Conflict of Interest and Recommendations for Explantation in Asymptomatic Patients Concerned About BIA-ALCL Risk

The September 2024 issue of Plastic and Reconstructive Surgery contains an original article by Clemens et al¹ reporting the recommendations of an expert consensus conference convened by the American Association of Plastic Surgeons (AAPS). The article is authored by international experts on breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL). These recommendations were first published online at the end of February 2024. This online publication was immediately followed, on February 28, 2024, by an email sent to all members of the American Society of Plastic Surgeons (ASPS) titled: “ASPS response to AAPS recommendations regarding textured implants.”² A society newsletter challenging the findings and recommendations of a scientific publication is extraordinary.

The unnamed authors of the email were clearly aware of the study well before its publication. The email reported that the “ASPS staff and an independent, external methodologist reviewed the original publication.”² The email stated that “ASPS believes some additional context is important to share with all stakeholders.” The email continues, “The Society believes that to demonstrate a risk reduction or protective effect, the analysis would need to include controls with or without BIA-ALCL to provide either a risk ratio or odds ratio.” The email does not include any names of authors or the identity of the methodologist. It does not include a disclosure regarding conflict of interest. This email correspondence was published simultaneously on the ASPS website and remains available to the public.²

A discussion accompanies the print publication.³ The discussant comments that the article by Clemens et al¹ “raised some concerns among stakeholders within the world of breast implant safety.” The discussant contends that, although the authors are respected experts in the field, some of the “broad-reaching implications” are not justified. He objects to the recommendation that, “in some patients with macrotextured implants, there may be a relative indication for explantation.”

The consensus statement referenced the findings of a systematic review of 248 cases of BIA-ALCL published by Santanelli di Pompeo et al.⁴ This review found that the rate of BIA-ALCL was 108 cases per 1000 patients per year in patients with a history of textured implants without removal or replacement. The incidence rate was 75 new cases per 1000 patients per year in patients who underwent implant removal/replacement and 48 cases per year in patients who underwent 2 exchange operations. The data suggest a risk benefit in patients undergoing explantation or implant replacement. However, the authors caution that the evidence for risk reduction remains limited.¹

As mentioned in the open letter posted on the ASPS website,² the discussant objects to the absence of randomization and a control group of patients without BIA-ALCL.³ In practice, it is impossible to perform a randomized controlled study in surgical patients who are free to participate in decision-making and choose their treatment option.^1,5 Moreover, a randomized controlled study would have to be prospective. Because of the 8- to 10-year delay between exposure to macrotextured implants and a diagnosis of BIA-ALCL,⁶ it would take at least a decade to obtain the needed data.

RISK/BENEFIT ANALYSIS

The US Food and Drug Administration (FDA) made its 2019 recommendations based on the relative risks of BIA-ALCL and explantation.⁷ The FDA statement read: “The FDA does not recommend removal for patients without symptoms due to potential risks.” Estimates of the risk of BIA-ALCL in women with textured implants have increased dramatically in recent years.⁸ Only 2 large prospective studies have reported BIA-ALCL risk in women with macrotextured breast implants. McGuire et al⁹ reported a risk of 1:4414. This incidence increased to 1:2207 after 4 additional patients were diagnosed following publication.¹⁰ In 2020, Cordeiro et al¹¹ reported a risk of 1:355 for women with Biocell (Allergan, an AbbVie company, North Chicago, IL) implants. Notably, this widely cited article authored by researchers working in New York City was published in the Journal of Plastic, Reconstructive, and Aesthetic Surgery. The risk of BIA-ALCL may be higher than these estimates because of the delay between implantation and diagnosis.⁶ Cordeiro et al¹¹ estimated a cumulative risk of 1:100 over 20 years in breast reconstruction patients.¹¹

By comparison, Santanelli di Pompeo et al¹² reported that there were zero deaths among almost 100,000 European breast implantation, explantation, and implant exchange patients treated over 8 years. Wixtrom et al¹³ reported a 1:72,000 risk of death for cosmetic breast outpatients, not necessarily implant patients, based on the American Association for Accreditation of Ambulatory Surgical Facilities database.

