Radioactive iodine (RAI) therapy is the most appropriate postoperative treatment in this patient who is at intermediate risk of cancer recurrence based on his age, the size of the primary tumor (between 2 and 4 cm), the presence of vascular invasion and extrathyroidal extension and the number of involved lymph nodes (>5). He therefore may benefit from adjuvant RAI therapy, due to his higher risk of persistent or recurrent disease. RAI therapy is given in conjunction with levothyroxine therapy, which is indicated in all patients who have had a total thyroidectomy. Because of his intermediate-risk disease, it may be appropriate to lower the thyroid-stimulating hormone level to less than 0.1 µU/mL (0.1 mU/L) in the absence of contraindications such as pre-existing cardiovascular disease or age greater than 65 years.

Traditional chemotherapeutic agents, such as doxorubicin, are generally ineffective in the management of differentiated thyroid cancer and would not be indicated for this patient. In patients with anaplastic carcinoma of the thyroid, however, some studies have demonstrated a possible benefit with concomitant use of paclitaxel-based chemotherapy and external-beam radiotherapy. This patient has classic papillary thyroid cancer histology and would not benefit from such treatment.

External-beam radiotherapy is rarely used in patients with differentiated thyroid cancer. An exception would be the management of patients with inoperable disease that threatens to cause local extension into vital structures in the neck such as the trachea, esophagus, or major blood vessels.

Because of the extent of disease found at surgery and this patient's high risk of recurrence, providing no additional therapy would not be an appropriate next step in management.