SCLC约占支气管来源癌症的15%。
在诊断时，约30%的SCLC患者原发肿瘤局限于一侧胸腔、纵隔或锁骨上淋巴结。这些患者的疾病被定义为局限期疾病（LD）。
患者肿瘤扩散超出锁骨上区域被称为广泛期疾病（ED）。
SCLC对化疗和放疗的反应优于其他类型的肺癌，但因SCLC在确诊时广泛扩散的可能性更大，故很难达到治愈效果。
在过去数十年内，在美国SCLC的总发病率与死亡率有所下降。
据估计，2020年美国肺癌（SCLC与非小细胞肺癌[NSCLC]）新发病例和死亡病例分别为：
年龄增长是大多数癌症发生的最重要危险因素。促进肺癌发生的其他危险因素包括下列：
肺癌可能表现出症状，或偶然从胸部影像中发现。症状与体征的产生可能来自原发性局部侵犯或对邻近胸腔结构的压迫、远端转移或副肿瘤综合征。发病时最常见的症状为咳嗽加重、呼吸短促和呼吸困难。其他症状包括：
症状产生的原因可能是局部侵犯或对邻近胸腔结构的压迫，例如压迫食管引起吞咽困难，压迫喉神经引起声音嘶哑，压迫上腔静脉引起面部水肿、头颈部浅静脉扩张等。也可能出现远端转移症状，例如脑转移引起神经源性损害或人格变化，或骨转移引起骨痛。
少数SCLC患者可能出现副肿瘤综合征症状与体征：
体格检查可能发现锁骨上淋巴结肿大、胸腔积液或肺不张、迁延性肺炎、或慢性阻塞性肺疾病等合并症相关体征。
患者治疗方法的选择取决于组织学、分期、一般情况和并发症等。对怀疑SCLC的患者，检查的主要目的是确诊和判断病变受累范围。
癌症的诊断方法包括：
在患者开始肺癌治疗之前，必须由一位经验丰富的肺癌病理科医师审阅病理材料。这一点十分关键，因为SCLC对化疗反应良好，通常不通过手术治疗，而SCLC与NSCLC的镜下表现可能相似。
免疫组化与电镜对诊断与分类的作用有限，但多数肺部肿瘤可以通过光镜标准分类。
（关于分期检查与步骤的更多信息，请参考本总结的SCLC章节分期信息的分期评价章节。）
尽管过去25年中SCLC的诊治手段有所发展，但除去分期因素，SCLC患者的预后大多不令人满意。如不经治疗，临床过程中SCLC是所有肺肿瘤中最具侵袭性的，距确诊的中位生存时间仅2-4月。只有约10%的SCLC患者在治疗后2年内无复发，而多数复发会在此期间发生。但是这部分患者仍有死于肺癌的风险（小细胞肺癌与非小细胞肺癌均为如此）。
5年总生存率为5%-10%。
SCLC的一个重要预后因素是肿瘤侵犯范围。局限期患者预后好于广泛期患者。据报道，局限期患者经当前治疗后中位生存时间为16-24个月，5年生存率为14%。
应鼓励确诊局限期的吸烟患者在接受综合治疗之前先戒烟，因为继续吸烟可能会影响患者生存期。
研究显示局限期患者经综合治疗可提高长期生存率。
[证据等级：1iiA]虽然单独行手术或化疗的患者中也有长期生存者，但化疗联合胸部放疗（TRT）是目前的标准治疗。
TRT联合化疗与单独化疗相比，绝对生存率提高约5%。
多项临床试验与荟萃分析评估了TRT距化疗的最佳时机，证据显示早期TRT有少量获益。
[证据等级：1iiA]
广泛期患者经当前治疗后的中位生存时间为6-12个月，但长期无病生存期十分罕见。
预防性脑照射有助于预防中枢神经系统复发，并提高对LD放化疗或ED化疗后达到完全缓解或极佳部分缓解且体能状态良好的患者的生存期。
[证据等级：1iiA]
胸部放疗还可改善这些患者的长期预后。
所有此类肿瘤患者在诊断时可考虑适合纳入临床试验。关于正在进行的临床试验信息，请访问NCI网站。
SCLC accounts for approximately 15% of bronchogenic carcinomas.
At the time of diagnosis, approximately 30% of patients with SCLC will have tumors confined to the hemithorax of origin, the mediastinum, or the supraclavicular lymph nodes. These patients are designated as having limited-stage disease (LD).
Patients with tumors that have spread beyond the supraclavicular areas are said to have extensive-stage disease (ED).
SCLC is more responsive to chemotherapy and radiation therapy than other cell types of lung cancer; however, a cure is difficult to achieve because SCLC has a greater tendency to be widely disseminated by the time of diagnosis.
The overall incidence and mortality rates of SCLC in the United States have decreased during the past few decades.
Estimated new cases and deaths from lung cancer (SCLC and non-small cell lung cancer [NSCLC] combined) in the United States in 2020:
Increasing age is the most important risk factor for most cancers. Other risk factors for lung cancer include the following:
Lung cancer may present with symptoms or be found incidentally on chest imaging. Symptoms and signs may result from the location of the primary local invasion or compression of adjacent thoracic structures, distant metastases, or paraneoplastic phenomena. The most common symptoms at presentation are worsening cough, shortness of breath, and dyspnea. Other presenting symptoms include the following:
Symptoms may result from local invasion or compression of adjacent thoracic structures, such as compression involving the esophagus causing dysphagia, compression involving the laryngeal nerves causing hoarseness, or compression involving the superior vena cava causing facial edema and distension of the superficial veins of the head and neck. Symptoms from distant metastases may also be present and include neurological defect or personality change from brain metastases or pain from bone metastases.