The risk of mortality from BIA-ALCL according to the FDA is about 1 in 20 (5%).¹⁴ Therefore, if the risk of BIA-ALCL is even 1:2200, the risk of mortality is 1:44,000, still greater than the risk of mortality from surgery.^12,13 One must also consider morbidity.¹⁴ The morbidity from implant exchange is typically minimal. The morbidity from a BIA-ALCL diagnosis is much greater.¹⁵ A woman diagnosed with BIA-ALCL requires a metastatic workup that includes a PET-CT scan, and she may need follow-up scans every 6 months for 2 years.^1,6 She will require bilateral explantation along with capsulectomies.^1,6 Depending on the stage of the disease, she may require additional surgery, radiation therapy, chemotherapy, or immunotherapy.^1,6 Unless her implants are replaced, she will be left with little or no breast volume, with obvious effects on self-esteem, which is the reason she chose to have implants in the first place. Capsulectomies are highly traumatic to the breasts.¹⁶ Some surgeons insist on autologous reconstruction in a patient after a diagnosis of BIA-ALCL,¹⁷ making the cosmetic patient a reconstructive patient. The financial consequences can be devastating, amounting to hundreds of thousands of dollars.¹⁸ Allergan offers only $7500 for patients with a diagnosis of BIA-ALCL.¹⁹

The role for capsulectomy is unclear.¹ No scientific data support capsule removal in asymptomatic patients with no sign of capsular pathology who undergo implant replacement because of concerns regarding BIA-ALCL risk. Implant replacement without a capsulectomy is a 30-minute procedure (Fig. 1).¹⁶ The risk/benefit analysis shifts toward explantation if the procedure is almost risk-free.²⁰

FIGURE 1.

A, C, E, This asymptomatic 38-year-old woman is shown before and (B, D, F) 6 weeks after replacement of her 290-mL Allergan Biocell textured silicone gel breast implants. She underwent open capsulotomies and insertion of new Allergan 405 mL round, smooth, moderate profile silicone gel implants. The same subpectoral pocket was used. She also underwent liposuction of her abdomen and flanks. Reprinted from Swanson.¹⁶

POTENTIAL FOR RISK REDUCTION

Clemens et al¹ conclude that, “based on the potential for risk reduction, prophylactic explantation of macrotextured surface implants can be deemed reasonable” (authors' italics). The authors explain that this does not necessarily mean advisable (authors' italics) and that the decision should be one between the patient and surgeon, balancing the perceived benefits of surgery with an individual surgical risk assessment. The authors' recommendation seems reasonable and avoids overstatement. Clemens et al¹ recognize that the patient's perception is relevant. Patients may have greater peace of mind having their textured implants removed. For some women, the knowledge that their implants carry a risk of cancer has a negative psychological impact.¹ Despite the authors' disclaimers, the discussant strongly takes issue with the notion that explantation may be a reasonable option.³

The discussant is also critical that the authors do not mention a “crucial point, the importance of surveillance.”³ In fact, the authors never suggest that explantation leaves “patients with no further risk and no need for continued surveillance.”³ On the contrary, the article emphasizes the importance of surveillance, mentioning it 9 times and repeatedly referencing the 2021 FDA recommendations.²¹ Patients are instructed to immediately report any swelling, lumps, pain, or any changes in or around their breast implants.⁷ Clemens et al¹ clarify that there is no recommended radiographic screening test specifically for BIA-ALCL.

An analogy may be found in the cancer risk caused by smoking.¹⁵ Smoking is known to increase the risk of lung cancer. A smoker who quits still has a risk of lung cancer. However, no clinician will recommend that smokers continue the habit anyway and simply return if they develop any clinical symptoms or signs of lung cancer, or return for chest radiographs on a regular basis. Surveillance is not enough. The triggering stimulus must be eliminated.

