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29. In H, Bilimoria KY, Stewart AK, et al. Cancer recurrence: an important but missing variable in national cancer registries. Ann Surg Oncol 2014;21:1520e1529. 30. Cooper GS, Virnig B, Klabunde CN, et al. Use of SEERMedicare data for measuring cancer surgery. Med Care 2002;40. Ive43e48.
Discussion DR NANCY PERRIER (Houston, TX): Drs Kiernan, Solorzano, and their colleagues report on data abstracted from the National Cancer Database on well-differentiated thyroid carcinoma. The work is bold. It compares what many regard as nonstandard therapy to nonstandard therapy. To best understand the context of the work, readers should be reminded that there are 3 steps to the treatment of thyroid cancer. Surgery is the primary treatment. Radioactive iodine is the adjuvant treatment for ablation of thyroid cells. The third, and not discussed, but perhaps most important, is feedback suppression of thyroid tissue growth, which is thyroid stimulating hormone (TSH) suppression. We recognize that thyroid cancer has an excellent survival, but in these patients, the bane of the disease is the recurrence. From that, we know that radioactive iodine in selected patients can improve that recurrence rate. The authors pose a seemingly fair question. First, are suggested guidelines being met with respect to thyroid cancer care in the US? The answer is not straightforward, as is so common in large database reviews. Sometimes that makes the picture even more murky than clear. More information from meaningful interpretation is necessary. The rationale for the choice of the treatment of radioactive iodine and thyroid lobectomy only is unknown in this dataset. Were there complications with the lobectomy, such as nerve injury or inadvertent parathyroid gland removal? What was the radioactive iodine dose? Was it low dose, high dose? Were there side effects, complications? Have we confirmed that the radiation therapy was not external beam, as was coded in some of the cases rather than radioactive iodine? Was the radioactive iodine initiated for diagnostic or for therapeutic purposes? One interpretation that could be problematic is to say that 1 in 5 of these patients, or 20% of them, did not have suggested recommendations as a recipe for care. I believe this may be an element of personalization that needed to occur with some of these patients. In fact, perhaps it is the art of medicine that is still doable and that these patients were treated this way for some reason that was personalized. Your work does, however, expose a really important question: is any treatment of the contralateral lobe, be it radioactive iodine or completion thyroidectomy, better than no treatment at all? Your title asks a question, and I will ask some questions back. 1. Do you support the statement that a patient undergoing thyroid lobectomy alone has worse survival than a patient undergoing lobectomy and radioactive iodine? 2. To be provocative, do you support recent reviews from this same large dataset that suggest that thyroid lobectomy has equal
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survival to that of total thyroidectomy, noting and acknowledging now that a significant percentage of the patients in that dataset underwent adjuvant therapy when only receiving lobectomy, especially in the setting that we are suggesting, that radioactive iodine does improve survival? 3. Will you help us and commit to dig deeper into value-based interpretations of best practice and cost? Surgeons are not the key decision-makers about prescribing radioactive iodine. Could the changes and charges of expansive ancillaries for nuclear medicine treatment and thyrogen stimulation have played a role in choosing radioactive iodine as a treatment rather than a wellperformed completion thyroidectomy? Congratulations. Thank you for asking the hard questions. Dr Kiernan, remember to stay curious, as we all should. The more we learn, the more we realize we do not know.
DR SAMUEL SNYDER (Temple, TX): The Vanderbilt group has done a yeoman’s job analyzing data from 1998 to 2011 in the National Cancer Database on the use of radioactive iodine after thyroid lobectomy for differentiated thyroid cancer. On the surface, it appears to promote radioactive iodine after thyroid lobectomy by demonstrating a small significant improvement in overall survival for patients treated between 1998 and 2006. This was particularly evident for larger tumors in advanced stage disease. The results seem counterintuitive. Statistics do not lie. However, they can confuse and confound. Currently, the standard of care for differentiated thyroid cancer found on initial lobectomy is completion total thyroidectomy, which then optimizes radioactive iodine treatment. Their study demonstrates the advantages and disadvantages of analyzing a large database. The large study numbers allow a small difference to become significant, in this case, a 2% increase in 5- and 10-year overall survival after the addition of radioactive iodine after thyroid lobectomy. However, radioactive iodine was used significantly more often in patients less than 45 years of age, who have an overall survival advantage to start with. The disadvantage of analyzing a large multi-institutional database lies in the multitude of variables that are inconsistently collected or not reported. Only a little more than half the patients treated with radioactive iodine had data on the presence or absence of distant metastasis, two-thirds on the Charlson comorbidity score, twothirds on the presence or absence of extrathyroidal extension, and only three-fourths with pathologic staging. Key missing data included disease-free survival, not overall survival; previous thyroid surgery, therefore affecting the definition of thyroid lobectomy; accurate positive lymph node assessment, 4% is too low; and radioiodine dosing. To clarify their results, I have 3 questions for the authors. 1. Your definition of thyroid lobectomy for this study included patients that also had a contralateral partial thyroidectomy, which could be a subtotal or near-total lobectomy. Why did you choose to include them? How many of your thyroid lobectomies fit this category? Did you try to analyze the data with excluding them? 2. The key result of improved overall survival for radioactive iodine after thyroid lobectomy represents only patients treated from
