The Antidote to Overdiagnosis – Is it Oversight?

 

“I hope that the investigators are successful in their terminology reform efforts, I encourage them to include among their goals the search for a better understanding of why the specialty of pathology was unable to escape from its stubborn devotion to turning lesions with a low or poorly defined risk into cancer. Also, why is there no backup mechanism analogous to the US Food and Drug Administration’s review to detect and respond in a timely fashion to a systemic problem like hazardous diagnostic criteria becoming the standard of care?”

Pathologist and Author,  Elliot Foucar, addressing the work of Laura Esserman et al in The Lancet

 

In 2014, Dr. Laura J. Esserman and colleagues published an influential paper which proposed a new term, IDLE (Indolent Lesion of Epithelial Origin), for many types of indolent tumors which are currently being labeled as “cancers”.  Among a number of cogent points of the article is this one: ” new guidance is needed to describe and label the heterogeneous diseases currently referred to as cancer.”

As noted by  Dr.Elliot Foucar, a retired pathologist who still publishes papers about errors in pathology, it has fallen to researchers outside of the discipline of surgical pathology to call attention to the problem of cancer overdiagnosis.  Foucar blames the failure of pathologists to challenge and police their system of an expert opinion “gold standard” for the intervention by outsiders such as Esserman et al  into the problem of over treatment of indolent tumors which are labeled as cancers.

Since its publication, Esserman’s article has been cited 274 times, and has brought a significant degree of attention to the problem of overdiagnosis.

 

 

NIFTP Full Disclosure: An Ethical Policy that should be Adopted

An article made available prior to copy editing appeared very recently in the medical journal Thyroid.   Entitled The Ethical Implications of the Reclassification of Non Invasive-Follicular Variant Papillary Thyroid Carcinoma , the article is authored by a group from Mt. Sinai Beth Israel Medical Center in New York City, and also a representative of the THANC Foundation.

This piece is of particular interest because in seeming contradiction to some opinions recently expressed in a CAP Today article regarding the NIFTP reclassification,  these authors state that it’s the physician’s” professional duty to make a sincere and reasonable effort to convey (the) information to the affected patients.”

In the aforementioned piece in CAP Today, an online publication of the College of American Pathologists, noted thyroid pathologist Virginia Livolsi stated that she would not go back and review her past cases of EFVPTC that would now likely be reclassified as NIFTP, a non-cancer.  One of the reasons given was that of differences in techniques for sampling encapsulated tumors.  The diagnostic criteria for NIFTP requires that the entire tumor capsule be submitted by the pathologist.  According to Virginia Livolsi, “older literature” called for the examination of ten sections of a nodule as opposed to the entire capsule.  However, her reasoning seems to be contradicted by Gerard Doherty, surgeon and professor at Boston University, earlier in the same CAP Today article.  According to Doherty, “I think expert pathologists have been examining the entire capsule for some time. That’s not to say it’s been universally done…”

Another of Livolsi’s apparent  objections to reviewing past cases of EFVPTC is her belief that a NIFTP diagnosis cannot be retroactive on principle.  With regard to a case of EFVPTC for which her  patient had requested a review, Livolsi states: “I have refused to revise the diagnosis, and I have refused to look back at the slides. That case was signed out in 2012. In 2012, that was the diagnosis.”  Doherty agrees with her in the article, stating, “We don’t see any clinical reason to go back and tell patients that a group of people has suggested we change the name of a low-risk disease they already knew they had. It doesn’t change clinical management at all. Changing the name doesn’t change the follow-up.”

However, the new article in Thyroid opines that with regard to NIFTP: “… the prudent course would be to attend to the requirements of medical ethics.”  In the opinion of the Mt. Sinai team, pathologists are therefore ethically obligated to review cases and contact patients about a  change in diagnosis.  The justification for the widespread adoption of this policy is that a cancer diagnosis causes “clinically significant” stress and also creates financial burdens for patients.  Perhaps most important of all is the primacy of a patient’s basic legal right to information about their own condition.

Famed Thyroid Pathologist Refuses to Review Possible NIFTP Cases

An article recently appeared in CAP Today,  a publication of the College of American Pathologists about NIFTP, which is a revised designation for a type of thyroid cancer.  Non-invasive encapsulated follicular variant (N-EFVPTC) was reclassified as being nonmalignant, a change which will likely significantly reduce the number of thyroid cancer cases which are diagnosed yearly in the USA and worldwide.

