Small-cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers. Among them, patients with extensive-stage SCLC (ES-SCLC) have an extremely poor prognosis, with a 5-year survival rate of only 1%–5%. Treatment is especially challenging for patients with high tumor burden (multisite metastases, large lesions).

This article presents the diagnosis and treatment course of a 67-year-old female patient with ES-SCLC (cT3N2M1 stage ⅣB). Through two MDT discussions and based on the latest clinical research evidence, an individualized regimen of “first-line immunotherapy + chemotherapy + anti-angiogenesis therapy → local radiotherapy → combined maintenance therapy” was formulated. The patient finally achieved stable disease and symptom relief, providing practical reference for the diagnosis and treatment of ES-SCLC with high tumor burden.

1. Case Overview: Baseline Status and Core Clinical Challenges

1.1 Baseline Status

Female, 66 years old. Chest CT showed a mass in the right upper lung (6.1×5.5 cm); abdominal CT showed a splenic mass (6.8×6.6 cm); PET-CT showed FDG-avid masses in the apical and posterior segments of the right upper lobe, accompanied by intrapulmonary metastases, mediastinal lymph node metastases (regions 3A, 4R), and splenic metastases. Contrast-enhanced brain MRI showed bilateral frontal lobe metastases.

Pathology of lung core needle biopsy: small-cell carcinoma. Immunohistochemistry: TTF-1 (partially weak +), Napsin A (−), P40 (−), Syn (+), CgA (weak +), CD56 (−), CK (+), Ki-67 (MIB1) (+80%). Pathology of splenic core needle biopsy was consistent with small-cell neuroendocrine carcinoma. Diagnosis: extensive-stage small-cell lung cancer.

Past medical history: 30-year history of hypertension, oral antihypertensive drugs regularly; 40+ years of smoking history.

1.2 Core Challenges

1. Extremely high tumor burden: primary tumor + intrapulmonary metastasis + mediastinal lymph node metastasis + splenic metastasis + subsequent brain lesion progression, meeting the definition of high tumor burden ES-SCLC. Traditional chemotherapy has limited efficacy and rapid progression.

2. Comorbidities: grade 3 hypertension (high risk), two previous surgeries, average performance status (ECOG 1). Treatment must balance efficacy and safety.

3. Highly aggressive disease: SCLC proliferates rapidly with early recurrence and metastasis, requiring intensified first-line and maintenance therapy.

First-Line Regimen: First MDT

For ES-SCLC, chemotherapy combined with immunotherapy is the first-line regimen recommended by high-level evidence. Beyond this standard approach, the MDT team (radiation, imaging, nuclear medicine, pathology, lung cancer center, medical oncology, radiation oncology) focused on two key issues: whether to add anti-angiogenic therapy in first-line treatment and the timing of radiotherapy.

Key Issue 1: Combine anti-angiogenic agents in first-line treatment?

Controversy: Can anti-angiogenic agents (e.g., anlotinib) combined with immunotherapy + chemotherapy further improve efficacy?

Evidence: The ETER701 trial showed that the four-drug combination of “PD-L1 inhibitor + anlotinib + EC chemotherapy” significantly prolonged PFS and OS in ES-SCLC patients. Subgroup analysis confirmed benefit in patients with high tumor burden and multiple metastatic sites, with no new safety signals.

Decision: Adopt four-drug combination: etoposide + carboplatin + durvalumab + anlotinib. Based on chemo-immunotherapy, anlotinib was added to intensify systemic therapy, inhibit tumor angiogenesis, improve the tumor microenvironment, and enhance immunotherapy sensitivity.

Key Issue 2: Optimal timing of radiotherapy?

Controversy: Interim radiotherapy during first-line systemic therapy, or consolidation radiotherapy after tumor shrinkage?

Evidence: Meta-analysis showed that thoracic consolidation radiotherapy (cTRT) after chemo-immunotherapy significantly improved OS and reduced local recurrence risk in ES-SCLC patients without increased severe adverse events.

Decision: Systemic therapy first to control widespread metastases; after tumor shrinkage or stabilization, deliver local consolidation radiotherapy to primary tumor, mediastinal lymph nodes, and splenic metastases to minimize potential radiotherapy-related risks.

