This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for FOcal Radiation for Oligometastatic Castration-rEsistant Prostate Cancer (FORCE) (NCT03556904), a randomized phase 2 study. The primary outcome is Median Duration of Response.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03556904 |
| Phase | Phase 2 |
| Condition | Prostate Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 14 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of Michigan Rogel Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Patients with oligometastatic castration-resistant prostate cancer, as described in the trial summary. The registry record does not report further eligibility details in the information available for this analysis.
Intervention
Standard of care systemic therapy plus ablative radiation. The arm description says radiation was to start within 8 weeks of randomization and be completed by day 84.
Comparator
Standard of care systemic therapy without the study radiation intervention. The treating medical oncologist determined the standard of care therapy; the description says current therapy was most commonly a second generation androgen pathway inhibitor, with other standard agents also mentioned.
Primary question
The trial summary asks whether adding radiotherapy to standard systemic therapy improves objective progression-free survival compared with systemic therapy alone. The registered primary outcome, however, is median duration of response at 12 Months. The posted primary endpoint values are not available because the registry reports insufficient events to estimate them.
3. Trial Design
FORCE (NCT03556904) is a Phase II randomized trial with a parallel-group design and no masking. The registry lists an enrollment of 14 and describes two arms: Standard of Care and Standard of Care + Ablative Radiation. The arm records list 9 participants for Standard of Care and 5 for Standard of Care + Ablative Radiation.
The trial began on 2018-12-10, had a primary completion date of 2023-07-28, and is recorded as completed. Those administrative details do not establish whether every planned analysis was performed or whether outcome data were estimable. The registry record does not report further details about the randomization procedure, allocation concealment, or the trial’s sample-size justification.
In the Standard of Care arm, systemic treatment was determined by the treating medical oncologist and was not itself the study intervention. The description says current systemic therapy was most commonly a second generation androgen pathway inhibitor, including enzalutamide or abiraterone, while other standard agents such as docetaxel and cabazitaxel were also mentioned. In the radiation arm, standard systemic therapy was combined with ablative radiation. The description says systemic therapy could continue in the absence of toxicities or other specified criteria per protocol.
The stated trial objective concerns objective progression-free survival. The registered primary outcome instead names median duration of response, with a timeframe of at 12 Months. That endpoint is reported as not available because of an insufficient number of participants with events. The registry also lists secondary outcomes including PSA, radiographic and overall survival measures, but the information available does not establish an estimable treatment comparison for those outcomes.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Standard of Care | Standard of Care + Ablative Radiation |
|---|---|---|
| STARTED | 9 | 5 |
| COMPLETED | 1 | 0 |
| NOT COMPLETED | 8 | 5 |
Reasons for not completing this period:
| Reason | Standard of Care | Standard of Care + Ablative Radiation |
|---|---|---|
| Disease Progression after treatment started | 3 | 3 |
| Sponsor Termination | 2 | 2 |
| Physician Decision | 2 | 0 |
| Withdrawal by Subject | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: NA- Per biostatistician, values must be reported as NA due to lack of data from insufficient number of participants with events. Data is not available now nor will it be available in the future
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.
| Characteristic | Unit | Standard of Care | Standard of Care + Ablative Radiation | Total |
|---|---|---|---|---|
| Participants analysed | 9 | 5 | 14 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 3 | 3 |
| Age, Categorical: >=65 years | Participants | 9 | 2 | 11 |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 9 | 5 | 14 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 9 | 5 | 14 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 8 | 4 | 12 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 9 | 5 | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Median Duration of Response, measured over At 12 Months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Standard Deviation |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
The primary outcome is titled Median Duration of Response, measured in months, with the timeframe listed as at 12 Months. Its definition starts the measurement when criteria for complete response (CR) or partial response (PR) are first met, and ends it when recurrent or progressive disease is objectively documented. The response assessment combines target and non-target lesions, bone lesions, and disease symptoms.
Progression for this measure is described as worsening pain or new disease sites on imaging. The definition also gives specific criteria for pain progression attributed to prostate cancer: evidence of disease at the pain site together with one or more palliative intervention. The response and progression definitions combine criteria proposed by RECIST v1.1 and the Prostate Cancer Working Group 3.
Duration of response addresses how long a documented response lasts, rather than simply whether a response occurred. A median can describe the middle of the observed response durations when enough outcome information is available. The registry reports the primary endpoint values as unavailable because an insufficient number of participants had events; consequently, it does not give a median estimate or an accompanying measure of spread. Although the outcome record labels dispersion as Standard Deviation, no standard deviation is posted.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record does not provide an estimable primary endpoint result. For both treatment arms, the posted median duration of response and its spread are absent. The record explains that values must be reported as NA because of an insufficient number of participants with events, and that the data are not available now or expected to be available in the future. Without estimates for the arms, there is no posted primary-endpoint contrast to interpret.
