Original Study
Survival Benefit of Palliative Local Treatments and Efficacy of Different Pharmacotherapies in Colorectal Cancer With Lung Metastasis: Results From a Large Retrospective Study

https://doi.org/10.1016/j.clcc.2017.12.005Get rights and content

Abstract

Background

For most colorectal cancer patients with initial lung metastasis (LM), the only suitable treatments are palliative, including palliative local therapy and pharmacotherapy. We investigated the role of palliative local treatments in prolonging survival and the efficacy of different pharmacotherapies.

Patients and Methods

After performing a medical record review of 2233 patients with metastatic colorectal cancer, 684 were identified as having LM. Their clinicopathologic characteristics, treatment patterns, and outcomes were analyzed retrospectively.

Results

For nonresectable initial LM, patients receiving palliative local therapy had significantly longer median progression-free survival (PFS) and overall survival (OS) than those treated with pharmacotherapy alone: PFS 16.1 months versus 7.4 months (P < .001) and OS 51.8 months versus 23.8 months (P < .001), respectively. Cox multivariate analysis confirmed the survival benefit induced by palliative local therapy. Chemonaive patients receiving single-agent fluoropyrimidine had shorter PFS and longer OS compared to oxaliplatin- or irinotecan-based doublets when used as first-line treatment (PFS 4.8, 7.4, and 7.3 months; and OS 28.7, 21.2, and 20.1 months, respectively); however, these differences were not statistically significant. The addition of targeted agents to cytotoxic drugs prolonged PFS (10.5 vs. 7.2 months, P = .005) but not OS (27.8 vs. 21.2 months, P = .454). Carcinoembryonic antigen level, LM-associated symptoms, extrapulmonary disease, and histopathologic type were independent pretreatment prognostic factors.

Conclusion

Local treatments of LM may confer a survival benefit in the palliative setting. First-line single-agent fluoropyrimidine may be used in patients with good prognosis.

Introduction

An increasing number of patients have been diagnosed with colorectal cancer (CRC) in the past few decades in China.1 Approximately 50% of the CRC patients will develop metastatic disease,2 among which 29% will have initial lung metastasis (LM).3 However, the characteristics of LM have not been well studied.4, 5

Although not based on well-designed randomized clinical trials, radical lung metastasectomy is the recommended treatment approach for resectable LM with good prognosis and no extrapulmonary disease.6, 7 Radiofrequency ablation and stereotactic body radiotherapy are alternative treatments in cases that are unsuitable for surgery.8, 9 Among the initial LM population, 10% were suitable for radical therapy, while others were only eligible for palliative pharmacotherapy with or without local therapy.3

Pharmacotherapy is frequently used in clinical practice, but few data are available regarding the efficacy of chemotherapy, with or without targeted therapy. Some early studies suggested a better response and longer survival with the FOLFOX regimen (5-fluorouracil/leucovorin plus oxaliplatin) compared to FOLFIRI (5-fluorouracil/leucovorin plus irinotecan), but the differences were not significant.10, 11 These studies were of great importance, but they failed to provide definitive recommendations on pharmacotherapy for LM. Moreover, the additional role of local therapy in the palliative setting has not been investigated.

We retrospectively investigated the characteristics of CRC patients presenting with initial LM, clarified the impact of palliative local treatments on survival, and explored the efficacy of chemotherapy with or without targeted agents.

Section snippets

Patients

A total of 2676 medical records of CRC patients who were treated in the Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, from January 1, 1996, through April 1, 2017, were reviewed. Of these, 2233 metastatic cases were identified, and among these, 731 patients were diagnosed with LM on the basis of chest computed tomographic scan or positron emission tomography–computed tomographic scan. LM was confirmed pathologically if necessary. After excluding the

Characteristics of LM

Overall, the number of patients diagnosed as having metastatic CRC (mCRC) has increased steadily over the past 20 years (Supplemental Figure 1 in the online version). Among the 684 patients included in the analysis of LM characteristics, 242 patients were identified as having isolated initial LM, 302 as having nonisolated initial LM, and 140 as having non–initial LM. The incidence of initial LM was higher in metastatic rectal cancer (32.5%, 304/934) than in colon cancer (18.5%, 240/1299).

Discussion

To our knowledge, no previous studies have investigated the epidemiology of LM in CRC patients in China. We found that there was a similar incidence of initial LM (24.4%) compared to a study in Italy (29.2%), and that the proportion of isolated LM among patients with initial LM was higher (46.4%, 140/302, vs. 37.7%, 154/409) in the Chinese population.3 Taking the increasing number of CRC patients1 and CRC-LM patients4 into consideration, LM has become a common diagnosis that many oncologists

Conclusion

The present study investigated the characteristics of LM in CRC. Palliative local treatment of LM was associated with longer OS than pharmacotherapy alone. Nonintensive first-line treatment with a single-agent fluoropyrimidine could be used in patients with good prognosis to improve quality of life without impairing survival. These encouraging results should be further investigated in prospective randomized clinical trials. Further, molecular profiling of CRC might provide new insights into the

Disclosure

The authors have stated that they have no conflict of interest.

Acknowledgment

We thank LetPub (http://www.letpub.com/) for English-language editorial help.

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