Small Cell Lung Cancer (SCLC) Guidelines

Updated: May 07, 2021
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Guidelines

Guidelines Summary

Guidelines on lung cancer screening have been issued by the following organizations:

  • American Cancer Society (ACS)
  • American College of Chest Physicians (ACCP)
  • American Association for Thoracic Surgery (AATS)
  • National Comprehensive Cancer Network (NCCN)
  • U.S. Preventive Services Task Force (USPSTF)

Most of the guidelines recommend offering annual screening with low-dose, computed tomography (LDCT) scanning to asymptomatic patients aged 55 to 74 years and who have at least a 30 pack-year smoking history and either continue to smoke or have quit within the past 15 years. [23, 28, 70, 27, 71, 24]

In March 2021, the USPSTF extended its screening recommendation to include persons aged 50 to 80 with at least a 20-pack-year smoking history. The USPSTF recommends discontinuing screening once 15 years have gone by since the patient stopped smoking, or if the patient develops a health problem that "substantially limits life expectancy or the ability or willingness to have curative lung surgery." [24]

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ACCP Diagnosis and Management Guidelines

The American College of Chest Physicians (ACCP) updated its comprehensive set of lung cancer guidelines in 2013. The guideline set of more than 275 recommendations includes an executive summary of current recommendations for diagnosis and treatment, along with additional recommendations for screening, chemoprevention, and treatment of tobacco use in patients with lung cancer. [28]

In 2015, the American Society of Clinical Oncology (ASCO) endorsed the ACCP guidelines, with the addition of minor qualifying statements.

Diagnosis of Pleural Abnormalities

The ACCP recommendations for diagnosis of pleural abnormalities include the following [28, 72] :

  • In patients suspected of having SCLC based on the radiographic and clinical findings, the diagnosis should be confirmed by the least invasive method (eg, sputum cytology, thoracentesis, fine needle aspiration (FNA), bronchoscopy including transbronchial needle aspiration), as dictated by the patient's presentation

  • For individuals who have a solitary extrathoracic site suspicious of a metastasis, tissue confirmation of the metastatic site should be obtained if FNA or biopsy of the site is feasible

  • In individuals in whom biopsy of a metastatic site would be technically difficult, diagnosis of the primary lung lesion should be obtained by the least invasive method

  • In patients suspected of having lung cancer who have an accessible pleural effusion, thoracentesis is recommended to identify the cause of the pleural effusion; ultrasound-guided thoracentesis is recommended for performing diagnostic thoracentesis

  • In patients suspected of having lung cancer who have an accessible pleural effusion, if pleural fluid cytology is negative, pleural biopsy (via image-guided pleural biopsy, medical or surgical thoracoscopy) is recommended as the next step

Diagnosis of Primary Tumor

The ACCP recommendations for diagnosis of primary tumor include the following [28, 72] :

  • If lung cancer is suspected and sputum cytology is negative for carcinoma, further testing should be performed

  • In patients who have a central lesion, bronchoscopy should be used to confirm the diagnosis; however, further testing should be performed if bronchoscopy results are non-diagnostic and suspicion of lung cancer remains

  • As an adjunct imaging modality when a tissue sample is required due to diagnostic uncertainty or poor surgical candidacy, radial endobronchial ultrasound can confirm in real time the ideal location of bronchoscopic sampling and increase the diagnostic yield over conventional bronchoscopy for peripheral nodules.

  • With peripheral lung lesions difficult to reach with conventional bronchoscopy, electromagnetic navigation guidance can be used if the equipment and the expertise are available; otherwise, transthoracic needle aspiration (TTNA) is recommended

  • In patients who have a peripheral lesion and who require tissue diagnosis before further management can be planned, TTNA is diagnostic option; however, further testing should be performed if TTNA results are nondiagnostic and suspicion of lung cancer remains

  • The possibility of an erroneous diagnosis of SCLC on a cytology specimen must be kept in mind if the clinical presentation or clinical course is not consistent with that of SCLC; in such a case, further testing should be performed to establish a definitive cell type

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Staging

The American Joint Commission for Cancer (AJCC) adopted the new tumor, node, metastasis (TNM) system in 2010. [31] In addition, the 2011 National Comprehensive Cancer Network (NCCN) clinical practice guideline for SCLC incorporated TNM staging into its diagnostic and therapeutic algorithms; the NCCN suggested that researchers begin to use the TNM staging system in an effort to more accurately assess prognoses and to more specifically personalize therapeutic options.

