Effect of Weight Loss on Prostate Cancer Pathology: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Weight Loss on Prostate Cancer Pathology (NCT00475982), a randomized na study. The primary outcome is Apoptotic Index of the Highest Gleason Grade Malignant Epithelium in the Radical Prostatectomy Specimen Obtained After 8-weeks of the Dietary Intervention.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group trial with no masking reported. The registry lists an enrollment of 44 and identifies the study as completed. The two assigned groups were Weight Loss and No Weight Loss. The record gives the study start as 2009-01 and primary completion as 2016-03. The phase is listed as NA, which does not describe a drug-development phase.

The primary endpoint summaries include 16.0 participants in the Weight Loss group and 18.0 in the No Weight Loss group. Those endpoint-specific numbers are not the same as the overall enrollment. The registry does not explain the difference, so reasons such as eligibility, missing specimens, or exclusions should not be inferred. The adverse-event summaries use different group denominators, addressed separately in the safety discussion.

The study focused on a biological measure in prostate tissue after surgery, rather than a reported clinical outcome such as recurrence or survival. The stated purpose was to examine whether weight loss before radical prostatectomy affects chemical substances in blood and prostate tissue that may be related to cancer development and progression. The posted primary result concerns the apoptotic index; the record also lists outcomes involving proliferation, serum analytes, ex-vivo activity, body weight, and body fat.

Further details about the randomization procedure, allocation concealment, the exact intervention, protocol deviations, and the trial's original sample-size rationale are not reported in the registry record. The record also does not describe masking of laboratory personnel or outcome assessors.

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 Apoptotic Index of the Highest Gleason Grade Malignant Epithelium in the Radical Prostatectomy Specimen Obtained After 8-weeks of the Dietary Intervention, measured over 8 weeks.

The primary endpoint is the apoptotic index in malignant prostate epithelium with the highest Gleason grade, measured in the radical prostatectomy specimen obtained after 8 weeks of dietary intervention. TUNEL staining identifies the cells counted for this measure. The index is expressed as the percentage of cells stained in the sample.

Apoptosis is a process of programmed cell death. In general, an index based on stained cells turns a tissue-level biological feature into a numerical measure that can be compared between groups. The registry's stated objective was to compare the group means. This makes the endpoint a continuous measure, for which the record presents means and standard deviations.

The endpoint is used to examine a biological response in the malignant tissue, not to establish whether participants experienced a clinical benefit. The registry record does not report that the endpoint is a validated surrogate for a clinical outcome, nor does it explain how the highest Gleason grade area was selected beyond the description in the endpoint definition. Consequently, the result should be interpreted as a comparison of this measured tissue feature, rather than as a direct measure of cancer progression, recurrence, or survival.

7. Results Posted in the Registry

• Arm 2: No Weight Loss: mean 5.00 versus 6.90 on control; difference -1.90 (95% CI -7.40 to 3.60), standardized effect d = -0.24; z-test p = 0.499.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Proliferative Index in Prostate Cancer Epithelium Specimen

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Arm 2: No Weight Loss: mean 5.79 versus 6.69 on control; difference -0.90 (95% CI -3.74 to 1.94), standardized effect d = -0.22; z-test p = 0.534.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm 2: No Weight Loss and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes covering proliferation in prostate cancer epithelium, serum IGF-related analytes, ex-vivo activity of patient sera on LNCaP cells, body weight, and percent body fat. The posted endpoint summaries include a proliferation measure in prostate tissue, as well as the primary apoptosis measure. The other listed outcomes address different biological or body-composition features, so they do not all answer the same question.

Across the secondary endpoints, the broad pattern is that they extend the investigation beyond the primary tissue measure to related laboratory and body-composition measures. They can add context about whether multiple features moved in a coherent way, but they do not independently establish a clinical effect. The registry record does not provide a comprehensive account of how the secondary outcomes were prioritized or how all analyses should be interpreted together.

