Only about a third of patients with medullary thyroid carcinoma (MTC) receive the recommended initial treatment of a total thyroidectomy in addition to central neck lymph-node dissection, despite recommendations in guidelines to combine the two to decrease the possibility of reoperative surgery.
“The low rate of adherence to American Thyroid Association (ATA) guidelines was one of the more puzzling findings of our study,” senior author Masha J Livhits, MD, of the section of endocrine surgery in the department of surgery at the University of California, Los Angeles (UCLA) David Geffen School of Medicine, told Medscape Medical News.
The results of the new study are published this week in JAMA Surgery by Eric J Kuo, MD, also of the department of surgery at UCLA David Geffen School of Medicine, and colleagues.
“The evidence for performance of central neck dissection is robust, [and] prior studies have shown that even in small medullary thyroid cancers less than 1 cm in size, the rate of lymph node metastasis is nearly 40%,” Dr Livhits noted.
“Therefore, the performance of [central neck] nodal dissection in medullary thyroid carcinoma is justified,” she stressed.
Dr Livhits ventured a couple of explanations for the low rates of adherence to the guidelines — one could simply be lack of awareness of the recommendations, she said. Or in some cases, it may be that the surgeon didn’t know the diagnosis was MTC until after the operation, because no preoperative biopsy was performed.
In an invited commentary accompanying the new study, Jessica E Gosnell, MD, and Quan-Yang Duh, MD, of the University of California, San Francisco department of surgery, noted that this latest work underscores the low adherence to ATA guidelines, as well as providing some key insights regarding reoperations.
Only 35% of Patients Had Central Neck Node Dissection at Time of Surgery
Even though only about 5% of thyroid cancer is medullary, this type is more aggressive; it also differs from other thyroid cancers in that patients have elevated calcitonin, for example.
The ATA guidelines for medullary thyroid carcinoma, first published in 2015, support the long-held recommendation of prophylactic central neck dissection with total thyroidectomy as standard treatment; however, population-level data on the practice has been lacking.
For the new research, Dr Kuo and colleagues conducted a retrospective analysis of data from the California Cancer Registry (CCR) and the Office of Statewide Health Planning and Development (OSHPD), identifying 609 patients with medullary thyroid carcinoma who were treated between January 1999 and December 2012 and had a minimum of 2 years postoperative follow-up.
The patients had a mean age at the time of diagnosis of 52.6 years and the mean tumor size was 2.8 cm, with extrathyroidal extension in 18.7% of patients.
Despite the ATA recommendation, only 35.5% (216 patients) had undergone central neck dissection at the time of their initial thyroidectomy.
Of the entire cohort, 99 required reoperation (16.3%), which is consistent with rates reported in the literature. The median time to reoperation was 6.4 months.
After adjustment for multiple factors, a leading risk factor for reoperation was the presence of lymph-node metastasis (hazard ratio [HR], 3.43).
Meanwhile, central as well as lateral neck dissection — which is indicated in the presence of lymph-node metastasis, was protective of the risk of reoperation (HR, 0.53).
“The performance of central and lateral neck dissection was associated with a decreased risk of reoperation, particularly for patients who were initially seen with regional disease,” the authors note.
But of interest, the ATA recommendation of central neck dissection, alone, with thyroidectomy was not significantly associated with a reduced risk of reoperation. However, Dr Livhits underscored the fact that this finding may have been the result of the study design.
“Our finding that central neck dissection alone was not protective of reoperation is likely a limitation of our data source,” she said. “We used an administrative data set that relies on procedure codes being accurately recorded. Codes for central neck dissection are less precise and prone to errors, which likely contributed to our inability to observe an effect in this group.”
Avoid Reoperation Due to Possibility of Complications
The 5-year disease-specific mortality rate for the entire cohort of patients was 13.5% (82 patients), and the strongest factors associated with this were: metastatic disease (HR, 21.08), regional disease (HR, 4.77), larger tumor size (HR, 2.83 for >2 cm to 4 cm and HR, 2.89 for >4 cm), and older age (HR, 1.36 per decade).