Infrequently, patients with SCLC may present with symptoms and signs of one of the following paraneoplastic syndromes:
Physical examination may identify enlarged supraclavicular lymphadenopathy, pleural effusion or lobar collapse, unresolved pneumonia, or signs of associated disease such as chronic obstructive pulmonary disease.
Treatment options for patients are determined by histology, stage, and general health and comorbidities of the patient. Investigations of patients with suspected SCLC focus on confirming the diagnosis and determining the extent of the disease.
The procedures used to determine the presence of cancer include the following:
Before a patient begins lung cancer treatment, an experienced lung cancer pathologist must review the pathologic material. This is critical because SCLC, which responds well to chemotherapy and is generally not treated surgically, can be confused on microscopic examination with NSCLC.
Immunohistochemistry and electron microscopy are invaluable techniques for diagnosis and subclassification, but most lung tumors can be classified by light microscopic criteria.
(Refer to the Staging Evaluation section in the Stage Information for SCLC section of this summary for more information about tests and procedures used for staging.)
Regardless of stage, the current prognosis for patients with SCLC is unsatisfactory despite improvements in diagnosis and therapy made during the past 25 years. Without treatment, SCLC has the most aggressive clinical course of any type of pulmonary tumor, with median survival from diagnosis of only 2 to 4 months. About 10% of the total population of SCLC patients remains free of disease during the 2 years from the start of therapy, which is the time period during which most relapses occur. Even these patients, however, are at risk of dying from lung cancer (both small and non-small cell types).
The overall survival at 5 years is 5% to 10%.
An important prognostic factor for SCLC is the extent of disease. Patients with LD have a better prognosis than patients with ED. For patients with LD, median survival of 16 to 24 months and 5-year survivals of 14% with current forms of treatment have been reported.
Patients diagnosed with LD who smoke should be encouraged to stop smoking before undergoing combined-modality therapy because continued smoking may compromise survival.
Improved long-term survival in patients with LD has been shown with combined-modality therapy.
[Level of evidence: 1iiA] Although long-term survivors have been reported among patients who received either surgery or chemotherapy alone, chemotherapy combined with thoracic radiation therapy (TRT) is considered the standard of care.
Adding TRT increases absolute survival by approximately 5% over chemotherapy alone.
The optimal timing of TRT relative to chemotherapy has been evaluated in multiple trials and meta-analyses with the weight of evidence suggesting a small benefit to early TRT.
[Level of evidence: 1iiA]
In patients with ED, median survival of 6 to 12 months is reported with currently available therapy, but long-term disease-free survival is rare.
Prophylactic cranial radiation prevents central nervous system recurrence and can improve survival in patients with good performance status who have had a complete response or a very good partial response to chemoradiation in LD or chemotherapy in ED.
[Level of evidence: 1iiA]
Thoracic radiation may also improve long-term outcomes for these patients.
All patients with this type of cancer may appropriately be considered for inclusion in clinical trials at the time of diagnosis. Information about ongoing clinical trials is available from the NCI website.
在小细胞肺癌（SCLC）患者开始治疗前，必须由一位经验丰富的肺癌病理科医师审阅病理材料。
当前的SCLC亚型包括：
神经内分泌细胞来源的SCLC，是特殊的肺神经内分泌癌。
神经内分泌肿瘤包括：
因上述肿瘤的临床表现、治疗、流行病学均不相同，故修订版世界卫生组织（WHO）肿瘤分类法分别对这些肿瘤进行了分类。修订版WHO分类中不再包括SCLC变异型--混合小细胞/大细胞癌，现在SCLC仅有一种变异型，即混合型SCLC，肿块中至少含有10%的非小细胞成分。
SCLC中增生的小细胞具有下列形态学特点：
混合型小细胞癌包括小细胞与大细胞混合型或小细胞与其他任何非小细胞成分混合型。SCLC成分占至少10%的肿瘤诊断为混合型SCLC，组织学为单纯SCLC的肿瘤才称为SCLC。SCLC与LCNEC成分混合的诊断为混合LCNEC的SCLC。
几乎所有的SCLC均对角蛋白、甲状腺转录因子1和上皮膜抗原有免疫反应。神经内分泌分化与神经分化的肿瘤表达多巴脱羧酶、降钙素、神经元特异性烯醇酶、嗜铬粒蛋白A、CD56（也称为核小体组蛋白激酶1或神经细胞黏附分子）、胃泌素释放肽和胰岛素样生长因子1。约75%的SCLC中可见至少一种神经内分泌分化标志物的表达。
尽管癌前病变和原位癌在非小细胞肺癌患者中较为常见，但在SCLC患者中很罕见。
Before initiating treatment of a patient with small cell lung cancer (SCLC), an experienced lung cancer pathologist should review the pathologic material.
The current classification of subtypes of SCLC includes the following:
SCLC arising from neuroendocrine cells forms one extreme of the spectrum of neuroendocrine carcinomas of the lung.
Neuroendocrine tumors include the following:
Because of differences in clinical behavior, therapy, and epidemiology, these tumors are classified separately in the World Health Organization (WHO) revised classification. The variant form of SCLC called mixed small cell/large cell carcinoma was not retained in the revised WHO classification. Instead, SCLC is now described with only one variant, SCLC combined, when at least 10% of the tumor bulk is made of an associated non-small cell component.
