Surgery With or Without Radiation Therapy in Untreated Nonmetastatic Retroperitoneal Sarcoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Surgery With or Without Radiation Therapy in Untreated Nonmetastatic Retroperitoneal Sarcoma (NCT01344018), a randomized na study. The primary outcome is Number of Patients With Abdominal Recurrence or Death.

2. Clinical Question

3. Trial Design

NCT01344018 is listed as a randomized, parallel-group trial with no masking. The registry identifies its phase as NA and its status as completed. The enrollment figure is 266. The sponsor is the European Organisation for Research and Treatment of Cancer - EORTC. The trial start is listed as 2012-01, and primary completion as 2019-03.

The study compared two treatment strategies for patients with untreated, nonmetastatic retroperitoneal soft tissue sarcoma: preoperative radiotherapy followed by surgery, and surgery alone. The radiotherapy arm description allows 3D-CRT or IMRT, with a stated dose of 50.4 Gy/28 daily fractions, followed by en-bloc surgery. The surgery-alone description specifies en-bloc resection of surrounding tissues and organs when located within 1 to 2 cm from the surface tumor, even when not infiltrated. The listed interventions are therapeutic conventional surgery and 3-dimensional conformal radiation therapy.

Random allocation is intended to balance, on average, measured and unmeasured baseline characteristics between treatment groups. That design can support a comparative interpretation, but randomization alone does not establish what the result was. The registry record does not report allocation concealment procedures, stratification factors, the sequence-generation method, adherence to assigned treatment, or crossover between arms. It also does not report further details of the surgical procedures or how radiotherapy delivery was monitored.

The trial lists eight outcome measures and four analyses. The primary outcome is abdominal recurrence or death; listed secondary outcomes include acute toxicity, perioperative and late complications, tumor response, abdominal recurrence, metastases or death, and survival. The registry record does not give the detailed analysis plan or explain how the four analyses relate to outcomes, treatment groups, or time points. The reported enrollment is a trial-level figure; arm-specific enrollment and analysis-population counts 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

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Abdominal Recurrence or Death, measured over ARFS was measured from date of randomization to date of abdominal relapse or death, whichever occurred first, up to a maximum of 7 years..

The primary outcome is titled “Number of Patients With Abdominal Recurrence or Death.” Its time frame describes abdominal recurrence-free survival (ARFS), measured from randomization until abdominal relapse or death, whichever occurred first, up to a maximum of 7 years. This combines an event count with a time-to-event definition: participants contribute the time they are followed without a recorded endpoint event, and the first qualifying event ends that interval.

The registry’s definition of abdominal recurrence includes several types of failure or loss of operability. These include local/abdominal or distant progressive disease during preoperative radiotherapy as per RECIST 1.1; the tumor or patient becoming inoperable, including an ASA score of 3 or involvement of the superior mesenteric artery, aorta, or bone; peritoneal metastasis found at surgery; macroscopic residual disease left at surgery (R2 resection); or local relapse after macroscopically complete resection. Liver metastases count as distant metastatic events. Patients with distant metastases were followed until local failure was detected.

Participants without a specified event were censored at their date of last follow-up. In general, censoring records that the endpoint event was not observed through the last known follow-up; it does not mean that the participant had the event. A time-to-event endpoint can account for different follow-up durations, but interpretation depends on how follow-up and censoring are handled. The registry record does not report endpoint estimates, event counts by arm, or a treatment-effect estimate. The rationale for choosing this endpoint beyond its definition is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help explain what the trial design and endpoint can answer. They also clarify what cannot be inferred when the registry record does not include the primary comparison statistics.

What randomization contributes

Randomization assigns participants to treatment groups by chance. In general, it aims to make groups comparable at the start of a trial, including with respect to factors that investigators have measured and factors they have not measured. If follow-up and analysis are also appropriate, a between-group comparison can estimate the effect of assignment to one strategy rather than the other. Randomization does not guarantee identical groups in a particular trial, and it does not eliminate bias from missing outcomes, departures from assigned treatment, or incomplete reporting.

