Things go better with Burch
CARE trial: Burch colposuspension at the time of prolapse surgery improves postop urinary control
IN THIS ARTICLE
OUR EXPERT PANELISTS
- Moderator Neeraj Kohli, MD, MBA OBG Management Board of Editors Director, Division of Urogynecology, Brigham and Women’s Hospital, and Assistant Professor, Harvard Medical School, Boston.
- Lead investigator of the CARE trial Linda Brubaker, MD, MS, Professor and Director, Division of Female Pelvic Medicine and Reconstructive Pelvic Surgery, Departments of Obstetrics and Gynecology and Urology, Loyola University Chicago.
- Mark D. Walters, MD, Head, Section of General Gynecology, Urogynecology, and Pelvic Reconstructive Surgery, Department of Obstetrics and Gynecology, Cleveland Clinic, Cleveland, Ohio.
- Anne M. Weber, MD, MS, Program Officer, Pelvic Floor Disorders Network, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md. Dr. Weber is an investigator in the CARE Trial.
Why should we care about the CARE (Colpopexy and Urinary Reduction Efforts) trial?
Because pelvic organ prolapse and urinary incontinence are already major problems facing women as they age, and will become even more pervasive as the baby boomer generation moves through menopause and beyond.
Because roughly one third of women who undergo prolapse or incontinence surgery require a second operation.
These are just a few of the factors that spurred the Pelvic Floor Disorders Network to undertake the CARE trial, published April 13 in the New England Journal of Medicine. OBG Management convened a panel of experts in female pelvic medicine, including 2 CARE trial investigators, to discuss the findings of this landmark study, its long-term implications, and the future of research into pelvic floor disorders.
How the trial was conducted
The CARE trial involved 322 women who required surgery to correct pelvic organ prolapse (POP) but lacked symptoms of stress urinary incontinence. All these women underwent sacrocolpopexy, an abdominal procedure in which graft material is attached between the vagina and sacrum to support the vagina and correct the prolapse. These women were randomized to undergo Burch colposuspension at the time of the sacrocolpopexy, or to undergo sacrocolpopexy only. The Burch procedure is performed through the same incision as the sacrocolpopexy and involves suturing the periurethral vaginal tissue to the iliopectineal ligaments on each side, providing urethral support.
Enrollment in the trial was halted after the first of 2 planned interim analyses because the frequency of postoperative stress incontinence was significantly lower in the group undergoing Burch colposuspension: 23.8% and 44.1% of women in the Burch and no-Burch groups, respectively, experienced stress symptoms by 3 months after the surgery.
Why the CARE trial is an epochal event
- First randomized trial of preventive incontinence surgery in women with prolapse
- Randomized design establishes cause and effect
- Subjects will be followed for 2 years
KOHLI: Dr. Brubaker, as lead investigator of the CARE trial, how would you characterize the study’s major strengths?
BRUBAKER: First, it is a well-designed, randomized, controlled trial and thus provides the highest level of evidence for clinical practice. Although there is no perfect study, this one minimized the risk of bias by involving multiple centers (7) and using multiple surgeons, making the findings more generalizable than would be the case in a single-surgeon case series.
In addition, the use of blinded urodynamic testing lent strength, because the ability of urodynamic testing to predict the need for a concomitant continence procedure was not known before the trial. Our follow-up manuscript, containing data presented at the recent Society of Gynecologic Surgeons meeting, will provide more details on this aspect of the trial.
WEBER: Randomized trials are held in such high esteem—provided all other aspects of study design and implementation are performed properly—because they support conclusions of cause and effect. The conclusion that Burch colposuspension prevents stress incontinence when performed at the time of abdominal sacrocolpopexy could only be drawn from a randomized trial.
Trial design standardized key elements
Many types of bias confound the results of nonrandomized studies, particularly selection bias (eg, when surgeons select which procedure to perform on the basis of patient characteristics), and valid conclusions of cause and effect cannot be drawn. However, with a randomized trial, subjects are separated into groups by chance and no other factor. Thus, the groups are equivalent at baseline—provided the sample size is large enough (and allowing for random differences)—and therefore any changes measured after the experimental intervention can be confidently attributed to the intervention itself.
Another strength of the trial is standardization. The subjects were “standardized” by rather broad inclusion and exclusion criteria to constitute an important clinical population and to ensure they were sufficiently similar so that the treatment (abdominal sacrocolpopexy) was appropriate for all. In addition, surgeons at the multiple participating sites agreed to standardization of the technical details of the Burch colposuspension so that the subjects received the same intervention regardless of site. And data collection in follow-up was performed in a standard way by research staff who were blinded to the subjects’ group assignment (intervention versus control), so the data were as free of bias as possible.
Homogeneous study population may be a weakness
KOHLI: I agree that the methodology of this well-designed study is its major strength. What are its weaknesses?
