Unlike non-small cell lung cancer, surgery is rarely used in the management of small cell lung cancer. This is due to the nature of small cell lung cancer to disseminate throughout the body at an early stage, rendering local treatment of the primary tumour less important than control of the entire disease process at once.

Management of Limited Stage (TAny NAny M0) Disease

Limited stage disease is potentially curable using chemoradiotherapy, and represents 1/3rd of patients with small cell lung cancer. It is important to accurately stage this group of patients, to exclude those patients who may not benefit from the more intensive therapy associated with this treatment (see Diagnosis). Despite the term 'limited' nearly all patients have microscopic levels of metastatic disease, necessitating the use of chemotherapy as the primary treatment.

Chemotherapy Alone

Chemotherapy is the main treatment for small cell lung cancer. Without treatment most patients quickly succumb to their disease. About 80-90% of patients with limited disease respond to chemotherapy but relapse generally occurs with median time of 8 months; local recurrence occurs in 90% of patients treated with chemotherapy alone. This led to the use of radiotherapy to local disease in an effort to improve local control and survival.
The most common chemotherapy regimen is carboplatin and etoposide. This is also used in concurrent therapy.


Radiotherapy was shown in two large meta-analyses of early studies to:

  • Improve local control (from 10% to 50%)
  • Improve survival (from 15% to 20% at 2 years)

Aspects of radiotherapy delivery have been evaluated in numerous trials.


Several studies have sought to identify the optimal dose for radiotherapy. Phase 1 dose escalation studies have shown that patients can tolerate > 70 Gy without excessive toxicity (which seems a bit crazy to me given known lung tolerances to radiation). Local control improves to about 96% in patients who receive doses of 60 Gy. However, these higher doses have become less common since altered fractionation schedules were introduced.


Accelerated fractionation has been explored in several studies.  The essential study for small cell lung cancer is the Turisi study from 1999.  This evaluated 45 Gy delivered concurrent with the 1st cycle of chemotherapy either as single dose or two doses per day.  Survival in the BD arm was significantly improved (25% at 5 years compared to 15% in the single-fraction per day arm).  These were the best results ever seen with radiotherapy and small cell lung cancer and has become standard of care for small cell lung cancer.  How the regime compares to 60 Gy in 30 fractions is not known.


Modern treatment targets the post-chemotherapy GTV and the pre-chemotherapy involved nodes as a CTV. This was established by a SWOG study which randomised patients between this more limited field and the previously conventional pre-chemotherapy volume; similar outcomes were seen in terms of disease control but toxicity was worse. Other trials which have used reduced field sizes show an out-of-field recurrence rate of < 10%.


Timing of radiotherapy includes:

  • Sequential vs concurrent chemoradiotherapy
  • Early vs late delivery of radiotherapy
Timing of Radiotherapy and Chemotherapy Delivery

The randomised JCOGS study compared sequential vs concurrent chemoradiotherapy. It demonstrated trends towards improved survival (p = 0.1) with concurrent treatment which is now used commonly.

Timing of Radiotherapy Delivery within Chemotherapy Course

The next direction of research was when within the delivery of chemotherapy the radiotherapy should be delivered. Three randomised studies demonstrate improved survival when radiotherapy is delivered with the first or second cycle of chemotherapy. This is now the standard of care.

Standard Approach to Limited Stage Small Cell Lung Cancer

Patients who are fit enough for treatment should receive chemoradiotherapy (meta-analysis) as it improves survival by 5%.

  • Radiotherapy dose should be 45 Gy in 30 fractions (Turisi protocol) or 60 Gy in 30 fractions as this provides the best rates of overall survival / local control
  • Radiotherapy volume should be the post-chemotherapy GTV and the pre-chemotherapy nodes included as CTV (randomised studies) as recurrences outside this volume are rare
  • Radiotherapy should be delivered concurrently with chemotherapy (randomised trial), and with the 1st or 2nd cycle of chemotherapy (multiple randomised trials eg. NCIC, JCOGS)

Prophylactic Cranial Irradiation (see below) should be offered to all patients who achieve a complete response as it improves overall survival and halves the risk of brain metastases developing at 2 years.

Management of Extensive Stage (TAny NAny M1) Disease

Patients with extensive stage disease should be treated with chemotherapy alone. There is no established role for radiotherapy to the primary site except for palliation of symptoms. Chemotherapy protocols are similar to those for limited stage disease.

Prophylactic Cranial Irradiation

Small cell lung cancer is one of the few sites where PCI has been shown to be beneficial. It is only used when patients have undergone a complete response to induction chemotherapy.

Limited Stage Disease

PCI is well established in the treatment paradigm for limited stage disease. There are numerous randomised studies and two meta-analyses that demonstrate a 5% improvement in overall survival (to 20%) at 3 years.

Extensive Stage Disease

Extensive stage disease is slightly more controversial. There is a single randomised trial that demonstrates, for patients who have had a response to chemotherapy:

  • An improvement in 1 year survival from 13 to 27%
  • Median survival 5.4 vs 6.7 months
  • Much lower rates of brain metastases (15 vs 40%)

This is often cited as evidence for use of prophylactic cranial irradiation in this patient population.
Notably, this trial included patients who had any response to chemotherapy, not a complete response.

Radiotherapy Delivery

The patient is simulated in a thermoplastic mask with the head in a neutral position. A CT is performed from the vertex to the mid neck.
Opposed lateral fields are used to cover the cranial vault.
The typical dose is 25 Gy in 10 fractions. The dose was evaluated in a randomised trial which compared 25 Gy in 10 # to 36 Gy in 20 #; survival was worse in the higher dose arm and outcomes were otherwise similar.


Patients receiving whole brain radiotherapy suffer from early and late toxicity.
Early toxicities include fatigue, nausea, vomiting, headaches, skin reaction and hair loss.
Late toxicities are difficult to characterise and there is minimal data. PCI typically uses a relatively low dose so serious toxicities (eg brain necrosis, optic pathway damage etc) are rare. Cataracts may occur with any radiotherapy to the head. There is minimal data on the long term cognitive effects following PCI in small cell lung cancer, and causes may be multifactorial (pre-existing, chemotherapy related, tumour related, radiotherapy).

Focused Management