This study is listed as randomized, parallel, and unmasked. A parallel design means the comparison is between groups followed under their assigned strategies, rather than each participant receiving both strategies in sequence. “Unmasked” means the registry does not indicate masking. The record does not describe allocation concealment or the exact randomization procedure. It also does not report the analysis population or whether the primary analysis followed an intention-to-treat principle, which generally retains participants in the groups to which they were randomized.

How to understand a time-to-event endpoint

Abdominal recurrence-free survival is defined from randomization to abdominal relapse or death, whichever occurred first, with follow-up up to a maximum of 7 years. Unlike a simple endpoint that only records whether an event ever occurred, a time-to-event analysis uses both event status and the time until the event or last observation. This is useful when participants have different follow-up durations. A participant whose endpoint event is not observed by the last follow-up is censored at that date, as stated in the endpoint definition.

Censoring is not the same as an event and is not necessarily a missing value. It indicates that the participant was known to be event-free through a particular date, after which the endpoint status is not available in the record. Standard time-to-event methods require assumptions about censoring; in general, estimates can be biased if loss to follow-up is related to the unobserved future event risk in ways that the analysis does not address. The registry record does not report the amount or pattern of censoring or the methods used to estimate ARFS.

The endpoint also has a composite definition. A composite endpoint counts the first occurrence of any component as an endpoint event. Here, the definition combines progression, inoperability under specified conditions, peritoneal metastasis, residual disease after surgery, local relapse, and death. Composite endpoints can capture multiple clinically relevant failure pathways, but components may differ in frequency, timing, or importance. A total composite result by itself would not show which component drove the comparison. The record does not report component-specific primary outcome results.

Estimates, uncertainty, and tests

A treatment-effect estimate would summarize the comparison between strategies using a specified statistical measure. For a time-to-event outcome, common approaches can include comparing event-time distributions or estimating a relative event rate over follow-up. These methods answer related but not identical questions and rely on different assumptions. The registry record does not identify the primary statistical model, the effect measure, or the method used to account for any design features.

A confidence interval expresses statistical uncertainty around an estimate. It is not a guarantee that the true effect lies in the interval, but under the method’s assumptions it provides a range of estimates compatible with the observed data at the stated confidence level. A p-value is not an effect size, and a small p-value does not by itself establish clinical importance. Conversely, a result that does not cross a significance threshold does not prove that the strategies are equivalent. Because the record gives no primary estimate, interval, or p-value, these interpretations cannot be applied to the trial’s efficacy comparison.

Multiplicity and planning illustrations

Multiplicity arises when several outcomes, comparisons, or repeated analyses are examined. The chance of at least one apparently unusual finding can increase when many statistical tests are conducted, unless the analysis plan accounts for that. The registry lists eight outcome measures and four analyses, but does not explain the relationship among them or report a multiplicity strategy. It is not possible to infer whether any adjustment was planned or performed.

The registry’s stated assumptions for sample-size illustrations describe a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. For time-to-event outcomes the illustration uses the total number of events with a Schoenfeld approach; for other outcomes, it gives participants per arm. These are planning illustrations based on an observed effect, not the original trial design or observed power. The original sample-size justification and any assumptions used when the trial was designed are not reported in the registry record. No numerical illustration values are reported in the record.

General statistical interpretation should therefore distinguish trial design details from unreported analysis details. The randomized design establishes the intended comparison, and the endpoint definition clarifies which events count. Neither reveals the numerical treatment effect. Without the outcome estimates, uncertainty measures, analysis population, and analysis methods, the registry record supports a description of the question and endpoint, but not a detailed appraisal of the primary efficacy result.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity, missing data, and analysis populations can affect how trial results are interpreted. The registry lists eight outcome measures and four analyses. It does not state which outcomes or analyses were considered primary for inference beyond the designated primary outcome, how the four analyses were structured, or whether a strategy for controlling multiplicity was used. The treatment of repeated tests or subgroup comparisons is not reported in the registry record. Without that information, the degree to which any reported statistical tests might require adjustment cannot be assessed.