In considering the etiology of BIA-ALCL, one must have a theory for its cause. Otherwise, it is difficult to make any rational recommendations regarding its prevention. The leading theory is that the textured surface causes chronic inflammation.²² Regardless of the specific carcinogen, the greater the exposure, the greater the risk.¹ The concept of risk reduction is already incorporated into treatment recommendations.¹ Risk reduction is the rationale for removing or replacing (with a smooth device) the contralateral implant in patients diagnosed with unilateral BIA-ALCL.⁶

THE UPSIDE OF ENGAGING PATIENTS

Plastic surgeons should not remain passive and simply respond to questions from patients. Roberts et al²³ demonstrated the value of contacting patients with textured implants and offering to consult with them regarding their options. Van Slyke et al²⁴ revealed that Biocell implants had the shortest times to explantation and the greatest risk of performance failure, including malposition, malrotation, seroma, rippling, capsular contracture, rupture, pain, and double capsules. Breast pain was reported by 21% of women with Biocell implants compared with 1.4% for other implants. These implants may be replaced with a superior product.

Being proactive is not only good medical practice, it is also good for plastic surgeons. Many patients wish to have asymmetry or a capsular contracture treated. Some patients are likely to have other procedures in addition to implant replacement, such as a breast lift, or unrelated cosmetic surgery (Fig. 1).²⁵ Cordeiro²⁶ reports that many of his breast reconstruction patients who have returned to have their Biocell implants replaced are more satisfied with their new smooth round implants. Santanelli di Pompeo²⁷ points out that most women will return for additional breast implant surgery regardless of BIA-ALCL concerns — 22.3% for primary augmentation and 71.5% for primary reconstruction. Patients with textured devices may choose to have their implant replacement surgery sooner rather than later,⁸ especially those with other breast issues that may be surgically remedied.

PATIENT ADVICE ON ASPS WEBSITE

The ASPS website provides answers for patients asking questions.²⁸ The first question asks, “Do I need to have my implants removed?” The answer reads, “No, the FDA has specifically stated that implant removal is not necessary at this point unless you are diagnosed with BIA-ALCL.” In response to the second question, “I have Allergan Biocell implants. What should I do?” the answer is, “Unless you are having the symptoms noted below, there is nothing to do at the present time other than routine continual breast examinations.” The ASPS website continues: “However, patients should note that the current risks associated with any surgery are higher than the risk of developing BIA-ALCL.” A video, first posted over 2 years ago on the ASPS website, advises: “There are currently no identified risk-reducing procedures.” A video spokesperson reiterates, “Patients should know that the current risks associated with surgery are higher than the risk of developing BIA-ALCL.”²⁹

HONEST PATIENT COUNSELING

This author has, on many occasions, asked surgeons and researchers privately at meetings whether they would recommend explantation in a family member with macrotextured implants.⁸ Invariably the answer is “yes.” Some surgeons are willing to go “on the record.”⁸ Others are not, citing concerns regarding their relationship with Allergan or ASPS. Allergan's pervasive influence is inevitable in view of the millions of dollars paid to ASPS and its members.^30–34

Plastic surgeons should not resist explantation in patients who request it. Such a response is arguably paternalistic and one they may regret if their patient returns years later with BIA-ALCL.⁸ To tell patients that “the FDA recommends against it” is not exactly true.⁸ The FDA does not recommend explantation but does not recommend against it either.⁷ One must also consider moral hazard. Surgeons who recommend against explantation do not have to bear the consequences if they are wrong. The word “stakeholders” is repeatedly used,^2,3 suggesting that the interests of industry and plastic surgeons are also relevant to recommendations. The only “stakeholder” that should concern plastic surgeons is our patient.

