Hormone Therapy Plus Chemotherapy as Initial Treatment for Local Failures or Advanced Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Hormone Therapy Plus Chemotherapy as Initial Treatment for Local Failures or Advanced Prostate Cancer (NCT02560051), a non-randomized phase 2 study. The primary outcome is Efficacy as Measured by Number Who Progressed.

2. Clinical Question

The study’s stated purpose was to assess the safety and benefit of ADT plus chemotherapy when used as initial treatment for local failures or advanced prostate cancer. The description says that the chemotherapy combinations and cycling differed from the current standard treatment; it does not present comparative results that would establish the consequences of those differences. The groups should therefore be read as separate treatment pathways for different clinical circumstances, not as randomized alternatives tested against one another.

The record lists pathology or biopsy positivity and PSA level among secondary outcomes. Those measures can describe disease findings or changes in a marker, but their results are not reported in the registry record. Consequently, the question that can be answered from this record is primarily descriptive: what treatment approach was planned, which outcomes were specified, and what safety counts were posted. The record does not answer whether the regimen reduced progression or how its efficacy compared with another approach.

3. Trial Design

This was a phase 2, non-randomized, parallel-group study sponsored by The University of Texas Health Science Center, Houston. The registry reports enrollment of 19 participants and a terminated status. It reports a start of 2015-11 and primary completion on 2017-09-12. The reason for termination is not reported in the registry record.

There was no masking. The three group descriptions corresponded to different disease situations: definitive local therapy, nodal-only or low-volume bone disease, and high-volume disease with no prior treatment. Each group was assigned a different treatment duration and number of chemotherapy cycles. The record describes chemotherapy with doxorubicin, ketoconazole, docetaxel, and estramustine alongside ADT with degarelix. The listed plans were 3 chemotherapy cycles and 12 months of ADT, 4 cycles and 18 months, or 5 cycles and 24 months, respectively.

Because allocation was non-randomized, treatment groups were not created to balance participant characteristics by chance. Their different disease descriptions and regimens mean that contrasts between groups would mix treatment differences with differences in the populations receiving those treatments. The group results are not a randomized estimate of comparative treatment effects.

The registry lists 17 outcome measures, including the primary progression count, pathology or biopsy positivity, and multiple PSA-level outcomes. It records 0 analyses. No statistical analysis plan, method for handling repeated measurements, or sample-size justification is reported in the registry record. The primary endpoint timeframe runs from informed consent until a participant was taken off-study or the study stopped, with an average of 10 months stated. That description does not establish that every participant had the same duration of observation.

The record’s design and status put the posted numbers in context: this was a small phase 2 study, not a randomized comparison, and it ended as a terminated study. The registry record does not report a reason for that status or provide primary efficacy results. Its descriptions support understanding the planned treatment groups and outcome definitions, but do not support a causal comparison among the regimens.

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 Efficacy as Measured by Number Who Progressed, measured over From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.

The primary endpoint is the number of participants who progressed. The registry defines progression as an increase in prostate-specific antigen (PSA) >0.3 ng/mL over 2 measurements or a larger or new lesion. The stated observation period begins when a participant signs informed consent and ends when that participant is taken off-study or the study is stopped; the record describes an average of 10 months.

A count of participants meeting a defined progression criterion is a binary-outcome summary: each participant is classified as having or not having the event during the stated observation period. Such an endpoint can provide a direct summary of how many participants met the protocol’s progression definition. Combining a PSA criterion with a lesion criterion allows the endpoint definition to include either marker-based or imaging/clinical evidence, as described in the record.

Interpretation depends on consistent outcome ascertainment and follow-up. The record does not report the progression count, the number assessed, or further details about how lesions were evaluated. It also does not report whether or how differing observation times were handled in an analysis. Although the endpoint is clearly defined, its result cannot be interpreted without the event data and the relevant analysis population. The primary progression result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a non-randomized design mean?