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1998 to 2006. How many patients are included in this study comparison? Why did you then choose to extend the study comparison to 2011 for the results reported in the manuscript? 3. I can honestly say that in my endocrine surgery practice, I have never had a patient treated with radioactive iodine after only thyroid lobectomy for differentiated thyroid cancer. After this study, what are your recommendations to me for the appropriate use of radioactive iodine after thyroid lobectomy for differentiated thyroid cancer? I applaud the authors for their intensive research on radioactive iodine use after thyroid lobectomy for differentiated thyroid cancer. It does pique interest in that treatment modality and call into question its value and appropriate use. DR DENISE M CARNEIRO-PLA (Charleston, SC): I would like to thank Dr Solorzano for shedding a light on the number of patients who undergo this type of treatment with lobectomy and radioactive iodine. Your presentation reinforces that it does not matter what you do with patients with thyroid cancer; they will not die very often. That being said, do you think that the deaths should be the final goal for the treatment of thyroid cancer, or should we focus more on recurrence and the morbidities of associated reoperations or more extensive procedures done in the future because of these potentially not fully treated patients? After working with this National Cancer Database (NCDB), especially with these large databases now being partially responsible for the changes in our guidelines, do you think they are very accurate? DR JENNIFER ROSEN (Washington, DC): I would like to thank Dr Solorzano and her colleagues for their very interesting use of the Commission on Cancer’s (COC) database, the NCDB. As the American College of Surgeons representative to the COC, I think this represents some of the most useful advice that we can get from the NCDB. It is advice that will help us in the management of our patients. To follow on Dr Carneiro-Pla’s question, I have 3 questions. 1. Did you consider including as a comparison group patients who underwent total thyroidectomy and then total thyroidectomy with radioactive iodine, as that may help separate out whether there truly were differences among the thyroid lobectomy group? 2. We know that volume matters. Did you look at the volume from the various centers as another factor in your multivariable analysis? 3. Do you have suggestions for us, as was illustrated by previous presenters, about usual practice vs best practice for those who do a low volume? DR COLLEEN M KIERNAN: Regarding Dr Perrier’s questions, we do support our statement that thyroid lobectomy alone is associated with worse overall survival. In the study, thyroid lobectomy with radioiodine was associated with improved overall survival when compared with lobectomy alone for all comers. Our study does not identify which select patients benefit the most from this treatment modality because it does not compare lobectomy with radioiodine to completion or total thyroidectomy with or without radioiodine, as others have mentioned. We need
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to compare those groups to further elucidate if and in whom this practice should be used. We do support the recent studies that have been published out of the NCDB, which state that thyroid lobectomy is equivalent to total thyroidectomy in select patients. It is important for us to remember that the 2 recent studies published out of the NCDB reporting equivalent survival compared only select patients and controlled for the use of radioiodine. They did not compare the survival of those who did or did not receive radioiodine. So we are unable to comment on the extent that radioiodine influenced the survival in each cohort. I accept your challenge to continue our work looking at best practice and venture into cost-based analysis. I think that the use of large data is very hypothesis-generating. Best practice and costbased analysis is certainly something that we must examine. I do not think that this is the database that will allow us to do it. I think it requires a multi-institutional approach. I welcome any of you to contribute to this study. Regarding Dr Snyder’s question about the definition of thyroid lobectomy, we chose to include patients who were coded as having partial removal of the contralateral lobe in our thyroid lobectomy cohort because we wanted to analyze the outcomes of patients who had less than total thyroidectomy who received radioiodine. This subset of patients represented 8% of the total population. We did, in fact, analyze the data excluding these patients. It actually increased the survival advantage for thyroid lobectomy with radioiodine compared with thyroid lobectomy alone. Our survival analysis included 20,751 patients who underwent thyroid lobectomy for thyroid cancer from 1998 to 2006. The NCDB does not include survival data from patients diagnosed after 2006 to ensure that all patients have had at least 5 years of follow-up. Our initial abstract reported survival data from 2003 to 2006. We did that so we could include comorbidity score in our multivariate analysis. In that analysis, the survival benefit derived from adjuvant radioiodine was present, but failed to reach statistical significance due to the low number of events and deaths. We therefore elected to include more patients at the cost of not controlling for comorbidities to appropriately power our study. Regarding recommendations for appropriate use of radioiodine after thyroid lobectomy for differentiated thyroid cancer, we do not feel that this study can adequately answer this question. The study was not designed to identify patients who would benefit most from the use of radioiodine after a lobectomy. Further studies comparing lobectomy alone, lobectomy with radioiodine, completion or total thyroidectomy with or without radioiodine, that look not only at overall survival but also disease-free survival and perhaps even quality of life of each approach, will be necessary to determine if this practice plays a definitive role in the management of thyroid cancer. We can, however, hypothesize that in select patients who cannot undergo completion thyroidectomy, radioiodine after lobectomy may provide a survival advantage over lobectomy alone. To answer Dr Carneiro-Pla’s questions, I agree, overall survival is not always the best end point in thyroid cancer and should not be the only outcome for developing guidelines for the management of thyroid cancer. Unfortunately, the NCDB does not report recurrence information. Therefore, disease-free survival, which may be
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a better outcomes measure for such indolent disease, is not available. Regarding the quality of the data, any database is limited by the consistency and quality of the data. Coding in the NCDB is performed by trained cancer registrars, but we have no way of knowing if that coding is correct. For instance, there is not a code for completion thyroidectomy. Patients who undergo a completion thyroidectomy may be miscoded as thyroid lobectomy when in fact they should be coded as a total thyroidectomy. I believe that further studies are needed to determine the accuracy
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of the data if we are going to use large data to change management strategies. Finally, addressing Dr Rosen’s questions, regarding the question about whether I considered including total thyroidectomy and total thyroidectomy with radioiodine in this cohort study, that will be our next study. We would be happy to present it next year. Dr Rosen also asked if we included the volume of those centers in our multivariate analysis. We did not. It is certainly something we should consider going forward.