Discussion
The aim of this study was to compare outcomes of minimal tracheal
invasion to the other forms of ETE, namely, strap muscle, RLN, esophagus
and larynx invasion. Our results demonstrated that minimal tracheal
invasion undergoing shave resection, has similar outcomes to strap
muscle invasion as opposed to the other forms of ETE. The analyses of
the various outcomes according to the updated AJCC, revealed that
minimal tracheal invasion may be more accurately staged as T3b rather
than T4a.
The conflicting results of studies on shave resection outcomes might be
attributed to inconsistencies of the study designs, such as varying
definitions of invasion, completeness of resection, various histology
and adjuvant treatments, and, most importantly, the lack of clear
patient selection criteria for shave excision.[18] Shave excision
for extensive tumors is likely to result in incomplete resection and
should be rejected outright. In cases of minimal tracheal invasion
(defined as Shin I and II), however, shave resection is a reasonable
option and one that apparently has good outcomes. We found a 14%
biochemical and structural recurrence rate with shave resection of the
trachea. The OS in the shave group with a median follow-up of 54.4±35.8
months was 100%. These results are comparable to those in papers that
showed recurrence rates ranging from 5-17%.[19, 20] In fact, the
latest (2014) American Head and Neck Society (AHNS) consensus statement
stipulates that a tracheal shave excision is appropriate if a short
segment of the trachea is invaded and there is minimal cartilage
invasion (section 6A).[4] Judicious management of the patients,
including appropriate postoperative RAI and intense follow-up, is
essential to achieve such excellent results.
One of the endpoints of this study was to analyze the new AJCC staging
system for thyroid cancer. We aimed to determine if all forms of
tracheal invasion should be automatically categorized as T4a, or if the
degree of visceral invasion should influence stage definition. With the
caveat of not having reached a level of statistical significance, most
probably as the result of the under-power of this study, the trend of
minimal tracheal invasion to “behave” more like a T3b disease warrants
further investigation. This trend (Fig. 1) yielded surprising results by
demonstrating that patients with minimal tracheal invasion whom are
considered T4a, have as good as, if not better, prognosis compared to
T3b patients. Since extrapolation of this trend seemed promising, we
performed another subgroup analysis in which we combined the patients
with T3b and T4a shave. The results were significant and persuasive;
they showed that patients with minimal tracheal invasion and/or strap
muscle involvement have a better prognosis compared to patients with
other structural involvement in the neck (Fig. 1). These results were
robust for the all ages groups as well as for the 55-year and over age
group.
In the
international
multi-institutional validation of age 55 years as a cutoff for risk
stratification in the AJCC/UICC staging system for WDTC,[21] the
authors concluded that 55 years (compared to 45 years in the older
version) improved the prognostic accuracy of the TNM staging model. This
conclusion was valid for the various T and N stages, and it improved the
distribution of outcomes between stages I and IV disease and led to a
down-staging of a significant percentage (12%) of patients. If, indeed,
such be the case, and minimal tracheal invasion has the same prognosis
as strap muscle involvement, patients older than 55 years might be more
correctly staged as stage 2 rather than stage 3 in the updated AJCC.
The precise biological basis for these results are not within the scope
of this study, but we can speculate that very low volume residual
disease in the minimal tracheal invasion group combined with proper
postoperative treatment plays a major role. The fact that the other ETEs
had higher rates of R1 resections compared to the shave group
(p= 0.022) also serves to explain their worse outcomes. The better
outcomes of the shave group correspond with earlier reports that
patients with ETE to the trachea with R1 resections have essentially the
same prognosis as after R0 resections.[22]
The other end result of the current study is the relatively good DFS of
the entire cohort, despite achieving a “non-oncological” surgical
resection. Adjuvant RAI has been shown to decrease recurrence rates in
WDTC.[23-25] Tuttle et al .[26] reported that even when
post-RAI whole-body scans showed residual disease in the neck, RAI
treatment resulted in a 70% loco-regional control rate. Furthermore,
the findings of several reports suggested that RAI treatment after
primary surgery may also improve OS in patients with high-risk features,
such as ETE.[27, 28]
There are obvious limitations to this study that bear mention. The most
important shortcoming is the fact that we did not reach a level of
statistical significance to prove that patients with minimal tracheal
invasion have a more favorable outcome compared to other T4a patients
among various age groups. The retrospective nature of this study and the
relatively short follow-up time for WDTC are additional drawbacks. We
were, however, able to show that patients with minimal tracheal invasion
combined with strap muscle involvement had a significantly better
outcome compared to other forms of ETE. We believe that these results
warrant further study to elucidate whether this trend will prove valid
in an appropriately powered investigation and that they may serve to
downstage thousands of patients worldwide.
In summary, patients with minimal tracheal invasion who undergo shave
resection had outcomes similar to patients with strap muscle invasion.
They may have a better prognosis than patients with other forms of ETE.
If that proves to be correct, patients with minimal tracheal invasion
should be staged as T3b rather than T4a (AJCC staging system).
REFRENCES
1. Shah, J.P., et al., Prognostic factors in differentiated
carcinoma of the thyroid gland. The American journal of surgery, 1992.164 (6): p. 658-661.
2. Andersen, P.E., et al., Differentiated carcinoma of the thyroid
with extrathyroidal extension. The American journal of surgery, 1995.170 (5): p. 467-470.
3. Hay, I.D., W.M. McConahey, and J.R. Goellner, Managing patients
with papillary thyroid carcinoma: insights gained from the Mayo Clinic’s
experience of treating 2,512 consecutive patients during 1940 through
2000. Transactions of the American Clinical and Climatological
Association, 2002. 113 : p. 241.