SCLC presents as a proliferation of small cells with the following morphological features:
Combined small cell carcinoma includes a mixture of small cell and large cell or any other non-small cell component. Any cases showing at least 10% of SCLC are diagnosed as combined SCLC, and SCLC is limited to tumors with pure SCLC histology. SCLC associated with LCNEC is diagnosed as SCLC combined with LCNEC.
Nearly all SCLC are immunoreactive for keratin, thyroid transcription factor 1, and epithelial membrane antigen. Neuroendocrine and neural differentiation result in the expression of dopa decarboxylase, calcitonin, neuron-specific enolase, chromogranin A, CD56 (also known as nucleosomal histone kinase 1 or neural-cell adhesion molecule), gastrin-releasing peptide, and insulin-like growth factor 1. One or more markers of neuroendocrine differentiation can be found in approximately 75% of SCLC.
Although preinvasive and in situ malignant changes are frequently found in patients with non-small cell lung cancer, these findings are rare in patients with SCLC.
小细胞肺癌（SCLC）有多种不同的分期系统。分期系统包括：
未获得广泛接受的此术语定义。局限期（LD）SCLC仅出现在一侧胸腔、纵隔或锁骨上淋巴结中，其可包含在可耐受的放射野内。
胸腔积液、肺巨大肿瘤和对侧锁骨上淋巴结转移患者在不同研究中被纳入或排除出局限期。
广泛期（ED）SCLC病变超出锁骨上区域，且超出局限期范围。远端转移（M1）均视为ED.
AJCC TNM将LD定义为除T3-4之外的任何T、任何N和M0，这是由于不适合在可耐受辐射野的多个肺结节。
这对应于TNM I期至IIIB期。 广泛期疾病为TNM IV期，有远端转移（M1），包括恶性胸腔积液。
（如需了解更多信息，请参阅非小细胞肺癌PDQ总结中的AJCC分期分组和TNM定义章节。）
IASLC使用第6版AJCC TNM肺癌分期系统对SCLC临床TNM分期进行分析。临床I、II期患者的生存时间与N2或N3的III期患者有显著差异。
有胸腔积液的患者预后介于局限期与伴有血源性转移的广泛期之间，这些患者为M1期（或广泛期）。TNM分期系统应用不影响患者治疗，但该分析显示在LD临床试验中，准确的TNM分期与分层至关重要。
SCLC分期对区分病变局限于胸腔和有远端转移有重要作用。确诊时约有三分之二的SCLC患者有转移证据，其余多数患者有肺门、纵膈广泛淋巴结受累，部分患者也有锁骨上区淋巴结受累。
确定癌症分期有助于评估预后与决定治疗，尤其可帮助局限期患者决定化疗联合手术切除或胸部放疗。如果确诊广泛期，应根据患者特有的症状体征进行个体化评估。标准分期程序包括：
正电子发射断层扫描（PET）的作用仍在研究中。SCLC是在主要部位和转移部位均呈高代谢状态的氟18F-脱氧葡萄糖（18F-FDG）。PET可能用于SCLC患者的分期，这些患者可能是在化疗中增加胸部放疗的候选者，因为PET可能导致患者分期上调或下调，以及由于发现其他部位的淋巴结转移而导致放射野改变。
证据（18F-FDG PET）：
Several staging systems have been proposed for small cell lung cancer (SCLC). These staging systems include the following:
No universally accepted definition of this term is available. Limited-stage disease (LD) SCLC is confined to the hemithorax of origin, the mediastinum, or the supraclavicular nodes, which can be encompassed within a tolerable radiation therapy port.
Patients with pleural effusion, massive pulmonary tumor, and contralateral supraclavicular nodes have been both included within and excluded from LD by various groups.
Extensive-stage disease (ED) SCLC has spread beyond the supraclavicular areas and is too widespread to be included within the definition of LD. Patients with distant metastases (M1) are always considered to have ED.
The AJCC TNM defines LD as any T, except for T3-4, due to multiple lung nodules that do not fit in a tolerable radiation field, any N, and M0.
This corresponds to TNM stages I to IIIB. Extensive disease is TNM stage IV with distant metastases (M1) including malignant pleural effusions.
(Refer to the AJCC Stage Groupings and TNM Definitions section in the PDQ summary on Non-Small Cell Lung Cancer for more information.)
The IASLC conducted an analysis of clinical TNM staging for SCLC using the sixth edition of the AJCC TNM staging system for lung cancer. Survivals for patients with clinical stages I and II disease are significantly different from those for patients with stage III disease with N2 or N3 involvement.
Patients with pleural effusion have an intermediate prognosis between LD and ED with hematogenous metastases and will be classified as having M1 disease (or ED). Application of the TNM system will not change how patients are managed; however, the analysis suggests that, in the context of clinical trials in LD, accurate TNM staging and stratification may be important.
Staging procedures for SCLC are important to distinguish patients with disease limited to their thorax from those with distant metastases. At the time of initial diagnosis, approximately two-thirds of patients with SCLC have clinical evidence of metastases; most of the remaining patients have clinical evidence of extensive nodal involvement in the hilar, mediastinal, and sometimes supraclavicular regions.