The article gives the views of several well-known pathologists and clinicians about the impact of the reclassification.  Surprisingly, although the reclassification has been touted as being especially beneficial because of its potential to reduce psychological harms to patients, the article suggests that many pathologists and clinicians do not see any reason to inform the thousands of individuals who have already received the N-EFVPTC diagnosis that their “cancer” has been reclassified.

The well-regarded thyroid pathologist and opinion leader, Virginia Livolsi, of the University of Pennsylvania goes so far as to belittle thyroid cancer patients who read the New York Times article about the NIFTP reclassification.  She states:

“They want their tumor from two years ago to be reviewed, which is totally inappropriate”…” Two years ago, the entity and the name did not exist. Patients were treated at the time according to the standards of the time”… “I feel strongly that research results—that’s what these are—do not belong in a patient’s medical record. To go back on the basis of somebody reading something in The New York Times? That’s wrong”.

Ironically, Virginia Livolsi is also quoted in the CAP Today article as having been impressed by a presentation given by Guy Maytal, of Harvard University during the course of the study which resulted in the nomenclature revision for NIFTP.  Dr. Maytal spoke about the psychological impact of a cancer diagnosis. According to the article:

Dr. LiVolsi called Dr. Maytal’s talk “absolutely amazing.”

What could be behind the apparent reluctance of Virginia Livolsi and some other pathologists and clinicians to review past cases of N-EFVPTC and therefore remove the stigma of a cancer diagnosis for these patients?

Keep reading this blog for a future article on this topic.

 

 

 

THYCA’s Grants are Weighted Heavily to Advanced Thyroid Cancer Cases

The Thyroid cancer Survivor’s Association announced the award of six new research grants for thyroid cancer.  The grants are heavily weighted to benefit patients with advanced thyroid cancer. Although advanced thyroid cancer is a worthy cause that is much in need of research dollars, the fact remains that only two out of the six grants may help with the much publicized problems of thyroid cancer overdiagnosis and over treatment.  These two grants may have applications for risk stratification of patients which could potentially help these lower risk patients to avoid being subjected to unnecessary interventions.

Given that the vast majority of thyroid cancer patients are low to intermediate risk following surgery with very low recurrence rates, it seems fair and ethical for THYCA to award more money and to pay more attention  to efforts which would mitigate the widespread over treatment of these patients.  Thyca’s less than enthusiastic response in handling the NIFTP reclassification may indicate a reluctance to address this pressing problem.

The new profile for the typical case of thyroid cancer is a middle aged woman with a microcarcinoma, as was found in this study from Hughes et al in 2011.  These cases are also among those which are the least likely to benefit from aggressive interventions such as total thyroidectomy and radioactive iodine.

Although funding research for Advanced thyroid cancers is an eminently worthy cause, it is troubling that a situation analougous to “robbing Peter to pay Paul” has been allowed to develop within the primary organization for Thyroid cancer survivors in the United States.

 

 

 

 

 

 

 

 

 

 

THYCA’s Feelgood Public Response to the NIFTP Reclassification was Inadequate

THYCA is the acronym for the Thyroid Cancer Survivor’s association. Founded in 1995, its stated mission is to “educate, participate, communicate and support research” in the area of thyroid cancer.  Back in the 1990’s and earlier, thyroid cancer was much rarer than today, and knowledge of the disease was limited.  To that end, THYCA has promoted public awareness and medical knowledge for thyroid cancer which in the past had been considered a rare disease but is now a leading cancer diagnosed in women.

Cancer “awareness”, however, can be a double-edged sword in that awareness activities may become an end in themselves thereby eclipsing the complex realities and heterogeneous nature of cancer.  The Susan G. Komen Foundation has faced criticism over its promotion of mammograms, which have more recently been linked to overdiagnosis and over treatment and are likely saving many fewer lives than had been previously  believed.  Breast cancer awareness activities involving the color pink and merchandise promotion have also been criticized as promoting “survivors” while concealing the realities of those who have either terminal or “overdiagnosed” cases of the disease.  The intimations that mammography has been overly hyped by medical professionals combined with doubts about the public “awareness” campaigns which are spearheaded by organizations such as Komen suggest that there has been simplistic thinking about breast cancer and that a course correction is now underway.