This means the record cannot establish the size or direction of a difference in response duration between standard systemic therapy alone and systemic therapy with ablative radiation. It also cannot establish the precision of such a difference. A missing estimate is not evidence that the groups had the same outcomes, nor does it show that one group had longer response duration. It indicates that the registry does not report values that permit that assessment.
The trial summary identifies objective progression-free survival as the clinical question, but the registered primary outcome is median duration of response. Those are not interchangeable endpoints: the former concerns progression-free time, while the latter begins only after a complete or partial response has been recorded and follows that response until recurrence or progression. The posted primary endpoint therefore cannot be used as a numerical answer to the summary’s stated progression-free-survival question.
The registry record lists enrollment and arm sizes, but group size alone does not supply outcome information. The posted results also do not include a sponsor-reported hazard ratio or other reported comparison in the analysis information described for this trial. As a result, there is no basis in the registry record for a numerical estimate of relative time-to-event effects or a significance test for the primary outcome.
Several secondary outcomes are named, including PSA progression-free survival, radiographic progression-free survival, overall survival, and prostate cancer-specific survival. Their presence as registered outcomes should not be confused with posted numerical results. The record does not provide enough outcome estimates in the information available to draw conclusions about these endpoints. The posted adverse-event counts describe reported safety events, not comparative efficacy.
In short, the primary endpoint result is unestimable in the registry record. Any interpretation should preserve that distinction: the trial was randomized, but randomization cannot yield a reported treatment-effect estimate when the outcome values needed for the comparison are not available.
9. Statistical Methods Explained
What does a median duration measure?
For a time-to-event outcome, the median is the time by which half of the relevant observed event distribution has occurred, when the data allow that quantity to be estimated. Duration of response is conditional on a response having been documented: its measurement begins when criteria for CR or PR are first met and ends at documented recurrence or progression. It therefore addresses persistence of a response, not the chance of achieving one in the first place.
Time-to-event data often include participants whose event has not been observed by the end of their follow-up. General statistical practice can account for such incomplete observation through censoring methods, but the registry record does not report the specific handling of censoring for this endpoint. More importantly, the record explicitly says the primary values are NA because there were too few participants with events. No median or uncertainty estimate can be inferred from the arm sizes alone.
What would an uncertainty interval tell a reader?
In general, a confidence interval describes a range of effect estimates compatible with the data under the analysis assumptions. A narrow interval indicates more precision than a wide interval; an interval that includes no difference may leave the direction or size of an effect uncertain. Such an interval cannot be interpreted when the underlying endpoint estimate is not reported. The registry does not post a primary-endpoint confidence interval, so no statement about its width or the precision of a treatment contrast is possible.
The outcome record names Standard Deviation as the dispersion measure, but its values are absent. A standard deviation describes spread around a mean and is not itself a confidence interval. The record does not explain how that measure was intended to accompany a median time estimate. No value or uncertainty range should be reconstructed from the information reported.
How do hazard ratios fit time-to-event analyses?
In general, a hazard ratio compares event rates over time between groups under a time-to-event model. It is not the same as a difference between two medians, and interpretation depends on the outcome definition and analysis assumptions. The registry record’s statistical description says that only sponsor-reported hazard ratios are used for time-to-event outcomes. No such estimate is listed in the analysis information available for this trial, and the record reports zero analyses. Therefore, no hazard ratio or associated inference can be discussed as a trial result.
The registered trial is randomized and parallel-group, but those design features do not substitute for a reported analysis. Randomization is intended to support a fair comparison of assigned groups; the registry record does not report the specific method used to generate or conceal allocation. It also does not report the statistical model, covariate adjustment, censoring rules, or analysis population for the primary endpoint. Those details should not be assumed.
What are planning illustrations?
In general, a sample-size calculation asks how much information a future study may need to detect a stated effect under specified assumptions. The registry’s planning-illustration description says the calculations are based on the observed effect, use a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event outcomes, the illustrations are described in terms of total events, while other outcomes are expressed as participants per arm.
These are planning illustrations, not observed power and not results from the randomized comparison. They depend on an effect estimate and assumptions that may not match a future study. The primary endpoint values in the registry are unavailable, and the record does not report the numerical illustration outputs in the information available for this analysis. No planning number can therefore be quoted or independently interpreted.
Why can over-dispersion matter?