Determining the stage of cancer allows an assessment of prognosis and a determination of treatment, particularly when chest radiation therapy or surgical excision is added to chemotherapy for patients with LD. If ED is confirmed, further evaluation should be individualized according to the signs and symptoms unique to the individual patient. Standard staging procedures include the following:
The role of positron emission tomography (PET) is still under study. SCLC is fluorine F 18-fludeoxyglucose (18F-FDG) avid at the primary site and at metastatic sites. PET may be used in staging patients with SCLC who are potential candidates for the addition of thoracic radiation therapy to chemotherapy, as PET may lead to upstaging or downstaging of patients and to alteration of radiation fields resulting from the identification of additional sites of nodal metastases.
Evidence (18F-FDG PET):
研究发现化疗与放疗改善小细胞肺癌（SCLC）患者的生存。
化疗可提高局限期（LD）或广泛期（ED）患者的生存率，但仅对少数患者有效。
由于SCLC患者往往出现远端转移，因此局部治疗（例如手术切除或放疗）很少能产生长期生存。
但是，将当前化疗方案纳入治疗方案后，患者的生存期得以延长，与未接受治疗的患者相比，中位生存时间至少延长四到五倍。
依托泊苷联合铂类是最常用的标准化疗方案。
[证据等级：1iiA] 铂类和非铂类联合治疗、增加剂量或给药频次、改变不同化疗药的给药方式（例如更换或序贯给药）或维持化疗，均未产生一致的生存获益。
[证据等级：1iiA]
SCLC具有高度放疗敏感性，胸部放疗改善局限期与广泛期患者的生存期。
[证据等级：1iiA] 预防性脑照射（PCI）可预防中枢神经系统复发，可延长对放化疗有反应的体能状态良好患者的长期生存期[证据等级：1iiA] 且可能缓解肿瘤转移产生的症状。
LD、ED或复发性SCLC患者的治疗总结见表1。
| 分期 | 标准治疗选择 |
|---|---|
| 复发性疾病 | |
| ED = 广泛期疾病；LD = 局限期疾病 | |
尽管治疗取得了进展，但即使有最有效的治疗方法，大多数SCLC患者也会死于肿瘤。尝试改善现有最佳治疗方法的临床试验使大部分SCLC患者的生存率得到提高。非常希望患者参与该研究。
关于正在进行的临床试验信息，请访问NCI网站。
Chemotherapy and radiation therapy have been shown to improve survival for patients with small cell lung cancer (SCLC).
Chemotherapy improves the survival of patients with limited-stage disease (LD) or extensive-stage disease (ED), but it is curative in only a minority of patients.
Because patients with SCLC tend to develop distant metastases, localized forms of treatment, such as surgical resection or radiation therapy, rarely produce long-term survival.
With incorporation of current chemotherapy regimens into the treatment program, however, survival is prolonged, with at least a fourfold to fivefold improvement in median survival compared with patients who are given no therapy.
The combination of platinum and etoposide is the most widely used standard chemotherapeutic regimen.
[Level of evidence: 1iiA] No consistent survival benefit has resulted from platinum versus nonplatinum combinations, increased dose intensity or dose density, altered mode of administration (e.g., alternating or sequential administration) of various chemotherapeutic agents, or maintenance chemotherapy.
[Level of evidence: 1iiA]
SCLC is highly radiosensitive and thoracic radiation therapy improves survival of patients with LD and ED tumors.
[Level of evidence: 1iiA] Prophylactic cranial ir (PCI) prevents central nervous system recurrence and may improve the long-term survival of patients with good performance status who have responded to chemoradiation therapy [Level of evidence: 1iiA] and offers palliation of symptomatic metastatic disease.
Treatment for patients with LD, ED, or recurrent SCLC is summarized in Table 1.
| Stage | Standard Treatment Options |
|---|---|
| Recurrent disease | |
| ED = extensive-stage disease; LD = limited-stage disease | |
Despite treatment advances, most patients with SCLC die of their tumor even with the best available therapy. Most of the improvements in the survival of patients with SCLC are attributable to clinical trials that have attempted to improve on the best available and most accepted therapy. Patient entry into such studies is highly desirable.
Information about ongoing clinical trials is available from the NCI website.
