Epidemiology-signs and symptoms-diagnosis-management-prognosis: this is the general flow of how we as physicians think. In fact, the malleable minds of wide-eyed medical students are often beaten into this shape; they are often told that it is the beat of the drum they have to march to if they are to succeed in medicine. 

At first glance, this general way of thinking about disease and treatment makes sense: it starts from the beginning and works its way to the end. Unfortunately, “prognosis” becomes almost an epilogue of sorts; some of us may feel it occupies a lesser place of importance because it is the most difficult to accurately pin down.

However, to the patient, nothing can be more important than the “prognosis” aspect of their treatment. Most of us will be familiar with desperate questions of, “How long till I get better, Doctor?” and “How much more time do I have to live?” 

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If we are to walk in our patients’ shoes, we must learn to study, improve, and explain “prognosis” in a new and better way. In this article, we will be looking at the “prognosis” aspect of patients with medullary thyroid carcinoma (MTC) with cervical lymph node metastasis. 

Making Prognostic Information More Meaningful 

Moses and colleagues conducted a study on the burden of nodal disease on patients suffering from MTC. Why MTC in particular? “MTC is more aggressive than differentiated thyroid cancer and distinct in that MTC cells do not concentrate radioactive iodine and are not sensitive to manipulation of thyroid stimulating hormone,“ they explained. “Surgical treatment is therefore the mainstay of therapy. MTC has a high propensity for lymph node involvement with positive nodes identified in greater than 70% of cases.”

Read more about MTC etiology 

In other words, from the very onset, MTC carries a poorer prognosis than other types of thyroid cancers. Combined with its propensity for lymph node involvement in the majority of cases, the chances of long-term survival is low. 

To carry out their study, Moses et al analyzed data from the National Cancer Database (NCDB) to investigate the burden of nodal disease on survival, as well as identify the ratio of involved nodes to dissected nodes as a prognostic indicator in patients with MTC. 

“Clinical staging and pathologic staging were compared and incidence of upstaging and downstaging was calculated for each stage,“ they wrote. Nodal disease burden was measured based on location (central neck vs lateral neck) the number of positive nodes (0, 1-10, 11-20, or >20 positive), and the ratio of positive to dissected nodes.

The research team managed to identify 2627 patients from 2004 to 2015 who fit their inclusion criteria. Among those, positive cervical lymph nodes were identified in 1433 patients (54.5%). Out of the 1433 patients, 542 (20.6%) had more than 10 positive cervical lymph nodes. The overall survival for this group of patients was 94.5% at 3 years and 89.6% at 5 years. 

Among patients with 11 to 20 positive cervical lymph nodes, the hazard ratio was 3.56 in a univariate analysis and 2.26 in a multivariable analysis. In addition, the researchers discovered that the ratio of positive to dissected cervical lymph nodes was associated with overall survival. 

“Machens et al reported that MTC patients with 1-10, 11-20, and >20 CLN metastases had small, intermediate, and high lifetime risks for lung metastases, highlighting the prognostic impact of nodal burden,” they noted. 

In Machens and colleagues’ work, their conclusion was that “N categories encompassing 1 to 10 (N1), 11 to 20 (N2), and more than 20 (N3) lymph node metastases are important prognostic classifiers that should be incorporated into MTC staging systems for better risk stratification.”

Read more about MTC prognosis 

In other words, both these studies indicate that lymph node metastases in patients with MTC is associated with poorer survival.

“We suggest that examining the impact of the number of positive nodes as well as the ratio of positive to dissected nodes on survival might provide more meaningful prognostic information for patients who undergo surgery for the treatment of MTC,” Moses and colleagues wrote.

“Our finding that the ratio of positive to dissected lymph nodes has the strongest association with survival is consistent with data reported in the studies mentioned earlier, reinforcing the conclusions of previous authors that the number of positive lymph nodes provides valuable information regarding risk of distant metastasis, chance of surgical cure, and overall survival.” 

Counseling Patients on Disease Prognosis 

Since multiple studies have arrived at the same finding, which is that lymph node metastases worsens the prognosis of patients with MTC, physicians should counsel their patients accordingly, with both integrity and empathy. 

What is the best way to break bad news to a cancer patient? There are countless studies that have attempted to answer that. To end this article, we will quote from Hauk and colleagues on their study on breaking bad news to cancer patients: 

“Breaking bad news is a necessary competency for nearly every physician. Life-altering events, like the diagnosis of malignancy, can be associated with various emotions like shock, fright, sadness, or reactions of avoidance, denial, or dissociation. Responding to such emotions is important when delivering unsettling information and has an impact on the patient’s trust in the physician, adjustment to illness, and treatment.”


Moses LE, Oliver JR, Rotsides JM, et al. Nodal disease burden and outcome of medullary thyroid carcinoma. Head Neck. 2021;43(2):577-584. doi:10.1002/hed.26511

Machens A, Dralle H. Prognostic impact of N staging in 715 medullary thyroid cancer patients: proposal for a revised staging system. Ann Surg. 2013;257(2):323-9. doi: 10.1097/SLA.0b013e318268301d

Hauk H, Bernhard J, McConnell M, Wohlfarth B. Breaking bad news to cancer patients in times of COVID-19. Support Care Cancer. 2021 Aug;29(8):4195-4198. doi: 10.1007/s00520-021-06167-z