As a general concept, over-dispersion occurs when variability in the observed data exceeds what a statistical model assumes. If ignored, it can make standard errors too small and confidence intervals too narrow, creating greater apparent precision than the data warrant. This concern is relevant to some count outcomes, but the registry record does not identify an over-dispersion model for this trial’s primary endpoint. The primary outcome is a response-duration measure, and no count-model specification is reported.
Overall, the available statistical information supports a limited reading: the endpoint definition and general planning assumptions are described, but the primary outcome estimate, its uncertainty, and the detailed analysis methods are not reported in the registry record. General statistical principles explain what those quantities would mean, but cannot replace the absent trial estimates.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 12 outcome measures and records 11 secondary outcomes as posted. Named secondary outcomes include median objective progression-free survival, median PSA progression-free survival, median radiographic progression-free survival, overall survival time, prostate cancer-specific survival time, non-irradiated metastases-free survival, and PSA response measures. Listing multiple outcomes raises a general multiplicity issue: when many hypotheses are tested, the chance of at least one apparently notable result can increase. The registry record does not report a multiplicity adjustment, a hierarchy for interpreting outcomes, or which outcomes were designated for confirmatory testing.
The primary endpoint values are explicitly unavailable because there were insufficient participants with events. The record also states that the data are not available now or expected to become available in the future. It does not report a missing-data method, censoring details, or whether any imputation was planned or performed. No such procedure should be inferred from the endpoint definition.
The registry record does not report the analysis population used for the primary endpoint, such as whether participants were analyzed according to randomized assignment or another population definition. It also does not give a detailed account of participant flow or explain the difference between enrollment and the arm counts in the outcome record. These are limitations on reconstructing the analysis, rather than evidence about how the trial was conducted.
Without an analysis plan, outcome estimates, or missing-data details, readers cannot assess how multiplicity, incomplete observations, or analysis-population choices may have affected results. These methods are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Standard of Care | 3 | 9 | 33.3% |
| Standard of Care + Ablative Radiation | 0 | 5 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Standard of Care | 2 of 9 |
| Standard of Care + Ablative Radiation | 2 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Standard of Care | 9 of 9 |
| Standard of Care + Ablative Radiation | 5 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | Standard of Care | Standard of Care + Ablative Radiation |
|---|---|---|---|
| Fall | General disorders | 1 of 9 | 0 of 5 |
| Fatigue | General disorders | 1 of 9 | 0 of 5 |
| Blood and lymphatic system disorders - Other, specify | Blood and lymphatic system disorders | 1 of 9 | 0 of 5 |
| Stroke | Nervous system disorders | 1 of 9 | 0 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Standard of Care | Standard of Care + Ablative Radiation |
|---|---|---|---|
| Fatigue | General disorders | 4 of 9 | 4 of 5 |
| Back pain | Musculoskeletal and connective tissue disorders | 2 of 9 | 2 of 5 |
| Dizziness | Nervous system disorders | 2 of 9 | 2 of 5 |
| Pain | General disorders | 3 of 9 | 1 of 5 |
| Buttock pain | Musculoskeletal and connective tissue disorders | 1 of 9 | 2 of 5 |
| Diarrhea | Gastrointestinal disorders | 1 of 9 | 2 of 5 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 2 of 9 | 1 of 5 |
| Fall | General disorders | 2 of 9 | 1 of 5 |
| Hyperglycemia | Metabolism and nutrition disorders | 2 of 9 | 1 of 5 |
| Hypertension | Vascular disorders | 1 of 9 | 2 of 5 |
Serious events with the highest arm-level rate: fall (11.1%), fatigue (11.1%), blood and lymphatic system disorders - other, specify (11.1%), stroke (11.1%).
The registry reports serious adverse events for Standard of Care in 3 of 9 participants at risk, and for Standard of Care + Ablative Radiation in 0 of 5 participants at risk. It reports other adverse events in 9 of 9 participants at risk in the Standard of Care arm and 5 of 5 in the radiation arm. Deaths are listed as 2 in each arm. These are descriptive counts; the record does not provide a comparative statistical analysis of these safety figures.
The listed top serious adverse event terms are Fall, Fatigue, Blood and lymphatic system disorders - Other, specify, and Stroke. Each is listed with 11.1%. The information available does not assign these terms to a particular arm, so they should not be attributed to one group. The term-level percentages also should not be treated as the overall serious adverse event rate.
Counts and percentages require attention to their denominators and definitions. The at-risk counts are reported separately for serious and other events; the registry does not explain further how event terms were counted or whether participants could contribute more than one event. Death counts are not identified as treatment-related, and the record does not report causality for the listed events. These figures describe what the registry reports, but do not establish why events occurred or support a causal comparison between arms.