The primary endpoint definition states that participants without a qualifying event were censored at the date of last follow-up. The registry record does not report how many participants were censored, the follow-up completeness, reasons for loss to follow-up, or methods for addressing missing endpoint information. In general, time-to-event methods use censoring information, but their interpretation depends on the relationship between censoring and future event risk.

The record gives an enrollment figure of 266, while the adverse-event record lists 128 and 127 participants at risk in the two groups. It does not explain the relationship between these figures or identify the population used for each efficacy analysis. Arm-specific randomized counts, exclusions, protocol deviations, and analysis-set definitions are not reported in the registry record. The primary analysis method, adjustment variables, handling of treatment changes, and approach to missing data are also not reported. These omissions limit assessment of whether the planned comparison was carried out as intended and whether all randomized participants contributed to the primary analysis.

11. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: intra-abdominal fluid collection (3.9%), subileus (3.9%), malnutrition (3.1%), pulmonary embolism (3.1%), anaemia (2.4%).

The registry’s adverse-event record gives counts of participants at risk and participants affected by serious events and other events, as well as death counts. For surgery alone, the figures are 128 at risk and 37 affected for serious events, 128 at risk and 124 affected for other events, and 22 deaths. For preoperative radiotherapy followed by en-bloc surgery, the figures are 127 at risk and 48 affected for serious events, 127 at risk and 127 affected for other events, and 25 deaths. These are counts as listed, not estimates of comparative risk.

The serious-event terms listed are intra-abdominal fluid collection (3.9%), subileus (3.9%), malnutrition (3.1%), pulmonary embolism (3.1%), anaemia (2.4%), and ascites (2.4%). The registry record does not clarify whether these percentages refer to one arm or both arms combined, nor does it give the time period or event-specific denominators. They should therefore be read as listed descriptive figures rather than assigned to a treatment group.

In general, safety counts need context such as exposure duration, definitions, event severity, and whether participants or event episodes are counted. The record does not report a statistical comparison of these safety outcomes or provide exposure-adjusted rates. The death counts in this adverse-event listing should not be treated as the primary endpoint results: the primary endpoint combines death with specified abdominal recurrence events and uses time from randomization, while the adverse-event record does not state a matching timeframe or endpoint definition.

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

This trial addresses a defined comparative question: whether a strategy of preoperative radiotherapy followed by en-bloc surgery differs from surgery alone for untreated, nonmetastatic retroperitoneal soft tissue sarcoma on a primary endpoint of abdominal recurrence or death. The randomized parallel-group design is relevant to that comparison. The endpoint definition includes several forms of progression, inoperability, residual disease, relapse, and death, and the time frame is measured from randomization up to a maximum of 7 years.

What the registry record does not provide is the numerical primary outcome result. There is no reported event count by arm, ARFS estimate, treatment-effect estimate, confidence interval, or p-value. Consequently, the record does not show whether the groups differed, how large any difference was, or how precisely it was estimated. A trial’s completion status and enrollment do not substitute for those results. The record also does not provide enough analysis detail to assess the statistical model, censoring, analysis population, or multiplicity approach.

The safety listing offers descriptive participant counts and a short list of serious-event terms with percentages. It does not report a formal comparison or specify the denominator and arm attribution for the event-term percentages. Differences between the listed counts should not be treated as evidence of a treatment effect without the appropriate analysis and context. In particular, adverse-event death counts are not interchangeable with the primary endpoint’s time-to-event result.

More generally, an endpoint estimate is interpreted together with its uncertainty and the prespecified analysis. A confidence interval helps show how much precision the data provide, while a p-value alone would not convey the size or importance of an effect. Neither is available for the primary comparison in this registry record. The findings therefore support description of the trial’s question, design, endpoint, and recorded safety counts, but not a conclusion that either treatment strategy was superior, equivalent, or without risk. Medical decisions require evidence and individual context beyond this registry record.

