Brandel France de Bravo, Cancer Prevention and Treatment Fund, June 21, 2012
I am pleased to have the opportunity to testify on behalf of the Cancer Prevention and Treatment Fund. We are dedicated to improving the health and safety of adults and children, and we do that by scrutinizing medical and scientific research to determine what is known and not known about specific treatments and prevention strategies.
According to a recent study in JAMA, 1 in 4 women who undergo a lumpectomy will have to have a second surgery because the pathology report found that the margins were not clear. For Ductal Carcinoma In Situ (DCIS), re-surgery rates are even higher, ranging from 21% to 50% -something we heard first hand last year when we conducted in-depth interviews with women treated for DCIS. Most patients were thoroughly unprepared for the possibility of a second surgery and all that it entailed; and several got fed up with the surgeon not being able to “get all the cancer out,” and opted for a mastectomy that was absolutely not medically necessary. In addition to the high re-lumpectomy rates, prophylactic mastectomies among DCIS patients are on the rise. Not surprisingly, we would welcome a device that reduces the likelihood of re-lumpectomy and makes breast conserving surgery a one-time solution, as mastectomy already is. Our organization has worked on DCIS for a decade so we were very heartened to learn that in a post market study carried out in Germany MarginProbe cut the re-operation rate for women with DCIS by half. Unfortunately, the re-operation rates in the Pivotal Study were not nearly so impressive: 20.8% in the device arm vs. 25.8% in the control arm.
In addition, we share some of the FDA’s concerns about the device, namely:
- Did the device perform better in Israel due to more extensive training prior to use, or because the design dataset was generated by an Israeli population that is not reflective of the U.S. one? Either way, what are the implications for women in the U.S.?
- Did the device perform better in the Pivotal Study because of design bias giving surgeons an additional opportunity to shave compared to the standard-of-care control arm?
- Also, why was the mastectomy conversion rate higher in the device arm? Was the slightly higher tissue volume causing women faced with re-operation to opt for mastectomy because they were dissatisfied with their appearance following the primary lumpectomy? Any future study would need to include qualitative data from patients after their primary lumpectomy and any subsequent lumpectomies regarding satisfaction with their appearance.
The FDA asks whether the device’s sensitivity is worth its poor specificity. We are somewhat less concerned than the FDA about the false positives and excessive tissue removal because that occurs with or without this device and patients can be informed about this choice. Patients should be asked: Is it more important to you to avoid repeat surgeries or to preserve as much breast tissue as possible?
Given that routine or complete shaving of the lumpectomy cavity is just as effective at converting to negative final margins, with only slightly more tissue removed, is the device worthwhile? The FDA worries that the extra 5 minutes of intraoperative time in the device arm muddied the results, favoring the device. We believe that this is a positive aspect of the device: it forced surgeons to spend more time assessing the margins.
While many of the FDA’s concerns could be effectively addressed in a post-market study, we know from long experience that post-market studies are rarely implemented with the rigor of pre-market studies, in part because the incentives to retain patients simply are not there: why eat your veggies after you’ve already been given dessert? Has the FDA ever withdrawn approval of a device because post-market studies weren’t carried out or because of poor results? I don’t think so, but certainly that is rare if it happens. Given Dune’s track record of responding “too little and too late” to FDA requests, there is no reason to believe that the company will follow FDA requirements better post-market than it did pre-market.
In summary, the benefits of this device are important, and the manufacturers have provided adequate proof of safety, but that is not the only issue here. While the POTENTIAL benefits of the device clearly outweigh the risks-the main risk being the possible removal of noncancerous tissue-the device’s actual benefits have not yet been fully established for the intended use in the U.S. At the very least, the large number of confusing outcome measures should be reduced and clarified prior to the FDA’s decision, so that patients and physicians can make an informed choice.