Unadjusted secondary results carry less weight because multiple outcomes and analyses create more opportunities for apparently notable findings to arise by chance. In general, multiplicity can increase the risk of false-positive conclusions when many tests are interpreted without an adjustment or a prespecified hierarchy. The record lists 17 analyses, but does not report a multiplicity adjustment or a strategy for controlling error across outcomes. Thus, individual secondary p-values should be treated as exploratory unless the record establishes otherwise.

Secondary results can help generate hypotheses and inform future research, but they should not be used to override the uncertainty in the primary comparison. They also cannot be combined into a single overall conclusion without a defined analysis plan and a rationale for how the measures relate to one another. The registry record does not report such a combined analysis.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Proliferative Index in Prostate Cancer Epithelium Specimen
• Change in Serum IGF-related Analytes: IGF-1
• Change in Serum IGF-related Analytes: IGFBP-1
• Ex-vivo Mitogenic and Apoptotic Activity of Patient Sera on LNCaP Cells
• Change in Body Weight
• Change in Percent Body Fat

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant's tissue specimen contributes an apoptotic-index value expressed as a percentage of cells stained. The registry reports the mean and standard deviation by group. In general, a mean describes the arithmetic average, while a standard deviation describes how dispersed individual observations are around that average. These summaries give a compact description of group results, but they do not show the full distribution of individual values.

What does the mean comparison represent?

The unadjusted recalculation compares the group means as No Weight Loss minus Weight Loss. Its estimate is -1.9, meaning that the observed average in the no-weight-loss group was lower by that amount on the stated scale. The sign depends on the order of subtraction; reversing the order would reverse the sign without changing the underlying group summaries. This is an unadjusted comparison based on the posted means and standard deviations, not a covariate-adjusted model.

The confidence interval accompanying that recalculation represents a range of values compatible with the observed data under the calculation's assumptions. In general, a confidence interval is not a guarantee that the true value lies within the observed interval, nor does it assign a probability to a particular effect after the data are observed. Its width conveys precision: a wider interval leaves more plausible values unresolved. The primary interval extends across zero, so the data do not isolate a direction for the mean difference.

Why is a rank-based test different?

The registry reports a Wilcoxon (Mann-Whitney) analysis. In general, this test compares the ordering or ranks of observations across independent groups rather than calculating a mean difference directly. It can be useful when the distributional pattern makes a rank-based comparison relevant. However, a rank-based test result is not automatically an estimate or test of a difference in means. The registry labels its reported parameter as Mean Difference (Final Values), but does not give further information about the implementation or the reason for choosing this method. The reported p-value and the recalculated mean-difference interval therefore address analyses that are not fully described as the same procedure.

A p-value describes how unusual data at least as incompatible with a specified null model would be, if that model and the analysis assumptions held. It does not measure the probability that the null hypothesis is true, the size of an effect, or its clinical importance. The registry-reported p-value is 0.965, while the unadjusted recalculation has p = 0.499. Neither figure should be read as a measure of the probability that weight loss did or did not affect the endpoint. The registry does not report whether the primary analysis was prespecified in its original protocol or whether any other analyses were considered.

Why does variability matter?

In general, greater variability makes estimates less precise because observations are more spread out around the group averages. The primary standard deviations differ between the groups, and the record gives no individual-level data with which to examine distribution shape, outliers, or whether a transformation would be appropriate. A normal approximation may be used for the posted planning illustration, but that is not evidence that the primary outcome itself followed a normal distribution.

Over-dispersion is a general concern when the observed variability is greater than a model assumes. If a model underestimates variability, its standard errors can be too small and its confidence intervals too narrow. If variability is modeled appropriately, uncertainty should reflect the observed spread. The registry does not report a model for over-dispersion or a diagnostic assessment for this endpoint, so no claim about such a model can be made.

What is and is not reported?

