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Managing Incidentally Identified Pulmonary Nodules

By Robert J. Albin, MD, FCCP, FAASM

Due to the ubiquitous availability of CT scanners, coupled with the ever-increasing propensity by physicians across all specialties to order advanced imaging studies, the number of incidentally detected pulmonary nodules has been soaring.

Over a recent 7-year stretch, one large integrated health sys-tem reported a 53 percent increase in the number of CT scans ordered. This trend has resulted in more than 1.5 million newly detected lung nodules in the U.S. annually. Exactly how best to manage these nodules has become an important but prickly dilemma, at times pitting the varied and potentially conflicting perspectives of patients, practitioners, medical societies and practice guideline directives against each other.

What has emerged and become clear is that the management of pulmonary nodules should be driven by the importance of distinguishing those that are malignant from those that are not by balancing the desire to intervene quickly for malignant nodules while avoiding and limiting procedures for those that are benign. What is not clear is how best to achieve this goal.

Figure 1: Right upper lobe [RUL] andleft upper lobe [LUL] solid nodules. The RUL nodule is irregular but contains central calcification. The LUL nodule has irregular borders and is non-calcified. These lesions have remained stable on follow-up exam.

One of the first issues to resolve is to be certain that we are all speaking the same language when it comes to describing nodules. The descriptive nomenclature associated with pulmonary nodules, while endeavoring to be more precise and useful, has created an ever-expanding vocabulary of important distinctions.

Nodules may be solid, subsolid, ground-glass or contain a mixture of these components. They may be ovoid, round, smooth-bordered, spiculated or irregular. It is important to state whether they contain calcium or are non-calcified. While some nodules are detected as solitary abnormalities, in other instances, multiple nodules may be identified. Precise size measurement using proper criteria [the average of long and short diameters, both obtained on the same transverse, coronal or sagittal reconstructed images] adds to prognostic significance. Lobar localization is important, as is the presence or absence of emphysema or fibrosis. These distinctions serve the purpose of trying to identify those nodules with a less than 1 percent probability of being malignant (pCA < 1%), in order to avoid unnecessary testing and procedures.

The Fleischner Society, an international multidisciplinary medical society for thoracic radiology founded in 1969, published their latest recommendations for managing pulmonary nodules this year. Its intent was to cut down on unnecessary follow-up exams and procedures. While extremely useful and worthy of summarizing here, they are not without limitations and controversy. These guidelines apply to incidentally detected nodules in individuals at least 35 years of age.

For a single, solid, non-calcified nodule less than 6 mm in a low-risk patient, no further follow-up is recommended. Even in high-risk patients, the likelihood of this nodule being malig-nant is reported as less than 1 percent. However, suspicious morphology or upper lobe location can raise pCA to the 1 percent to 5 percent range, so a 12-month follow-up study can be considered in this subgroup of patients.

For a nodule 6-8 mm in size in a low-risk patient, a 6-12 month follow-up should suffice if stable. If high risk, additional imaging at 18-24 months should be considered. If the nodule is greater than 8 mm, PET-CT at 3 months is recommended as pCA now approaches 3 percent.

If there are multiple solid, non-calcified nodules less than 6 mm, no routine follow-up is recommended, as this typically represents healed granulomas or intrapulmonary lymph nodes. In a high-risk patient, consider a 12-month follow-up. If any nodule is greater than 6 mm, perform 3-6 month follow-up with optional follow-up at 18-24 months.

For a solitary, pure ground-glass opacity [GGO] less than 6 mm, no routine follow-up is recommended, although 2- and 4-year follow-up should be considered in selected high risk populations. If greater than 6 mm in size, 6-12 month follow-up CT is recommended and repeat imaging every 2 years through 5 years total.

For solitary part-solid nodules, no follow-up is necessary if less than 6 mm. If greater than 6 mm with the solid component less than 6 mm, obtain a follow-up scan in 3-6 months and then annually for 5 years. If greater than 6 mm with a solid component greater than 6 mm, obtain a follow-up scan at 3-6 months. For suspicious morphology or a solid component greater than 8 mm, consider PET-CT, biopsy or resection.

For multiple subsolid nodules less than 6 mm, these are likely infectious or inflammatory. If repeat imaging is stable at 3-6 months, consider scanning at 2 and 4 years. If at least one nodule is 6 mm or larger, rescan at 3-6 months. If persistent, consider multiple primary adenocarcinomas as a potential etiology.

If these recommendations seem confusing or even un-sound, take solace in knowing that you are not alone in this opinion. Unfortunately, the guidelines are based upon very low-quality evidence, as clearly stated in the Society paper. However, despite this, they are generally considered to rep-resent best practice parameters.

Additional shortcomings include the inability to accurately define “low-risk” versus “high-risk” populations. Given that the greatest recent percentage jump in the incidence of lung cancer is among never smokers, who then can be considered to be at “low risk”? Also, how can size be an absolute cutoff criterion for benign versus malignant disease? Every lung cancer was less than 6 mm at some point in its biology. In my opinion, size depends upon when, in the history of this nodule, the scan was performed. A single point in time has never been able to predict a trend.

Figure 2: Multiple bilateral ground-glass opacities of varying sizes. Biopsies have proven these to be multicentric lepidic adenocarcinomas. Management has included surgical resection as well as stereotactic body radiation therapy [SBRT].

I take these guidelines for exactly what they are – guidelines. Good clinical judgment and intuition must always weigh into the decision process. From my perspective, there is no nodule (other than a densely calcified, smooth bordered one) that does not merit additional follow-up imaging. While an extra CT(s) does add to the patient’s total radiation exposure burden, I believe the benefit outweighs the risk and so do the majority of patients.

Not surprising to me, a recent report comparing physicians’ assessment of pretest probability of whether a nodule was benign or malignant demonstrated that physicians were better at predicting malignancy than the frequently cited Mayo Clinic or VA prediction calculators. This is a very sobering finding and reaffirms the importance of clinical experience and “gut” instincts.

In the absence of strong evidence upon which to propose guidelines, the perspective and preferences of the patient and the clinician can and should play a critical role in the decision-making process. Successful management of what has now become a commonplace clinical problem depends upon shared values, concerns and frank dialogue between providers and patients.

Looking ahead, enhancing existing prediction calculators by including novel radiographic measurements, as well as analysis of exhaled, serum and bronchoscopic biomarkers, may aid in distinguishing benign from malignant disease. Until then, it might be a good idea to follow this old medical adage – what would you do if this was your mother?


References

1. Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Im-ages: From the Fleischner Society 2017. Radiology 2017.

2. Iaccarino JM, Wiener RS. Pulmonary Nodule Guidelines: What Physicians do When Evidence-Based Guidelines Lack High-Quality Evidence. Chest. 2017; 152(2):232-234.

3. Physician Assessment of Pretest Probability of Malignancy and Adherence with Guidelines for Pulmonary Nodule Evaluation. Chest. 2017; 152(2):263-270.

4. Swensen SJ, Silverstein MD, Edell ES et al. Solitary Pulmonary Nodules: Clinical Prediction Model Versus Physicians. Mayo Clin Proc. 1999; 74(4):319-329

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