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Reply to Counterpoint
Staging of Thyroid Carcinoma–
Steven I. Sherman,
Section of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson
Cancer Center, Houston, Texas.
See editorial counterpoint on pages 844 –7 and
referenced original article on pages 1012–21, this
Address for reprints: Steven I. Sherman, M.D.,
University of Texas M. D. Anderson Cancer Center,
1515 Holcombe Blvd., Box 15, Houston, TX 77030.
Received June 15, 1998; accepted June 19, 1998.
© 1998 American Cancer Society
or physicians who care for patients with thyroid carcinoma, one of
the most frustrating yet critical early management functions is to
attempt to predict a patient’s prognosis. The inescapable reality is
that approximately 10% of patients eventually will die of their tumor
and significantly more patients may face morbidity due to disease
recurrence and metastasis.1 The ability to provide patients with an
accurate estimate of their risk for morbidity and mortality and to use
this information in planning treatment and follow-up is a fundamental responsibility for the treating physician. Furthermore, appropriate
clinicopathologic information must be made available to the physician to assist in this task.2
Thus, the accompanying editorial regarding our analysis of
clinical staging approaches using the data of the National Thyroid
Cancer Treatment Cooperative Study (NTCTCS) is disappointing.
The author’s preference for patient stratification as a binary function of low versus high risk is oversimplified, not recognizing the
broad spectrum of morbidity and mortality that occurs with these
diseases. For example, as patient follow-up extends out multiple
decades from the initial diagnosis of papillary carcinoma, it becomes clear that there remains a finite risk of disease recurrence
and disease-related death,3 and that decisions made even in those
early years of treatment potentially can affect long term outcomes.
Furthermore, the options available to clinicians for treatment are
far from binary. Locoregional disease control likely depends on the
extent of initial surgery, which requires decisions not only regarding the amount of thyroid resection but also the magnitude and
location of lymph node dissection as well. Radioiodine ablation
itself contains multiple options, including variations in the amount
of administered activity to achieve ablation if appropriate. Decisions regarding adjuvant therapies also come with multiple choices; clinicians not only must select whether or not to use thyroidstimulating hormone (TSH)-suppressive levothyroxine therapy,
but also must identify a degree of suppression appropriate for a
patient’s risk status.4 Adjuvant external beam radiotherapy also
may be appropriate for certain groups of patients at risk for locoregional recurrence.5 And with each of these choices, an individualized risk:benefit analysis is required to counterbalance the
potential complications of a therapy versus the potential gain from
treating the disease. Results from a recent survey of thyroid spe-
Reply to Counterpoint/Sherman
cialists6 and from an analysis of practice patterns
within the NTCTCS7 support the concept that thyroid carcinoma management reflects a range of possibilities rather than a binary choice.
Viewing a patient’s risk as occurring on only two
levels also reduces the amount of prognostic information gained by applying a disease stage to a patient. As
demonstrated by both the retrospective single hospital
data set published in 19978 and our current analysis,
use of a dichotomous risk assignment yields among
the lowest predictive values for disease mortality from
differentiated thyroid carcinoma.
The limitations of a binary classification also are
apparent in designing an appropriate follow-up
strategy for the patient. Again, a continuous range of
options exists, including inclusion or frequency of
tests such as thyroglobulin determination, chest Xray, neck ultrasound, radioiodine imaging, or other
diagnostic modalities.9 This flexibility of patient
monitoring will only be augmented by the anticipated availability of recombinant human TSH for
stimulating radioiodine uptake and thyroglobulin
Dr. Cady’s editorial takes issue with the inclusion of multiple histologies of thyroid carcinoma in
the NTCTCS staging classification. In particular, it
criticizes the inclusion of patients with medullary
carcinoma of neuroendocrine lineage, as well as
those with anaplastic carcinoma, an aggressive yet
follicular cell-derived malignancy. Nonetheless, the
core element of any commonly used oncologic staging remains anatomic extent rather than tissue
type.11 For example, the TNM staging approach to
both prostate and lung carcinomas completely ignores the cells of origin for these diverse diseases,
applying the same criteria for the staging of both
epithelial and neuroendocrine tumors within each
of these respective organs.11 In contrast, the
NTCTCS classification provides distinctly different
criteria for the staging of differentiated, medullary,
and anaplastic thyroid carcinomas. The editorial
touts the TNM thyroid classification, but even this
approach provides staging criteria for medullary
and anaplastic carcinomas. Therefore, the argument
to remove these two diseases from the analysis is
inconsistent with the usual and accepted approach
to cancer staging, and appears to be inconsistent
internally with other aspects of the editorial. From a
practical viewpoint, the analogy provided to gastric
sarcoma and lymphoma suffers in that these diseases often are treated by different groups of specialists within cancer centers; in contrast, there usually is little difference in the caregiving team
involved in the management of patients with thyroid carcinoma, regardless of the tumor histology,
and it is only sensible that we pool our patient
experiences together in a cooperative study such as
Issue also must be taken with the criticism regarding the inability to separate prognoses of patients with
Stage I and II disease. Given the early stage of follow-up for this tumor registry, I believe it shortsighted
to expect that the outcomes of such patients would yet
diverge. It has been a traditional fallacy of many retrospective studies to draw conclusions regarding the
results of treatment in these lower risk stages with
limited follow-up. Instead, we fully anticipate that
these patient cohorts will demonstrate disease-related
morbidities and mortality in the years and decades to
come, requiring an ongoing intensive effort to continue to collect and analyze these events prospectively.
Finally, one of our primary responsibilities as
clinicians is to the patient sitting there, desiring as
accurate an answer as possible to the question,
‘‘Doctor, what is my prognosis?’’ As the generally
poor predictive values in our analysis demonstrate,
not only is the current ‘‘surfeit’’ of staging classifications inadequate, but newer approaches clearly
will be necessary in the future. Only when we have
developed and validated such improved methods
will it be likely that clinicians observe Dr. Cady’s
laudable goal of modifying disease management
based on appropriate application of a prognostic
staging classification. Until such time, we must use
the best classifications we have available, including
the NTCTCS, to guide communication among physicians, to assist in patient management, and to
guide future clinical studies.
Robbins J, Merino MJ, Boice JD Jr., Ron E, Ain KB, Alexander
HR, et al. Thyroid cancer: a lethal endocrine neoplasm. Ann
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Sherman SI. Toward a standard clinicopathologic staging
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Metab 1996;81(12):4318 –23.
Farahati J, Reiners C, Stuschke M, Muller SP, Stuben G,
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CANCER September 1, 1998 / Volume 83 / Number 5
Solomon BL, Wartofsky L, Burman KD. Current trends in
the management of well differentiated papillary thyroid carcinoma. J Clin Endocrinol Metab 1996;81(1):
Cooper DS, Specker B, Ho M, Sperling M, Ladenson PW,
Ross DS, et al. TSH suppression and disease progression in
patients with differentiated thyroid cancer: results from the
National Thyroid Cancer Treatment Cooperative Study Registry. Thyroid. In press.
Brierley JD, Panzarella T, Tsang RW, Gospodarowicz MK,
O’Sullivan B. A comparison of different staging systems
predictability of patient outcome. Thyroid carcinoma as an
example. Cancer 1997;79(12):2414 –23.
9. Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med 1998;338(5):297–306.
10. Ladenson PW, Braverman LE, Mazzaferri EL, Brucker-Davis
F, Cooper DS, Garber JR, et al. Comparison of administration of recombinant human thyrotropin with withdrawal of
thyroid hormone for radioactive iodine scanning in patients
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11. American Joint Committee on Cancer. AJCC cancer staging
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