The record reports group summaries and a named rank-based test, but does not report a detailed statistical analysis plan, covariate adjustment, handling of missing outcomes, or analysis population definitions. It does not report an interim analysis plan. The randomization method and any stratification factors are also not reported in the registry record. These omissions limit assessment of whether the analyses followed prespecified choices and whether all randomized participants were included in the intended analysis.

The planning figures are illustrative calculations based on an observed effect, with the stated assumptions discussed in the sample-size reading. Such calculations are prospective planning aids, not evidence about the probability that the completed trial detected an effect. They should not be confused with the observed uncertainty represented by the endpoint confidence interval.

11. Confidence Intervals and Precision

The unadjusted primary mean difference is -1.9, with a 95% confidence interval from -7.404 to 3.604. The interval includes zero and spans values consistent with a lower mean in the no-weight-loss group as well as values consistent with a higher mean in that group. The estimate alone is therefore not precise enough to establish the direction of the underlying mean difference.

In general, a confidence interval describes uncertainty in an estimate under the assumptions of the calculation. It is not a range containing every individual participant's result, and it is not a direct measure of clinical importance. The primary interval is wide in relation to its point estimate. That width is consistent with limited information from the endpoint groups and the variation in the observed measurements. The standard deviations were 10.4 for the Weight Loss group and 4.5 for the No Weight Loss group.

The registry-reported Wilcoxon analysis has no confidence interval listed. Its p-value alone does not show the range of effect sizes compatible with the data. Also, because the reported method is rank-based while the recalculation is a mean comparison, the two results cannot be combined into one confidence interval or treated as duplicate estimates from the same procedure. More detail about the sponsor's analysis is not reported in the registry record.

Confidence intervals describe statistical precision, not whether the endpoint is a meaningful proxy for patient outcomes. The registry record does not report a clinically important threshold for the apoptotic index. It is therefore not possible to use the interval to classify the range of values as clinically important or unimportant.

12. 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, not total events. They use two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is defined as the stated fraction of the observed effect. The figures are planning illustrations based on the observed effect, not the trial's original design assumptions; those original assumptions are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under the planning assumptions, if that effect and the assumptions were correct. The 90% power column gives the corresponding number per arm for a 90% chance. These are planning probabilities, not guarantees about a future study and not descriptions of what happened in this completed trial.

The entries for 100% of the observed effect are 268 participants per arm for 80% power and 358 participants per arm for 90% power. Planning for 75% of the observed effect gives 476 participants per arm for 80% power and 637 participants per arm for 90% power. Planning for 50% of the observed effect gives 1,069 participants per arm for 80% power and 1,432 participants per arm for 90% power. Smaller effects need more participants to detect under the same assumptions, and a higher target power also requires a larger planned sample.

These values are not observed power. They do not change the interpretation of the completed trial's confidence interval or p-values. They illustrate how sample-size needs depend on the chosen target effect and planning assumptions, rather than establishing what the original investigators intended to enroll.

13. 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 = -1.900; pooled standard deviation σ = 7.840.
2. n = 2 × (1.96 + 0.842)² × 7.840² / -1.900² = 267.2, rounded up to 268 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 <- -1.9                      # observed difference in means
sigma <- 7.83950333248223                     # 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(475982)
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 = 268 (80% power), 358 (90% power)
 75% of observed effect: n per arm = 476 (80% power), 637 (90% power)
 50% of observed effect: n per arm = 1,069 (80% power), 1,432 (90% power)
power.t.test: 268.2 
Simulated power at n = 268 per arm: 0.797 (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.

14. Analyses Reported by the Sponsor

The registry-reported analysis compares the two groups using a Wilcoxon (Mann-Whitney) method. It reports a parameter label of Mean Difference (Final Values), a value of 0.965, and p = 0.965; no confidence interval is listed. The separate unadjusted recalculation uses the posted group means and standard deviations and reports a mean difference of -1.9, with a 95% confidence interval from -7.404 to 3.604 and p = 0.499.

