No discussion of pulmonary metastasis would be complete without discussing Pastorino’s study from the International Registry of Lung Metastases. Between 1991 and 1995, 5,290 patients were enrolled from 18 centers in nine counties across Europe and America, dating back to 1945, with Memorial Sloan Kettering providing the largest series, 1,075 patients. Forty-three percent of metastases were from an epithelial tumor and 42 % from sarcoma. This study demonstrated an actuarial 5-year survival of 36 % across all tumor types, after complete resection. Five-year survival after incomplete resections was only 13 %. Multivariate analysis identified germ cell histology, disease-free interval of 36 months or more and a single metastasis as favorable prognostic factors (Table 21.2). Metastases to hilar/mediastinal lymph nodes was not routinely or systematically performed and therefore, fell out of analysis (<9 % of patients) [5, 6].

Fifty-three percent of patients had a recurrence, with a median time to recurrence of 10 months (8 months for sarcoma and 12 months for epithelial tumors). Intra-thoracic recurrence was common in sarcoma (66 %) whereas extra-thoracic recurrence was common in melanoma (73 %). A longer 5-year survival of 44 % occurred after a second metastasectomy. Germ cell tumors were outliers. These tumors had multiple metastases in 57 % of patients and a 5-year survival of 68 %, much higher than the 30 % seen with other tumors. They only accounted for seven percent of tumors in the registry, however.

As part of the European Society of Thoracic Surgery Workgroup on pulmonary metastasis, Pfannschmidt reviewed studies concerning non-seminomatous germ cell tumors. They reported an overall survival between 73 and 94 %. First line therapy for this malignancy is chemotherapy, which is highly effective. Surgery has a role in diagnosis of residual nodules, salvage therapy for those that become unresponsive and resecting benign enlarging teratomatous elements. Often residual nodules are only necrosis and the decision to resect may not always be clear. Salvage surgery still has a relatively good 42 % 5-year survival [7].

Colorectal cancer is the most common of the tumors that metastasize to the lungs, though very few patients come to resection. Wade evaluated outcomes of metastatic colorectal cancer in the Veterans Administration hospital system and found that 12 % (2,659/22,715) of patients undergoing colectomy develop pulmonary metastases and of these, only 2.9 % (76/2,659) had pulmonary resection [8]. Fiorentino, as part of a group planning for a clinical trial, analyzed 51 papers of colorectal pulmonary metastases with series having mid-point dates from 1965 to 2000, 3,504 patients. Twenty-five papers gave 5-year survival data after a single pulmonary metastasectomy allowing these authors to estimate a 50 % ± 5 % 5-year survival. They found that elevated CEA correlated with shorter survival and that increasing numbers of patients over the 35 years were undergoing metastasectomy who had bilateral disease or previous pulmonary and hepatic metastasectomy. They concluded that, without a control group, no judgment can be made as to whether surgery actually prolongs survival and performing further small, uncontrolled studies is without merit [9]. This resonates with an earlier systematic review performed by Pfannschmidt wherein predictors of survival were not pooled as disease-free interval and number of pulmonary metastases were significant on multivariate analysis in only two and five of nineteen studies, respectively [10].

Gonzalez and Salah performed more recent analyses. Gonzalez performed a meta-analysis of all studies from 2000 to 2011, with more than 40 patients each; 25 studies were included, totaling 2,925 patients. Seventy-five percent of patients had a solitary pulmonary metastasis; 5-year survival for an R0 resection varied widely from 27 to 68 %. Hazard ratios (HR) were calculated for significant prognostic factors that came from a variable number of studies included: higher number of metastases—HR 2.04 (95 % CI 1.74–2.4); elevated CEA—HR 1.91 (95 % CI 1.57–2.32); positive mediastinal/hilar lymph nodes—HR 1.65 (95 % CI 1.38–2.02), disease free interval—HR 1.59 (95 % CI 1.27–1.98). Previous liver metastases resection did not portend a poor survival [11].

Salah collected data from eight studies (the number they were able to collect data from) published 2000 to 2012 with more than 20 patients/study, R0 resections and isolated lung metastases, totaling 927 patients. Calculated 5-year survival was 54.3 %. Multivariate analysis revealed similar independent prognostic factors: two or more metastases—HR 2.05 (95 % CI 1.58–2.65), pre-thoracotomy CEA > 5 ng/ ml—HR 1.84 (95 % CI 1.43–2.38); disease-free interval < 36 months—1.39 (95 % CI 1.03–1.86). The authors divided patients into low, intermediate and high risk groups based on the presence of 0–1, 2 or three risk factors, giving 5-year survivals of 68.2, 46.4 and 26.1 % respectively [12]. More complex nomograms for survival after resection of colorectal cancer pulmonary metastasis using these variables exist with external validation [13].

Fiorentino presented a provoking math “thought experiment” demonstrating the possibility of elevated survival data being due to selection bias. Given a 5 % 5-year survival in stage IV disease, 50 patients out of 1,000 patients would be alive at 5 years. If we exclude half of patients over three separate rounds of selection for surgery based on favorable prognostic factors and are able to retain the 50 long-term survivors in the surgery group, we get 50/500, 50/250, 50/125 with 10, 20 and 40 % 5-year survivorship [14].

Treasure’s group systematically reviewed all English language articles published 1990 and 2011 evaluating outcomes of pulmonary resection for bone and soft tissue sarcoma metastases with over 20 patients/study. A total of 115 studies were found but only 18 studies qualified for analysis, totaling 1,357 patients. The proportion of sarcoma patients who develop pulmonary metastasis varied from 18 to 50 %, while the proportion of patients with pulmonary metastasis who had metastasectomy ranged from 5 to 88 %. The population base from which patients derived varied considerably between studies. Five-year survival for bone sarcoma was calculated as 34 % (range 23–38 %) and for soft tissue sarcoma 25 % (range 18–44 %). Though not directly compared, cancer registry 5-year survival data for all stage four patients is given for perspective: bone 25 %, soft tissue sarcoma 15 %. Prognostic factors were not addressed and much of the paper discusses the issue of survivor bias and inappropriate interpretation of data [15].

Ruiterkamp’s recent extensive review of stage IV breast cancer included a review of seven studies regarding metastasectomy for breast cancer lung metastasis covering patients treated 1960–2007. Five-year survival rates ranged 31–54 % with recurrence rates of 60 % (13–28 % intra-thoracic). Prognostic factors for survival were disease-free interval > 36 months, < four metastases, hormone receptor positive tumor, stage I cancer and small size of metastasis. One of the included studies compared surgical to non-operated patients with less than four metastases. Non-operated patients were either not offered or refused surgery. Follow-up was 50 months. Four-year survival was 82.1 % in the surgery group and 31.6 % in chemotherapy/hormonal therapy only group. Though all patients had limited metastatic disease, 73 % of the surgery group and only 33 % of the medical group has solitary pulmonary nodules [16]. Diaz-Canton studied the MD Anderson experience of patients with metastatic breast cancer isolated to lung and treated only with chemotherapy (88 patients). Disease burden was quantified as minimal, moderate or extensive with long-term survivors in each category. Thirty-seven percent of patients had a complete response. While 5- and 10-year survivals were 15 % and 9 %, respectively, four of ten patients with minimal disease were alive at 10 years [17].

Resection of pulmonary metastasis from melanoma has a lower survival. Caudle reviewed six studies reporting 5-year survivals between 20 % and 33 %. Incomplete resection has a similar survival to those not undergoing resection, 0–4 % 5- year survival. Prognostic factors included: complete resection, disease free interval > 36 months, two or fewer nodules, prior response to chemo/immunotherapy and no nodal disease [18].