Should we rename DCIS to counter the problem with over-diagnosis?

Transcription

1 Should we rename DCIS to counter the problem with over-diagnosis?

2 Linguistic Debate From Linguistically Challenged Scotland/Brooklyn

3 Low Points in Renaming History 1) FREEDOM FRIES instead of French Fries. 2) Big Ben is now Elizabeth Tower 3) Rapunzel is now Flynn Rider 4) N.O. Hornets now the Pelicans

4 What SHOULD be renamed? 1) Friendly fire 2) Internet of Things (IoT) 3) Utah JAZZ 4) Given the long history of violence, dishonesty, abuse and aggressive behavior the Washington Redskins will now be know as just

5 THE REDSKINS

6 Fun With Renaming Rename your home Wi Fi network POLICE SURVEILLANCE VAN #2

7 The Cells That Comprise DCIS ARE Cancer Cells

8 Overdiagnosis Breast Cancers Found at Autopsy A substantial reservoir of DCIS is undetected during life. Invasive DCIS Nielsen % 20% Kramer 1.4% 4.3% Alpers 0 5.6% Nielsen % 23% Nielsen, Thomsen, Primdahl et al; Breast Cancer and Atypia Among Young and Middle Aged Women: a Study of 110 Medicolegal Autopsies Brit J Cancer ,

9 Subgroups of Cancers and the Putative Impact of Screening Cancer Incidence and Mortality Change A) Diagnosis increased and mortality decreased due to screening (early detection or more effective treatments) B) Diagnosing (and treating) precancerous conditions decreasing both incidence and mortality C) Earlier detection but no real improvement in mortality 1975 through 2010 United States of America A B C

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11 The recommendations of this panel were recently published in the Journal of the American Medical Association: Overdiagnosis and Overtreatment in Cancer, An Opportunity for Improvement. The authors provide five recommendations: 1. Physicians and patients alike need to acknowledge that screening results in overdiagnosis especially in breast, lung, prostate and thyroid tumors. 2. The term cancer should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated. 3. Create observational registries for low malignant potential lesions in order to better understand prognosis and best treatment options. 4. Mitigate overdiagnosis with an ultimate goal of preferential detection of consequential cancer while avoiding detection of inconsequential disease. 5. Expand the concept of how to approach cancer progression by controlling the environment in which cancerous conditions arise.

12 1. Physicians and patients alike need to acknowledge that screening results in overdiagnosis especially in breast, lung, prostate and thyroid tumors. 2. The term cancer should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated. 3. Create observational registries for low malignant potential lesions in order to better understand prognosis and best treatment options. 4. Mitigate overdiagnosis with an ultimate goal of preferential detection of consequential cancer while avoiding detection of inconsequential disease. 5. Expand the concept of how to approach cancer progression by controlling the environment in which cancerous conditions arise. 1) Screening saves lives, reduces the need for morbid treatments. 99% of patients will choose overdiagnosis to underdiagnosis.

13 1. Physicians and patients alike need to acknowledge that screening results in overdiagnosis especially in breast, lung, prostate and thyroid tumors. 2. The term cancer should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated. 3. Create observational registries for low malignant potential lesions in order to better understand prognosis and best treatment options. 4. Mitigate overdiagnosis with an ultimate goal of preferential detection of consequential cancer while avoiding detection of inconsequential disease. 5. Expand the concept of how to approach cancer progression by controlling the environment in which cancerous conditions arise. 2) Class prediction in DCIS is very primitive and limited. We do not have the tools necessary to subset lesions. Likely that in BRCA-1 heterozygotes DCIS progresses rapidly to invasive cancer; in the 8 th decade of life very slowly.

14 1. Physicians and patients alike need to acknowledge that screening results in overdiagnosis especially in breast, lung, prostate and thyroid tumors. 2. The term cancer should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated. 3. Create observational registries for low malignant potential lesions in order to better understand prognosis and best treatment options. 4. Mitigate overdiagnosis with an ultimate goal of preferential detection of consequential cancer while avoiding detection of inconsequential disease. 5. Expand the concept of how to approach cancer progression by controlling the environment in which cancerous conditions arise. 2) In extensive DCIS the presence of invasive cancer is missed in 5% to 20% of cases; less than 5% of total tumor is visualized by pathology

15 1. Physicians and patients alike need to acknowledge that screening results in overdiagnosis especially in breast, lung, prostate and thyroid tumors. 2. The term cancer should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated. 3. Create observational registries for low malignant potential lesions in order to better understand prognosis and best treatment options. 4. Mitigate overdiagnosis with an ultimate goal of preferential detection of consequential cancer while avoiding detection of inconsequential disease. 5. Expand the concept of how to approach cancer progression by controlling the environment in which cancerous conditions arise. 3) There is no accommodation in today s medical legal world to elect to observe DCIS; no data to support primary therapy with SERM or AI (Esserman, NPR interview, 2013)

