes can describe the extent of mapping observed with the procedures used in each group.

A mean is a summary of a continuous or count-valued measure: it adds the observed values and expresses their average. The registry identifies the outcome measure as a mean with standard deviation. A standard deviation describes how dispersed individual values are around the group mean; it is not a measure of uncertainty in the mean itself. The posted result is therefore about average node counts and their variability, rather than the proportion of participants in whom mapping succeeded.

The count is relevant to the trial’s stated interest in SLN mapping, but it does not by itself establish the accuracy of mapping or whether detected nodes contain metastasis. Although the study summary discusses sensitivity, specificity, and false-negative results as clinical motivations, the primary endpoint posted in the registry is not any of those measures. The registry names a secondary outcome concerning negative predictive value in relation to the number of nodes with metastasis, but does not post its result. The endpoint should be interpreted as a descriptive comparison of recorded node counts, not as a direct test of diagnostic performance or patient benefit.

7. Results Posted in the Registry

• ICG Dye, FireFly Fluorescence Imaging: mean 2.03 versus 1.25 on control; difference 0.78 (95% CI 0.62 to 0.94), standardized effect d = 0.95; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a mean, a measure of the central tendency of a set of observations. Here, each observation is a pelvic SLN count, and the reported mean is the average count within the group as labeled. The standard deviation describes how much individual counts vary around that average. The ISB, standard-white-light result has a mean of 1.25 nodes and a standard deviation of 0.901; the ICG, FireFly result has a mean of 2.03 nodes and a standard deviation of 0.72. These summaries do not reveal the full distribution of individual counts, such as how many participants had no detected nodes or unusually high counts.

What does a mean difference express?

A mean difference subtracts one group mean from another, with the direction depending on which group is treated as the reference. The posted comparison gives a mean difference of 0.78 nodes, listing the ICG group as the comparison group and the other mean as 1.25. In plain terms, the reported average is higher in the ICG group. The difference remains a group-level summary: it does not say that every participant had more nodes detected, or that a specific participant would have a particular count.

The registry lists a pooled standard deviation of 0.820 and a standardized mean difference of 0.951 in the comparison summary. A pooled standard deviation combines variability information across groups for a standardized comparison. A standardized effect expresses the mean difference relative to that pooled variability, rather than in the original unit of nodes. These summaries can help describe the magnitude of a contrast in statistical terms, but they do not establish clinical importance. The registry does not report a clinical threshold for a meaningful difference in node counts.

How should the p-value be understood?

The unadjusted p-value is p < 0.001. In general, a p-value describes how incompatible the observed data are with a specified null model, under the assumptions of the statistical procedure. It is not the probability that the findings arose by chance, and it does not measure the size or practical importance of an effect. The word “unadjusted” indicates that the posted value is not presented as adjusted for other variables or for multiple comparisons. The registry record does not identify the exact test, its assumptions, or whether any alternative analyses were conducted.

For count outcomes, the distribution can be skewed or have more variability than a simple model assumes. In general, over-dispersion means that the observed variability exceeds what a particular count model expects. If over-dispersion is present, a model that ignores it can misstate uncertainty. The registry reports means and standard deviations, but does not report a count-model analysis, a distributional assessment, or an over-dispersion check. No conclusion about those features can be made from the posted summaries alone.

What do randomization and masking contribute?

Random allocation is recorded, which generally aims to make comparison groups similar with respect to measured and unmeasured factors at the start of a trial. The registry does not describe the random sequence method or allocation concealment, so those procedural details are not reported in the registry record. Masking is listed as none. In general, lack of masking can matter when procedures, outcome assessment, or decisions could be influenced by knowledge of group assignment. The record does not explain whether node counting was assessed independently or whether any safeguards were used.

The comparison summary gives group sizes of 200 and 180 and reports standard errors of 0.064 and 0.054, respectively. In general, a standard error describes the estimated uncertainty of a sample mean, and it tends to be smaller when the estimate is based on more observations or less variable measurements. These values are statistical summaries, not measures of variation among individual participants. The registry also reports a confidence interval for the mean difference. The methodological details behind the interval are not reported in the registry record.

The record identifies zero posted analyses and does not include a full statistical analysis plan. Consequently, the method used for the sponsor’s original analysis, the handling of missing observations, the exact analysis population, and any planned sensitivity analyses are not reported in the registry record. The available comparison should be treated as a summary of the posted results, not as a complete account of every analysis undertaken.

10. Confidence Intervals and Precision

The comparison reports a mean difference of 0.78 nodes and a confidence interval with both limits above zero. A confidence interval gives a range of values compatible with the data and the method used to calculate it. It conveys uncertainty about the estimated difference: a narrower interval represents greater precision than a wider interval, all else being equal. The interval does not guarantee that the true difference lies within its limits, and its interpretation depends on the statistical method and assumptions.

The interval’s position above zero agrees with the direction of the posted mean difference and with the unadjusted p-value of p < 0.001. This indicates that the reported comparison is statistically distinguishable from a zero difference under its calculation method. It does not show whether the difference is important for clinical decisions, nor does it account for ambiguity in how the registry labels the outcome populations. The registry record does not describe the confidence-interval method or the assumptions used to calculate it.

