The aim of these guidelines is to facilitate decision making in the treatment of patients with a solitary pulmonary nodule (SPN).1–3 These guidelines are not intended to be rigid, since the treatment of SPN is an example of how estimation of the probability of malignancy (PM), access to the various diagnostic and therapeutic techniques and patient preferences work together to mold the optimal decision. This process should be individualized in the clinical setting and for each particular situation. Since accessibility to some diagnostic techniques may vary, depending on the setting, a general strategic algorithm is proposed (Fig. 1) with two alternatives, depending on the degree of accessibility to positron emission tomography (PET) (Figs. 2 and 3). The recommendations have been graded according to strength (strong 1, weak 2) based on the relationship between the foreseeable benefits and the risks for the patient; and the quality of the scientific evidence, as high (A), moderate (B), low (C) or very low (D), according the GRADE system.4 A summary of these recommendations2,4,6 is given in Table 1. The extended version of these recommendations is available as an online supplement, along with additional tables and figures (S) (Appendix 1).

Fig. 1.

Algorithm for the management of PN: initial classification and observation of SPN≤8mm and subsolid SPN. m: months, PN: pulmonary nodule; SPN: solitary pulmonary nodule; CT: computed tomography, including thin sections. Follow-up with low-radiation CT, provided no growth is detected. Numbers and letters in brackets refer to the sections in the text where they are discussed.

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Fig. 2.

Algorithm for the management of PN>8mm: clinical setting with easy access to PET-CT. m: months, PN: pulmonary nodule; SPN: solitary pulmonary nodule; PET-CT: positron emission tomography with computed tomography; PM: probability of malignancy; CT: chest computed tomography, including thin sections. Follow-up with low-radiation CT, provided no growth is detected. Numbers and letters in brackets refer to the sections in the text where they are discussed.

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Fig. 3.

Algorithm for the management of PN>8mm: clinical setting with difficult access to PET-CT or preference for cytohistological study of SPN. FB: fiberoptic bronchoscopy and guided biopsy; m: months; SPN: solitary pulmonary nodule; PET-CT: positron emission tomography with computed tomography; PM: probability of malignancy; CT: chest computed tomography, including thin sections. Follow-up with low-radiation CT, provided no growth is detected. Numbers and letters in brackets refer to the sections in the text where they are discussed.

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SPN is defined as a single, spherical, distinct, radiological opacity with a long axis of ≤30mm, primarily surrounded by aerated lung and without associated atelectasis, hilar enlargement or pleural effusion.1–3 SPNs may be observed on chest X-ray or chest computed tomography (CT) performed to study other diseases or for diagnostic screening for lung cancer (LC).3,6,7 Millimetric nodules (≤8mm in diameter)1,2,6 and subsolid nodules (SSNs)2,5 (Fig. 4), requiring different management,5–7 may be detected on CT (Fig. 1). SSNs include both ground glass nodules and partially solid nodules that combine a ground glass component with a solid component.2,5–7

Fig. 4.

Mixed subsolid solitary pulmonary nodule in the left upper lobe. Chest computed tomography with 2mm thin sections in a patient with a solitary pulmonary nodule in the left upper lobe. Axial slice (A) in upper lobes and coronal (B) and sagittal (C) reconstructions in the left upper lobe. An 18-mm ground-glass solitary pulmonary nodule is observed, with a 7-mm solid component in the interior. Resection by video-assisted thoracoscopy revealed adenocarcinoma.

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Nodules are estimated to occur at a rate of 1 or 2 per 1000 X-rays.1,3,8 The prevalence of nodules on CTs performed in adult smokers for LC screening is very high, between 20% and 50%, and are generally less than 10mm in size; the incidence in successive annual CTs is 10%.1,3,6,7

When evaluating SPNs with CT, other small nodules are often found. When they are few or one is clearly dominant, they should be considered as independent SPNs, since, even if the situation is LC, accompanying subcentimeter nodules are commonly benign.1,2,6,7 Moreover, in up to 20% of cases, the malignant nodule is not the largest.7

SPN is the radiological manifestation of many diseases3 (online Appendix–Table 1S). However, most nodules are caused by pulmonary malignancies, granulomas and hamartomas.1 The prevalence of malignancy varies between series8,9: from between 5% and 70%, depending on whether the figures are retrieved from health checks or studies of diagnostic techniques, and to a lesser extent in SPNs detected in LC screening programs, where the prevalence is 1%–10%, depending on nodule size.3,7 The PM of SPNs increases notably in patients with previous tumor disease.3,10

