Proponents of routine PCND argue that because the central compartment is the major site for nodal metastasis in DTC, prophylactically removing lymph nodes will decrease the rate of recurrence from microscopic occult nodal metastases.3,4–8,13 The proposed benefits of PCND are reduction in local recurrence and increased accuracy in TNM staging which assists with subsequent treatment. This is in part due to the fact that identification of micrometastasis “upstages” PTC from Nx to N1a disease in the American Joint Committee on Cancer (AJCC) staging system, and N1a PTC is considered “stage III” PTC in patients >45 years.4 Additionally, a PCND should promote reduction in surgical morbidity associated with reoperation.6,8,13 Conversely, those against the use of routine PCND argue that there is no clear evidence which shows a reduction in recurrence or mortality, it increases operative time, and it increases risk for complications and short-term morbidity.3,6,13 Since the publication of the ATA’s recommendations for PCND in the management of DTC, there has been a great deal of research published on the topic. Most notably, five different meta-analyses have been published on the effects and outcomes of PCND.6–8,14,15 These studies provide valuable information on the effects of PCND on local recurrence, morbidity and complications, and subsequent treatment of DTC.
Effects on Survival
With the 10-year survival rate for DTC being greater than 90%, the effect of PCND on survival is extremely difficult to determine due to the length of follow-up required and other causes of death that occur in the follow-up period. For this reason, there are very few studies in the literature which examine the effect of PCND on survival, with most studies opting to examine the effect of PCND on local recurrence and surgical morbidity. One retrospective study by Barczynski et al. did analyze 10-year disease-specific survival for patients with PTC who underwent TT alone versus TT with PCND. They examined 640 patients and found that those who underwent TT alone and TT with PCND had 10-year survival rates of 92.5% and 98%, respectively.16
This difference was statistically significant and suggests that PCND may improve long-term survival. However, the patients who received a PCND were also more than twice as likely to receive radioactive iodine ablation (RAI) therapy, and thus the data do not definitively conclude that PCND improves survival. As mentioned before, no prospective randomized controlled trials exist which examine the effect of PCND.
Effects on Local Recurrence
Since the central compartment is a common site of recurrence, the basis of a PCND is to reduce the risk of local recurrence both by removing potential metastatic sites and by providing lymph nodes for histological analysis to identify micrometastasis.4,17
Since 2010, four meta-analyses were published that investigated the effect of TT with PCND on local recurrence rates in comparison to TT alone. None of these studies was able definitively to conclude that TT with PCND significantly decreased the risk of local recurrence.6–8,14
Three of the studies were able to demonstrate a trend of reduced local recurrence in TT with PCND versus TT alone; however, they were unable to show statistical significance.6,8,14
Lang et al. were able to show a statistically significant reduction of 35% in local recurrence for the TT with PCND group in comparison to TT alone. However, in their study, the TT with PCND patient group was also shown to be more likely to receive RAI therapy than the TT alone patient group. This difference was found to be statistically significant, and the authors were unable to conclude that the reduction in local recurrence was due to the PCND and not the increased use of RAI.7
In this study, the reduction was shown for short-term follow-up (<5 years), and due to the indolent nature of DTC a longer follow-up is needed to examine the long-term recurrence rates.12
The retrospective study by Barczynski et al., however, was able to show a significant reduction in the 10-year local recurrence rate of TT with PCND versus TT alone in the absence of RAI. They showed in patients who did not receive RAI therapy that PCND with TT had a 10-year local recurrence rate of 3.9% compared to the TT alone rate of 14.8%.This statistically significant difference was lost when TT with PCND and TT alone were compared in the presence of RAI therapy following surgery.16
In a retrospective study by Moreno et al., the absence of macroscopic nodal metastasis on preoperative ultrasound of the central compartment was found to be to be a predictor of recurrence-free survival in patients with PTC.18 They examined the effect of histological analysis of lymph nodes obtained from PCND on 10-year recurrence-free survival. The data obtained showed that the 10-year recurrence-free survival in patients with micrometastasis identified after PCND compared to node-negative patients after PCND was not statistically significant.18 Thus, the identification of macroscopic nodal metastasis in the central compartment on ultrasound is a significant prognostic factor in DTC, whereas micrometastasis identified pathologically in patients after PCND is not. In a review, Steward and colleagues also assert that the discovery of micrometastasis in the central neck compartment does not alter 10-year-survival and thus discovery of these is not sufficient to justify a PCND.13 With the identification of microscopic nodal metastasis occurring frequently, the identification must be used carefully when staging a patient.4 Upstaging a patient from N0 to N1a upgrades a patient >45 years old from stage I to stage III on the AJCC staging system. This is problematic, as microscopic nodal metastases do not display the same risk for recurrence as macroscopic nodal metastases and can cause an unnecessary increase in radioactive iodine utilization.4 Thus, PCND should not be used with the intention of reducing recurrence and improving staging by identifying and removing micrometastases.
Morbidity of Central Neck Dissection
An important area for consideration in regard to PCND is the associated risks, which is why the ATA stated with Recommendation 36 that its recommendations should be considered in light of surgical expertise. There is increased cost and morbidity in patients with recurrent disease, given that reoperative cervical surgery is associated with higher risk of recurrent laryngeal nerve injury and hypoparathyroidism, both transient and permanent.19,20
This is due in part to the more extensive dissection of the central compartment, which is more likely to damage the recurrent laryngeal nerve and blood supply to the parathyroids in comparison to TT alone.1,6,14
Four meta-analyses on PCND in the treatment of DTC have been published that address the complications of PCND and its effects on morbidity. A fifth meta-analysis by Zetoune et al. examined the morbidity associated with the addition of PCND to TT; however, only two of the studies included in their analysis examined the associated complications, and, as such, this study does not carry as much weight as the four others.8
In these five meta-analyses, the only significant complication found with TT with PCND compared to TT alone was temporary hypoparathyroidism.6–8,14,15
The risks of permanent hypoparathyroidism, and temporary and permanent recurrent laryngeal nerve damage, were not found to be different between the two groups. Nonetheless, it does come with an increased risk of temporary hypoparathyroidism and, as such, should be performed in the hands of an experienced surgeon.19
With the knowledge that PCND is relatively safe with rare long-term morbidities, the argument that PCND will prevent the potential morbidity associated with reoperation seems attractive. However, because PCND has not been shown to reduce local recurrence rates, the argument for routine PCND to prevent reoperation is problematic, as a reoperation is only necessary in the setting of disease recurrence.