MANUFACTURER RESPONSIBILITY

Ordinarily, when a manufacturer is faced with a defective product, it issues a recall. For example, if an accelerator pedal on an automobile is defective it is replaced.³³ It is difficult to reconcile a ban on macrotextured implants while, at the same time, not recommending their removal in women who have them.³³ It is very unusual for a company to be relieved of the financial responsibility of recalling and replacing a defective or dangerous product. Allergan does not reimburse asymptomatic patients for the costs associated with explantation or replacement with smooth implants. This nonreplacement policy creates a windfall for the manufacturer. This multibillion dollar international corporation could afford to take the morally correct position and provide financial assistance for any woman who, because of the risk of BIA-ALCL, wishes to have her implants replaced. Its surrogates are helping to defend it, placing corporate interests (and their own financial interests) ahead of their patients' best interests.^33,34

CORPORATE SUBSIDIES IN PLASTIC SURGERY

Conflict of interest is the biggest problem facing plastic surgery today.^30–34 Dr Goldwyn was most concerned about Plastic and Reconstructive Surgery selling out to special interests when he stepped down as editor in 2004.³⁵ His concerns have not just been realized but wildly exceeded.³⁴ In 2018, Allergan distributed almost $10 million to plastic surgeons.³⁶ Over half of the payments (53%) were categorized as gifts, and 27% were categorized as compensation for services other than consulting.”³⁶ The magnitude of payments to our societies is not generally known but presumed to be millions of dollars.³⁷ Society officers, journal editors, and reviewers are among those who receive payments, establishing a quid pro quo.³⁴ Unfortunately, plastic surgeons do not have a good track record of disclosing their financial conflicts.³² An ASPS proposal to report the ranges of dollar amounts of industry payments³⁷ was never implemented.³²

OPEN PAYMENTS DATABASE AND “CONSULTING FEES”

The Centers for Medicare & Medicaid Services (CMS) regards most payments from industry to doctors as equivalent to bribes.³⁸ Some physicians accepting kickbacks have faced serious consequences, including criminal indictments.³² These indictments were the inspiration for the creation of the CMS Open Payments Database. This database is analogous to an “ethical EKG” for physicians, revealing industry reimbursement that often does not appear in disclosure statements in scientific journals.³⁴ Today, many plastic surgeons, as well as a growing number of patients, consult this open database to determine the extent of an author's financial conflicts. The ideal “rhythm” should be “asystole,” a flat line signaling no industry payments (Fig. 2).^34,39

FIGURE 2.

Open payments database of the Centers for Medicare and Medicaid Services. General payments to Dr Eric Swanson, 2017–2023.³⁹ The blue line indicates payments made to Dr Swanson. The green line represents the mean payments to plastic surgeons. Thirteen payments were reported to the database for food and beverage, totaling $814.

The appropriateness of labeling payments as consulting fees is questionable.³⁴ Consultancy fees are meant for the provision of objective technical advice paid at fair market value, documented in written contracts.³¹

CONFLICT OF INTEREST AND SOCIETY OFFICERS

An editor, society officer, or committee member is a prized target for manufacturers because of their influence within a specialty.³² In 2010, the Council of Medical Specialty Societies published a code for interactions with companies, with a provision that prohibits society officers and journal editors from accepting any compensation from industry.⁴⁰ In 2015, Dr Ed Luce³⁷ proposed banning conflicted editors, reviewers, and discussants from editorial boards. This bold recommendation was dismissed by the authors of 2 discussions that accompanied his article.^41,42 The 3 authors of the discussions, all former ASPS presidents, were paid more than US $4.4 million from industry between 2015 and 2021, according to the CMS database.^32,34

CONFLICTED DISCUSSANTS

David Sackett,⁴³ one of the founders of modern evidence-based medicine, once commented, “The first sin committed by experts consists in adding their prestige and their position to their opinions, which give the latter far greater persuasive power than they deserve on scientific grounds alone.” A tenet of evidence-based medicine is that no degree of personal or institutional authority can take precedence over the facts.^5,43

The publication by Brody et al⁴⁴ is one of the most outstanding contributions ever made in plastic surgery. It has stood the test of time. The link to texture remains solid. Not a single patient with a known history of only smooth implants has developed BIA-ALCL.¹ Brody⁴⁵ first noticed that the emergence of BIA-ALCL coincided with implant surface texturing. This pioneering work was instrumental in having this disease recognized by the World Health Organization.⁴⁶ It eventually led to the FDA request for a recall of macrotextured devices.⁷ This action prevented untold suffering and saved lives.

