What is the clinical benefit of the addition of surgery to definitive chemoradiotherapy in stage IIIA (N2) NSCLC?

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What is the clinical benefit of the addition of surgery to definitive chemoradiotherapy in stage IIIA (N2) NSCLC?

Introduction

Jutta's info icon.png 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.

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Stage III NSCLC encompasses a broad spectrum of disease extent from tumour involving a single nodal station identified only postoperatively despite extensive pre-operative staging to involvement of multiple contralateral mediastinal nodes and supraclavicular nodes appreciated on clinical examination. In patients with clinically equivocal involvement, pathological confirmation of nodal status should be made if it will influence management options.

The decision as to operability should be made in a multidisciplinary setting.

Patients with Stage III NSCLC may be deemed inoperable because of patient factors (the patient’s respiratory function or co-morbidities may preclude operative intervention or the patient may choose not to proceed with surgery) or tumour factors (the extent or location of gross disease might make surgical resection technically impossible, for example left sided tumours with mediastinal nodes to the right of the aorta, N3 nodal involvement and most T4 tumours).

In the absence of other factors precluding surgery, patients with N1 disease should be considered for surgery. Patients with confirmed N2 disease should not be treated by surgery as the sole modality, but resectable cases may be considered for a multimodality approach. There is no consensus on the distinction between resectable and unresectable N2 disease. Factors influencing assessment of resectability include nodal size, number of stations involved, extracapsular extension and involvement of the recurrent laryngeal nerve.

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.







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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.




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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 recommendationQuestion mark transparent.png Grade
Unselected patients with biopsy confirmed stage IIIA (N2) disease are best treated with chemoradiotherapy alone.

Last reviewed December 2015

B


Practice pointQuestion mark transparent.png

Induction chemoradiotherapy followed by surgery in selected patients with cIIIA (N2) disease is feasible and improves progression-free survival. Provided the patient does not require a pneumonectomy, the addition of surgery may improve overall survival.
Last reviewed December 2015

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References

  1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer. NCCN 2011;Version 3 Abstract available at http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.
  2. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17873172.
  3. 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. 4.0 4.1 4.2 Albain KS, Swann RS, Rusch VW, Turrisi AT 3rd, Shepherd FA, Smith C, et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet 2009 Aug 1;374(9687):379-86 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19632716.

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Appendices

Further resources

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