局限期小细胞肺癌（SCLC）患者的标准治疗选择包括：
依托泊苷联合顺铂加胸部放疗（TRT）的联合治疗方法是局限期（LD）SCLC患者最常用的治疗。
证据（联合治疗）：
有放疗禁忌证的患者可接受单纯化疗。出现上腔静脉综合征的患者可根据症状严重程度立即选择联合化疗、放疗或二者结合。
（如需了解更多信息，请参见PDQ心肺综合征总结。）
手术对治疗SCLC患者的作用尚未证实。一些小型病例分析研究与人群研究报道了少数LD患者非常局限的肿瘤，局限于原发肺的小肿瘤或经手术加辅助化疗的局限于肺和同侧肺门淋巴结的患者预后较佳。
[证据等级：3iiiDii] 经手术后确诊的SCLC患者通常接受辅助化疗，伴或不伴放疗。对于已经接受了放化疗的患者，再经手术不会延长生存期。
[证据等级：3iiiDii] 因缺乏随机临床试验证据，讨论手术对单个SCLC患者的作用时必须考虑到手术的潜在获益及其风险。
证据（手术的作用）：
达到完全缓解的患者可考虑接受PCI。肿瘤控制在脑外范围的患者在开始治疗后2-3年内发生中枢神经系统（CNS）转移的风险为60%。
其中绝大多数患者仅有脑部转移复发，几乎所有CNS复发患者均死于脑转移。PCI可使CNS转移的风险降低50%以上。
证据（PCI的作用）：
回顾性研究表明，SCLC的长期生存者（从治疗开始> 2年）的CNS损害发生率较高。
前瞻性研究表明，与未经治疗的患者相比，接受PCI治疗的患者的神经心理功能明显较差。
大多数SCLC患者在开始PCI治疗前均存在神经心理异常，并且在开始PCI治疗后长达2年的时间内其神经系统状态均未检测到下降。
从开始到接受治疗两年后，SCLC患者的神经心理功能持续下降。
在确定PCI不会引发智力下降之前，需要对开始治疗后超过2年的患者进行额外的神经心理学检测。
针对老年患者的最佳治疗方式尚不明确。一项人群分析显示年龄增加与体能状态评分下降、合并症增多相关。
老年患者接受联合放化疗、强化化疗与PCI的可能性较小。老年患者经治疗后缓解几率更小，而生存预后通常更差。但该现象是否与年龄、合并症或次优治疗相关尚不明确。
目前尚无已发表的专门针对LD SCLC老年患者开展的III期临床试验，但已发表的2个协作组研究中共3项次要分析评估了年龄大于等于70岁老年患者的结果。
两项研究均发现老年患者的生存结果与年轻患者相同。但与年轻患者相比，老年患者的毒性反应发生率较高，尤其是血液学毒性反应。EST-3588试验比较了依托泊苷联合顺铂加每日一次或每日两次放疗的效果，发现老年患者的治疗相关死亡率显著升高（年龄＜70岁患者为1%，年龄≥70岁患者为10%；P=0.01）。
因为该III期临床试验入组的老年患者可能并非普通人群中LD SCLC患者的典型代表，故将这些结果推广至普通老年人群必须慎重。
处于临床评价阶段的LD SCLC治疗选择如下所示：
利用我们先进的临床试验检索工具查找NCI支持的癌症临床试验（当前正在招募患者）。可通过试验地点、治疗类型、药物名称和其他标准缩小检索范围。还可获得关于临床试验的基本信息
Standard treatment options for patients with limited-stage small-cell lung cancer (SCLC) include the following:
Combined-modality treatment with etoposide and cisplatin with thoracic radiation therapy (TRT) is the most widely used treatment for patients with limited-stage disease (LD) SCLC.
Evidence (combined modality treatment):
Patients with a contraindication to radiation therapy could be treated with chemotherapy alone. Patients presenting with superior vena cava syndrome are treated immediately with combination chemotherapy, radiation therapy, or both, depending on the severity of presentation.
(Refer to the PDQ summary on Cardiopulmonary Syndromes for more information.)
The role of surgery in the management of patients with SCLC is unproven. Small case series and population studies have reported favorable outcomes for the minority of LD patients with very limited disease, with small tumors pathologically confined to the lung of origin or the lung and ipsilateral hilar lymph nodes from surgical resection with adjuvant chemotherapy.
[Level of evidence: 3iiiDii] Patients who have undergone surgery and then been diagnosed with SCLC generally receive adjuvant chemotherapy with or without radiation therapy. In patients who receive chemotherapy with radiation therapy, there is no improvement in survival with the addition of surgery.
[Level of evidence: 3iiiDii] Given the absence of data from randomized trials, the role of surgery in the management of individual patients with SCLC must be considered, both in terms of potential benefit and risk from the surgical procedure.
Evidence (role of surgery):
Patients who have achieved a complete remission can be considered for administration of PCI. Patients whose cancer can be controlled outside the brain have a 60% actuarial risk of developing central nervous system (CNS) metastases within 2 to 3 years after starting treatment.
Most of these patients relapse only in their brain, and nearly all of those who relapse in their CNS die of their cranial metastases. The risk of developing CNS metastases can be reduced by more than 50% with the administration of PCI.
Evidence (role of PCI):
Retrospective studies have shown that long-term survivors of SCLC (>2 years from the start of treatment) have a high incidence of CNS impairment.
Prospective studies have shown that patients treated with PCI do not have significantly worse neuropsychological function than patients not treated.
Most patients with SCLC have neuropsychological abnormalities present before the start of PCI and have no detectable decline in their neurological status for as long as 2 years after the start of their PCI.
Patients treated for SCLC continue to have declining neuropsychologic function after 2 years from the start of treatment.
Additional neuropsychologic testing of patients beyond 2 years from the start of treatment will be needed before concluding that PCI does not contribute to the decline in intellectual function.
The optimal therapeutic approach in older patients remains unclear. A population analysis showed that increasing age was associated with a decreased performance status and increased comorbidity.
Older patients were less likely to be treated with combined chemoradiation therapy, more intensive chemotherapy, and PCI. Older patients were also less likely to respond to therapy and had poorer survival outcomes. Whether this was a result of age and its associated comorbidities or suboptimal treatment delivery remains uncertain.
No specific phase III trial in older patients with LD SCLC has been reported; however, three secondary analyses of two cooperative group trials have been published evaluating outcomes in patients aged 70 years or older.
The survival outcomes for the older patients were identical to their younger counterparts in both trials. The older patients experienced more toxic effects, particularly hematologic, compared with younger patients. There was a significant increase in treatment-related mortality in the EST-3588 trial ( that compared etoposide and cisplatin with either once-daily or twice-daily radiation therapy (1% for patients aged <70 years vs. 10% for patients aged ≥70 years; P = .01).
Because the older patients enrolled in these phase III trials may not be representative of LD SCLC patients in the general population, caution must be exercised in extrapolating these results to the general population of older patients.
