Small cell lung cancer, a competition of treatment options at home and abroad (2023.2 version)

NCCNClinical Practice Guidelines for Non-Small Cell Lung Cancer 2022.
5 (Chinese) (1), (2).

NCCNSmall Cell Lung Cancer Clinical Practice Guidelines 2023.
2 (Chinese)

CSCOGuidelines for the diagnosis and treatment of small cell lung cancer (2022)

CSCO VS NCCN

Similar to non-small cell lung cancer, small cell lung cancer also has TNM stage, which divides small cell lung cancer into stages I-IV in detail, but the more clinically used stage is the AJCC TNM staging method and VALG Combination of two-stage staging method , small cell lung cancer is divided into limited and extensive stage
.
The specific staging principles are as follows:

『Small cell lung cancer limited stage』

Stages I-III (any T, any N, M0) of AJCC (8th edition) can be safely treated
with clear radiotherapy doses.
Exclude T3–4 because of multiple pulmonary nodules or large tumor/lymph nodes to be included in a tolerated radiotherapy plan
.

『Extensive stage of small cell lung cancer』

AJCC (8th edition) stage IV (any T, any N, M1a/b), or T3–4 cannot be included in a tolerated radiotherapy schedule due to multiple pulmonary nodules or tumor/lymph node size that is too large.

There are different treatment options
for different stages and different physical conditions of patients.

Treatment of limited-stage small cell lung cancer

        Limited period

T1-2，N0

1.
Patients suitable for surgery

Level I is recommended (both are Class 2A).

Initial treatment: lobectomy + hilar and mediastinal lymph node dissection;

Adjuvant therapy: N0 (adjuvant chemotherapy, etoposide + cisplatin/carboplatin); N1 (adjuvant chemotherapy± mediastinal radiotherapy); N2 (systemic therapy + mediastinal radiotherapy).

Class II recommendation: prophylactic brain radiotherapy (PCI) (class 1).

2.
Patients who are not suitable for surgery or are unwilling to operate

Level I recommendation: chemotherapy after stereotactic radiosurgery (SBRT/SABR) (class 2A); chemotherapy + synchronized/continued radiotherapy (class 1)

Class II recommendation: PCI (class 1) in patients with CR or PR

Exceeding T1-2，N0

PS 0-2 (both Class 1)

Grade I recommendation: chemotherapy + synchronous/sequential radiotherapy (chemotherapy regimen: etoposide + cisplatin/carboplatin).

Class II recommendation: PCI in patients with CR or PR

PS 3-4 (due to SCLC).

Grade I recommendation: chemotherapy ± radiotherapy (chemotherapy regimen: etoposide + cisplatin/carboplatin) (2A).

Class II recommendation: PCI (class 1) in patients with CR or PR

PS 3-4 (not caused by SCLC).

Optimal supportive care

        Limited period

I-IIA：T1-2,N0,M0

1.
Mediastinal pathological staging is negative

Initial treatment: lobectomy + mediastinal lymph node dissection or sampling

Adjuvant therapy: 1) R0 resection: N0 (systemic therapy, treatment plan see below, the same below); N1 (systemic therapy± mediastinal radiotherapy, synchronous/continuation); N2 (systemic therapy + mediastinal radiotherapy, synchronous/continuation).

2) R1/2 resection: systemic treatment ± simultaneous radiotherapy

2.
The body cannot tolerate surgery or decides not to undergo surgical removal

1) Stereotactic ablative radiotherapy → systemic therapy (if radiotherapy is delayed, systemic therapy can also be given first).

2) Systemic therapy + simultaneous radiotherapy

IIB-IIIB：T3-4,N0,M0； T1-4,N1-3,M0

PS 0-2

Initial treatment: systemic therapy + concurrent radiotherapy

PS 3-4 (due to SCLC).

Initial treatment: systemic therapy± radiation therapy (simultaneous/continuated)

PS 3-4 (not caused by SCLC).

Individualized treatment includes supportive care

Initial treatment of extensive-stage small cell lung cancer (first-line)

Extensive period

No local symptoms and no brain metastases

PS 0-2 & PS 3-4 (caused by SCLC).

Grade I recommendation (class 1): chemotherapy + immunotherapy: atrolizumab + etoposide + carboplatin maintenance therapy after 4 cycles of atezumab (preferred); durvalumab + etoposide + carboplatin/cisplatin maintenance therapy after 4 cycles of dulvalumab (preferred); Chemotherapy: (etoposide + cisplatin/carboplatin; irinotecan + cisplatin/carboplatin).

Class II recommendation (2A): etoposide + loplatin; Patients with CR or PR, chest radiotherapy, prophylactic brain radiotherapy; Traraciclib/G-CSF (chemotherapy ± pre-immunizational prophylaxis).

Grade III recommendation: serplulimab + etoposide + carboplatin maintenance therapy after 4 cycles of dusplulimab (class 1).