The registry does not explain why the reported analysis is rank-based while its parameter label refers to a mean difference, or how the reported value was calculated. A rank-based result and a mean-based recalculation need not yield the same estimate or p-value because they use different information from the outcome distribution. The reported analysis and recalculation should therefore be read as distinct results rather than reconciled by assuming that one is a rounding variant of the other.

The registry record does not mark a discrepancy between the sponsor-reported analysis and the recalculation. It also does not provide enough methodological detail to determine which analysis was prespecified or to reproduce the reported test. The recalculation is unadjusted and based on summary statistics; it does not replace the registry-reported analysis or supply missing details about the sponsor's procedure.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists 17 analyses and several secondary outcome domains. It does not report whether the investigators adjusted for multiple comparisons, used a hierarchy of endpoints, or designated a limited set of confirmatory tests. In general, testing many outcomes can increase the chance that at least one result appears unusual even when there is no underlying effect. Without a documented multiplicity strategy, secondary findings should be interpreted cautiously and not as a collection of independent confirmations.

The record does not report how missing outcome data were handled, how many randomized participants contributed to each analysis beyond the group summaries, or why endpoint-specific denominators differ from the enrollment total. It does not describe imputation, complete-case analysis, sensitivity analyses, or exclusions from the primary analysis. These details matter because missingness can affect both the precision and the interpretation of a group comparison, particularly if availability of a specimen is related to participants or outcomes.

Analysis population definitions are also not reported in the registry record. It is not specified whether the primary analysis included all randomized participants, only participants with an evaluable prostatectomy specimen, or another defined group. The endpoint summaries are therefore best understood as the posted analyzed groups, without assuming an intention-to-treat or per-protocol approach.

The registry does not report an interim analysis plan or a detailed statistical analysis plan. It is not possible to determine from the record whether interim looks at the data occurred, whether the endpoint and method were prespecified, or whether analysis decisions changed during the study. These are reporting limitations; they do not establish that any particular practice did or did not occur.

16. 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 5% reporting threshold.

The adverse-event summary lists 23 participants at risk for serious adverse events in the Weight Loss group and 21 in the No Weight Loss group. It reports zero serious adverse events in each group. Other adverse events are also reported as zero in both groups, using the same at-risk denominators. Death counts are not reported.

These figures describe what the registry reports for the listed safety groups. They do not establish that no adverse events of any kind occurred outside the definitions or observation period used for the registry summary. The record does not provide event definitions, collection windows, severity details beyond the serious category, or information about how safety data were collected. It also does not explain why these denominators differ from the group counts in the primary endpoint summaries.

Zero reported events in a limited study does not demonstrate that an intervention is free of risk. The safety figures should be read as a descriptive registry report, not as a comprehensive assessment of safety or as medical guidance.

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

The posted primary summaries describe average apoptotic-index values of 6.9 in the Weight Loss group and 5.0 in the No Weight Loss group. The unadjusted recalculation gives a mean difference of -1.9 for No Weight Loss minus Weight Loss, with a 95% confidence interval from -7.404 to 3.604. The interval includes zero and leaves uncertainty about the direction and magnitude of the mean difference. The registry-reported rank-based analysis gives p = 0.965, but the record does not provide its confidence interval or enough detail to fully interpret how its reported parameter was derived.

The result concerns a biological tissue measure obtained after 8 weeks, not a direct measure of cancer progression, recurrence, survival, or quality of life. The registry's stated scientific motivation links weight loss to chemical substances in blood and prostate tissue that may affect cancer development and progression, but the primary result by itself does not answer whether weight loss changes those longer-term clinical outcomes.

The posted data also do not establish that the groups were equivalent. A confidence interval spanning zero can reflect uncertainty about the effect, rather than proof that the groups have identical outcomes. Conversely, a difference in group averages would not by itself prove a clinically important benefit. The registry record does not report a threshold for clinical importance for the apoptotic index or evidence that it is a validated surrogate endpoint.