This recommendation is also reflected in the current NCCN and European Society for Medical Oncology (ESMO) practice guidelines. [27, 12] However, the American College of Chest Physicians (ACCP) guidelines recommend use of both the TNM system and the Veterans Administration Lung Study Group (VALSG) system (limited-stage vs extensive-stage) to classify the tumor stage. [28]

SCLC consists of two stages: limited-stage and extensive-stage. Under the AJCC TNM staging system, limited-stage SCLC is defined as any T, any N, M0; the exception is T3-4, owing to multiple lung nodules that extend beyond a single radiation field. [31]

Extensive-stage disease describes tumors that extend beyond the ipsilateral hemithorax, such as those that reach the contralateral lung and/or contralateral lymph nodes or that find their way to distant organs (eg, bone marrow). The AJCC TNM staging system classifies extensive-stage disease as any T, any N, M1a/b, and T3-4, due to involvement of multiple nodules. [31]

The ACCP does not recommend positron emission tomography (PET) scanning in the routine staging of SCLC. [28] However, in a qualifying statement, the American Society of Clinical Oncology (ASCO) recognizes that PET scanning is a widely used initial staging tool in patients with lung cancer, and recommends that when a PET scan is obtained for patients with either limited-stage or extensive-stage disease, a bone scan may be omitted. [73] The NCCN guidelines recommend combined PET–computed tomography scanning if limited-stage disease or metastasis is suspected. [27]

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Treatment for Limited-Stage SCLC

The American College of Chest Physician (ACCP) guidelines recommend that limited-stage small cell lung cancer (LS-SCLC) be treated with curative intent, based on an expected 20% to 25% 5-year survival. [28] The ACCP recommendations for treatment of LS-SCLC also include the following: 

  • Surgical resection is indicated for carefully selected stage I SCLC after a thorough evaluation of distant and invasive mediastinal stage

  • Patients who have undergone surgical resection should be treated with platinum-based adjuvant chemotherapy

  • Accelerated hyper-fractionated radiation therapy (twice-daily treatment) should be administered early in the course of treatment, concurrently with chemotherapy consisting of four cycles of a platinum agent and etoposide

In addition, National Comprehensive Cancer Network (NCCN) clinical practice guidelines recommend sequential therapy for patients unable to tolerate concurrent chemoradiation. Chemotherapy is given first, followed by radiation therapy, because of the high rate of responsiveness to chemotherapy for SCLC. [27]

The 2021 European Society for Medical Oncology (ESMO) practice guidelines include the following treatment recommendations for patients with clinical stages I and II (cT1-2N0) SCLC [12] :

  • Surgery may be considered in patients following a multidisciplinary board decision.
  • Pathological mediastinal staging is required.
  • Sublobular resection is not recommended.
  • Surgery should include systematic nodal dissection.

For patients with pT1-2/N0-1 disease who have an R0 resection, ESMO recommends four cycles of adjuvant cisplatin plus etoposide. Carboplatin may be substituted for cisplatin if that agent is contraindicated because of comorbidities.

Concurrent thoracic radiation therapy (RT) and adjuvant chemotherapy is recommended in patients with an R1-R2 resection or positive mediastinal lymph nodes (N2) and in patients with T1-4/N0-3/M0 tumors and a good performance status (PS 0-1).

Thoracic RT should be initiated as early as possible, preferably on the first or second chemotherapy cycle. The recommended dose fractionation schedule is 45 Gy BID in 30 fractions. Sequential chemoradiotherapy (CRT) is an option for patients who are not candidates for concurrent CRT due to poor PS, comorbidities and/or disease volume. Selective node irradiation (ie, RT for involved nodes defined as FDG avid on PET–CT, enlarged on CT, and/or biopsy-positive) is preferred.

Granulocyte colony-stimulating factor (G-CSF) is an option to prevent hematologic toxicity.