In a randomized study, chance assignment is used to make treatment groups comparable on average in both measured and unmeasured characteristics. This study was non-randomized. Its groups were based on distinct disease descriptions and received different treatment schedules. As a result, a direct difference in observed outcomes between groups would not be attributable to treatment alone. General statistical reasoning therefore treats these groups as descriptive pathways rather than exchangeable arms in a controlled comparison.

Adjustment methods can sometimes account for measured differences, but they cannot guarantee removal of confounding, especially when important characteristics are unmeasured or when groups have limited overlap. The registry record lists 0 analyses and does not report an adjusted comparison or a statistical plan. No adjusted effect estimate should be inferred from the group descriptions.

How should a participant count be read?

The primary outcome is a count of participants who met a progression definition. For a binary endpoint, a participant is classified as having the event or not having it under the stated criteria. A count is easiest to interpret when the number of participants assessed is also clear and when the observation period and outcome ascertainment are comparable. Here, the primary progression count and its analysis denominator are not reported in the registry record. The safety section does include group counts for serious adverse events, but those counts are not a substitute for the missing efficacy result.

For a binary endpoint, an effect estimate could describe a difference or ratio between groups, depending on the planned analysis. Such measures would need an appropriate comparison and uncertainty estimate. The record does not report a primary efficacy comparison, and no new effect estimate can be derived from the available information. General statistical interpretation should distinguish a raw event count from an estimate of treatment effect.

What does uncertainty add?

A point estimate is a single summary of the observed data. A confidence interval adds information about sampling uncertainty under a specified statistical model and analysis. A narrow interval indicates greater precision than a wide interval, while an interval that includes values representing little or no difference may leave substantial uncertainty about direction or size. These are general concepts; the registry record does not report a primary progression estimate or confidence interval for this study.

Small groups generally produce less precise estimates than larger groups, because each participant can have a substantial influence on a group-level summary. The posted safety groups contain 6, 8, and 5 participants at risk. Those denominators make the safety counts useful as a description of this record, but they do not support confident comparisons across disease groups. No precision estimates for the serious-event counts are reported.

Why does follow-up matter?

The primary timeframe extends from informed consent until a participant was taken off-study or the study was stopped, with an average of 10 months stated. Participants may not all have been observed for the same length of time. A simple count of participants with an event does not necessarily account for differences in time at risk. Time-to-event methods can incorporate the timing of events and censoring, but the registry record does not report such an analysis for the primary outcome. The endpoint is described as a participant count, and no analysis methods are listed.

In general, censoring occurs when the event has not been observed before follow-up ends, so the exact event time is unknown beyond that point. The handling of participants who stopped treatment, left the study, or had incomplete follow-up can affect an analysis. The registry record does not report participant-level follow-up, censoring rules, or missing-data methods. These details should not be assumed.

How should a sample-size rationale be interpreted?

Sample-size planning estimates how many participants may be needed to answer a question with a chosen design and assumptions. A planning calculation is not an observed result and is not proof that a study had adequate power. In general, such calculations depend on the target effect, outcome frequency, allocation, significance level, and analysis method. The registry record does not report its sample-size justification or protocol assumptions. The posted enrollment of 19 is the number enrolled, not a sample-size rationale.

Power is a property of a study design under specified assumptions, not a measure of whether a particular observed result is reliable. Observed power should not be used to explain a null or unavailable result. The registry record gives no primary efficacy estimate from which to assess precision and does not report a planned power calculation. Any planning illustration based on an observed effect would be a separate calculation, not the study’s original design justification, and cannot establish what the study was designed to detect.

Why do multiple outcomes matter?

When a study assesses many outcomes or makes many comparisons, the chance of at least one apparently notable result can increase. Statistical methods may control or describe this multiplicity, but the appropriate approach depends on the prespecified questions and analysis plan. The registry record lists 17 outcome measures and does not report a multiplicity strategy. It also does not report analyses for the listed outcomes. General concerns about multiple testing cannot be resolved without knowing which outcomes were analyzed and how they were selected for reporting.

Overall, the methods information supports a careful reading of the study as a non-randomized, small phase 2 record with defined endpoints but no posted efficacy analyses. The concepts above explain what would be needed to interpret estimates; they are not claims that those analyses were conducted.

