What is the clinical benefit of the addition of surgery to definitive chemoradiotherapy in stage IIIA (N2) NSCLC?
What is the clinical benefit of the addition of surgery to definitive chemoradiotherapy in stage IIIA (N2) NSCLC?
Introduction
Defining operable and inoperable disease in stage III
The management of Stage III NSCLC has been divided into sections dependent on whether the disease is considered operable or inoperable at the time of diagnosis.
Definitive chemoradiotherapy (CRT) is a standard of care in clinical N2 NSCLC.[1][2][3] Theoretical improvements in local control with the addition of surgery must be balanced against the increased morbidity and mortality of surgery.
Induction chemoradiotherapy and surgery: Randomised controlled trials
Albain et al (RTOG 93-09 / Int 139)[4] randomised 396 patients with operable T1-3, biopsy proven N2, M0 NSCLC to concurrent chemotherapy (cisplatin and etoposide) and daily radiotherapy (45 Gy) followed in the absence of progression by either surgical resection or continued radiotherapy (16 Gy). Both groups received two cycles of consolidative chemotherapy. Patients had baseline FEV1 > 2L or PPO FEV1 > 800 ml on quantitative V/Q, good performance status and less than 10% weight loss with in the previous three months.
The trial was well powered (93%) to detect a 10% difference in the primary end point of overall survival and analysed on an intention to treat basis. There was no significant difference in overall survival between the two treatment groups (HR = 0.87, 95% CI: 0.69 - 1.10 [P = 0.24]). Progression-free survival was improved in the surgical arm (HR = 0.77, 95% CI: 0.62 - 0.96 [P = 0.017]). At 5 years, 22% of participants in the CRT/surgery arm were disease-free compared with 11% of participants in the CRT arm.
Eight percent of participants died from treatment related causes in the CRT/surgery group compared with 2% in the CRT group. The majority of treatment-related deaths in the surgical group occurred after pneumonectomy (14 out of 16), with only one death occurring after lobectomy. Post hoc subgroup analysis suggested there may be an improvement in overall survival in those who are judged to be suitable for lobectomy at the outset of treatment.
Evidence summary and recommendations
Evidence summary | Level | References |
---|---|---|
CRT (45 Gy) followed by surgery compared to definitive CRT (61 Gy) in unselected patients with cIIIA (N2) NSCLC does not result in improved overall survival.
Last reviewed December 2015 |
II | [4] |
CRT (45 Gy) followed by surgery compared to definitive CRT (61 Gy) in unselected patients with cIIIA (N2) NSCLC results in improved progression free survival.
Last reviewed December 2015 |
II | [4] |
Evidence-based recommendation![]() |
Grade |
---|---|
Last reviewed December 2015 |
Unselected patients with biopsy confirmed stage IIIA (N2) disease are best treated with chemoradiotherapy alone.
B |
References
- ↑ National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer. NCCN 2011;Version 3 Available from: http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.
- ↑ Robinson LA, Ruckdeschel JC, Wagner H Jr, Stevens CW, American College of Chest Physicians. Treatment of non-small cell lung cancer-stage IIIA: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007 Sep;132(3 Suppl):243S-265S Available from: http://www.ncbi.nlm.nih.gov/pubmed/17873172.
- ↑ Australian Cancer Network Management of Lung Cancer Guidelines Working Party. Clinical Practice Guidelines for the Prevention, Diagnosis and Management of Lung Cancer. The Cancer Council Australia and Australian Cancer Network, National Health and Medical Research Council Canberra 2004.
- ↑ 4.0 4.1 4.2 .