The most important aspect of lung cancer management is determining the stage of disease. There are several stages:

  • Localised disease that can be treated surgically
  • Localised disease that is unable to be resected due to comorbid patient conditions
  • Locally advanced disease (IIIA, IIIB) that can be treated with chemoradiotherapy or neoadjuvant therapy
    • This includes potentially resectable disease, which is somewhat department specific based on availability of surgical staff
    • Potentially resectable disease includes a small group of patients with IIIA disease who have limited mediastinal node involvement
    • The remaining patients in stage III are not surgical candidates and are treated with chemoradiotherapy or palliative therapy
  • Metastatic disease or other incurable stage of disease

Important factors in the management decision are:

  • Patient factors (fitness, ECOG)
  • Tumour factors (type, location, stage)
  • Treatment options (surgery, RT, CT, targeted, palliative).


  • 40% of patients present with metastases
  • 30% present with locally advanced disease
  • 30% present with lung-limited disease

Surgically Resectable Disease

This includes T1-3 with negative or N1 nodes in patients with sufficient respiratory reserve to survive the procedure and aftermath. Some patients with a single N2 node may be operable; however those with multiple N2 nodes are unable to have a complete surgical resection and should proceed with chemoradiotherapy (if tolerable).
Adjuvant therapy depends on margin status:

  • Patients with clear margins and T2 or greater disease should receive adjuvant chemotherapy (using cisplatin / vinorelbine)
  • Patients with clear margins and IIIA disease (N2) should have adjuvant chemotherapy. The use of radiotherapy in this group is controversial as it has not been associated with a survival benefit.
  • Patients with positive margins and T1/T2 and N0 should have re-resection if feasible or radiotherapy
  • Patients with positive margins and nodal disease should consider chemoradiotherapy

Adjuvant Therapies


Radiotherapy following surgical resection is only considered when:

  • There is mediastinal lymph node involvement, or
  • There are positive margins

The PORT lung study demonstrated worse survival in patients with stage I and II disease who received radiotherapy. The findings in patients with stage N2 disease were equivocal. The standard dose is 50 Gy in 25 fractions unless there is macroscopic residual disease. Unlike definitive chemoradiotherapy for stage IIIB disease, adjuvant radiotherapy aims to cover the nodal regions of the mediastinum electively (rather than only involved nodes).


Systemic therapy has been shown to improve survival by 5% at 5 years. This only applies to stage II and III patients. Stage IA patients suffer detriment from systemic therapy whereas IB patients have conflicting evidence; chemotherapy is usually recommended given the poor prognosis in this group. In general, cisplatin + vinorelbine is used. There is no strong evidence for use of EGFR inhibitors in the adjuvant setting.


For medically fit patients with stage IIIA disease or less, and who are able to tolerate surgery based on lung function and other performance factors, should undergo lobectomy/pneumonectomy.

  • All patients except those with IA disease should be considered for systemic therapy
  • Patients with IIIA or IIIB disease, with unexpected N2 nodes or positive margins, should consider radiotherapy to the region of positive margin and the mediastinum.

Superior Sulcus Tumours (Pancoast's Tumour)

These tumours present with brachial plexopathy and Horner's syndrome (anhydrosis, pupil dilatation and ptosis on the affected side). Radiotherapy has an established role in the management of these tumours, and more recently chemoradiotherapy has been shown to provide even greater benenfits pre-operatively. Staging of the tumour is particularly important:

  • T stage (either T3 or T4); T4 lesions typically have worse outcomes
  • N stage - N1 disease is treated with surgery whereas N2 lesions are not. Patients with ipsilateral supraclavicular nodes (N3) may still be resectable if N1 and N2 stations are not involved.

Usual management for IIIA disease (T3-T4 N0-1) is:

  • Pre-operative chemoradiotherapy (45 Gy in 25# with concurrent cisplatin/etoposide days 1-3 and 29-31).
  • Surgical resection at 4-6 weeks.

This approach gives 5 year survival of 50% and good local control rates. There is no randomised evidence for chemoradiotherapy but this technique compares favourably with historical controls.
Patients with N2 disease, extensive brachial plexus or vertebral involvement, or involvement of subclavian vessels, are usually considered unresectable and should be treated with definitive chemoradiotherapy (see locally advanced disease below).