13. Why This Trial Matters Statistically

The trial is statistically notable for the way its primary endpoint combines multiple events and uses time from randomization. The endpoint is not limited to later local relapse: the definition also includes progression during preoperative radiotherapy, specified causes of inoperability, peritoneal metastasis at surgery, macroscopic residual disease, and death. This breadth is important because a composite result can reflect different components. A single overall estimate, if reported, would need to be interpreted alongside component-specific information to understand what contributed to it.

The randomized parallel design is suited to comparing treatment strategies, but statistical conclusions depend on the analysis and on complete reporting. The registry record does not report the primary outcome estimate, its uncertainty, or the analysis method. It also does not describe multiplicity handling despite listing multiple outcome measures and analyses. These gaps illustrate why a trial’s design and endpoint definitions are not enough to evaluate the evidence for a treatment contrast.

The endpoint definition also makes the handling of follow-up consequential. Participants without a specified endpoint event are censored at last follow-up, and distant metastases are handled in a particular way in the definition. Understanding the amount and pattern of follow-up, censoring, and events would help readers evaluate a time-to-event estimate, but those details are not reported in the registry record.

Finally, the safety record illustrates the distinction between descriptive counts and comparative statistical evidence. Counts of participants with serious or other events can inform a basic description, while percentages for selected event terms need clear denominators and arm attribution. Those details and formal safety comparisons are not reported. The record therefore highlights an important statistical principle: transparent endpoint definitions, complete result reporting, and quantified uncertainty are all needed to interpret a randomized trial.

14. 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 interpreting this trial from the registry record is that it does not report numerical results for the primary endpoint. There are no arm-specific counts of abdominal recurrence or death, no ARFS estimates, and no effect estimate, confidence interval, or p-value. The primary efficacy comparison therefore cannot be quantitatively assessed from this record.

Several details needed to evaluate the time-to-event analysis are also absent. The record does not report the statistical method, event and censoring counts by group, the distribution of follow-up, or the handling of missing endpoint data. Although it defines the endpoint and says that participants without an event were censored at last follow-up, it does not provide enough information to assess the practical impact of censoring.

The registry lists eight outcome measures and four analyses, but does not describe the relationship among them or whether multiplicity was addressed. The analysis populations, arm-specific randomized counts, adherence, exclusions, and treatment changes are not reported. The record also does not provide the original sample-size justification or other original design assumptions. Any planning illustrations based on the observed effect are not substitutes for that original justification or for the observed comparison.

Safety reporting is limited as well. The record lists serious and other adverse-event counts and deaths but does not provide a statistical comparison, exposure-adjusted rates, or time periods for these counts. The listed serious-event percentages are not identified as arm-specific or pooled in the record. These limitations constrain interpretation of both efficacy and safety and prevent a complete appraisal of the trial’s statistical results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Surgery With or Without Radiation Therapy in Untreated Nonmetastatic Retroperitoneal Sarcoma — NCT01344018.
• Registry record last updated 2023-04-24; status last verified 2023-04.
• Results first posted 2023-04-24.
• 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.

18. Record Summary

NCT01344018 is a completed randomized, parallel-group trial with no masking, listed as phase NA. It enrolled 266 participants and was sponsored by the European Organisation for Research and Treatment of Cancer - EORTC. The trial start is listed as 2012-01 and primary completion as 2019-03.

The study compared surgery alone with preoperative radiotherapy followed by en-bloc surgery for untreated, nonmetastatic retroperitoneal soft tissue sarcoma. The radiotherapy arm description specifies 3D-CRT or IMRT to 50.4 Gy/28 daily fractions. The primary endpoint was abdominal recurrence or death, measured as abdominal recurrence-free survival from randomization to the first qualifying event, up to a maximum of 7 years.

The registry record does not report the numerical primary outcome comparison, its uncertainty, or the statistical analysis method. It lists secondary outcomes concerning toxicity, complications, tumor response, recurrence, metastases, and survival. Its adverse-event record gives participant counts for serious and other events and deaths, plus selected serious-event terms and percentages, but does not provide enough context for a formal between-arm safety interpretation.