4. Shindo, M.L., et al., Management of invasive
well‐differentiated thyroid cancer: An American head and neck society
consensus statement: AHNS consensus statement. Head & neck, 2014.36 (10): p. 1379-1390.
5. Honings, J., et al., The management of thyroid carcinoma
invading the larynx or trachea. The Laryngoscope, 2010.120 (4): p. 682-689.
6. Frazell, E.L. and F.W. Foote Jr, Papillary cancer of the
thyroid. A review of 25 years of experience. Cancer, 1958.11 (5): p. 895-922.
7. Mellière, D.J., et al., Thyroid carcinoma with tracheal or
esophageal involvement: limited or maximal surgery? Surgery, 1993.113 (2): p. 166-172.
8. Keum, K.C., et al., The role of postoperative external-beam
radiotherapy in the management of patients with papillary thyroid cancer
invading the trachea. International Journal of Radiation Oncology*
Biology* Physics, 2006. 65 (2): p. 474-480.
9. Cody, H.S. and J.P. Shah, Locally invasive, well-differentiated
thyroid cancer: 22 years’ experience at Memorial Sloan-Kettering Cancer
Center. The American Journal of Surgery, 1981. 142 (4): p.
480-483.
10. Czaja, J.M. and T.V. McCaffrey, The surgical management of
laryngotracheal invasion by well-differentiated papillary thyroid
carcinoma. Archives of Otolaryngology–Head & Neck Surgery, 1997.123 (5): p. 484-490.
11. Nishida, T., K. Nakao, and M. Hamaji, Differentiated thyroid
carcinoma with airway invasion: indication for tracheal resection based
on the extent of cancer invasion. The Journal of thoracic and
cardiovascular surgery, 1997. 114 (1): p. 84-92.
12. Park, C.S., K.W. Suh, and J.S. Min, Cartilage‐shaving
procedure for the control of tracheal cartilage invasion by thyroid
carcinoma. Head & neck, 1993. 15 (4): p. 289-291.
13. Kasperbauer, J.L., Locally advanced thyroid carcinoma. Annals
of Otology, Rhinology & Laryngology, 2004. 113 (9): p. 749-753.
14. Shin, D.-H., et al., Pathologic staging of papillary carcinoma
of the thyroid with airway invasion based on the anatomic manner of
extension to the trachea: a clinicopathologic study based on 22 patients
who underwent thyroidectomy and airway resection. Human pathology,
1993. 24 (8): p. 866-870.
15. Tuttle, R.M., B. Haugen, and N.D. Perrier, Updated American
Joint Committee on Cancer/Tumor-Node-Metastasis Staging System for
differentiated and anaplastic thyroid cancer: what changed and why?2017, Mary Ann Liebert, Inc. 140 Huguenot Street, 3rd Floor New
Rochelle, NY 10801 USA.
16. Hartl, D.M., et al., Resection margins and prognosis in
locally invasive thyroid cancer. Head & neck, 2014. 36 (7): p.
1034-1038.
17. HaugenBryan, R., et al., 2015 American Thyroid Association
management guidelines for adult patients with thyroid nodules and
differentiated thyroid cancer: the American Thyroid Association
guidelines task force on thyroid nodules and differentiated thyroid
cancer. Thyroid, 2016.
18. Chernichenko, N. and A.R. Shaha, Role of tracheal resection in
thyroid cancer. Current opinion in oncology, 2012. 24 (1): p.
29-34.
19. McCarty, T.M., et al., Surgical management of thyroid cancer
invading the airway. Annals of surgical oncology, 1997. 4 (5):
p. 403-408.
20. Tsukahara, K., I. Sugitani, and K. Kawabata, Surgical
management of tracheal shaving for papillary thyroid carcinoma with
tracheal invasion. Acta oto-laryngologica, 2009. 129 (12): p.
1498-1502.
21. Nixon, I.J., et al., An international multi-institutional
validation of age 55 years as a cutoff for risk stratification in the
AJCC/UICC staging system for well-differentiated thyroid cancer.Thyroid, 2016. 26 (3): p. 373-380.
22. Brauckhoff, M., et al., Impact of extent of resection for
thyroid cancer invading the aerodigestive tract on surgical morbidity,
local recurrence, and cancer-specific survival. Surgery, 2010.148 (6): p. 1257-1266.
23. Mazzaferri, E.L. and S.M. Jhiang, Long-term impact of initial
surgical and medical therapy on papillary and follicular thyroid
cancer. The American journal of medicine, 1994. 97 (5): p.
418-428.
24. Sawka, A.M., et al., An updated systematic review and
commentary examining the effectiveness of radioactive iodine remnant
ablation in well-differentiated thyroid cancer. Endocrinology and
metabolism clinics of North America, 2008. 37 (2): p. 457-480.
25. Tuttle, R.M., G. Rondeau, and N.Y. Lee, A risk-adapted
approach to the use of radioactive iodine and external beam radiation in
the treatment of well-differentiated thyroid cancer. Cancer Control,
2011. 18 (2): p. 89-95.
26. Tuttle, R.M., et al., Radioactive iodine administered for
thyroid remnant ablation following recombinant human thyroid stimulating
hormone preparation also has an important adjuvant therapy function.Thyroid, 2010. 20 (3): p. 257-263.
27. Samaan, N.A., et al., The results of various modalities of
treatment of well differentiated thyroid carcinomas: a retrospective
review of 1599 patients. The Journal of Clinical Endocrinology &
Metabolism, 1992. 75 (3): p. 714-720.
28. Jonklaas, J., et al., Outcomes of patients with differentiated
thyroid carcinoma following initial therapy. Thyroid, 2006.16 (12): p. 1229-1242.