There was no significant association between reoperation and an increased risk of mortality; among the 99 patients who underwent reoperation, fewer than half, 45.5% (45), were disease-free at a median follow-up of 7.7 years.
The lack of an association between reoperation and mortality likely represents the selection of appropriate patients, Dr Livhits said.
“In our opinion, this finding indicates that selected patients who have recurrent medullary thyroid cancer, which is amenable to reoperation, still do well following a second surgery,” she noted.
“This supports reoperation when necessary in appropriately selected patients.”
She added that “prior studies have reported that patients whose calcitonin level (a tumor marker for medullary thyroid cancer) is not too high prior to reoperation and who did not have extensive lymph-node dissection during the initial surgery can be cured following reoperation.”
Nevertheless, measures to avoid reoperation in the first place are considered necessary out of concern for the array of potentially serious complications that can arise in a reoperation, particularly relating to the development of scar tissue in a site previously operated on, Dr Livhits explained.
“This makes dissection and identification of important structures more difficult.”
In such situations, the recurrent laryngeal nerve can be placed at risk, which can result in temporary or permanent vocal-cord paralysis, for example.
Also at risk are the parathyroid glands, which, if injured could compromise calcium levels, subsequently resulting in various cardiac, neurologic, and musculoskeletal symptoms.
Adherence to ATA Guidelines for Surgery for MTC Will Reduce Reoperations
Reasons for the relatively low rates of adherence to the ATA guidelines regarding central neck dissection could vary, Dr Livhits speculated.
“In some cases, the surgeon may have not known that the patient had medullary thyroid cancer until after the surgery — [for instance], if the diagnosis was not made on preoperative biopsy, but only made on examination of pathology following surgery,” she said.
“In other cases, it may be due to a lack of awareness of guidelines.”
Evidence in support of the ATA guidelines includes studies showing that central neck metastases are frequently present in medullary thyroid cancer even when not identifiable pre- or intra-operatively.
“It follows that not doing central neck dissection in these patients would leave residual micrometastases that would eventually become clinically significant,” Dr Livhits said.
In addition, other previous research, including a recent study (Ann Surg Oncol. 2015;22:1207–1213), meanwhile have shown fewer reoperations in association with adherence to the ATA guidelines.
In terms of the inclusion of lateral neck dissection, the ATA guidelines indicate that, in addition to the presence of lymph-node metastasis, if patients have very high calcitonin levels, “the likelihood of lateral neck metastasis is high enough to consider lateral neck dissection at the outset as well,” Dr Livhits explained.
“However, to say that lateral neck dissection should be performed routinely in the absence of abnormal lymph nodes seen on preoperative imaging is likely overreaching.”
Study Provides Several Important Lessons
In their commentary, Drs Gosnell and Duh say: “There are several important lessons from this population study of patients with medullary thyroid cancer.
“First, despite the recommendation for total thyroidectomy and bilateral central neck dissection in patients with clinically diagnosed medullary thyroid cancer, a fair proportion of affected patients are not getting these operations.
“Second, neck dissection performed at the initial operation may be protective, [and] third, while many patients with medullary thyroid cancer develop recurrent disease, reoperations are not associated with increased mortality.
“The potential benefits of proactive surgical treatment appear clear,” they state.
The overall message is that “even patients with recurrent and metastatic medullary thyroid cancer can be treated with repeated reoperations and still live full and active lives.” Because of this, it “is therefore critically important to minimize complications along their sometimes decades-long disease course.”
The study received partial support from the H & H Lee Research Program. The authors of the study and editorial had no relevant financial relationships.
JAMA Surgery. Published September 27, 2017. Abstract, Editorial
For more diabetes and endocrinology news, follow us on Twitter and on Facebook.
Tidak ada komentar:
Posting Komentar