A discussant to this 2015 article opined, “Therefore, any conclusions drawn in the article are forced to be based more on conjecture and innuendo than actual fact. For example, even the primary assertion of a link between ALCL and implants with ‘lost salt’ texturing does not have enough substantial associated data to make the conclusion scientifically or statistically significant.”⁴⁷ A second discussant was also highly critical of the methodology.⁴⁸ He accused the authors of ignoring (nonexistent as it turned out) patients who were diagnosed with this malignancy after receiving smooth implants. He surmised that the risk of a patient developing BIA-ALCL is less than being “struck by an asteroid” and that “texture is not the primary problem.” The commonality between these discussants, both of whom were unable to recognize the importance of this scientific contribution, was conflict of interest. Both discussants were heavily compensated by Allergan.^34,49

PLASTIC SURGEON TESTIMONY ON PANELS

Credibility matters. One panelist at the 2019 ASPS meeting was inserting macrotextured implants as recently as 2019,⁵⁰ well after most American plastic surgeons had abandoned them and only months before the FDA requested a recall. By comparison, another panelist, Dr McGuire, stopped using Biocell implants at the end of 2016.⁵⁰ This author, also on the 2019 panel, has inserted smooth implants exclusively for 24 years. In fact, all surgeons should have stopped inserting these dangerous devices shortly after Brody et al⁴⁴ warned everyone of a link between textured implants and BIA-ALCL in 2015. Such an action would likely have spared some patients from developing this malignancy (those treated subsequently up until the July 24, 2019 FDA action).³³

The sinister effect of corporate subsidies was on full display at the 2019 FDA Hearing.^18,33,51 Plastic surgeons unanimously testified before the panel in defense of keeping macrotextured devices on the market. In stark contrast, all BIA-ALCL patients pleaded with the FDA for their removal from the marketplace.^18,51 The FDA, no doubt influenced by plastic surgeons, initially ruled to keep the devices available⁵² before finally making the correct call on July 24, 2019, after additional deaths were reported.⁷

ETHICAL REQUIREMENTS

The ASPS Code of Ethics⁵³ provides that “a member's clinical judgment and practice must not be affected by economic interest in, commitment to, or benefit from professionally related commercial enterprises or other actual or potential conflicts of interest. Disclosure of professionally-related commercial interests and any other interests that may influence clinical decision-making is required in communications to patients, the public, and colleagues.” Videos meant to educate patients should not include conflicted speakers who are essentially spokespeople for the manufacturer.²⁹ If they do, the video must include the caption, “Paid Allergan Spokesperson.”³⁴ This ethical requirement is no different from a spokesperson advertising a product on television.⁵⁴ Patients (and plastic surgeons) need to know about financial motives.³⁴

CONCLUSIONS

Sadly, our specialty has not learned from the textured implant crisis, which is a case study in the dangers of financial conflicts.^33,34 “Conflict of interest” is a polite way of saying “corruption.”³⁴ In the case of BIA-ALCL, the consequences of corruption can be fatal. It is time, indeed past time, to stop allowing highly conflicted individuals, with nontransparent agendas, to participate as officers in our societies, panelists, and discussants.^32,34,37 Our societies, journals, and authors should not be exposed to the influence of industry surrogates and their efforts to impede important scientific contributions.^34,37

Tolerance and insisting on reporting of conflicts are not enough.^34,37 It is time to reclaim our specialty and eliminate the harmful influence of financial conflicts. It is also time to put our patients first. If women wish to have their textured implants replaced, they should not be discouraged or patronized.⁸ Our patients deserve to be treated the same way as a loved one.