The trial's randomized design is relevant to the comparison, but assessment is limited by unreported details about randomization, missing outcomes, analysis populations, and the original statistical plan. The endpoint-specific sample sizes are lower than total enrollment, and the reasons are not reported. These limitations mean the posted summaries should be interpreted narrowly: they describe the measured endpoint among the participants included in those summaries.

18. Why This Trial Matters Statistically

This trial illustrates a common challenge in clinical research: a randomized comparison can focus on a biological measure that is scientifically relevant without directly measuring a clinical outcome. The apoptotic index is a tissue-level endpoint expressed as a percentage of stained cells. Its meaning depends on the measurement procedure and on how well that biological feature relates to outcomes that matter to patients. The registry record does not report validation of the index as a surrogate.

The trial also highlights why effect estimates and uncertainty are more informative together than a p-value alone. The recalculated mean difference is accompanied by a confidence interval that includes zero and spans a range of possible values. The sponsor-reported rank-based p-value is another result, but it does not replace an estimate with an interval, and its relation to the mean-based recalculation is not explained in the record.

Differences among the analytic populations, outcome types, and denominators matter. Overall enrollment, endpoint-specific group counts, and safety denominators are not interchangeable. Without explanations of missing data and analysis populations, readers cannot determine why each summary includes its stated number of participants.

Finally, the planning illustrations demonstrate how assumed effect size and target power influence sample-size requirements. They do not reconstruct the original trial's design, which is not reported. Separating planning calculations from observed evidence is essential: the illustrations do not change the uncertainty in the completed trial's results and are not a measure of its observed power.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record leaves important design and analysis details unspecified. It does not report eligibility criteria in detail, participant characteristics, the randomization procedure, allocation concealment, the exact behavioral intervention, or whether outcome assessors or laboratory personnel were masked. Masking is listed as none, but the record does not clarify whether this applies to every stage of outcome measurement.

The primary endpoint summaries include 16.0 participants in the Weight Loss group and 18.0 in the No Weight Loss group, whereas enrollment is 44. The safety groups use denominators of 23 and 21. The registry does not explain these differences or report a flow of participants from randomization through analysis. Missing-data methods and analysis-population definitions are not reported, limiting assessment of selection and attrition.

The reported sponsor analysis uses a Wilcoxon (Mann-Whitney) method while labeling the parameter Mean Difference (Final Values). The record does not include a confidence interval for that analysis or methodological detail sufficient to reproduce it. The unadjusted recalculation is a distinct summary-based mean comparison. The registry does not report the original statistical analysis plan, any covariate adjustment, or whether the reported analysis was prespecified.

The record lists multiple analyses but does not report a multiplicity strategy. It also does not report a clinical-importance threshold for the tissue endpoint, validation of the endpoint as a surrogate, or longer-term clinical outcomes. These omissions limit both statistical and clinical interpretation; they do not establish that the unreported procedures or information were absent from the study itself.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Effect of Weight Loss on Prostate Cancer Pathology — NCT00475982.
• Registry record last updated 2019-01-31; status last verified 2018-08.
• Results first posted 2019-01-31.
• 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.

23. Record Summary

NCT00475982 is a completed randomized, parallel-group study titled Effect of Weight Loss on Prostate Cancer Pathology. It enrolled 44 participants and compared a Weight Loss group with a No Weight Loss group. The registry lists no masking and gives a primary completion date of 2016-03.

The primary endpoint was the apoptotic index in malignant prostate epithelium with the highest Gleason grade, measured by TUNEL staining in a radical prostatectomy specimen after 8 weeks. The unadjusted mean comparison is -1.9 for No Weight Loss minus Weight Loss, with a 95% confidence interval from -7.404 to 3.604. The registry-reported Wilcoxon analysis gives p = 0.965, without a confidence interval.

The endpoint summaries and reported analysis leave uncertainty about the primary tissue comparison. Details about the original statistical plan, missing data, and analysis populations are not reported in the registry record. The results address a biological measure and do not by themselves establish an effect on longer-term clinical outcomes.