Title
Authors
Nguyen PL, Je Y, Schutz FA, Hoffman KE, Hu JC, Parekh A, Beckman JA, Choueiri TK.
Summary
Goal
determine whether ADT causes excuess cardiovascular deaths,
perform review and meta-analysis of randomized trials to determine whether ADT is associated with cardiovascular mortality, PCSM, and all-cause mortality in men with unfavorable-risk, non-metastatic prostate cancer.
Data Source
Study Selection
Inclusion require nonmetastatic disease.
- Intervention group with ADT
- Control group with no immediate ADT
Complete information on cardiovascular deaths and median follow-up of more than 1 year.
Data Extraction
by 2 independent reviewers.
Introduction
Androgen Deprivation Therapy (ADT) in the form of a gonadotropin-releasing hormone (GnRH) agonist is mainstay of prostate cancer treatment, but several studies suggested that ADT may cause dying from cardiovascular.
Method
Selection of Studies
search terms “prostate cancer” from MEDLINE and EMBASE citations and CCRCT [1041 studies]
If more than 1 publication was identified from the same clinical trial, use the most recent or complete report. [Remove duplicate, 655 left]
requirement: with randomized controlled trials, patients with specific disease and had intervention with ADT & control group without ADT. predominantly use a GnRH agonist, have adequate information on CV deaths, median follow-up of at least 1 year, but not those who received orchiectomy. [read abstract, 18 left, read full context, 11 left]
For analysis of PCSM and all-cause mortality, only require trial to report those 2 end points. [8 left for CV, 11 for all-cause mortality and PCSM]
Quality was assessed using Jadad/Oxford quality scoring.
Data Extraction and Clinical End Points
extract the following information:
first author’s name, year of publication, median age of patients, number of enrolled patients, inclusion criteria, treatment groups, type of ADT, duration of ADT, number of cardiovascular deaths in ADT and control groups, definition of cardiovascular death, median follow-up, number of PCSM deaths, and number of overall deaths.
the definition of CV death was accepted as defined if defined, ow. Include events broadly related to cardiac disease and vascular disease.
Statistical Analysis
the number of patients with CV death and the number of patients with ADT/placebo.
Proportion of patients with those adverse outcome and 95% CI, RR and CI for RR were derived. To calculate the CI for RR, the variance of a log-transformed study-spefic RR was derived using the $\delta$ method.
For 0 events, use half-integer correction to calculate RR and variance.
Do similar analysis of PCSM and all-cause mortality(overall survival) as well.
Statistical heterogeneity among trials was assessed by Cochran Q statistics, Inconsistency was quantified with the $I^2$ statistics, which estimates the percentage of total variation across studies due to heterogeneity rather than by chance. The assumption of homogeneity was considered invalid if $p < 0.1$.
When substantial heterogeneity was NOT observed, the summary estimate calculated on the basis of **fixed-effect ** ** using inverse variance method. , o.w. random-effects model using DerSimonian and Laird method that considers both within-study and between-study variations.
For studies with separate treatment groups evaluating varying durations of ADT, we combine 2 ADT groups for the overall analysis.
To determine RR of CV death due to ADT within particular groups, perform subgroup analysis on trials of short course or long course, with median age of younger than 70 years or 70years or older, the trials in which radiation was used. To test for variation in RR of CV death due to ADTby duration of ADT or median age, we conducted a meta-regression analysis by modeling a log-transformed study-specific RR as a dependent variable and duration of ADT or median age as a predictor.
Publication bias was evaluated through funnel plots and with the Begg and Egger tests, two-tailed $p < 0.05$ was considered statistically significant.
software: Stata/SE
Reference
- Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials.
Paul L. Nguyen, Youjin Je, Fabio A. B. Schutz, Karen E. Hoffman, Jim C. Hu, Arti Parekh, Joshua A. Beckman, Toni K. Choueiri
JAMA. 2011 Dec 7; 306(21): 2359–2366. doi: 10.1001/jama.2011.1745