Treatment options under clinical evaluation for patients with LD SCLC include the following:
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
广泛期小细胞肺癌（SCLC）患者的标准治疗选择包括：
广泛期（ED）SCLC患者的化疗常为铂类与依托泊苷两药联合治疗，所用剂量与至少中度毒性反应相关（与局限期[LD]SCLC相似）。
顺铂具有明显毒性反应，需要补液，这对于心血管疾病的患者而言较为困难。卡铂也是SCLC治疗常用药物，需根据肾功能决定剂量，非血液学毒性反应较少。
其他治疗方案似乎能达到相似的生存结果，但相关研究及应用均较少。
| 标准治疗 | 依托泊苷+顺铂 |
| 依托泊苷+卡铂 | |
| 其他治疗方案 | 顺铂+伊立替康 |
| 异环磷酰胺+顺铂+依托泊苷 | |
| 环磷酰胺+阿霉素+依托泊苷 | |
| 环磷酰胺+阿霉素+依托泊苷+长春新碱 | |
| 环磷酰胺+依托泊苷+长春新碱 | |
| 环磷酰胺+阿霉素+长春新碱 |
当前治疗计划所用的剂量与方案对ED患者总缓解率在50%-80%，完全缓解率在0%-30%。
[证据等级：1iiA]
小细胞肺癌的颅内转移灶对化疗的反应可能与其他器官转移一样好。
证据（标准治疗方案）：
证据（其他联合化疗方案）：
证据（治疗持续时间）：
证据（剂量强化）：
与LD患者相比，确诊时体能状态严重受损的ED SCLC患者更多。该患者的预后较差，对积极化疗或联合治疗的耐受性较差。已经为这些患者开发了单剂静脉注射、口服和低剂量两周一次治疗方案。
多项前瞻性随机研究表明，与接受单药、低剂量治疗方案或简化治疗疗程的患者相比，接受常规治疗后预后较差的患者的生存期更长。一项将每三周一次化疗与根据症状控制所需治疗进行比较的研究表明，接受常规治疗的患者的QOL有所改善。
[证据等级：1iiDii]
其他研究评估了强化单药或双药治疗方案的有效性。英国医学研究理事会进行的一项研究表明，依托泊苷加长春新碱治疗方案和四药治疗方案的疗效相似。
后一种治疗方案与更高的毒性反应和早期死亡风险有关，但在缓解症状和心理困扰方面则显优。
[证据等级：1iiC]研究比较了便捷口服治疗方法和口服依托泊苷单药治疗与联合治疗，结果显示口服依托泊苷组的总缓解率和OS明显较差。
[证据等级：1iiA]
按年龄分组的SCLC患者的II期和III期试验的亚组分析表明，与年轻患者相比，老年患者的骨髓抑制和阿霉素诱导的心脏毒性反应更严重，并且老年患者的治疗相关的死亡率往往偏高。
但是，约80％的老年患者获得了最佳治疗，其生存率与年轻患者相当。适用于一般人群的标准化疗方案也可用于总体状况良好（例如，体能状态评分为0-1，器官功能正常且无合并症）的老年患者。无证据表明，老年患者与年轻患者的缓解率、无病生存期（DFS）或OS存在差异。
ED SCLC患者的标准治疗选择是对转移病灶部位进行放疗，但不可能立即通过化疗缓解，尤其是脑、硬膜外和骨转移灶。采用全脑放疗治疗脑转移灶。
有时对上腔静脉综合征进行胸部放疗，但单独化疗以及对无反应的患者保留放疗为合适的初始治疗。（如需了解更多信息，请参见PDQ心肺综合征总结。）
接受过化疗治疗的ED患者如已达到缓解效果，可以考虑进行胸部放疗。
证据（胸部放疗）：
接受过化疗治疗的ED患者如已达到缓解效果，可以考虑进行PCI治疗。
证据（PCI）：
与单独化疗相比，联合化疗加胸部放疗并未延长ED SCLC患者的生存期。
处于临床评价阶段的ED SCLC治疗选择如下所示：
利用我们先进的临床试验检索工具查找NCI支持的癌症临床试验（当前正在招募患者）。可通过试验地点、治疗类型、药物名称和其他标准缩小检索范围。还可获得关于临床试验的基本信息。
Standard treatment options for patients with extensive-stage small-cell lung cancer (SCLC) include the following:
Chemotherapy for patients with extensive-stage disease (ED) SCLC is commonly given as a two-drug combination of platinum and etoposide in doses associated with at least moderate toxic effects (as in limited-stage [LD] SCLC).
Cisplatin is associated with significant toxic effects and requires fluid hydration, which can be problematic in patients with cardiovascular disease. Carboplatin is active in SCLC, is dosed according to renal function, and is associated with less nonhematological toxic effects.
Other regimens appear to produce similar survival outcomes but have been studied less extensively or are in less common use.
| Standard treatment | Etoposide + cisplatin |
| Etoposide + carboplatin | |
| Other regimens | Cisplatin + irinotecan |
| Ifosfamide + cisplatin + etoposide | |
| Cyclophosphamide + doxorubicin + etoposide | |
| Cyclophosphamide + doxorubicin + etoposide + vincristine | |
| Cyclophosphamide + etoposide + vincristine | |
| Cyclophosphamide + doxorubicin + vincristine |
Doses and schedules used in current programs yield overall response rates of 50% to 80% and complete response rates of 0% to 30% in patients with ED.
[Level of evidence: 1iiA]
Intracranial metastases from small cell carcinoma may respond to chemotherapy as readily as metastases in other organs.
