A retrospective analysis using the National Cancer Registry in The Netherlands has found that patients with metastasis to a single organ have a better prognosis compared with patients with metastasis in multiple organs, particularly when they also have a low TN status [Hendriks LE et al. Ann Oncol. 2015]. The analysis was conducted in patients with stage IV non–small cell lung cancer (NSCLC) to evaluate the prognostic effect of the number of organs with metastasis, the specific organs with metastasis, as well as the local disease status, and it was presented by Lizza E. Hendriks, MD, Maastricht University Medical Center, Maastricht, The Netherlands.

A total of 11 094 patients with histologically confirmed NSCLC entered into the database between January 2006 and December 2012 were included in this analysis. Study exclusions included a malignancy within the previous 5 years, stage IV disease according to TNM6 based solely on pulmonary metastasis, no documented metastasis sites or TNM classification, and no survival data. Their mean age was 65 years; 60% were men; and 73% had adenocarcinoma (AdC). Staging of the N compartment was conducted using clinical data, including histology and imaging studies (eg, computed tomography and positron emission tomography [PET]).

Metastasis to a single organ was identified in 5676 (51.2%) of patients, and bone was the most frequent site of metastasis (41.3%) in the overall cohort. Bone, brain, pleura, and lymph node metastases were more common in patients with AdC compared with squamous cell carcinoma. The investigators found that patients with single-organ metastasis were more likely to be older and have squamous NSCLC and a low TN status.

The median overall survival (OS) was significantly higher in patients with disease classified as TNM7 with intrathoracic metastasis (M1a) compared with distant metastasis (M1b) and compared with patients with TNM6 stage IV NSCLC (Table 1).

In patients with metastasis to only 1 organ, compared with multiple organs, the OS was significantly higher (Table 2). The risk for a shorter OS increased as the number of organs with metastasis increased (HR, 1.3 for 2 vs 1 organ; HR, 1.9 for ≥ 3 vs 1 organ; P < .001 for both). The multivariable analysis showed that OS was significantly better in patients who were younger (< 50 years) and those who were women, as well as those who had AdC, TNM7 M1a cancer, metastasis to 1 organ, and limited local disease.

The OS was longer in patients whose disease was staged using 18-fluoro-deoxyglucose PET imaging compared with the total cohort (Table 2). As the number of organs with metastasis increased, the risk of a shorter OS also increased for this subgroup (HR, 1.4 for 2 vs 1 organ; HR, 2.2 for ≥ 3 vs 1 organ; P < .001 for both).

Single-organ metastasis plus a low TN status, compared with single-organ metastasis with a high TN status, conferred a longer OS in the total cohort (8.5 vs 6.5 months; HR, 1.4; P < .001) and in the 18-fluoro-deoxyglucose PET cohort (11.6 vs 8.2 months; HR, 1.6; P < .001). Moreover, it also conferred a longer OS in the subgroup of patients who were receiving active anticancer treatment. In these patients, the median OS was 10.4, 7.3, and 5.7 months for metastasis to 1, 2, or ≥ 3 organs, respectively; the HR was 1.4 and 1.9 for metastasis to 2 vs 1 organ and ≥ 3 vs 1 organ (P < .001).

The TN status also predicted survival, with a median OS of 13.7 vs 9.9 months for patients with a low vs high TN status (HR, 1.5; P < .001). In patients with single-organ metastasis, the OS was better only with intrathoracic M1a and extrathoracic lymph node metastasis, which included only current M1b lymph nodes. The HR was 0.6, 0.8, and 0.8 for pulmonary, pleural, and extrathoracic lymph node metastasis, respectively.

In conclusion, the prognosis was better in stage IV NSCLC patients who had metastasis to only a single organ and a low TN status, who had metastasis limited to the intrathoracic region, and who were receiving active anticancer treatment. In the patients with distant metastasis, only those with an extrathoracic lymph node metastasis (ie, lymph nodes currently staged as M1b) had a better OS.