PS 3-4 (not caused by SCLC).

Optimal supportive care

Local symptoms and no brain metastases

Superior vena cava syndrome (both 2A)

Class I recommendation: severe clinical symptoms: radiotherapy + chemotherapy; Patients with mild clinical symptoms: chemotherapy + radiotherapy

Class II recommendation: PCI in patients with CR or PR

Spinal cord compression (both 2A).

Grade I recommendation: local radiotherapy to control compression symptoms + EP/EC/IP/IC regimen chemotherapy

Bone metastasis (both 2A).

Level I recommended: EP/EC/IP/IC chemotherapy + local palliative external beam radiotherapy; Patients at high risk of fracture can undergo orthopaedic fixation

With brain metastases

asymptomatic

Grade I recommendation: first atezumab + EC regimen, followed by whole brain radiotherapy (1A); Cindulvalumab + etoposide + carboplatin/cisplatin regimen, followed by whole-brain radiotherapy (1A); EP/EC/IP/IC chemotherapy + whole brain radiotherapy (2A);

Class II recommendation (2A): patients with CR or PR, chest radiotherapy; Traracillide/G-CSF (chemotherapy ± pre-immunizational prophylaxis).

Grade III recommendation: preserplulimab + etoposide + carboplatin, followed by whole-brain radiotherapy (1A)

Symptomatic

Grade I recommendation: whole brain radiotherapy first, and chemotherapy (class 1) after atrolizumab + EC regimen after stable symptoms; First whole brain radiotherapy, then duvalumab + etoposide + carboplatin/cisplatin regimen (class 1); Whole brain radiotherapy first, symptoms stabilized followed by EP/EC/IP/IC chemotherapy (2A).

Class II recommendation: patients with CR or PR, chest radiotherapy (2A).

Extensive period

No local symptoms and no brain metastases

PS 0-2 & PS 3-4 (caused by SCLC).

Initial therapy: systemic therapy, supportive therapy

PS 3-4 (not caused by SCLC).

Initial treatment: individualized treatment includes supportive care

Local symptoms and no brain metastases

Superior vena cava syndrome, lobar obstruction, bone metastases

Initial treatment: systemic therapy± radiotherapy to symptomatic sites; If there is a high risk of fracture due to bone disruption, consider orthopaedic fixation and palliative external beam radiotherapy

Spinal cord compression

Initial treatment: radiation therapy to symptomatic areas prior to systemic therapy, unless immediate systemic therapy is required

There are brain metastases

asymptomatic

Initial treatment: systemic therapy may be given before starting cerebral radiation therapy

Symptomatic

Initial treatment: cerebral radiation therapy prior to systemic therapy, unless immediate systemic therapy is required

Remarks (CSCO)

1.
Standard treatment for patients with T1-2N0 limited stage SCLC: surgery + adjuvant chemotherapy; Postoperative N+ patients: adjuvant chest radiotherapy
is recommended.

2.
Standard treatment for patients exceeding T1-2N0: synchronized/sequential chemoradiotherapy (concurrent chemoradiotherapy is better than sequential chemoradiotherapy).

3.
Limited-stage prophylactic radiotherapy
to the brain.
PCI: chemoradiotherapy for patients with PR/CR; Discretionary PCI: patients with stage I SCLC undergoing radical surgery and systemic chemotherapy are controversial; PCI is not recommended: advanced age, PS> 2, neurocognitive impairment
.

4.
Extensive stage: a.
no local symptoms and no brain metastasis, early treatment up to CR/PR: chest radiotherapy can be considered, carefully consider PCI; b.
There are local symptoms, radiotherapy mainly does palliative effect; c.
brain metastasis, PCI efficacy needs to be further explored
.

Evaluation of efficacy after initial treatment

Similar to NCCN

Complete or partial remission

Limited period

Prophylactic brain irradiation (PCI) or brain MRI monitoring, after completion of initial therapy: every 3 months for 1-2 years; 3rd year, reviewed every 6 months; From now on, it will be reviewed once
a year

Extensive period

Monitoring brain MRI ± consideration of PCI; Consider radiation to the chest
.
After completion of initial therapy: 1st year, repeated every 2 months; 2-3 years, review every 3-4 months; 4-5 years, review every 6 months; From now on, it will be reviewed once a year

The disease is stable

Limited period

After completion of initial therapy: 1-2 years, repeated every 3 months; 3rd year, reviewed every 6 months; From now on, it will be reviewed once
a year

Extensive period

After completion of initial therapy: 1st year, repeated every 2 months; 2-3 years, review every 3-4 months; 4-5 years, review every 6 months; From now on, it will be reviewed once a year

Primary disease progression

See "Late-line therapy" below

Second-line treatment for small cell lung cancer

Relapse ≤ 6 months

PS rating 0-2 points

Level I recommendation: topotecan (class 1); Clinical trials

Level II recommendation (2A): irinotecan; Paclitaxel; Docitaxel; gemcitabine; oral etoposide; Vinorelbine; Temozolomide; Traraciclib/G-CSF (prophylactic use of topotecan).

