With the recent release of its latest Clinical Practice Guidelines, the European Society for Medical Oncology has set the stage for the management of individuals with small-cell lung cancer (SCLC) for years to come.  

The guidelines provide key recommendations for managing the disease, and cover such areas as clinical and pathological diagnosis, staging and risk assessment, treatment, and follow-up. 

Reporting in Annals of Oncology, the authors noted that SCLC should be diagnosed according to the World Health Organization criteria. With respect to pathological diagnosis, histology is preferred over cytology.  

Staging and risk assessment should utilize the tumor-node-metastasis (TNM) staging classification, with an initial assessment that considers smoking history, physical examination, complete blood count, liver enzymes, sodium, potassium, calcium, glucose, LDH, creatinine and lung function.  

The guidelines also recommend contrast-enhanced CT of the chest and abdomen and imaging of the brain (preferably MRI) in localized disease and for stage-IV patients not undergoing prophylactic cranial irradiation (PCI).  

With respect to concurrent chemoradiotherapy in limited-stage disease, the guidelines recommend adjuvant chemotherapy after surgical resection of SCLC, with cisplatin plus etoposide preferred in patients with limited-stage disease. In those cases where cisplatin is contraindicated because of comorbidities, carboplatin plus etoposide is a viable alternative.  

Radiotherapy scheduling recommends that individuals with T1-4N0-3M0 tumors and a good performance status (PS; 0-1) should be treated with concurrent chemotherapy and thoracic radiotherapy; the recommended dose fractionation schedule is 45 Gy bid in 30 fractions. In terms of timing, thoracic radiotherapy should be initiated as early as possible, on the first or second cycle of chemotherapy.  

Radiotherapy treatment volume is also discussed in the guidelines, in case of response to chemotherapy, the pre-chemotherapy nodal stations and post-chemotherapy primary tumor should be included in the radiation field. The omission of elective node irradiation is also recommended, in favor of selective node irradiation. 

The experts recommend that patients with stage-III SCLC with a response after chemoradiotherapy and a PS of 0-1 should be offered PCI. PCI can also be considered in patients with a PS of 2. The recommended PCI regimen is 25 Gy/10 fractions. On the other hand, the role of PCI is not particularly well defined in patients with stage I-II SCLC or in those >70 years of age or who are frail.  

Finally, the role of PCI or consolidation thoracic radiotherapy in combination with immunotherapy is not well defined in patients with extensive-stage SCLC. 

Treatment of individuals with extensive-stage SCLC is also a focus of the guidelines, where they recommend an anti-PD-L1 inhibitor in combination with four cycles of a platinum and etoposide. Such treatment regimen may be offered to all patients with treatment-naive extensive-stage SCLC, a PS of 0, 1 and no contraindications for immunotherapy.  

In extensive-stage patients ineligible for immunotherapy, the preferred first-line chemotherapeutic treatment for extensive-stage SCLC is four to six cycles of a platinum plus etoposide. Cisplatin can be substituted with carboplatin, through cisplatin might be preferred after taking age, PS, and toxicity profile into account.  

PCI can be offered to treatment-responsive patients with stage III SCLC and a PS of 0-1 (25 Gy/10 fractions); PCI can also be considered in patients with a PS of 2. The role of PCI is not as well defined in other circumstances.  

The guidelines also address second-line therapy and beyond, noting that individuals with platinum-refractory SCLC have a poor prognosis; in these individuals, best supportive care or participation in a clinical trial is recommended. In patients with platinum-resistant or platinum-sensitive relapse (<3 months treatment-free interval), either oral or IV topotecan is recommended; cyclophosphamide plus doxorubicin and vincristine (CAV) is another option in these cases.  

In addressing follow-up, long-term implications, and survivorship, the guidelines recommend a CT scan every 3-6 months for two years – with lengthening of intervals thereafter – among patients with limited-stage disease who have received potentially curative treatment. In patients who have not undergone PCI, on the other hand, regular brain MRIs are advised every three months in the first year, and every six months thereafter.  

The guidelines also note that individuals with a history of lung cancer are at high risk of developing a second primary cancer, and therefore recommend consideration of yearly follow-up with a low-dose CT. 


By Michael Vlessides, /alert Contributor