The group standard deviations, 0.901 and 0.72, describe spread among observed node counts, while the standard errors of 0.064 and 0.054 describe uncertainty in the respective means. These quantities have different meanings. Individual counts can vary considerably even when a group mean is estimated with relatively small uncertainty. A confidence interval for the difference concerns uncertainty in the group contrast, not the range of outcomes expected for an individual participant.

Precision should also be considered alongside the recorded sample sizes and population note. The outcome description says the ISB-only group of 20 and the ICG group of 180 are combined because both received ISB, while the results list an ISB group of 200 and an ICG group of 180. Since the record does not clarify that labeling, the interval’s numerical precision does not resolve uncertainty about exactly which observations define the contrast.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for a continuous mean comparison, not total event counts. They are planning illustrations based on the observed mean difference, not a record of the trial’s original design calculations. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The trial’s own original design assumptions are not reported in the registry record.

For planning for 100% of the observed effect, the illustration gives 18 participants per arm for 80% power and 24 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 31 participants per arm for 80% power and 42 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 70 participants per arm for 80% power and 93 participants per arm for 90% power.

In plain terms, the 80% power column gives the estimated number per arm under which the planning method would have an 80% chance of detecting the specified effect at the stated significance level, if its assumptions hold. The 90% power column expresses the corresponding target with a greater chance of detection. Requiring more power generally entails planning for more participants, and the illustrations show that smaller effects need more participants than larger effects. These figures are not observed power.

The illustrations use equal allocation, even though the registry reports group counts of 20 and 180 for the two intervention groups. They also use the observed effect as their reference, which may not be the effect a future study considers important. The numbers should be read as conditional planning examples, not as evidence that the trial was designed with those targets or that its actual allocation followed the planning assumption.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.780; pooled standard deviation σ = 0.820.
2. n = 2 × (1.96 + 0.842)² × 0.820² / 0.780² = 17.4, rounded up to 18 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.78                      # observed difference in means
sigma <- 0.820281921790875                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2068820)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 18 (80% power), 24 (90% power)
 75% of observed effect: n per arm = 31 (80% power), 42 (90% power)
 50% of observed effect: n per arm = 70 (80% power), 93 (90% power)
power.t.test: 18.4 
Simulated power at n = 18 per arm: 0.789 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists one secondary outcome: negative predictive value of pelvic SLN in endometrial cancer in relation to the number of nodes with metastasis. Its result is not posted. Although the registry identifies three outcome measures overall, it does not provide results for all of them in the available record. The relationship between the listed outcome count and the posted results is not explained.

Multiplicity arises when several outcomes, time points, subgroups, or analyses are tested. In general, testing many hypotheses can increase the chance of at least one apparently strong result if no adjustment or prespecified hierarchy is used. The registry does not report whether the investigators planned a primary-outcome hierarchy, controlled a family-wise error rate, or adjusted for multiple comparisons. It is therefore not possible to determine how multiplicity was handled. The posted p-value is described as unadjusted.

The record does not report how missing outcome observations were handled, whether every randomized participant was included in the primary analysis, or whether the analysis followed intention-to-treat principles. The outcome population description identifies an ISB-only group of 20 and an ICG group of 180, but the posted results list an ISB group of 200 and an ICG group of 180. The record does not explain whether the 200-person summary is an aggregation, how participants were assigned to analysis populations, or how the two descriptions are reconciled.

The registry does not report a protocol-level analysis plan, exclusions after randomization, missing-data patterns, imputation methods, or sensitivity analyses. These details are not reported in the registry record. Without them, readers cannot assess the possible effect of missingness or determine whether the posted analysis represents all randomized participants. These gaps limit assessment of the statistical process, independently of the numerical result.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 reports serious adverse events affecting 0 of 20 participants in the ISB-only group and 0 of 180 in the ICG group. In plain terms, no serious adverse events are recorded as affecting participants in either group during the reported safety accounting. The record does not list any serious adverse-event terms.

The registry also reports other, non-serious adverse events affecting 5 of 20 participants in the ISB-only group and 29 of 180 in the ICG group. These are separate from the serious-event figures. The record does not give event descriptions, severity grades, timing, duration, or an account of how events were attributed to the intervention. Death counts are not reported in the registry record.

Zero recorded serious events does not establish that no such events occurred outside the reported period or that the interventions have no safety risks. The registry does not specify the safety observation period or provide enough detail to assess how events were collected. These figures describe the adverse-event information posted for the trial and should not be treated as a complete safety assessment.

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

The primary result is a difference in average pelvic SLN counts: 1.25 nodes in the ISB, standard-white-light group and 2.03 nodes in the ICG, FireFly fluorescence-imaging group. The registry comparison reports a mean difference of 0.78 nodes and an unadjusted p-value of p < 0.001. The comparison’s confidence interval lies above zero. These figures describe the posted outcome and indicate that the reported group averages differ under the analysis reflected in the registry.

