Appropriate Treatment
per Disease Stage

Once diagnosed with SCLC, the initial approach to treatment varies substantially by disease stage.1 The Veterans Administration Lung Study Group’s (VALSG) 2-stage classification is used to define the extent of the disease.2

To learn more about SCLC stage classifications click on the limited-stage and extensive-stage tabs below.

Limited- and Extensive-Stage SCLC

DEFINITION

Cancer is only on 1 side of the chest/lung/lymph nodes and can be treated with a single radiation field3

Disease may involve the mediastinal and hilar nodes1

TNM STAGING

Includes TNM Stages I to III (T any, N any, M0)4

DEFINITION

Cancer has spread widely throughout the lung, to the other lung, to lymph nodes on the other side of the chest, or to other parts of the body (including bone marrow and fluid around the lung)3

TNM STAGING

Includes TNM Stage IV (T any, N any, M1a/b/c)4

  • Patients diagnosed with LS-SCLC have a better prognosis than those with ES-SCLC5
  • The distant metastases associated with ES-SCLC make it difficult to achieve lasting remission5,6
  • Approximately 10% of patients present with brain metastases at initial diagnosis.7 Another 40%-50% subsequently develop brain metastases at disease progression; therefore, CT/MRI of the brain should be part of the work-up1

  • Uses of TNM Staging

    TNM staging provides anatomic discrimination for the measurement of outcome, prognostic information, and more precise lymph nodal staging.1 It can also identify the <5% of patients for whom resection may be beneficial, as well as radiation planning.7,8

    • T describes the original (primary) tumor8
    • N tells whether the cancer has spread to the nearby lymph nodes8
    • M tells whether the cancer has metastasized to distant parts of the body8

STAGING WORK-UP

  • A diagnostic and staging work-up should be performed as quickly as possible after symptom presentation1

Clinical Testing and Work-up7

Medical History and Physical Examination Drawing

Medical history and physical examination

CT Scan Drawing

Chest/abdomen/
pelvis CT with contrast, and/or positron emission tomography (PET)/CT scan (skull to thigh) if neededto clarify stagec

Medical History and Physical Examination Drawing

Medical history and physical examination

Telescope Pathology Review Drawing

Pathology reviewa

Telescope Pathology Review Drawing

Pathology reviewa

Counseling Message Bubbles Drawing

Smoking cessation counseling

Blood Count Drawing

Complete blood cell count (CBC)

Brain Drawing

Brain MRI (preferred) or CT with contrastb

Blood Count Drawing

Complete blood cell count (CBC)

Liver Drawing

Electrolytes, liver function tests (LFTs), blood urea nitrogen (BUN), creatinine

CT Scan Drawing

Chest/abdomen/
pelvis CT with contrast, and/or positron emission tomography (PET)/CT scan (skull to thigh) if needed to clarify stagec

Counseling Message Bubbles Drawing

Smoking cessation counseling

Brain Drawing

Brain MRI (preferred) or CT with contrastb

DNA Molecular Profiling Drawing

Molecular profilingd

Liver Drawing

Electrolytes, liver function tests (LFTs), blood urea nitrogen (BUN), creatinine

DNA Molecular Profiling Drawing

Molecular profilingd

aTo determine the histological classification of lung tumors and relevant staging parameters.

bBrain MRI is more sensitive than CT for identifying brain metastases and is preferred over CT.

cIf PET/CT is not available, bone scan may be used to identify metastases. Pathologic confirmation is recommended for lesions detected by PET/CT that alter stage.

dMolecular profiling may be considered in never smokers with extensive-stage SCLC to help clarify diagnosis and evaluate potential targeted treatment options.

  • Because of the neuroendocrine origin of SCLC, it can have a significantly rapid doubling time9
    • Therefore, timely diagnosis and treatment are essential as delays can lead to missed opportunities for both curative and life-prolonging therapies10

LIMITED STAGE (LS) SCLC

Disease Progression in LS-SCLC

DIAGNOSIS3

One in Three Patients Drawing

~1 of 3

PATIENTS HAVE LS-SCLC AT TIME
OF DIAGNOSIS

PATIENTS HAVE LS-SCLC AT TIME OF DIAGNOSIS

RELAPSE1

75 Percent of Patients Drawing

~75%

OF PATIENTS WITH LOCALLY
ADVANCED DISEASE RELAPSE
WITHIN 2 YEARS OF TREATMENT

OF PATIENTS WITH LOCALLY ADVANCED DISEASE RELAPSE WITHIN 2 YEARS OF TREATMENT

SURVIVAL5

16 to 24 Months Calendar Drawing

PATIENTS TYPICALLY SURVIVE

16-24
MONTHS AFTER DIAGNOSIS

PATIENTS
TYPICALLY
SURVIVE
16-24
MONTHS AFTER DIAGNOSIS

LIMITED STAGE: CHEMOTHERAPY AND RADIOTHERAPY

  • The role of concomitant chemotherapy with radiotherapy is well established in the management of LS disease1