12. What the Result Does, and Does Not, Mean
The registry record establishes that FORCE was a randomized Phase II trial comparing standard systemic therapy with the same standard-care approach plus ablative radiation in patients described as having oligometastatic castration-resistant prostate cancer. It also provides the registered definition of the primary response-duration endpoint and descriptive adverse-event counts. Those details help define what the trial set out to assess and what safety information was recorded.
The posted primary endpoint does not provide a numerical estimate. The record attributes that absence to an insufficient number of participants with events and says the data are not available now or in the future. It is therefore not possible to tell from this endpoint whether response duration differed between the two arms, how large any difference might have been, or how precisely it could be estimated.
This absence should not be interpreted as proof of no effect, proof of benefit, or proof of harm. Nor does a randomized design alone resolve the uncertainty: a treatment comparison requires outcome data and an analysis. The registry record does not provide those for the primary endpoint.
The trial summary’s stated objective concerns objective progression-free survival, whereas the registered primary outcome is median duration of response. A response-duration result would address how long a recorded response persisted; it would not by itself answer every question about progression-free survival, overall survival, or the other listed outcomes. The record’s outcome list is not a substitute for posted estimates.
The serious and other adverse-event counts are useful descriptive information, but the record does not report a causal attribution or statistical comparison for them. They should be read separately from efficacy outcomes. In practical statistical terms, the strongest conclusion is about the limits of the available evidence: this registry record documents the design and outcome definitions, but does not provide an estimable primary result from which to quantify a treatment effect.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the distinction between having a randomized design and having an interpretable numerical result. Randomization can support a comparison by reducing systematic differences between assigned groups, but an endpoint still needs enough observed events and reported outcome data to estimate the effect. The registry explicitly says the primary endpoint could not be estimated because of an insufficient number of participants with events.
It also highlights why endpoint definitions matter. The trial summary frames the question around objective progression-free survival, while the registered primary endpoint is median duration of response. Response duration begins only after a CR or PR is recorded and ends at recurrence or progression. That focus differs from measuring progression-free time across a broader population, so readers should not treat the endpoint labels as interchangeable.
The record also demonstrates the limits of interpreting short descriptive counts. The adverse-event numbers are reported by arm, but the registry does not provide a comparative safety analysis or causal attribution. The figures can describe recorded events without establishing whether the treatment groups differ in underlying risk.
Finally, the registry names a range of secondary outcomes and describes planning illustrations, while key inferential details—including the analysis plan and missing-data approach—are not reported in the registry record. That makes transparent reporting of estimable effects and uncertainty especially important. When those estimates are unavailable, the appropriate statistical conclusion is uncertainty, not a claim that the groups are equivalent or that an intervention has a particular effect.
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 central limitation is that the primary outcome is not estimable in the registry record. The record states that an insufficient number of participants had events and that the data will not be available in the future. It gives no arm-specific median duration of response, standard deviation, confidence interval, or other numerical treatment contrast.
The stated trial objective and registered primary endpoint differ in wording and focus: the summary describes objective progression-free survival, while the primary outcome is median duration of response. The record does not explain this distinction or report a numerical result for the primary endpoint that could clarify its relationship to the stated objective.
Important analysis details are not reported in the registry record, including the randomization procedure, analysis population, statistical model, censoring approach, and missing-data methods. The record also does not report multiplicity handling for the several listed outcomes or provide enough information to reconstruct participant flow. No statistical plan or sample-size justification should be inferred.
Safety reporting is descriptive. The registry lists serious and other adverse events and deaths, but does not report event attribution, an inferential comparison, or further details on how event terms were counted. The listed serious-event terms are not assigned to an arm in the information available for this analysis. These limitations constrain interpretation of both efficacy and safety and prevent a numerical assessment of treatment differences.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: FOcal Radiation for Oligometastatic Castration-rEsistant Prostate Cancer (FORCE) — NCT03556904.
- Registry record last updated 2026-01-15; status last verified 2025-12.
- Results first posted 2026-01-15.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
FORCE (NCT03556904) is recorded as a completed, randomized, unmasked, parallel-group Phase II trial sponsored by University of Michigan Rogel Cancer Center. The registry lists an enrollment of 14 and two arms: Standard of Care and Standard of Care + Ablative Radiation. Its primary outcome is Median Duration of Response, measured in months at 12 Months.
The primary endpoint values are reported as NA because of an insufficient number of participants with events. The registry lists secondary outcomes and descriptive adverse-event counts, but the available record does not provide a numerical primary treatment comparison, its uncertainty, or detailed analysis methods. Consequently, the record describes the trial question and outcome definitions but does not establish an estimable primary efficacy result.