Evidence (standard regimens):
Evidence (other combination chemotherapy regimens):
Evidence (duration of treatment):
Evidence (dose intensification):
More patients with ED SCLC have greatly impaired performance status at the time of diagnosis than patients with LD. Such patients have a poor prognosis and tolerate aggressive chemotherapy or combined-modality therapy poorly. Single-agent intravenous, oral, and low-dose biweekly regimens have been developed for these patients.
Prospective, randomized studies have shown that patients with a poor prognosis who are treated with conventional regimens live longer than those treated with the single-agent, low-dose regimens or abbreviated courses of therapy. A study comparing chemotherapy every 3 weeks with treatment given as required for symptom control showed an improvement in QOL in those patients receiving regular treatment.
[Level of evidence: 1iiDii]
Other studies have tested intensive one-drug or two-drug regimens. A study conducted by the Medical Research Council demonstrated similar efficacy for an etoposide plus vincristine regimen and a four-drug regimen.
The latter regimen was associated with a greater risk of toxic effects and early death but was superior with respect to palliation of symptoms and psychological distress.
[Level of evidence: 1iiC] Studies comparing a convenient oral treatment with single-agent oral etoposide versus combination therapy showed that the overall response rate and OS were significantly worse in the oral etoposide arm.
[Level of evidence: 1iiA]
Subgroup analyses of phase II and phase III trials of SCLC patients by age showed that myelosuppression and doxorubicin-induced cardiac toxic effects were more severe in older patients than in younger patients and that the incidence of treatment-related death tended to be higher in older patients.
About 80% of older patients, however, received optimal treatment, and their survival was comparable with that of younger patients. The standard chemotherapy regimens for the general population could be applied to older patients in good general condition (i.e., performance status of 0–1, normal organ function, and no comorbidity). There is no evidence of a difference in response rate, disease-free survival (DFS), or OS in older patients compared with younger patients.
Radiation therapy to sites of metastatic disease unlikely to be immediately palliated by chemotherapy, especially brain, epidural, and bone metastases, is a standard treatment option for patients with ED SCLC. Brain metastases are treated with whole-brain radiation therapy.
Chest radiation therapy is sometimes given for superior vena cava syndrome, but chemotherapy alone, with radiation reserved for nonresponding patients, is appropriate initial treatment. (Refer to the PDQ summary on Cardiopulmonary Syndromes for more information.)
Patients with ED treated with chemotherapy who have achieved a response can be considered for thoracic radiation therapy.
Evidence (thoracic radiation therapy):
Patients with ED treated with chemotherapy who have achieved a response can be considered for administration of PCI.
Evidence (PCI):
Combination chemotherapy plus chest radiation therapy does not appear to improve survival compared with chemotherapy alone in patients with ED SCLC.
Treatment options under clinical evaluation for patients with ED SCLC include the following:
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
复发性小细胞肺癌（SCLC）患者的标准治疗选择包括：
在复发时，许多SCLC患者可能适合进一步治疗。
对于复发性小细胞肺癌患者，使用抗程序性死亡配体1（抗PD-L1）抗体进行免疫检查点调节可能产生持久反应，无论是单药还是与细胞毒性T淋巴细胞抗原4（抗CTLA-4）。正在随机试验中评估这些方法对长期生存期的影响。
尽管二线化疗已显示可导致肿瘤消退，但反应通常较短暂。二线治疗后，中位生存期很少超过12个月，通常少于6个月。
对一线化疗的反应可预测对二线治疗的后续反应。
与其他化疗敏感性肿瘤（例如霍奇金淋巴瘤和卵巢上皮癌）一样，已经描述了接受二线化疗的两类主要患者：敏感性和耐药性。敏感患者的一线治疗反应在治疗完成后持续超过90天。这些患者从二线化疗中获益最大。患有敏感疾病的患者中，对相同的初始治疗方案的反应率达约50％；但是，可能产生累积的毒性反应。
耐药性患者对一线化疗无反应或最初有反应，但在完成主要治疗后90天内复发。
托泊替康、伊立替康和吉西他滨等药物的II期研究结果表明，对药物的反应率取决于患者是否患有敏感、耐药或难治性疾病。
[证据等级：3iiiDii]
托泊替康是复发性SCLC的标准化疗方案。患有敏感疾病的患者可能会对多种药物产生反应，包括托泊替康、伊立替康、紫杉烷、长春瑞滨、紫杉醇或吉西他滨。
[证据等级：3iiiDii]联合用药的反应率通常高于单药的反应率，
一项III期研究报告显示，接受顺铂、依托泊苷和伊立替康联合治疗的敏感性疾病患者的生存期得到改善。然而，毒性反应发生率提高。
证据（托泊替康和其他化疗药）：
早期研究表明，既往接受过含铂类药物化疗治疗后疾病进展的广泛期SCLC患者具有持久反应；但是，不存在完全客观缓解。鉴于这些患者的治疗选择不多且预后不良，未选择的PD-L1患者需要考虑接受纳武利尤单抗联合或不联合易普利姆玛治疗；PD-L1阳性疾病的患者可考虑接受帕博利珠单抗治疗。使用这些方法的III期试验结果正在等待中。
证据（纳武利尤单抗联合或不联合易普利姆玛）：
证据（帕博利珠单抗）：
有中枢神经系统（CNS）复发的患者通常加用化疗和或放疗可缓解症状。一项回顾性综述发现CNS复发后增加化疗的患者中43%对二线化疗有良好反应。
大多数接受放疗的患者在放疗后达到客观缓解，并得到相应改善。
一些因肿瘤引起的内生性支气管内阻塞性病变或外在压迫的患者已通过支气管激光治疗（仅针对支气管病变）和/或近距放射治疗成功缓解症状。
对于恶性肿瘤气道梗阻患者，可在局麻下经气管镜放入膨胀式金属内支架以缓解症状、改善肺功能。
初次化疗失败后的进展性胸内肿瘤患者可通过外部放疗达到显著的肿瘤缓解、症状缓解并实现短期局部控制。但是，仅有极少数患者在挽救性放疗后可长期生存。
处于临床评估阶段的复发性SCLC患者的治疗选择包括新药I期和II期临床试验。
利用我们先进的临床试验检索工具查找NCI支持的癌症临床试验（当前正在招募患者）。可通过试验地点、治疗类型、药物名称和其他标准缩小检索范围。还可获得关于临床试验的基本信息。
Standard treatment options for patients with recurrent small-cell lung cancer (SCLC) include the following:
At the time of recurrence, many SCLC patients are potential candidates for further therapy.
