We report on a large series of 162 patients with a single pulmonary metastasis who underwent a PM from 2003 to 2018. Our data indicates that these patients present favourable overall survival (median 31.5 months; 5-year OS of 67%). However, a majority of patients (57.4%) developed recurrences with a short median DFI2 (11 months) after PM.
A PM is generally proposed when the following selection criteria are met: a controlled primary tumour, no extra-thoracic or mediastinal lymph node metastatic spread and sufficient pulmonary reserves to tolerate the resection of all identified metastases . The improvement of surgical techniques and radiological imaging and the recent advances in systemic therapies with the development of new chemotherapeutic agents have contributed to an increase in the numbers of PM procedures. Patients with solid tumours frequently present a single pulmonary nodule, which may not necessarily be a metastasis. Indeed, pulmonary metastases may radiologically resemble other conditions, such as primary lung cancers or benign inflammatory lesions. Surgical resection is sometimes the only way to histologically confirm or infirm the diagnosis of a metastatic disease. Interestingly, in a recent series of cancer patients, VATS resection of solitary nodules allowed the diagnosis of metastases in only 50% of cases . This point is particularly relevant in the context of the development of non-surgical therapies, such as stereotaxic radiotherapy or radiological ablative techniques, where histological diagnosis is rarely reported.
In surgical series, the presence of a solitary metastasis is a frequent situation and represents 47% to 70% of all pulmonary metastatic cases [5, 12]. Many studies have reported that the number of pulmonary metastases is a prognostic factor of survival [5, 13,14,15,16,17]. In colorectal cancer patients, a recent large systematic review including 8361 patients undergoing PM reported that the isolated unilateral lung metastases represented a favourable prognostic factor . A meta-analysis including more than 20 studies showed an increased risk of death (HR 2.04) for multiple lung metastases . In a large series of 615 patients with colorectal cancer, Cho et al. also demonstrated that the number of pulmonary metastases directly influenced the survival, with an overall 5-year survival rate of 70% in the subgroup with single pulmonary metastases compared to 56.2% in the subgroup with 2–3 metastases (p < 0.001) . Similar results with better survival for patients with a solitary pulmonary metastasis were also described for other primary tumours: sarcoma (HR 1.16, 95% CI 1.10–2.503, p = 0.016), melanoma (HR 1.4, 95% CI 1.1–1.7, p = 0.013) and renal cell carcinoma (HR 1.55, 95% CI 1.18–2.03, p = 0.002) [13, 18, 19].
In our study, we decided to focus on the population of patients bearing one pulmonary metastasis only because this population represents a non-negligible fraction of all pulmonary metastatic patients, and because it is by definition most amenable to surgical cure of its disease. Our aim was to evaluate risk factors for recurrence and risk factors for worse survival specifically for this population. Most of the PM were performed by VATS (84%). Pulmonary metastases are generally peripheral and small-sized (median diameter: 10 mm), making them easily accessible for a non-anatomical resection by VATS. However, some surgeons still perform thoracotomies in order to palpate the lung and identify other lesions. Nowadays, this paradigm is changing for solitary metastases and VATS approach is becoming the preferred approach, as showed in a survey of cardiothoracic surgeons in Great Britain and Ireland reporting that VATS was used by 85% of surgeons in case of isolated pulmonary metastatic lesions . Indeed, the 1-mm thin-slice CT-scans are very sensitive and can detect nodules of less than 5 mm in diameter, making the bimanual palpation obsolete.
The concordance between radiological imaging and pathological findings was analyzed by the Spanish prospective registry of PM . In this study, solitary nodules were present in 73% of colorectal cancer patients who underwent thoracotomy with bimanual palpation of the lung. The radiological and pathological agreement was 95%. In another series, only 7% of patients with single nodule on pre-operative CT-scan presented more metastatic lesions on pathological analysis after resection by thoracotomy . Thus, these recent results suggest that VATS is a valid approach, at least for patients with a single lesion on pre-operative imaging. In our study, the Cox regression analysis did not find any correlation between the surgical approach (VATS vs. thoracotomy) and the increased risk of recurrence (HR 1.15, 95% CI 0.61–2.17, p = 0.66).