Initial Treatment Options for LS-SCLC1,11

Small Cell Lung Cancer (SCLC) Chemotherapy Drawing

COMBINATION CHEMOTHERAPY

Use in
LS-SCLC

Recommended first-line therapy is platinum plus etoposide (platinum doublet) for eligible patients7,a

Efficacy and Safety Results

Superior to alternatives in efficacy and toxicity
Small Cell Lung Cancer (SCLC) Radiotherapy Drawing

RADIOTHERAPY

Use in
LS-SCLC

Given concurrently or sequentially to combination chemotherapy7,a

Efficacy and Safety Results

Chemoradiotherapy results in:
  • Response rates of 70-90%
  • Median overall survival of 24-30 months
  • 5-year overall survival rates of 25-30%
However, chemoradiotherapy increases the risk of:
  • Esophagitis
  • Pulmonary toxicity
  • Hematologic toxicity
Brain Drawing

PROPHYLACTIC CRANIAL IRRADIATION (PCI)b

Use in
LS-SCLC

Offered to patients who respond to initial concurrent chemoradiotherapy (CRT) and have a performance status of 0-11

Evidence supporting PCI is not as clear in patients1:
  • With a performance status of 2 after CRT
  • >70 years of age
  • With pre-existing neurological conditions

Efficacy and Safety Results

Meta-analysis of data from PCI trials shows:
  • Nearly 50% reduction in the 3-year incidence of brain metastases
  • Prevention, not merely a delay, of the emergence of brain metastases

aSee the NCCN Guidelines for SCLC for detailed recommendations.

bCurrent randomized trials are evaluating whether brain MRI surveillance alone is non-inferior to MRI surveillance plus PCI on overall survival.7

In LS-SCLC, patients do not receive maintenance therapy as part of their initial regimen.7 As a result, there may be less frequent follow-up visits. It is important to monitor for early signs of relapse.

EXTENSIVE-STAGE (ES) SCLC

Disease Progression in ES-SCLC

DIAGNOSIS3

Two In Three Patients Drawing

~2 of 3

PATIENTS HAVE ES-SCLC AT TIME OF DIAGNOSIS

RELAPSE1

90 Percent People Drawing

>90%

OF PATIENTS WITH METASTATIC DISEASE
RELAPSE WITHIN 2 YEARS OF TREATMENT

SURVIVAL5

6 to 12 Months Calendar Drawing

PATIENTS TYPICALLY SURVIVE

6-12

MONTHS AFTER DIAGNOSIS

PATIENTS
TYPICALLY
SURVIVE
6-12 MONTHS AFTER DIAGNOSIS

EXTENSIVE-STAGE: CHEMOTHERAPY AND RADIOTHERAPY

  • Combination chemotherapy with immunotherapy is recommended for eligible patients with ES-SCLC1,7,a

Initial Treatment Options for ES-SCLC1,12

Small Cell Lung Cancer (SCLC) Chemotherapy Drawing

COMBINATION CHEMOTHERAPY + IMMUNOTHERAPY

Use in
ES-SCLC

Systemic therapy:
  • Platinum agent plus etoposide plus immunotherapy7,a
About chemotherapy:
  • Standard duration: 4-6 cycles
  • For patients who respond with at least disease control:
    • Continue with immunotherapy alone until:
      • Disease progression
      • Unacceptable toxicity

Efficacy and Safety Results

Platinum-based chemotherapy plus immunotherapy
  • Significantly increased median OS
  • Improved PFS rates
Small Cell Lung Cancer (SCLC) Radiotherapy Drawing

RADIOTHERAPY

Use in
ES-SCLC

If patients respond to initial treatment, radiation to the chest may be given
  • Typically reserved for palliation, including painful bone metastases

Efficacy and Safety Results

May improve OS rates
Brain Drawing

PROPHYLACTIC CRANIAL IRRADIATION (PCI)b

Use in
ES-SCLC

Controversial in this context:

Recent randomized phase 3 data suggest limited or no patient benefit

Efficacy and Safety Results

N/A

PFS=progression-free survival.

aSee the NCCN Guidelines for SCLC for detailed recommendations.