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("Definitive Local Therapy", "Nodal Only/Low-volume Bone", "High Volume/no Prior tx")
n      <- c(6, 8, 5)
events <- c(0, 0, 2)
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  Definitive Local Therapy  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Nodal Only/Low-volume Bone  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6
ARM  High Volume/no Prior tx  5  2  40.0  5.3  85.3  11.8  76.9  11.8  77.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures, including the primary progression count, pathology or biopsy positivity, and multiple PSA-level outcomes. Assessing multiple outcomes can raise multiplicity concerns: when many hypotheses are tested, the chance of at least one result appearing notable by chance can increase. A prespecified hierarchy or adjustment may address that concern, but the registry record does not report a multiplicity plan or indicate which outcomes, if any, were treated as confirmatory.

The record lists 0 analyses. It does not report a primary efficacy result, secondary outcome results, or a statistical analysis plan. The intended analysis population, handling of participants who withdrew, missing-data assumptions, and rules for incomplete outcome measurements are not reported in the registry record. The record also does not state whether all enrolled participants were included in every outcome assessment.

These omissions limit both reproducibility and interpretation. If outcome data are missing, the amount and pattern of missingness can matter; excluding participants or imputing outcomes can lead to different estimates under different assumptions. These are general statistical considerations, not descriptions of methods used in this study. No missing-data method should be attributed to the investigators based on the available record.

The registry’s terminated status does not by itself explain whether outcomes were collected completely or why the study ended. The reason for termination, any interim analyses, and any changes to the planned analyses are not reported in the registry record. Without these details, the listed outcomes should be treated as registered measures rather than evidence that results were analyzed or reported.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fever (50.0%), white blood cell decreased (25.0%), hypoalbuminemia (25.0%), anorexia (25.0%), dyspnea (25.0%).

The registry reports serious adverse events for each treatment group as participants at risk and participants affected. In the definitive local therapy group, 3 of 6 participants were affected; in the nodal-only or low-volume bone group, 2 of 8 were affected; in the high-volume or no-prior-treatment group, 0 of 5 were affected. Deaths are listed as 0 for each group. These are participant counts, not counts of all event episodes.

The record lists fever at 50.0%, white blood cell decreased at 25.0%, hypoalbuminemia at 25.0%, anorexia at 25.0%, dyspnea at 25.0%, and fatigue at 16.7% among the top serious-event terms. The registry does not provide further context in these entries about timing, duration, severity grading, or whether individual participants experienced more than one term.

These data describe the posted serious-event information; they are not a randomized safety comparison. The groups differed in disease status and regimen, and the group sizes are small. Differences in raw counts cannot establish that one regimen caused more or fewer serious events. A count of zero in a group means no affected participants were recorded for that group in this entry; it does not prove that the regimen has no risk. The registry record does not report a full comparison or an uncertainty analysis for these safety figures.

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

The record establishes that a phase 2, non-randomized study enrolled 19 participants and evaluated ADT with chemotherapy across three disease-status groups. It specifies the drugs, planned cycle counts, ADT durations, and a primary progression definition. It also reports selected serious adverse-event counts and lists deaths as 0 in each group. These are descriptive details about the registered study.

The record does not establish how many participants progressed. It reports no primary efficacy analysis, no secondary outcome results, and no estimates of treatment effect or precision. It therefore cannot show whether the regimen changed progression, PSA, or biopsy findings, nor can it quantify how certain any efficacy estimate would be. A named outcome is not the same as a reported result.

The non-randomized groups are not direct treatment alternatives with a like-for-like comparison. Participants were grouped by different disease situations, and the treatment schedules differed. The observed safety counts cannot be used to conclude that one group’s regimen was safer or less safe. General statistical caution is especially important when interpreting small group counts and when the analysis population and follow-up completeness are not reported.

The terminated status is also not an explanation of the study’s outcome. The reason for termination is not reported in the registry record, so it should not be attributed to efficacy, safety, recruitment, or any other cause. The record can inform readers about the design and what was registered, but it cannot support a treatment recommendation or a conclusion that the approach works or does not work.