Thyroid cancer has been oft touted as the most rapidly rising cancer for women in the United States.  Although a few studies have asserted that there has been a concomitant “true” increase in incidence, it has now been generally accepted that the dramatic rise in cases is overwhelmingly attributable to opportunistic detection methods and most likely a lowering of diagnostic thresholds by pathologists.  A striking illustration of this reality came to public attention with the recent reclassification of a type of thyroid cancer to a non-cancer, as reported by the New York Times.  Since the identification of noninvasive EFVPTC as a type of thyroid cancer first identified by pathologists in the 1980’s, cases had increased sharply and diagnostic thresholds appeared to drop in a haphazard manner.  Although many pathologists had long suspected that noninvasive EFVPTC was an extremely indolent tumor,a few experts had encouraged an expansion of diagnostic criteria.  In the United States and elsewhere, there are no formal oversight or quality control mechanisms  on the validity of expert opinion in cancer pathology.  Because of this situation a few experts can operate as gatekeepers for an entire disease domain in a largely unchallenged manner. Consequently, it took many years for someone to finally initiate and organize a nomenclature revision for noninvasive EFVPTC. During this period, however, a number of academic articles were published which suggested that the tumor now designated as NIFTP was a problematic diagnostic category.

Although a representative from THYCA, medullary cancer survivor Kathyrn Wall, is listed as a co-author of the JAMA article which proposed the reclassification of noninvasive FVPTC to NIFTP; the THYCA organization had never previously publicized the pending reclassification, nor had it shared any articles about the controversies surrounding the tumor on its official website.  Nothing has yet been published by THYCA about Wall’s participation in the study, nor what type of input she contributed to it.  On the day the study was published (April 14th, 2016), a post appeared on THYCA’s Facebook page announcing the reclassification and which stated in part:

We know many people will be upset that they received RAI as part of their treatment for their encapsulated Follicular Variant of Papillary Thyroid Cancer. Please keep in mind that the care you received was considered the correct standard of care at the time. The care we received has helped contribute to the research which has led to this important change and hopefully many more changes in our care to come.

This comment, appearing in conjunction with the publication of the JAMA study, surely glosses over important facts surrounding NIFTP as a reclassified type of thyroid cancer.   The diagnostic standard for this tumor, although heavily influenced by the opinions of a few “expert” pathologists such as Virginia Livolsi of UPENN, had been contentious for a number of years and as such there was no “standard of care” for the administration of radioactive iodine that had been proven as beneficial or widely recommended. Perhaps more troubling, and given THYCA’s participation in the two- year reclassification effort, its official announcement can be viewed as a lapse in its stated mission to empower patients through “education” and communication.  Had THYCA truly been interested in educating patients with EFVPTC, it had the option of providing information about the tumor on its website or at its annual conferences which are held at various locations in the USA and which are usually well attended by experts on thyroid cancer.  Instead, it held back critical information in favor of promoting “awareness” about thyroid cancer and calling for neck checks. Subsequently, most patients with this diagnosis were taken by surprise when the reclassification was announced.  Many of those that had been treated with radioiodine  may have been spared this intervention had they known of the pending downgrade of EFVPTC by a panel of expert pathologists.

Although THYCA receives donations for its activities from Drug Companies and other corporations, it relies heavily on patient membership in order to support and publicize its awareness activities and to fund research grants.  To this end, THYCA’s web site and other educational materials have usually emphasized that thyroid cancer is the “fastest growing cancer” because the number of cases has been increasing every year for several decades.  Because of the NIFTP reclassification and also other developments, the total number of thyroid cancer cases in the United States and worldwide can now be expected to fall significantly.  Logically, this means that THYCA’s membership is likely to drop because of past cases of thyroid cancer that will now be reclassified and future cases that will no longer be diagnosed as malignant.  Aside from the possible negative financial consequences to THYCA, the reclassification of EFVPTC is also likely to impact the reputation of thyroid cancer itself as serious type of cancer that is worthy of public awareness.

