Thyroidectomy Outcomes in Patients Identified With RET Pathogenic Variants Through a Population Genomic Screening Program

Abstract

ImportancePopulation-based genomic screening can facilitate early detection of medullary thyroid carcinoma (MTC) in patients with pathogenic/likely pathogenic (P/LP) RET variants.ObjectiveTo evaluate the clinical treatment and patient outcomes after identification of P/LP RET proto-oncogene variants associated with the risk of MTC via a population genomic screening program.Design, Setting, ParticipantsThis retrospective cross-sectional study was completed between June 1, 2016, and May 31, 2022, for a mean follow-up period of 22.4 months (range, 2-76 months). The study included patients who were identified as having P/LP RET variants through a population genomic screening program at a rural tertiary care center and who underwent thyroidectomy after results disclosure.Main Outcomes and MeasuresThe outcomes of interest were preoperative evaluation and treatment-related outcomes. Measures included imaging and laboratory findings, extent of surgery, pathologic diagnosis, and staging.ResultsSeventy-five patients were identified as having P/LP RET variants exclusively through genomic screening. Twenty of these patients (27%; 11 women [55%] and 9 men [45%]; median age, 48 years [range, 22-73 years]) underwent total thyroidectomy; 13 of these patients (65%) also had a central neck dissection. No patients had clinically apparent disease at the time of surgery. Pathologic findings indicated MTC for 12 patients and papillary thyroid carcinoma in 2. Of patients with MTC, 10 had stage I disease, 1 had stage II disease, 1 had stage III disease, and none had stage IV disease. Based on postoperative surveillance imaging and laboratory results, no patient had evidence of recalcitrant disease.Conclusions and RelevanceIn this cross-sectional study, all malignant neoplasms identified on surgical pathology were clinically occult, with surgical intervention based solely on the identification of the P/LP RET variant via population genomic screening. This finding suggests that genomic screening may provide opportunities for early detection and treatment of MTC, with the potential for improved patient outcomes.

Medullary Thyroid Carcinoma and Population Screening—The Promise and Pitfalls of Genetic Testing

“…We actually do not know the natural history of MTC; it may have similarities to papillary thyroid, breast, and prostate cancer, a subclinical reservoir of clinically inactive disease that may never become active or may grow extremely slowly, with low risks to the patient’s health . As has been noted in the ATA guidelines and by the authors, the most aggressive variants, even if we were to detect them through screening, may still require other drivers to become fully active, and there may be variable penetrance of the more moderate variants identified in this group of patients, meaning that the presence of the variant may not always result in the development of a cancer …”

“…2 The popularity of the program suggests that as broader testing begins to penetrate US health care outside of specialized programs like the Geisinger one, we can expect to see many more patients in our offices who present after having learned they have one of these variants. In this issue of JAMA Otolaryngology-Head and Neck Surgery, Pichardo et al 3 report pathology findings after thyroidectomy in patients identified with RET pathogenic variants through the MyCode program. These findings offer an important early look into the issues we are likely to face as a specialty as these programs spread and how we might interpret and act on RET-positive results of genetic testing in asymptomatic people.…”

“…While, broadly speaking, a mass genomic screening program for US citizens might seem reasonable based on these principles, this would come with a large opportunity cost, because MTC is so rare . In the case of the study by Pichardo et al, of the 184 293 participants, 85 were found to have a RET variant. Effective screening requires a detailed system to communicate results, such as that used in the Geisinger system, and there must be resources available to treat the identified risks or diseases.…”

“…The authors further state the goal “to identify patients at risk for MTC through genomic screening and offer surgical treatment in appropriate patients.” While this approach certainly has an appeal when the risks of cancer are high, it will be essential to gather more data about what level of cancer risk warrants the risks of prophylactic surgery. Thus, the authors’ identification of “appropriate patients” will need to be carefully defined in the future.…”

Population-Based Genomic RET Screening

“…To the Editor We commend Pichardo et al on their innovative publication, “Thyroidectomy Outcomes in Patients Identified With RET Pathogenic Variants Through a Population Genomic Screening Program.” This research casts a spotlight on the opportunities, as well as current challenges, for early detection and treatment of hereditary medullary thyroid cancer (MTC) and the potential for improved outcomes.…”