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Surgery for NSCLC in the era of personalized medicine

Nature Reviews Clinical Oncology volume 10, pages 235–244 (2013)Cite this article

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Abstract

The discovery in 2004 of activating mutations in the EGFR gene opened the era of personalized medicine in thoracic oncology. Treatment with drugs that target EGFR typically results in dramatic tumour response compared with conventional chemotherapy in patients with non-small-cell lung cancer. Subsequently, newer driver oncogenes such as ALK, ROS1 and RET have been discovered. Nevertheless, surgery has become safer and less invasive in the past 10–15 years. In the era of personalized medicine, thoracic surgeons have to think about their evolving roles. In this article, we discuss four topics relevant to this issue. Firstly, the value of surgical specimens as opposed to biopsy specimens for further understanding tumour biology is discussed. Secondly, extended indication of surgery in the era of targeted therapy is considered. Thirdly, in clinical trials that examine neoadjuvant therapy in patients selected by appropriate biomarkers, the important role of surgeons is highlighted. Finally, the possibility of personalizing the surgical procedure itself according to lung cancer subtypes defined by biomarkers is reviewed.

Key Points

  • Non-small-cell lung cancer (NSCLC)—especially adenocarcinoma—can be subdivided according to the presence of mutated driver oncogenes (for example, EGFR and ALK), which are crucial to efficient treatment selection

  • Surgery for NSCLC has become considerably safer and less invasive since the advent of optical, stapling and energy devices and progress in perioperative management

  • Surgical specimens are valuable for studying the genetics of this cancer type, which was shown to have more genetic alterations and to be more heterogeneous than previously thought

  • Surgery can be an efficient measure of treating patients with acquired resistance to targeted therapy

  • Surgery combined with drug therapy given either postoperatively or preoperatively for patients selected by distinct biomarkers is an attractive approach that is being tested

  • Personalization using biomarkers of surgical procedures remains an important subject for future research

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Figure 1: Various classes of tumour heterogeneity in adenocarcinoma of the lung.
Figure 2: Phylogenetic relationships of the tumour regions as deduced from deep-sequencing analysis of renal cell carcinoma in two patients treated with everolimus.
Figure 3: Role of surgery in managing resistance in the treatment of lung cancer.

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Acknowledgements

We thank Helena A. Yu and co-authors for sharing their manuscript before publication, and Masahiro Tsuboi and Pasi Janne for their helpful comments.

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Authors and Affiliations

  1. Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan

    Tetsuya Mitsudomi

  2. Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Kenichi Suda

  3. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Yasushi Yatabe

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T. Mitsudomi researched the data for the article, and all authors made a substantial contribution to discussion of the content. T. Mitsudomi and K. Suda wrote the article, and all authors reviewed and edited the manuscript prior to submission.

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Correspondence to Tetsuya Mitsudomi.

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T. Mitsudomi receives honoraria from AstraZeneca, Boehringer-Ingelheim, Chugai, Roche and Pfizer. His department receives research funding from AstraZeneca, Boehringer-Ingelheim, Chugai, and Pfizer. The other authors declare no competing interests.

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Mitsudomi, T., Suda, K. & Yatabe, Y. Surgery for NSCLC in the era of personalized medicine. Nat Rev Clin Oncol 10, 235–244 (2013). https://doi.org/10.1038/nrclinonc.2013.22

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