The result does not establish that ICG improves the detection of metastatic disease. A higher number of nodes detected is not equivalent to higher sensitivity, higher specificity, or a lower false-negative rate. Those measures require information about which detected nodes contained disease and how results compared with a reference assessment. The registry’s stated primary endpoint is a node count, and the secondary negative predictive value outcome is not reported.

The result also does not show that SLN biopsy can replace full lymphadenectomy, reduce peri-operative morbidity, or alter patient outcomes. Those possibilities appear in the study rationale, but the posted primary results do not measure them. The registry does not report recurrence, survival, or a comparison of surgical morbidity as trial outcomes in the results presented.

The group descriptions warrant caution: the outcome population note says the ISB-only group of 20 and ICG group of 180 are combined because both received ISB, while the results list an ISB group of 200 and an ICG group of 180. The registry does not explain this discrepancy in presentation. The numerical difference and its statistical precision cannot resolve that uncertainty.

Overall, the posted data support a narrow interpretation about average numbers of pelvic SLNs recorded in the described groups. They do not answer the broader diagnostic or clinical questions motivating the trial. The available statistical information is also incomplete: the exact test, missing-data handling, analysis population, and multiplicity approach are not reported in the registry record.

16. Why This Trial Matters Statistically

This trial illustrates the difference between a procedural measure and a diagnostic-performance outcome. A count of mapped nodes is straightforward to summarize as a mean, but the clinical rationale also raises questions about whether metastatic disease is identified correctly. Those questions require outcomes such as sensitivity, specificity, or negative predictive value, which are not interchangeable with the number of nodes detected. The registry names a negative predictive value outcome but does not post its result.

It also shows why understanding the analysis population matters. The posted primary outcome includes an explicit note about combining participants because both groups received ISB, while the result labels and sample sizes present an ISB group of 200 alongside an ICG group of 180. A reader needs a clear account of which participants and measurements contributed to each mean in order to interpret the contrast. The record does not supply that clarification.

Statistically, the mean difference, confidence interval, and p-value answer related but distinct questions. The difference expresses the size and direction of the contrast in nodes; the interval expresses uncertainty around that contrast; and the p-value assesses compatibility with a zero-difference null model under a statistical procedure. None of these alone establishes clinical importance, diagnostic accuracy, or benefit.

The record also emphasizes the value of separating trial design information from later planning illustrations. The sample-size estimates are based on the observed effect and stated planning assumptions. They are not evidence of the original design justification. Keeping those distinctions clear avoids treating a post-result planning calculation as an account of the trial’s prospective statistical plan.

17. 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.

Several limitations are specific to the available trial record. First, the outcome population description and the posted group labels do not align transparently. The note identifies an ISB-only group of 20 and an ICG group of 180, combined because both received ISB, while the results list an ISB standard-white-light group of 200 and an ICG group of 180. The registry does not explain how the 200-person result was constructed or how it relates to the randomized groups. This limits clarity about the directness of the comparison.

Second, the primary endpoint is a count of nodes detected, not a diagnostic accuracy measure. The study summary discusses sensitivity, specificity, false-negative rates, and possible implications for lymphadenectomy, but the primary results do not report those outcomes. The secondary negative predictive value outcome is named but has no posted result. No inference about those endpoints follows from the node-count comparison alone.

Third, the record gives limited information about the analysis. The exact statistical test, analysis population, missing-data handling, multiplicity approach, and prespecified analysis plan are not reported in the registry record. Masking is listed as none, and the record does not describe independent outcome assessment or safeguards against influence on measurement. The trial’s own original sample-size assumptions are also not reported.

Finally, the primary outcome timeframe is through 6 weeks post-operative, and the registry provides no further detail about measurement timing within that period. The record does not report the distribution of individual counts or results by clinical subgroup. These gaps limit evaluation of variability, robustness, and applicability beyond the groups and endpoint described.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Detection of SLN in Patients With Endometrial Cancer Undergoing Robotic Assisted Staging: Comparison of ISB and ICG — NCT02068820.
• Registry record last updated 2019-09-10; status last verified 2019-08.
• Results first posted 2019-09-10.
• 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.

21. Record Summary

NCT02068820 is a completed, randomized, parallel-group trial of robotic-assisted SLN mapping in patients with endometrial cancer. Enrollment is listed as 200, with primary completion in 2015-01. The interventions were ISB dye with standard white-light imaging and an ICG plus FireFly fluorescence-imaging approach that also used ISB first.

The primary outcome was the mean number of pelvic SLNs detected through 6 weeks post-operative. The posted means are 1.25 nodes for the ISB, standard-white-light group and 2.03 nodes for the ICG, FireFly group. The registry reports a mean difference of 0.78 nodes and an unadjusted p-value of p < 0.001. The population note and reported outcome group labels are not fully reconciled in the record.

The registry does not post results for the named secondary negative predictive value outcome or report detailed statistical methods, missing-data handling, or the original sample-size justification. It records 0 serious adverse events in each group; other adverse events affected 5 participants in the ISB-only group and 29 in the ICG group.