Patterns and risks of postoperative recurrence in completely resected EGFR-mutant non-small cell lung cancer: prognostic significance of routine immunohistochemical markers

Jianjiao Ni; Tiantian Guo; Yuan Li; Xi Yang; Yida Li; Liqing Zou; Li Chu; Xiao Chu; Shuyan Li; Luxi Ye; Yawei Zhang; Zhengfei Zhu

doi:10.21037/tlcr.2019.12.02

Patterns and risks of postoperative recurrence in completely resected EGFR-mutant non-small cell lung cancer: prognostic significance of routine immunohistochemical markers

Transl Lung Cancer Res. 2019 Dec;8(6):967-978. doi: 10.21037/tlcr.2019.12.02.

Authors

Jianjiao Ni^{1

2

3}, Tiantian Guo^{1

2

3}, Yuan Li^{2

3

4}, Xi Yang^{1

2

3}, Yida Li^{1

2

3}, Liqing Zou^{1

2

3}, Li Chu^{1

2

3}, Xiao Chu^{1

2

3}, Shuyan Li^{1

2

3}, Luxi Ye^{1

2

3}, Yawei Zhang^{2

3

5}, Zhengfei Zhu^{1

2

3}

Affiliations

¹ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
³ Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China.
⁴ Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
⁵ Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Abstract

Background: Recent studies indicate that EGFR-mutant non-small cell lung cancer (NSCLC) is a heterogeneous disease with varying prognosis. In order to design an optimized surveillance strategy and identify potential candidates for adjuvant therapy, the patterns and risks of postoperative recurrence in completely resected EGFR-mutant NSCLC should be investigated, which are currently largely unknown.

Methods: Consecutive patients with curatively resected EGFR-positive NSCLC receiving standard adjuvant chemotherapy without EGFR tyrosine kinase inhibitors (TKI), with or without adjuvant radiotherapy, from January 2007 to December 2017 in our cancer center, were retrospectively reviewed. Prognostic significance of ten routine immunohistochemical (IHC) markers were examined.

Results: After a median follow-up of 32 (range, 5-122) months, disease recurrence occurred in 197 (37.1%) of the 531 enrolled patients. The frequencies of thoracic recurrence, brain recurrence, bone recurrence, abdominal recurrence and neck recurrence, were 69.0%, 20.8%, 20.8%, 7.1% and 6.6%, respectively. Using the Cox regression model, tumor size, Ki67, CK20, and N stage were identified as independent predictors of overall recurrence. A nomogram predicting the 1-, 2-, and 3-year cumulative rate of overall recurrence was then developed and internally validated, with a bias-corrected C-index of 0.723 (95% CI, 0.675 to 0.771) and a small extent of "over-fitting" (0.8%). Risk factors of site-specific recurrence were also discovered. Additionally, using competing risk analyses, N stage, lymphovascular invasion (LVI) and CK5/6 were found as independent predictors of loco-regional recurrence. Among patients with N2-positive disease (n=91), adjuvant radiotherapy tended to prolong disease free survival (DFS) (P=0.067), but not overall survival (OS) (P=0.271).

Conclusions: This study provides the proof of concept of using routine IHC markers, along with common clinical-pathological parameters, in predicting postoperative recurrence among completely resected EGFR-mutant NSCLC. Adjuvant radiotherapy may improve DFS, but hard to prolong OS in N2-positive EGFR-mutant NSCLC without further biomarker-guided patients' selection.

Keywords: EGFR mutation; Non-small cell lung cancer (NSCLC); adjuvant therapy; immunohistochemical markers; recurrence.