First-Line Treatment Course and Disease Response

During four-drug combination therapy, the patient developed mild leukopenia, which resolved after granulocyte colony-stimulating factor treatment. Chemotherapy doses were adjusted, and the planned regimen was completed successfully.

After 4 cycles of four-drug therapy, imaging showed reduction in intrapulmonary primary and metastatic lesions; disease remained stable after 6 cycles. Tumor markers: CEA decreased from 539 ng/mL to 27.1 ng/mL; pro-gastrin-releasing peptide decreased from 3605 pg/mL to 127 pg/mL, confirming effective systemic tumor control.

After four-drug therapy, local radiotherapy was delivered to primary and metastatic lesions: right lung + mediastinal lymph nodes (45 Gy), splenic metastasis (32.5 Gy). Mild thrombocytopenia occurred during radiotherapy and recovered after treatment; no severe adverse events such as radiation pneumonitis. Local therapy further eliminated residual disease and reduced local recurrence risk, especially for splenic metastasis.

Maintenance Regimen: Second MDT

After 6 cycles of systemic therapy + local radiotherapy, follow-up brain MRI showed enlargement of the right frontal lobe lesion with headache and nausea, suggesting progression of brain metastasis; other lesions were stable. The MDT team re-discussed optimization of maintenance therapy and management of brain metastasis.

Key Issue 1: Management of brain metastasis?

Controversy: Whole-brain radiotherapy (WBRT) or stereotactic radiotherapy (SRT)?

Evidence: For ES-SCLC with limited brain metastases (≤3 lesions), SRT is an alternative to WBRT with lower neurotoxicity. For progressive brain lesions, short-course radiotherapy rapidly relieves symptoms and avoids long-term neurological damage.

Decision: Local radiotherapy to brain metastasis (27 Gy/3 fractions) plus dehydration and intracranial pressure reduction to quickly control neurological symptoms.

Key Issue 2: Upgrade maintenance to combination therapy?

Controversy: Add lurbinectedin to durvalumab maintenance vs. durvalumab monotherapy?

Evidence: Lurbinectedin, a novel chemotherapeutic agent, synergizes with immunotherapy and is highly selective for SCLC. The IMforte trial showed that lurbinectedin plus immunotherapy significantly prolonged PFS and OS, reducing progression risk by 46% vs. immunotherapy monotherapy after induction therapy for ES-SCLC.

Decision: Lurbinectedin combined with durvalumab for maintenance therapy to sustain tumor control in this high tumor burden patient.

Maintenance Treatment Course and Disease Response

SRT for brain metastasis was completed smoothly, with marked relief of headache and nausea. Maintenance therapy with durvalumab + lurbinectedin was administered without significant adverse events. After 2 cycles, brain and other lesions remained stable.

The patient has survived for more than 7 months since diagnosis. With the stepwise strategy:first-line immunotherapy + chemotherapy + anti-angiogenesis → local consolidation radiotherapy → brain radiotherapy + combined maintenance therapy, the outcomes are:

· Tumor control: primary and metastatic lesions (lung, mediastinum, spleen, brain) are stable without progression; tumor markers remain low.

· Safety: adverse events were mainly mild hematologic toxicity and hypertension, manageable with supportive care; no severe adverse events, good tolerance.

· Survival benefit: current PFS > 7 months, far exceeding the median PFS of traditional ES-SCLC treatment; ongoing follow-up.

Four-drug combination is an option for first-line treatment of high tumor burden ES-SCLC,Rapid systemic disease control created conditions for subsequent local therapy, validating clinical value. Anti-angiogenic agents improve tumor microenvironment, enhance immunotherapy sensitivity, and show manageable safety.

Precision radiotherapy in ES-SCLC: individualized timing and dosageStage-localized radiotherapy to primary, mediastinal, splenic, and progressive brain lesions achieved dual goals of systemic control and local eradication.

Combined maintenance: a new strategy Novel chemotherapy plus immunotherapy synergizes to sustain tumor control and prolong survival in high-risk, rapidly progressive ES-SCLC.

MDT is the cornerstone of care for high tumor burden ES-SCLC Two MDT discussions integrated latest evidence and cross-disciplinary expertise to personalize first-line selection, radiotherapy timing, and post-progression adjustment. This ensured scientific, balanced efficacy and safety, achieving long-term disease stability and highlighting the core value of MDT in complex oncology.