WEBER: No doubt there are several, only some of which may be apparent at this time. For example, most women in the study were Caucasian, and very few were Hispanic, Asian, or black. Although we have no scientific reason to believe that Burch colposuspension has different responses in women of different racial and ethnic backgrounds, the trial’s subjects are not diverse enough to analyze the data by subgroups to confirm or refute the hypothesis that response to the Burch procedure is independent of race or ethnicity.
BRUBAKER: Another weakness: Because this study was closed after the first interim analysis, some of our secondary analyses will be underpowered, although we clearly demonstrated a difference in our primary endpoint.
It is important to remember that this study is not “finished.” Our participants are still in active follow-up for 2 years following surgery. It will be interesting to see what happens during the longer follow-up, especially with regard to prolapse and incontinence. We are also doing additional in-depth analyses of urodynamic and other parameters.
KOHLI: Again, I think the study design and analysis were well thought out. It would have been interesting to see how the results broke down according to site, to see if there was variation—which could indicate variation in surgical technique.
BRUBAKER: We have not done this analysis and do not plan to at this time.
Why paravaginal repairs were allowed
KOHLI: What about the decision to include surgeries that involved paravaginal repair?
WEBER: That generated a fair amount of discussion during trial design, as there was no clear “right” answer. Perhaps it would have been “cleaner” to eliminate the option of performing paravaginal repair, but when the trial was designed, we lacked unequivocal evidence that paravaginal repair at the time of abdominal sacrocolpopexy provides additional support for the anterior vagina. Therefore, we decided to allow the decision to be based on surgeon judgment.
Some surgeons perform paravaginal repair with abdominal sacrocolpopexy in almost all women because they believe quite strongly that this reduces the risk of recurrent anterior vaginal prolapse. Others never perform paravaginal repair with abdominal sacrocolpopexy and feel just as strongly that their patients are adequately treated and protected from subsequent anterior vaginal prolapse.
Investigators feared paravaginal repairs could dilute Burch effects
Study surgeons did agree that paravaginal repair reduces the likelihood of postoperative stress incontinence, although not as effectively as Burch colposuspension. Thus, our dilemma: If paravaginal repairs were performed in a large number of subjects, thereby improving their postoperative continence status regardless of whether Burch was performed, the effect of Burch could be so diluted as to be lost. On the other hand, if paravaginal repairs were completely excluded, that would restrict some surgeons’ practices and potentially reduce the number of women who would be offered participation in the study if their surgeons felt their anterior vaginal prolapse would be potentially undertreated.
We resolved the dilemma as follows:
- A relatively low proportion—about one quarter—of surgeons performed paravaginal repairs regularly with abdominal sacrocolpopexy, so the potential impact in the trial would not be great.
- Paravaginal repairs were allowed, but only when declared necessary by the surgeon before randomization; this step prevented surgeons from changing their minds about the necessity of paravaginal repair if the subject was assigned to the Burch group (ie, the woman would be receiving additional anterior vaginal support by way of the Burch).
- We stratified for paravaginal repair in the randomization, so women with paravaginal repair were equally distributed between the intervention and control groups.
Are subjective or objective measures better?
- Subjective measures convey a patient’s foremost concerns and how she is doing clinically
- Correlating symptoms with objective measures yields valuable insights into treatment
KOHLI: The CARE trial uses both objective and subjective measures of incontinence. Which do you think are most important?
BRUBAKER: I prefer subjective measures because I think they reflect what is most important to patients in quality-of-life disorders. However, I believe we need to understand the relationship between subjective outcomes and traditional “objective” outcomes.
WEBER: I think the research community is reaching a consensus that “subjective” measures—better described as patient-oriented outcomes—are more important than objective measures, particularly for conditions that affect patients in “subjective” ways, ie, ways that affect their health-related quality of life, rather than quantity of life. This does not mean that objective measures are useless—although we should first evaluate each measure critically to make that determination on the basis of evidence.
Nevertheless, when a patient seeks and receives treatment based on symptoms and how those symptoms impact her daily life, I think it is incumbent upon researchers and clinicians to ensure that the treatment that is considered most effective actually results in a change that the patient finds worthwhile.
What is “success”?
WALTERS: When it comes to incontinence, for which there is an imperfect correlation between various objective and subjective measures, I think both types of measures are valuable and important. Gathering several different types of outcomes for each patient helps us better understand the nuances of how well an intervention works.
I can understand why some clinicians and researchers place greater reliance on subjective measures of incontinence, such as a diary of incontinence episodes and quality-of-life measures, because these measures tell us exactly how the patient is doing clinically and how she feels about the intervention. If she reports that she is completely cured and “perfect,” then objective measures are irrelevant. However, for any subjective outcome short of perfect, correlation with the objective measures such as cough stress test, physical examination, and urodynamic tests can help investigators understand the reason for the imperfect outcome and point to areas of possible improvement.
KOHLI: In my practice, some women who continue to leak slightly after an incontinence procedure consider their surgery a complete success, whereas, as a surgeon, I consider it a suboptimal result. Both objective and subjective results are important.