Most malignant SPNs are LC, most frequently adenocarcinomas and large cell carcinomas.2,3 In malignant SSN, the most common strains are in the adenocarcinoma spectrum,5,11,12 ranging between atypical adenomatous hyperplasia in the smallest nodules, adenocarcinoma in situ, minimally invasive adenocarcinoma and invasive adenocarcinomas, if a solid component is present, particularly in mucinous nodules and those with lepidic growth.5,11,12

Malignant SPNs differ from benign SPNs in certain clinical and radiological aspects, described in more detail in the extended version of these guidelines (see online supplement). The factors most closely associated with malignancy are the size of the SPN, margin features, density, patient age, accumulated tobacco consumption, existence of other malignancy and detection of growth.2,3,6,7,10,28-30 Central, laminar or total calcification of the SPN is considered a good criterion for benignancy,2,3 as is radiological stability for more than 24 months, implying a doubling time of over 730 days. This criterion is not valid for SSN, for which the observation must be extended to at least 3 years.1–3,5

Most clinicians estimate PM intuitively, but several SPN models and classification rules have been proposed7,28–32 and there are even calculators available online (online Appendix–Table 2S) or as a smartphone application (Medcalc medical calculator). Table 2S of the online Appendix gives a set of formulas obtained from different logistical models and Figure 1S is a valid nomogram for SPNs in chest X-ray.

This estimation of PM guides the subsequent diagnostic process.1,2,31 Logically, when predicting malignancy, the results of all the examination techniques are reviewed, including the PET-CT results,31,32 the biopsy or aspiration results and the evaluation of growth, if suitable images are available.

Along with PM, the foreseeable benefits and risks of the treatment must be assessed. There is a threshold PM indicating observation, i.e., any PM for which the most reasonable option is prospective observation of the stability or growth of the SPN; and a threshold for surgery, for which surgery is clearly recommended since the probability of early stage cancer is high. These thresholds depend on the expected benefits; for example, probability of cure or treatment response in cases of malignant disease, the surgical risks, that may vary between patients and the personal attitude and preference of the patient.1

The aim of evaluating an SPN is to diagnose and treat SPNs that represent active disease, in particular LC, since 5-year survival is 70%–80% in early stage disease.20 Another aim is to avoid submitting patients with granulomas, hamartomas and other benign lesions to costly and risky treatments. There is no singly accepted procedure. The key elements for evaluation are estimation of the probability of malignancy, accessibility to different diagnostic tests and the expertise of clinicians in these techniques, and the preferences of the patient.1,2

Figs. 1–3 show the proposed sequential evaluation of SPN: Fig. 1 describes the initial classification by SPN size, density and solidity or subsolidity, separating patients who require individualized management and those who can be diagnosed from the outset. Figs. 2 and 3 describe the proposed strategy for indeterminate solid SPNs>8mm, depending on whether access to PET-CT is easy (Fig. 2) or more difficult (Fig. 3).

• A.

  Diagnosis of benignancy: Patients with a specific diagnosis on CT, such as hamartomas, arteriovenous malformations, cystic lesions, rounded atelectasis, mycetomas, pseudonodules or calcified nodules, or who have criteria for benignancy, e.g., documented stability for at least 2 years, in the case of solid nodules, or at least 3 years for subsolid nodules2,3: grade of recommendation, 2C.

• B.

  Radiological observation: Indicated in SPNs with low PM, or with intermediate PM when PET-CT is negative, grade of recommendation, 2C. This may also be indicated in undiagnosed SPNs if the risk of surgery is very high or if the patient refuses surgery: grade of recommendation, 2C.

  For SPN>8mm with low PM, CT monitoring is recommended at 3–6 months, again at 9–12 months and again at 24 months.2 There are specific strategies for SPN≤8mm and SSN2,5,6 (Fig. 1 and Table 2): grade of recommendation, 2C. Surveillance CTs must be performed with low-dose and non-contrast: grade of recommendation, 1C.

• C.

  Diagnostic-therapeutic surgery: Operable patients with undiagnosed SPN and PM greater than low should be offered resection: grade of recommendation, 2C. Although video-assisted thoracoscopy is the method of choice (grade of recommendation, 1C), each surgical team will decide on the best approach. Intraoperative biopsy is recommended for completing appropriate resection in the case of LC: grade of recommendation, 1C.

• D.

  Specific diagnosis: This is the etiological diagnosis of SPN. If LC is diagnosed, specific local staging and treatment protocols will be applied.20

  The algorithm cannot be completed without re-emphasizing that the optimal decision must include the opinion and the preferences of the appropriately informed patient2: grade of recommendation, 1C.

The authors state that they have no conflict of interests.