bCurrent randomized trials are evaluating whether brain MRI surveillance alone is non-inferior to MRI surveillance plus PCI on overall survival.7

As with any medical therapy, it is essential to weigh the risks and benefits of available treatments for SCLC.1 After relapse, you should choose the appropriate treatment option for your patient.1,7



Discover FDA-approved
treatments for SCLC

►

ASSESSMENT, SURVEILLANCE, AND SECOND-LINE TREATMENT

Response Assessment Is an Important Aspect of Patient Management7

LS-SCLC

ES-SCLC

After adjuvant chemotherapy alone or chemotherapy with concurrent RT for patients with LS-SCLC, response assessment using CT with contrast of the chest/abdomen/pelvis should occur only after completion of therapy; repeating CT scans during therapy is not recommended7

For systemic therapy alone or sequential systemic therapy followed by RT in patients with LS-SCLC, response assessment using CT with contrast of the chest/abdomen/pelvis should occur after every 2 cycles of systemic therapy, and again at completion of therapy7

During systemic therapy for patients with ES-SCLC, response assessment using CT with contrast of the chest/abdomen/pelvis should occur after every 2 to 3 cycles of systemic therapy, and again at completion of therapy7
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Frequency of follow-up depends on7:

  • Disease stage
  • Response to treatment (partial or complete, stable disease)

arrow

Since relapse is highly likely1,13:

  • Schedule time for routine monitoring
  • Offer salvage treatment if appropriate

RT=radiotherapy.

FREQUENCY OF FOLLOW-UP VISITS IS DEPENDENT ON DISEASE STAGE

For Complete Response/Partial Response/Stable Disease7

LIMITED STAGE

After completion of initial therapy
  • Every 3 months during years 1-2
  • Every 6 months during year 3
  • Then annually

EXTENSIVE STAGE

After completion of initial
or subsequent therapy
  • Every 2 months during year 1
  • Every 3-4 months during years 2-3
  • Every 6 months during years 4-5
  • Then annually
  • NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend follow-up visits. At each such visit:
    • A history, physical exam, and CT scans of the chest ± abdomen/pelvis are recommended7
    • Brain MRI (preferred) or CT is typically performed every 3-4 months during year 1 and every 6 months during year 27
  • Patient follow-up should also include the management of the multiple comorbidities often associated with the disease, including cardiac and respiratory comorbidities1
    • This may provide better symptom control, and possibly, better patient outcomes1

SCLC has poor prognosis due to high relapse rates. It is important to evaluate optimal therapy.1,7

NCCN=National Comprehensive Cancer Network® (NCCN®)

    REFERENCES:
  1. Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Primers. 2021;7(1):3. doi:10.1038/s41572-020-00235-0
  2. Carter BW, Glisson BS, Truong MT, Erasmus JJ. Small cell lung carcinoma: staging, imaging, and treatment considerations. RadioGraphics. 2014;34(6):1707-1721.
  3. Small cell lung cancer stages. American Cancer Society. https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/staging-sclc.html. Accessed May 7, 2021.
  4. Rami-Porta R, Asamura H, Travis WD, Rusch VW. Lung. In: Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th ed. Springer International Publishing; 2017:431-456.
  5. Small Cell Lung Cancer Treatment (PDQ®)–Health Professional Version. National Cancer Institute. https://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq. Accessed May 7, 2021.
  6. Huber RM, Tufman A. Update on small cell lung cancer management. Breathe. 2012;8(4): 315-330.
  7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed December 21, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  8. Cancer staging. American Cancer Society. https://www.cancer.org/treatment/understanding-your-diagnosis/staging.html. Accessed May 7, 2021.
  9. Harris K, Khachaturova I, Azab B, et al. Small cell lung cancer doubling time and its effect on clinical presentation: a concise review. Clin Med Insights: Oncol. 2012;6:199-203.
  10. Vidaver RM, Shreshneva MB, Hetzel SJ, Holden TR, Campbell TC. Typical time to treatment of patients with lung cancer in a multisite, US-based study. J Clin Oncol. 2016;12(6):e643-e653.
  11. Faivre-Finn C, Snee M, Ashcroft L, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomized, superiority trial. Lancet Oncol. 2017;18(8):1116-1125. doi:10.23937/2378-3419/1410111
  12. Takahashi T, Yamanaka T, Seto T, et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(5):663-671.
  13. Alvarado-Luna G, Morales-Espinosa D. Treatment for small cell lung cancer, where are we now? – a review. Transl Lung Cancer Res. 2016;5(1):26-38.