In short, the posted record is informative about study structure and selected safety reporting, while leaving the central efficacy question unanswered. That distinction separates what is documented from what would require complete outcome data and an appropriate analysis.

14. Why This Trial Matters Statistically

This study illustrates why a trial’s design and its posted results must be read together. A non-randomized design can be useful for describing treatment delivery and collecting safety information, but it does not create balanced groups for estimating comparative effects. In this study, group membership reflected different disease situations, and each group had a different treatment schedule. A simple contrast among those groups would therefore have limited causal meaning.

The registry also demonstrates that an endpoint definition alone is not an endpoint result. The progression criterion is specified as a PSA increase >0.3 ng/mL over 2 measurements or a larger or new lesion, yet the number of participants meeting that definition is not reported. Without the event count, denominator, and analysis details, readers cannot judge the observed outcome or its precision.

Safety figures have a similar interpretive boundary. Counts of serious adverse events and deaths are useful descriptive information, but small denominators and non-randomized group formation make comparative claims difficult. General principles of statistical inference call for attention to uncertainty, follow-up, and differences between groups, not just the direction of raw counts.

The registry lists many outcomes but no analyses. This highlights the importance of reporting which outcomes were analyzed, how missing observations were handled, and how multiplicity was addressed. Those details help readers distinguish prespecified analyses from exploratory findings and assess whether results could be reproduced. The reason for termination and the study’s sample-size justification are not reported in the registry record.

Statistically, the record’s value lies in showing both the scope of the planned question and the limits of the available evidence. Clear definitions and group descriptions are important, but they do not replace posted outcome data. A careful interpretation preserves that distinction rather than filling gaps with assumptions.

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 main limitation for interpreting efficacy is that the registry record does not report the primary progression count or any analysis of that endpoint. It also does not report results for the listed secondary outcomes. Consequently, the record cannot provide an efficacy estimate, an uncertainty interval, or a comparison with another treatment approach.

Non-randomized allocation limits comparison among groups. The groups corresponded to different disease descriptions and had distinct chemotherapy cycle counts and ADT durations. Any differences in outcomes could reflect these population differences as well as treatment. The record lists 0 analyses and does not report adjustment for confounding.

The enrolled population was 19, and the posted serious adverse-event denominators were 6, 8, and 5. These small group counts can yield imprecise descriptions, and the record does not report uncertainty estimates for the safety data. It also does not provide details about event timing, repeated events, or follow-up by participant.

The primary timeframe is described as ending when a participant was taken off-study or the study stopped, with an average of 10 months. The record does not report individual follow-up, the number assessed for the primary endpoint, or how incomplete observations were handled. The reason for termination is not reported in the registry record. Neither a sample-size justification nor details of interim analyses are reported.

Finally, multiple outcomes are listed without a reported statistical analysis plan or multiplicity strategy. The record does not establish which outcomes were analyzed or whether the posted safety information is complete for all adverse events. These limitations mean the available information is best interpreted descriptively, not as a basis for estimating comparative efficacy or safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Hormone Therapy Plus Chemotherapy as Initial Treatment for Local Failures or Advanced Prostate Cancer — NCT02560051.
• Registry record last updated 2018-11-28; status last verified 2018-11.
• Results first posted 2018-10-11.
• 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

This phase 2 study was non-randomized, unmasked, and conducted in parallel groups. The registry reports enrollment of 19 participants and a terminated status. It describes ADT with degarelix plus doxorubicin, ketoconazole, docetaxel, and estramustine for three disease-status groups, with different cycle counts and ADT durations.

The primary endpoint was the number of participants who progressed, using a definition based on a PSA increase >0.3 ng/mL over 2 measurements or a larger or new lesion. The stated timeframe averaged 10 months. The registry lists 17 outcome measures and 0 analyses; the primary and secondary efficacy results are not reported in the registry record.

Serious adverse events were reported for 3 of 6, 2 of 8, and 0 of 5 participants across the three groups. Deaths were listed as 0 in each group. The reason for termination, sample-size justification, analysis populations, and missing-data methods are not reported in the registry record.