Melamed M R
Department of Pathology, New York Medical College, Valhalla 10595, USA.
Cancer. 2000 Dec 1;89(11 Suppl):2356-62. doi: 10.1002/1097-0142(20001201)89:11+<2356::aid-cncr8>3.3.co;2-q.
Anecdotal reports of radiologically occult early stage lung carcinomas detected by sputum cytology suggested that screening by cytology might lead to earlier diagnosis, more effective surgical therapy, and lower death rates from lung carcinoma. Thus, a randomized study was undertaken to evaluate sputum cytology as a lung carcinoma screening technique supplementing the chest X-ray.
Three major medical centers participated in the study, recruiting approximately 10,000 cigarette smoking men older than 45 years of age at each center: Memorial Sloan-Kettering Cancer Center (MSKCC) in New York, NY, Johns Hopkins Hospital in Baltimore, MD, and The Mayo Clinic in Rochester, MN. At MSKCC, the men were divided randomly into two groups: a dual screen group received four monthly sputum cytology examinations in addition to annual posteroanterior and lateral chest X-rays and an X-ray only group received annual chest X-rays but no sputum examinations. The men suspected of lung carcinoma because of radiologic or sputum cytology findings were referred immediately for evaluation, and those with operable lung carcinoma were recommended for surgery and treated with intent to cure.
The men who entered into the study remained in the screening program for 5- 8 years, depending on their date of enrollment, and were followed for 2 years after screening. Follow-up was completed on more than 99%. There were 53 of the 10,040 men in the study who were found to have lung carcinoma on initial examination (prevalence): 23 were in the X-ray only group; of 30 found in the dual screen group, 9 (all with squamous cell carcinoma) were detected by cytology alone. During the entire study and the 2-year follow-up period, 354 of the 10,040 men developed lung carcinoma, equally divided between the dual screen and X-ray only groups. Nearly two-thirds (190 men) had lesions that were detected by screening, and over 50% (100 men) were in Stage I. Excluding oat cell carcinoma, during the screening period 175 of 250 carcinomas (70%) were detected by screening. In contrast, during the 2-year post-screening period, 61 lung carcinomas were diagnosed of which only 12 (20%) were Stage I. Chest X-ray was most effective in detecting peripheral adenocarcinomas of the lung, which were the most common cell type. Cytology was most effective in detecting early epidermoid carcinomas of major bronchi. The epidermoid carcinomas grew slowly, metastasized late, and after becoming visible by X-ray could be treated equally effectively as in the earlier occult stage. Forty percent of all the lung carcinomas were detected in Stage I, and at least two-thirds of the patients with Stage I lung carcinoma treated by complete resection did not die of their disease. Overall 5-year survival of all patients with lung carcinoma who had enrolled in the detection program was 35%, compared with 13% for the United States as a whole during this same time period.
Sputum cytology and the chest X-ray complemented each other as lung carcinoma detection techniques. The chest X-ray best detected peripheral adenocarcinomas of the lung, which are the most common type of lung carcinoma. Sputum cytology detected epidermoid carcinomas arising in major bronchi, but these are slow growing tumors that can be resected and cured after becoming visible by chest X-ray. Thus, for subjects at risk of lung carcinoma who could be followed by annual chest X-rays, sputum cytology did not improve survival, but for high risk subjects who had only a single screening examination, sputum cytology increased the number of early lung carcinomas detected. The design of the current study did not permit evaluation of chest X-ray screening versus nonscreening for prevention of death from lung carcinoma. However, the large proportion of Stage I lung carcinomas and the high survival rate of patients in this study compared with Surveillance, Epidemiology, and End Results program data strongly suggested that screening for lung carcinoma in high risk populations is a valuable public health measure.
痰细胞学检查发现放射学隐匿性早期肺癌的轶事报道表明，细胞学筛查可能会带来更早的诊断、更有效的手术治疗以及更低的肺癌死亡率。因此，开展了一项随机研究，以评估痰细胞学作为补充胸部X线检查的肺癌筛查技术。
三个主要医疗中心参与了该研究，每个中心招募了约10000名年龄超过45岁的吸烟男性：纽约州纽约市的纪念斯隆凯特琳癌症中心（MSKCC）、马里兰州巴尔的摩市的约翰霍普金斯医院以及明尼苏达州罗切斯特市的梅奥诊所。在MSKCC，男性被随机分为两组：双筛组除每年进行后前位和侧位胸部X线检查外，还接受4次每月一次的痰细胞学检查；仅X线组仅接受年度胸部X线检查，但不进行痰检。因放射学或痰细胞学检查结果怀疑患有肺癌的男性立即被转诊进行评估，那些患有可手术肺癌的患者被建议进行手术并接受根治性治疗。
根据入组日期，参与研究的男性在筛查项目中持续5至8年，并在筛查后随访2年。随访完成率超过99%。研究中的10040名男性中有53名在初次检查时被发现患有肺癌（患病率）：仅X线组有23名；双筛组发现的30名中，9名（均为鳞状细胞癌）仅通过细胞学检查发现。在整个研究和2年随访期内，10040名男性中有354名患肺癌，双筛组和仅X线组各占一半。近三分之二（190名男性）的病变通过筛查发现，超过50%（100名男性）为I期。排除燕麦细胞癌，在筛查期间，250例肺癌中有175例（70%）通过筛查发现。相比之下，在筛查后2年期间，诊断出61例肺癌，其中仅12例（20%）为I期。胸部X线在检测最常见的肺外周腺癌方面最有效。细胞学在检测主支气管早期表皮样癌方面最有效。表皮样癌生长缓慢，转移较晚，在通过X线可见后，与早期隐匿阶段一样可以得到有效治疗。所有肺癌患者中有40%在I期被发现，接受根治性切除治疗的I期肺癌患者中至少三分之二没有死于该疾病。参与检测项目的所有肺癌患者的总体5年生存率为35%，而同期美国整体的5年生存率为13%。
痰细胞学和胸部X线作为肺癌检测技术相互补充。胸部X线在检测最常见的肺外周腺癌方面效果最佳。痰细胞学检测主支气管发生的表皮样癌，但这些是生长缓慢的肿瘤，在通过胸部X线可见后可以切除并治愈。因此，对于有年度胸部X线检查随访条件的肺癌高危人群，痰细胞学检查并不能提高生存率，但对于仅进行一次筛查的高危人群，痰细胞学检查增加了早期肺癌的检测数量。本研究的设计不允许评估胸部X线筛查与不筛查对预防肺癌死亡的效果。然而，与监测、流行病学和最终结果项目数据相比，本研究中I期肺癌的高比例和患者的高生存率强烈表明，对高危人群进行肺癌筛查是一项有价值的公共卫生措施。