The ACCP and the NCCN guidelines recommend prophylactic cranial irradiation (PCI) in patients with limited-stage disease who have achieved a complete remission or in those with stage I disease who have undergone a complete resection, although the NCCN advises against its use in patients with poor performance status or impaired neurocognitive function. [27, 28]

ESMO practice guidelines recommend offering PCI to patients with a PS of 0-1 and a response to CRT, and considering PCI in patients with a PS of 2. The recommended dose is 25 Gy in 10 daily fractions. ESMO recommends shared decision making regarding PCI in patients with stage I-II SCLC, who have a lower risk of developing brain metastases, and in those of age > 70 years or who are frail, as the role of PCI is not as well defined in those circumstances. [12]

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Treatment for Extensive-Stage SCLC

Guidelines from the American College of Chest Physicians (ACCP), the National Comprehensive Cancer Network (NCCN), and the European Society for Medical Oncology (ESMO) recommend that patients with extensive-stage disease be treated with combination chemotherapy alone. [12, 27, 28]

The ACCP recommends combining palliative care with standard oncology care early in the treatment course. Conversations about the goals of care and end-of-life options should be initiated with all patients with extensive-stage SCLC. [28]

In patients who have mixed histologic features of SCLC and non-SCLC, the ACCP and NCCN guidelines recommend following treatment recommendations for SCLC. [27, 28]

According to the NCCN guidelines, dose-dense or dose-escalation chemotherapy regimens are not recommended outside of a randomized clinical trial. [27]

The ACCP recommends offering further chemotherapy to patients with relapsed or refractory SLCL. [28] However, except in the setting of a clinical trial, the ACCP does not recommend either of the following:

  • Maintenance treatment for patients with limited- or extensive-stage disease that is in partial (PR) or complete remission (CR)

  • Dose-dense/intense initial/induction or maintenance treatment for limited- or extensive-stage disease

ESMO recommendations for extensive-stage SCLC are as follows [12] :

  • A PD-L1 inhibitor (atezolizumab or durvalumab) can be added in patients with treatment-naive extensive-stage SCLC, a PS of 0-1, and no contraindications for immunotherapy.
  • For immunotherapy-ineligible patients, the preferred first-line treatment of extensive-stage SCLC (PS 0-1 and PS 2 due to SCLC) is four to six cycles of a platinum agent plus etoposide.
  • Alternative treatment options are cisplatin with irinotecan or oral topotecan and, in poor- prognosis patients, gemcitabine plus carboplatin.
  • In patients responsive to chemotherapy and with a PS of 0-2, RT to the residual primary tumor and lymph nodes (30 Gy/10 fractions) is a treatment option.
  • Prophylactic cranial irradiation (PCI), 20 Gy/5 fractions and 25 Gy/10 fractions, is justified without prior MRI staging or follow-up in patients of age < 75 years and a PS of 0-2 who have responded to chemotherapy.
  • PCI can be omitted in patients with extensive-stage SCLC who do not have brain metastases on MRI after chemotherapy and who can be followed up with regular brain MRI.
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Treatment of SCLC in the Elderly

The American College of Chest Physicians (ACCP) recommends that elderly patients with small-cell lung cancer (SCLC) who have a good performance status (PS) (ie, Eastern Cooperative Oncology Group [ECOG] PS 0 or 1) and intact organ function receive standard carboplatin-based chemotherapy. However, even patients who have poor prognostic factors (eg, poor PS, medically significant concomitant conditions) may still be considered for chemotherapy if appropriate precautions are taken to avoid excessive toxicity and further decline in PS. [28]

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Long-Term Monitoring

The National Comprehensive Cancer Network recommends that after recovery from primary therapy, patients should receive oncology follow-up visits on the following schedule [27] :

  • Years 1-2: Every 3–4 mo
  • Years 3-5: Every 6 mo
  • Subsequent years: Annuallly

At every visit, the patient should receive the following:

  • History and physical examination
  • Chest imaging (with workup for potential new primary if a new pulmonary nodule is detected)
  • Blood work as clinically indicated
  • Smoking cessation intervention, if necessary

Positron emission tomography/computed tomography (PET/CT) is not recommended for routine follow-up.

The European Society for Medical Oncology recommends that patients with limited-stage SLCLC who have received potentially curative treatment  undergo CT scans every 3-6 months for 2 years, with lengthening of intervals thereafter. Regular brain MRIs (every 3 months in the first year and then every 6 months) are advised in patients who did not undergo prophylactic cranial irradiation. [12]

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