For patients with recurrent small-cell lung cancer, immune checkpoint modulation with anti–programmed death-ligand 1 (anti–PD-L1) antibodies may lead to durable responses either as single agents or in combination with cytotoxic T lymphocyte antigen-4 (anti–CTLA-4). Impacts on long-term survival from these approaches are being assessed in randomized trials.
Although second-line chemotherapy has been shown to produce tumor regression, responses are usually short lived; the median survival is rarely more than 12 months and usually less than 6 months after second-line therapy.
Response to first-line chemotherapy predicts for subsequent response to second-line therapy.
As in other chemosensitive tumors (e.g., Hodgkin lymphoma and ovarian epithelial cancer), two main categories of patients receiving second-line chemotherapy have been described: sensitive and resistant. Sensitive patients have a first-line response that lasted more than 90 days after treatment was completed. These patients have the greatest benefit from second-line chemotherapy. Patients with sensitive disease respond to the same initial regimen in approximately 50% of cases; however, cumulative toxic effects may ensue.
Resistant patients either did not respond to first-line chemotherapy or responded initially but relapsed within 90 days of completion of their primary therapy.
Results from phase II studies of drugs such as topotecan, irinotecan, and gemcitabine indicate that response rates to agents vary depending on whether patients have sensitive, resistant, or refractory disease.
[Level of evidence: 3iiiDii]
Topotecan is a standard chemotherapy for recurrent SCLC. Patients with sensitive disease may achieve response to a number of agents including topotecan, irinotecan, taxanes, vinorelbine, paclitaxel, or gemcitabine.
[Level of evidence: 3iiiDii] Response rates for combination agents are generally higher than those reported for single agents,
and one phase III study has reported improved survival for patients with sensitive disease who are treated with combination cisplatin, etoposide, and irinotecan; however, higher rates of toxicity have been seen.
Evidence (topotecan and other chemotherapy agents):
Early phase studies have demonstrated durable responses in some patients with extensive-stage SCLC that has progressed after previous platinum-based chemotherapy; however, none of the objective responses were complete. Given the paucity of treatment options and dismal prognosis for these patients, options to be considered include nivolumab with or without ipilimumab for PD-L1 unselected patients or pembrolizumab for patients with PD-L1-positive disease. Results from phase III trials using these approaches are awaited.
Evidence (nivolumab with or without ipilimumab):
Evidence (pembrolizumab):
Patients with central nervous system (CNS) recurrences can often obtain palliation of symptoms with additional chemotherapy and/or radiation therapy. A retrospective review showed that 43% of patients treated with additional chemotherapy at the time of CNS relapse responded to second-line chemotherapy.
Most patients treated with radiation therapy obtain objective responses and improvement after radiation therapy.
Some patients with intrinsic endobronchial obstructing lesions or extrinsic compression caused by the tumor have achieved successful palliation with endobronchial laser therapy (for endobronchial lesions only) and/or brachytherapy.
Expandable metal stents can be safely inserted under local anesthesia via the bronchoscope, which results in improved symptoms and pulmonary function in patients with malignant airways obstruction.
Patients with progressive intrathoracic tumor after failing initial chemotherapy can achieve significant tumor responses, palliation of symptoms, and short-term local control with external-beam radiation therapy. Only the rare patient, however, will experience long-term survival after receiving salvage radiation therapy.
Treatment options under clinical evaluation for patients with recurrent SCLC include phase I and II clinical trials of new drugs.
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
定期审查PDQ癌症信息总结内容，并在获得最新信息后进行更新。 本章节描述了截至上述日期对本总结所做的最新变更。
更新了2020年估计的新发病例和死亡病例的统计数据（引用美国癌症协会的数据作为参考文献3）。
本总结由PDQ成人治疗编辑委员会撰写并维护，其编辑内容独立于NCI。 总结反映了独立审查文献，不代表NCI或NIH的政策声明。 如需了解更多关于总结政策和PDQ编辑委员会在维护PDQ总结内容中作用的信息，请参见有关“本PDQ总结”和“PDQ®-NCI综合癌症数据库”页。
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Updated statistics with estimated new cases and deaths for 2020 (cited American Cancer Society as reference 3).
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of small cell lung cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Small Cell Lung Cancer Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”
The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Small Cell Lung Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of small cell lung cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Small Cell Lung Cancer Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”
The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Small Cell Lung Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.