Class III recommendation: Bendamustine (class 2B).

Relapse > 6 months

Choice of original solution[1]

Remark:

Not indicated in patients with first-line combination immunotherapy, and re-initiation of etoposide + cisplatin/carboplatin
is recommended for patients who relapse >after 6 months of immune maintenance therapy.

Relapse ≤ 6 months

PS rating 0-2 points

Preferred regimen: topotecan oral or intravenous infusion; Lurbinectedin； Clinical trials

Other regimens: paclitaxel; Docitaxel; irinotecan; Temozolomide; cyclophosphamide/doxorubicin/vincristine; oral etoposide; Vinorelbine; gemcitabine; nivolumab; pembrolizumab; Bendamustine (class 2B).

Relapse > 6 months

First scenario: Original scheme

Other regimens: topotecan oral or intravenous infusion; Paclitaxel; Docitaxel; irinotecan; Temozolomide; cyclophosphamide/doxorubicin/vincristine; oral etoposide; Vinorelbine; gemcitabine; nivolumab; pembrolizumab; Lurbinectedin； Bendamustine (class 2B).

Note: Relapse ≤ 6 months or > 6 months, right Patients with PS score 2 should be considered dose reduction or growth factor support

Third-line treatment for small cell lung cancer

Third-line and above treatment

PS 0-2

Level I recommendation: anlotinib (2A).

Level II recommendation: participation in clinical trials; pembrolizumab (2A); Nivolumab (2A)

Post-line therapy 

Relapse or primary disease progression

PS 0-2

Subsequent systemic therapy; Palliative care (including local radiation therapy to symptomatic areas)

PS 3-4

Palliative care (including local radiation therapy to symptomatic areas)

NCCNSystemic regimen of initial or adjuvant therapy

Limited period (4 cycles recommended)

Preferred regimen: cisplatin 75mg/m 2 Day 1 + Etoposide 100mg/m 2 Days 1, ², 3; cisplatin 60mg/m 2 Day 1 + Etoposide 120mg/m 2 Days 1, ², 3

Other regimens: cisplatin 25mg/m 2 days 1, ², 3 + etoposide 100mg/m ² Days 1, 2, 3; Carboplatin AUC 5-6 Day 1 + Etoposide 100 mg/m 2 Days 1,², 3

Remark:

Planned cycle length: should be every 21-28 days during concurrent radiotherapy;

During systemic therapy + radiotherapy, cisplatin / etoposide (class 1) is recommended;

During simultaneous systemic therapy + radiotherapy, the use of myeloid growth factor is not recommended (without GM-CSF is class 1).

Extensive period

(4 cycles are recommended, some can be 6 cycles depending on efficacy and tolerability).

Preferred: carboplatin AUC 5 day 1 + etoposide 100mg/m2 days 1, 2, 3 + atecilizumab 1200mg Day 1 (repeated every 21 days× 4 cycles) followed by sequential atezumab maintenance therapy 1200mg (repeated every 21 days) (class 1);

Carboplatin AUC 5 Day 1 + Etoposide 100mg/m2 Days 1, 2, 3 + Atezumab 1200mg Day 1 (repeated every 21 days× 4 cycles) followed by sequential atezumab maintenance therapy 1680mg (repeated every 28 days) (Class 1);

Carboplatin AUC 5-6 Day 1 + etoposide 80-100mg/m2 Days 1, 2, 3 + durvalumab 1500mg Day 1 (repeated every 21 days× 4 cycles) then sequential durvalumab maintenance therapy 1500mg (repeated every 28 days) (class 1);

cisplatin 75-80mg/m2 Day 1 + etoposide 80-100mg/m2 Days 1, 2, 3 + durvalumab 1500mg Day 1 (repeated every 21 days× 4 cycles) Reordered desavalumab maintenance therapy 1500mg (repeated every 28 days) (Class 1)

Other regimens: carboplatin AUC 5-6 day 1 + etoposide 100mg/m 2 days 1, ², 3; cisplatin 75mg/m 2 Day 1 + Etoposide 100mg/m 2 Days 1, ², 3; cisplatin 80mg/m 2 Day 1 + Etoposide 80mg/m 2 Days 1, ², 3; cisplatin 25mg/m 2 days 1, 2, 3 + etoposide 100mg/m 2 days 1,², 3

Regimen for certain conditions: carboplatin AUC 5 day 1 + irinotecan 50 mg/m² days 1, 8, 15; cisplatin 60mg/m 2 Day 1 + irinotecan 60mg/m² Days 1, 8, 15; cisplatin 30mg/m 2 days 1 and 8 + irinotecan 65 mg/m² days 1 and 8

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