16 1. Physicians and patients alike need to acknowledge that screening results in overdiagnosis especially in breast, lung, prostate and thyroid tumors. 2. The term cancer should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated. 3. Create observational registries for low malignant potential lesions in order to better understand prognosis and best treatment options. 4. Mitigate overdiagnosis with an ultimate goal of preferential detection of consequential cancer while avoiding detection of inconsequential disease. 5. Expand the concept of how to approach cancer progression by controlling the environment in which cancerous conditions arise. 4) Who does not get a mammogram? Who does not get a biopsy? Which lesions do we not biopsy? Finger-pointing not helpful or productive Pollyanna

17 1. Physicians and patients alike need to acknowledge that screening results in overdiagnosis especially in breast, lung, prostate and thyroid tumors. 2. The term cancer should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated. 3. Create observational registries for low malignant potential lesions in order to better understand prognosis and best treatment options. 4. Mitigate overdiagnosis with an ultimate goal of preferential detection of consequential cancer while avoiding detection of inconsequential disease. 5. Expand the concept of how to approach cancer progression by controlling the environment in which cancerous conditions arise. 4) Pollyanna is a 1913 novel by Eleanor H. Porter that is now considered a classic of children's literature, with the title character's name becoming a popular term for someone with the same optimistic outlook. The book was such a success that Porter soon produced a sequel, Pollyanna Grows Up (1915). Eleven more Pollyanna sequels, known as "Glad Books", were later published, Two new sequels recently published. Pollyanna has grown up and gone to medical school.

18 1. Physicians and patients alike need to acknowledge that screening results in overdiagnosis especially in breast, lung, prostate and thyroid tumors. 2. The term cancer should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated. 3. Create observational registries for low malignant potential lesions in order to better understand prognosis and best treatment options. 4. Mitigate overdiagnosis with an ultimate goal of preferential detection of consequential cancer while avoiding detection of inconsequential disease. 5. Expand the concept of how to approach cancer progression by controlling the environment in which cancerous conditions arise. 5) Great idea capitalize on epigenetic factors, chemoprevention via estrogen blockade, reduce dietary risk factors. Or we could take the DCIS out.

19 And I want to eliminate war and rude people. These five recommendations describe a Utopian circumstance that, practically speaking does not exist today. They are worthwhile, laudable goals that are, for the most part, not ready for primetime. Even the authors are unable to articulate exactly how to implement these recommendations.

20 Evidence Based Medicine and Practice Guidelines

21 The Downside of a Name Change 30 years of clinical trial work cannot be undone by renaming DCIS The medical-legal implications of treatment approaches cannot be undone by renaming DCIS The innate biologic behavior of DCIS cannot be undone with a new name. There is absolutely no evidence that changing the name would change behavior. What might happen if the country was to simply adopt the new name?

22 Sequelae Insurance carriers: No longer willing to pay for surgery, radiation therapy, reconstructive surgery, endocrine ablative strategies. No longer willing to pay for diagnostic mammograms Getting research grants and foundation money to study a BENIGN disease would be all but impossible in today s climate. We would close the door to finally getting an answer about disease class prediction in DCIS. So where might the answer lay?

23 αvβ6 (alpha v beta 6) integrin molecule to predict invasive potential of DCIS Researchers looked at 583 breast tissue samples from normal breasts and those with DCIS, and showed there to be a link between levels of αvβ6 in myoepithelial cells (cells which form part of the milk duct walls) and whether breast tissue was normal, had DCIS or had progressed to invasive breast cancer. There was almost no αvβ6 in cells from normal tissues, whereas over half of the DCIS cases had αvβ6 in the surrounding cells (52% of non-high grade DCIS and 69% of high grade DCIS) and nearly all DCIS cases that had already started to become invasive breast cancer had αvβ6.

24 A multigene assay can predict the risk of recurrence among patients with ductal carcinoma in situ who undergo surgery alone, researchers reported at the CTRC-AACR San Antonio Breast Cancer Symposium (Abstract S4-6) 2011 The assay can be used to identify low-risk patients who can safely avoid radiation therapy, said principal investigator Dr Lawrence Solin, chair of the department of radiation oncology at Einstein Medical Center in Philadelphia. Importantly, the assay provides independent information on the risk of an ipsilateral breast event either a new DCIS or an invasive cancer beyond clinical and pathologic variables. We're not just inventing the wheel with this new molecular tool, commented Dr Solin. The ten-year risk of recurrence is generated by the 21-gene breast cancer test, using a prespecified DCIS Score algorithm, Dr Solin said. The 21-gene assay is already used to identify patients with invasive cancer who might be able to avoid chemotherapy because of a low risk for recurrence. The DCIS test uses information from 12 of the 21 genes, he said.

25 DCIS Score and Risk of DCIS Recurrence or Invasive Carcinoma Low Intermediate High Risk 10-year risk of local recurrence of DCIS 10.6% 26.7% 25.9% 10-year risk of invasive carcinoma 3.7% 12.3% 19.2%

26 There is no justification nor anticipated upside to simply renaming DCIS at this time. Instead we should redouble our efforts to understand the disease better at a fundamental level. Matching the management with the disease will only occur when we move from a descriptive understanding to a functional understanding of DCIS. CONCLUSION