The present study retrospectively examined patients at our institution with primary lung cancer, who underwent surgical resection, and had pre-treatment PET/CT and post-treatment CT imaging. Patient and imaging characteristics as well as pathological findings of the pulmonary lesions were analyzed to assess for predictors of lung cancer recurrence and extra-pulmonary metastatic disease. This study demonstrated that the two predictors of extra-pulmonary metastatic lung recurrence were: 1) the presence of > 1 recurrent pulmonary lesion and 2) the presence of suspicious lymphadenopathy, on post-treatment CT imaging. Furthermore, lesion size, imaging characteristics, recurrence location relative to surgical bed, or chest wall invasion were not significant predictors of extra-pulmonary metastatic lung cancer recurrence. The reason that the presence of chest wall invasion did not show an association with extra-pulmonary metastatic lung cancer recurrence in this study may have been due to the small number of patients with that characteristic in this cohort.
Many researchers have examined pre-treatment CT imaging to evaluate different factors that may predispose patients to lung cancer recurrence, including CT imaging characteristics and malignancy subtype, to name a couple. However, few researchers have examined post-treatment CT imaging to predict extra-pulmonary metastatic disease with lung cancer recurrence. The current study examined both pre- and post-treatment CT imaging and demonstrated that the presence of > 1 recurrent pulmonary lesion and suspicious lymphadenopathy in follow-up CT examinations can predict metastatic recurrence outside of the thoracic cavity. Therefore, in the presence of these two findings on follow-up chest CT, the clinician can predict the likelihood of metastatic recurrence without the additional expended costs (time, resources, money, and radiation) of additional imaging. This additional information may help clinicians and patients decide on whether or not they wish to undergo further treatment or investigations if the likelihood of extra-pulmonary metastatic disease is higher.
The present study also demonstrated that age, gender, malignancy type, lesion size, lesion CT imaging characteristics, and the presence of suspicious lymphadenopathy on pre-treatment PET/CT imaging were not significant predictors of lung cancer recurrence. Whereas, other researchers have shown a poorer prognosis with solid nodules when compared to subsolid nodules [10, 16], or a more favorable prognosis in nodules with GGO [11, 17]. In regard to predicting prognosis based on lesion size, research groups have found that this comparison should only occur in the pure solid component of nodules [16, 17], with larger size corresponding with worse prognosis [16, 18–22]. The current study was inclusive of all subtypes of NSCLC, whereas other research groups have looked at different subtypes individually [10, 12, 14, 18, 23]. The present study did not find a correlation between malignancy type and disease recurrence, whereas Takei et al.  found the poorest prognosis with large cell neuroendocrine carcinoma. Compared to the present study, this disparity may be due to the lack of patients in our experimental group with neuroendocrine histological subtype (Table 1). The reason that lymph node metastasis did not show an association with disease recurrence in this study may have been due to the small number of lymph node metastases in this cohort.
This study had multiple limitations. This was a retrospective, single-center study, and it may not be generalized to other population cohorts. The subject population was small (76 patients) compared to most research groups investigating lung cancer recurrence. The majority of histological diagnoses were adenocarcinoma and SCC (93% of the recurrence group), with few patients with neuroendocrine or other NSCLC tissue diagnoses. Lesion size was measured manually without using computer-aided diagnosis, which lends itself to measurement variabilities . CT exams were read by a single reader and the reports were retrospectively analyzed to populate the dataset. The current study also only included patients who underwent surgical resection. This criterion was used because surgical resection allowed for pathologic correlation as well as to ensure full resection of the lesion. Therefore, the results of the current study would not adequately apply to patients undergoing only chemotherapy and radiotherapy.