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. 2023 Jun 30;30(7):6289–6315. doi: 10.3390/curroncol30070465

Table 1.

Summary of Recommendations on the Management of ES-SCLC.

Recommendations for Pathological Assessment
1. SCLC should be diagnosed according to the most recent World Health Organization criteria.
2. If available, tissue biopsies and cytology samples should be correlated to ensure accurate diagnosis of SCLC.
3. The presence of any adenocarcinoma component in a C-SCLC or a new diagnosis of SCLC in a non-smoker should prompt molecular testing for driver mutations for the consideration of targeted therapy.
4. Currently there is no routine predictive biomarker available for SCLC and biomarker testing is not recommended in routine clinical practice.
Recommendations for Diagnosis and Staging
5. A complete diagnostic/staging workup should include a physical examination, hematologic and biochemical laboratory profiles, CT chest, abdomen, and pelvis, as well as MRI or CT imaging of the brain.

  1. MRI of the brain is preferred over CT to detect asymptomatic brain metastases.

  2. PET can be considered when ambiguity exists regarding the diagnosis of limited-stage SCLC (LS-SCLC) vs. ES-SCLC.
    1. PET is only relevant if the disease outside the chest has not been documented.
    2. If PET is not available, a bone scan may be used to identify bone metastases.
6. Prompt treatment initiation is of greater importance than complete staging once the extensive disease is evident due to the rapid progression of untreated ES-SCLC. Staging may continue during and immediately after the initiation of treatment.
Recommendations for First-line Systemic Therapy in ES-SCLC
7. Preferred first-line systemic therapy for ES-SCLC should include four cycles of EP in combination with a PD-L1 inhibitor (atezolizumab or durvalumab) if there are no contraindications.

  1. The choice between carboplatin and cisplatin should be based on toxicity profile and co-morbidities.
8. Alternatives could include platinum with irinotecan or treating with CAV for a platinum-free regimen. These regimens have not been approved in combination with PD-L1/PD-1 inhibitors.

  1. If using irinotecan, clinicians should be aware of the increased risk of neutropenia and diarrhea. Irinotecan is a radiosensitizing agent that might interact with radiation therapy.
9. Patients with poor PS (Eastern Cooperative Oncology Group [ECOG] ≥ 3) may become eligible for a PD-L1 inhibitor if their PS improves after 1–2 cycles of chemotherapy.

  1. If available in the treating jurisdiction, the addition of a PD-L1 inhibitor may be based on clinical judgement and improvement of PS.
10. During systemic therapy and PD-L1 maintenance, patients with ES-SCLC could be assessed with imaging every 2–3 months, depending on disease sites and the burden of the disease.
Recommendations for Subsequent Lines of Therapy
11. Retreatment with the initial platinum-based doublet chemotherapy should be considered for platinum-sensitive patients (treatment-free interval ≥ 90 days) who are able to tolerate it.
12. For patients with ES-SCLC who experience progression on or within 3 months of completing first-line chemotherapy, one should consider CAV or IV topotecan. Lurbinectedin could also be considered. Irinotecan is an option.
13. For patients with poor PS (ECOG ≥ 3) with progression while on or after initial therapy, symptom management with best supportive care should be considered.
14. Upon the second progression, subsequent lines of therapy are generally less effective than the initial treatment but may provide significant palliation for some patients. Symptom control and improved quality of life are the primary goals of treatment.
Recommendations for Thoracic Radiation Therapy
15. RT to the residual primary tumour and lymph nodes could be offered to patients with documented response to systemic therapy presenting with residual thoracic disease, limited extra-thoracic disease and ECOG PS 0–2 who achieve a response after chemotherapy +/− PD-L1 inhibitor.
  1. Dosing and fractionation of consolidative thoracic RT should be individualized depending on the symptoms, urgency to treat, and PS.
    1. In total, 30 Gy in 10 fractions was used in the largest randomized trial; 20 Gy in 5 daily fractions may be appropriate due to logistics or for those receiving symptomatic palliation or 40 Gy in 15 daily fractions may be considered in patients with good PS.
    2. Consolidative thoracic RT after chemotherapy +/− PD-L1 inhibitor may be considered for patients with documented response to systemic therapy presenting with residual thoracic disease, limited extra-thoracic disease and ECOG PS 0–2 during or before maintenance with a PD-L1 inhibitor.
Recommendations for PCI
16. For ES-SCLC patients with good PS who have had a complete or very good partial response to chemotherapy +/− PD-L1 inhibitor as part of their first-line systemic therapy, both PCI and observation with regular brain MRI surveillance are acceptable options. An individualized discussion should be held with patients to evaluate the risks and benefits of each approach.

  1. The preferred dose for PCI to the whole brain is 25 Gy in 10 daily fractions. A shorter course (eg, 20 Gy in five fractions) may be appropriate in selected patients with ES-SCLC.

  2. A higher total RT dose (≥36 Gy) should be avoided in patients receiving PCI.
17. Due to the high risk of developing brain metastases, MRI surveillance imaging (every 3 months during the first year and every 6 months thereafter) for brain metastases should be recommended for all patients regardless of PCI status.
Recommendations for ES-SCLC Patients with Brain Metastases
18. Patients with ES-SCLC who present with asymptomatic brain metastases could receive systemic therapy, followed by radiation therapy upon completion of induction therapy.
19. Those with symptomatic brain metastases should receive radiation therapy, followed by systemic therapy.
20. Serial brain MRI imaging is recommended in patients who have asymptomatic brain metastases and are receiving systemic therapy before brain RT

  1. Brain MRI is recommended every 3 months during the first year and every 6 months thereafter. Brain CT is only an option if MRI cannot be used, because CT is inferior to MRI for detecting brain metastases.
21. In patients with solitary brain metastases, SRS may be an acceptable alternative to WBRT +/− HA, despite the lack of trial data; however, the choice between SRS and WBRT +/− HA depends on the location, size, and number of intracranial lesions and extent of extracranial disease.
Recommendation for Emerging Biomarkers
22. Although one can assess novel biomarkers and SCLC subtypes, at present, they should not be used to make treatment-related decisions. Testing for the biomarkers is a research tool that may be used for screening potential trial candidates.