More and more frequently, we are seeing examples of physicians who are becoming attuned to the harms of cancer overdiagnosis, both psychological and physical.  Patient advocacy and awareness organizations have an ethical responsibility to incorporate this growing trend into their activities and materials and to thereby stop promoting uncritical attitudes about cancer as a homogeneous condition.  While it is surely laudable to educate and support those who are suffering from true cancers, it should not be considered expedient for patient advocacy organizations to gloss over or withhold vital information from those patients who are potentially being over treated because of their own ignorance about their condition.

 

NIFTP: Primum Non Nocere – First Do No Harm

The Journal of the American Thyroid Association, Thyroid, has published an editorial ahead of print entitled:  Changing the Cancer Diagnosis:  The Case of Follicular Variant of Papillary Thyroid Cancer-Primum Non Nocere and NIFTP.   Although the full editorial is not currently available to the public, the first page can be viewed on the Journal’s website.

The authors of the editorial are also among the authors of the JAMA article which proposed the reclassification of N-EFVPTC to NIFTP.  They are Steven Hodak of NYU Langone; R. Michael Tuttle of Memorial Sloan Kettering Cancer Center; Guy Maytal of Massachusetts General Hospital and Harvard Medical School;  Yuri Nikiforov of UPMC Pittsburgh; and Gregory Randolph,  Of The Massachusetts Eye and Ear Infirmary, Mass General and Harvard Medical School.

The editorial states that for many thyroid cancer patients, physicians may be violating the important dictum in medicine, “First, do no harm.”  This is because recent studies have indicated that thyroid cancer imposes significant financial and emotional burdens on patients which have apparently gone largely unacknowledged until now.

Instead of recognizing these burdens, physicians have traditionally relied upon a policy of “social utilitarianism”, meaning trying to to the most good for the greatest number of patients through the implementation of cookie cutter treatments.  Under this philosophy, both high and low risk patients have received almost identical interventions for thyroid cancer.

The editorial appears to make a strong case that pathologists, endocrinologists and surgeons who are involved in the field of thyroid cancer have an ethical obligation to their patients with respect to NIFTP.  This means not only an obligation to reduce harm through implementation of the reclassification, but an additional moral imperative to go back and correct past harms by reviewing cases which were classified as N-EFVPTC over the years.

Potential NIFTP Patients: Your Pathologist May not Feel an Ethical Obligation to Review Your Case

A blog was published on Medscape by the pathologist Thomas Wheeler in which he seems to opine that it’s optional for pathologists to inform recent patients with non-invasive encapsulated FVPTC that their “cancer” has been reclassified, and also unnecessary for them to undertake an investigation into potential cases which are not considered to be “recent”.  Entitled ” Thyroid Cancer Yesterday, Benign Thyroid Today!“,  the blog post appears to criticize the principle author of the JAMA article which called for the reclassification of  N-EFVPTC, Yuri Nikiforov.  Nikiforov stated in a New York Times article that he felt there was an ethical obligation to inform impacted thyroid cancer patients that their cancer had been reclassified to a non-malignant condition.

Thomas Wheeler’s article, which is potentially disturbing to affected patients, can be found on Medscape by running a google search on the article’s title.  A free membership to Medscape may be required to view the article which includes a poll of pathologists. According to the poll,  many pathologists do not have firm plans to review past cancer cases that may not be considered as malignant under the new diagnostic criteria.

Given recent research which quantified the deleterious psychological impact of a thyroid cancer diagnosis, why would some pathologists not feel obligated to “correct” the record for NIFTP cases which are on their books as “cancer” diagnoses?  A portion of the reason may be purely logistical in nature.  It is likely that in many older cases, the original samples are no longer available for re- evaluation.  In other instances, there simply may not be enough resources within a department to undertake a comprehensive review.  For these types of situations, the responsible pathologists may feel it’s better to “let sleeping dogs lie.”

But in his post, Dr. Wheeler mentions another possible reason for not evaluating past cases that could be reclassified as NIFTP.  He writes, “if on review another expert did not consider that the nuclear features were diagnostic of EFVPTC even by the old criteria, that would be problematic”.  He is concerned that EFVPTC’s checkered history of “diagnostic disagreements” will come back to haunt pathology departments, creating embarrassment and other possible repercussions.  There may be a modicum of validity to his concerns. However the implication that some pathologists would be willing to let a patient go on believing that they had “cancer” rather than owning up to the uncomfortable truth makes it appear that the professionals involved are more interested in covering for themselves and their colleagues than they are in patient care.