Resectable but Medically Unfit

This is a small but important group of patients, particularly for the radiation oncologist. The introduction of stereotactic body radiotherapy has been most important for this group of patients who are presented with a potential curative option.
Standard of care currently is external beam radiotherapy, delivering a dose of 60 Gy in 30 fractions. This provides 5 year survival of ~ 20%.
Stereotactic radiotherapy has been evaluated predominately by the RTOG. A dose escalation study found that 60 Gy in 3 fractions could be delivered stereotactically to tumours < 5 cm. Complications arise from centrally located tumours (11 times more likely, and a contraindication to standard stereotactic treatment) or from lesions abutting the chest wall (fractures/pain, 10-15% risk) or brachial plexus (tolerance 26 Gy in 3#), although these are typically less severe. There are ongoing studies examining more fractionated stereotactic treatments (eg. 50 Gy in 5#) for central tumours.
In the US and some European countries, early results from stereotactic treatments have seen it become standard of care for patients with T1 and T2a tumours that are > 2 cm away from the trachea, main and lobar bronchi. This is supported by retrospective observations of improving lung cancer survival rates since the introduction of stereotactic therapies. TROG is running the CHISEL study examining the outcomes of stereotactic vs conventional RT for Stage I/II lung cancers. This may establish the role of stereotactic RT in Australia.

Locally Advanced Disease

Potentially Resectable Disease

There is some interest in the use of neoadjuvant therapies to make borderline resectable cases surgically resectable. The evidence for this is conflicting; small series have shown improvements in outcomes but large studies comparing neoadjuvant versus adjuvant approaches have shown mixed results. This approach is favoured for tumours with limited N1 or N2 disease in the US; I have rarely seen neoadjuvant therapy given in Australia and when it has been used it has been ineffective.

Definitive Chemoradiotherapy

This historical approach to IIIA/IIIB unresectable disease was radiotherapy which was associated with some improvement in median survival. When chemotherapy became a viable option for lung cancer treatment, sequential therapy with cisplatin/etoposide was demonstrated to be superior to radiotherapy alone (CALBG trial). An RTOG study (9410) compared concurrent cisplatin/vinorelbine with sequential therapy, and demonstrated a further median survival advantage (17 vs 14 months). Unlike sequential therapy, there appears to be a long term survival advantage (15% vs 10%).
Concurrent chemoradiotherapy is therefore the favoured treatment in modern times for stage IIIA/B disease (30% local control, 16% 3 year survival). This involves:

  • Treatment of gross tumour to 60 Gy and microscopic disease to 50 Gy; dose escalation up to 75 Gy is preferred but difficult given tissue tolerances
    • Radiotherapy is delivered to all sites of gross disease (primary + nodes); elective nodal irradiation is not associated with improved outcomes
  • Treatment should be administered concurrently with a cisplatin based chemotherapy regimen (either with etoposide or vinblastine)

There is no evidence for consolidation therapy or surgery after chemoradiotherapy.
In patients unable to tolerate concurrent chemoradiotherapy, sequential therapy can be used but is associated with poorer outcome; it is still better than radiotherapy alone.

Definitive Radiotherapy

In patients unfit for chemoradiotherapy, radiotherapy alone provides a remote chance of cure (5%). The dose is similar (60 Gy in 30#).

Altered Fractionation

Hyperfractionation, accelerated raidotherapy, and combined hyperfractionation and accelerated radiotherapy (CHART) have been evaluated in numerous trials. Although individual series show potential benefit, meta-analysis of altered fractionation studies have shown only modest benefits (survival increased by 1 month) at the cost of significant oesophageal toxicity. Especially in the era of chemoradiotherapy, interest in altered fractionation has waned.

Palliative Radiotherapy

A number of patients will not be able to receive chemoradiotherapy or definitive radiotherapy due to poor lung function or extent of tumour relative to normal lung. Symptoms can be controlled by a more tolerable dose of radiotherapy (30 Gy in 10#). The timing of radiotherapy was compared in a randomised trial; there was no advantage in survival or symptom control by administering radiotherapy while patients were asymptomatic.

Role of Prophylactic Cranial Irradiation in NSCLC

Prophylactic Cranial Irradiation (PCI) is commonly used in small cell lung cancer, where it has a demonstrable impact on overall and disease-free survival for limited stage disease. The prognosis for non-small cell lung cancers with a similar stage is typically very poor despite treatment of the primary tumour, and historically there has been no evidence for use of PCI in NSCLC.
A pair of studies by Gore et al in 2011 demonstrated (for stage IIIA/IIIB disease) that PCI led to:

  • A reduction in brain metastases at 1 year
  • No improvement in overall survival in 1 year
  • Significant reduction in memory at 1 year
  • No change in cognition (measured by MMSE) at 1 year

They have suggested that PCI should not be routinely recommended.

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