Wedge resections using staplers accounted for 74.1% of cases. Anatomical resections (segmentectomy or lobectomy) were reserved for centrally located or larger lesions, the objective being to achieve safe margins, a result known to improve prognosis . We did not find any association between the type of surgical resection and the survival prognosis (HR 0.93, 95% CI 0.44–2.48, p = 0.93). Major resections could be justified for selected patients with larger or centrally located pulmonary metastases with favorable results, as demonstrated in a multicenter prospective study reporting an increased survival rate in comparison with non-anatomical resections for colorectal cancer patients with pulmonary metastases (55 vs. 28.3 months) .
The post-operative outcomes were favourable with an overall low morbidity of 11.7% with minor complications and a 30-day mortality rate of 0%. These results are consistent with other surgical series about pulmonary metastases [25, 26].
Despite our expectation to observe better prognosis for patients bearing solitary nodules, we observed a recurrence rate of 57.4% in that population. We identified three prognostic factors of recurrence: age under 70 years (HR 1.77, 95% CI 1.06–2.96, p = 0.03), prior treatment of extra-thoracic metastases (HR 1.61, 95% CI 1.05–2.47, p = 0.03) and non-colorectal origin (HR 1.84, 95% CI 1.14–2.96, p = 0.01). These elements are generally correlated with a biologically aggressive behaviour of the primary tumour, which are more prone to generating recurrences.
In our study, of the 93 (57.4%) patients who presented a recurrence, only 35 (21.6%) fulfilled the criteria to undergo an RPM, due to the invasion of other organs or poor residual lung capacity. Our indications for redo surgery are identical to the indications for initial surgery. Interestingly, most of the RPM have been performed by VATS (77.1%) and by wedge resection (77.1%). We observed that VATS procedures induced fewer adhesions and chest wall sequelae than thoracotomies. Thus, repeated VATS procedures were easier to perform.
The 5-year overall survival rate of single PM was 67%, which compares favourably with data from recent literature. With our results, we could identify two factors predictive of shortened survival: non-colorectal tumour origin (HR 2.40, 95% CI 1.11–5.22, p = 0.03) and mediastinal lymph nodes involvement (HR 3.42, 95% CI 1.03–11.41, p = 0.04). The primary tumour origin has been shown to influence survival with better survival rates in epithelial cancers than in sarcomas or melanomas . Hirai et al. showed that colorectal cancer patients had a better survival rate than patients with other primary organs involved (p = 0.003) . In our study, we chose to analyse only two subgroups of primary tumours (colorectal and non-colorectal) because of the high frequency of colorectal tumours (31.5%) compared to other types. The non-colorectal subgroup included melanoma, sarcoma, and others (germ cell, head and neck, breast, urological, gynaecological, thyroid and other).
Many studies have reported a long DFI as being a favourable prognostic factor of survival [5, 13]. In a recent meta-analysis of renal cancer patients with pulmonary metastases, both the synchronous metastases and a short DFI were associated with poor survival rates . In our study, a DFI1 < 12 months did not have any correlation with prognosis.
Lymph node dissection was realized in 22.2% of cases and only nine patients (5.6%) presented hilar or mediastinal lymph node involvement, which was correlated to worse survival rate (HR 3.42, 95% CI 1.03–11.41, p = 0.04). While survival of pulmonary metastatic patients is affected by metastatic invasion of the lymph nodes, it remains unclear if systematic lymph node dissection during solitary PM brings any benefits in terms of local recurrence or survival . Lymph node dissection was not performed routinely for solitary peripheral lesions and was reserved for centrally located or larger lesions requiring an anatomical resection. Our rate of lymph node dissection is relatively low in comparison with other series, but does not seem to correlate to the survival rate in this group of patients and in the timeframe that we studied.
Our study presents several limitations, the first one being the retrospective single-center design with a small collective of patients. Next, our study included only patients who underwent a surgical resection of their single pulmonary metastasis. Other patients with a single pulmonary metastasis who were not treated by surgery were not included, thus creating a selection bias. However, our selection criteria mentioned this factor and 5-year survival and other outcomes were described only for included patients, namely those who underwent surgery. Another limitation is the variety of primary tumor types, thus inducing a heterogeneity of the studied population. However, we selected only the patients with a single pulmonary metastasis and reported the primary tumor types, which we stratified along clear lines. Moreover, the patients were included over a 15-year period, thus smoothing out influences on the prognosis that might be due to the evolution of systemic and radiologic therapies. It should be noted also that the exact 5-year survival figures could only be calculated on a fraction of the patient population (those treated until 2015).