While active surveillance is being considered an option in managing low-risk small PTC, there is still a debate about the best treatment approach in these cases. And despite this debate, there is a lack of large and controlled trials that compared the outcomes between surgical management and active surveillance, especially in the US.
To our knowledge, this is the largest real-world study that compared the survival outcome in small DTC between patients who had surgical resection versus patients who did not have surgical resection. And while most of the studies that looked at the active surveillance in DTC focused on papillary thyroid cancer, in our study we evaluated the survival benefit of surgical resection in all histologic types of DTC. We found that patients who were treated with surgical resection had better OS compared to the ones who did not have surgery. The survival benefit of surgery was seen in all histologic types of DTC and different tumor sizes (< 1cm and 1-2cm).
The active surveillance (AS) approach was first introduced by Akira Miyauchi and his team after his observation of increase thyroid cancer incidence rate without an increase in mortality rate around the world, in addition to having different studies showing frequent detection of PMC, defined as well-differentiated tumors 1 cm or less in size with no lymph node or distant metastasis and no extrathyroidal involvement, on autopsy studies of patients who died of other reasons than thyroid cancer[14, 17, 18]. This proposal was a trigger to start experimental observation with no surgical resection for low risk PMC in two hospitals in Japan and multiple studies reported very low percentage of tumor size increase and lymph node metastases development[11–13, 19].
Yasuhiro Ito and Akira Miyauchi, along with other researchers, conducted several studies evaluating the outcome of AS in PMC in Japan. Ito et al. between 1993 and 2004 followed a total of 1,395 patients with PMC; 340 patients underwent observation and 1,055 patients had immediate surgical treatment for an average of 74 months. Both groups had the same rate of lymph node metastases. It was noted that 32% of the observation group patients required surgery during the study period for various reasons mainly due to tumor enlargement or tumor location, but none of these patients had disease recurrence after surgery. More recently, Ito et al. conducted a study of 1235 low-risk PMC patients who were followed with AS between 1993 and 2011. It was reported that 8.0% of the patients had tumor enlargement and 3.8% developed lymph node metastases at 10 years (more significant in less than 60 years old patients), but there was no death or distant metastases in any of the study patients. Sugitani et al. followed 230 patients with asymptomatic PMC for a mean time of 5 years. They found only 7% of tumors increased in sizes with no extrathyroidal invasion or distant metastasis. Oda et al. also compared the outcomes between AS and surgical resection in 2,153 patients with low-risk PMC (defined as < 1cm tumor size with no nodal or distant metastasis, macroscopic extrathyroidal extension, high-grade malignancy on cytology, or evidence of progression) in Japan. There was no significant difference in developing lymph node metastases between the two groups (0.5% in AS group and 0.2% in surgical treatment group) and none of the 2,153 patients developed distant metastases or died of thyroid cancer. In addition to that, few studies found AS to be cost-effective compared to early surgical resection in PMC[22, 23]. The reported findings of the mentioned studies played a significant role in adopting AS approach in Japan in 2010 by the Japanese Association of Endocrine Surgeons and the Japanese Society of Thyroid Surgeons[24, 25].
In the US, very few studies evaluated the AS approach. In 2017, Tuttle et al. in a study of 291 patients with low-risk PTC (defined as intrathyroidal tumors < 1.5 cm) were followed for a median time of 25 months. The findings were very similar to the Japanese studies, 3.8% of the patients had tumor growth of 3mm or more and no regional or distant metastases reported during the active surveillance. Wang et al. on the other had reported a retrospective study of 29,512 patients with PTMC using SEER database. They split the cohort into three groups according to the treatment approach they had: 1.4% did not have surgery, 25.2% had partial thyroidectomy and 73.4% had total thyroidectomy. There was no significant difference between the two surgical approaches, but patients who did not have surgery had lower disease specific survival. Also 5-year OS was 25% in the observation group compared to 97.6% for patients who underwent either partial or total thyroidectomy (p < 0.001). In the last few years, the AS approach started getting more popular in the US and the 2015 ATA guideline mentioned active surveillance as an option in selected patients with PMC who have low-risk tumors (no metastases or local extension and no cytological indication of aggressive disease)[28–31].
Our study has some limitations that are worth mentioning. First, lack of details if patients who did not have surgical resection were followed with active surveillance or not. Second, other than overall survival, NCDB doesn’t have details about other oncologic endpoints like disease-free survival and cancer-specific survival. Therefore, one might argue that higher mortality in the no surgery group is derived by non-thyroid cancer deaths rather than thyroid cancer deaths (particularly given the imbalance in baseline characteristics between both groups with older age and more comorbidity in the no surgery group). It is possible that factors like age and comorbidity were part of the reason why some of those patients did not have surgery in the first place. In order to mitigate the impact of this limitation, we conducted multivariable analyses (to adjust for age, comorbidity and other non-thyroid cancer factors), propensity score matching, as well as multiple subgroup analyses. Third, we did not have the details about all high-risk features, like aggressive histological subtypes or history of prior neck irradiation. Fourth, the retrospective nature of the study and data collection within the NCDB carry different types of bias that might affect the accuracy of the analyses and result interpretation. Despite these limitations, this study represents the largest observational study to compare the survival outcomes in small DTC between patients who were managed with surgical resection and patients who did not have surgical resection. Further prospective randomized studies and/or multi-center studies are needed to further compare the outcomes between surgical approach and active surveillance in small DTC.