Neoadjuvant Therapy Combined With Radical Surgery for the Treatment of Small Cell Lung Cancer (SCLC) in II and IIIA Stage

Before chemotherapy is widely used in clinical work, surgery is the main method for the treatment of lung cancer. However, the prognosis of patients with small cell lung cancer (SCLC) is significantly worse than that of other histological types of lung cancer. The only two prospective studies comparing the surgery with other treatments (surgery vs. radiotherapy alone; induction chemotherapy + surgery vs. chemotherapy + radiotherapy) found that patients in surgery group had a poorer prognosis. Thus, small cell lung cancer was determined to be a non-surgically treated disease. Therefore, for patients with stage II and III A SCLC, combined radiotherapy and chemotherapy are currently recommended. The first-line chemotherapy regimens are etoposide plus cisplatin and carboplatin. Surgical treatment is currently only recommended for very early stage SCLC (T1-2N0M0) with postoperative adjuvant chemotherapy, but these patients only account for about 5% of all SCLC patients. Despite the sensitivity to chemotherapy, the long-term survival of small cell lung cancer remains unsatisfactory. For patients with limited SCLC, even if combined with local radiotherapy, there are still 1/4 to 1/3 of patients progressing due to recurrence of local lesions. So the status of surgical treatment is expected to be reassessed. In recent years, retrospective analysis results of some large databases in Europe and the United States have provided a basis for the role of surgery in the treatment of small cell lung cancer (SCLC). It is believed that surgery should be used as one of the treatment options for SCLC. Based on the results of prospective studies and retrospective studies, a well-designed, phased, prospective study is urgently needed to explore the role of surgery in the treatment of SCLC.

In neoadjuvant therapy combined with radical surgery, neoadjuvant chemotherapy is based on the combination of etoposide and cisplatin/carboplatin. Doses of the drugs are taken from the NCCN guideline for the recommended adjuvant chemotherapy for the limited-period SCLC: namely etoposide 120 mg/m2 through intravenous infusion on Day 1, 2, and 3; cisplatin 60 mg/m2 through intravenous infusion on Day 1 (or carboplatin where area under the curve AUC = 5-6); 4 weeks for a cycle, with a total of 2 cycles of neoadjuvant chemotherapy. Radical surgery is performed according to the growth of SCLC patients after neoadjuvant chemotherapy, using lobectomy or pneumonectomy combined with mediastinal lymph node dissection or sampling. 4 weeks after surgery, chemotherapy and concurrent radiotherapy will be performed. The chemotherapy regimen is the same with that of neoadjuvant chemotherapy, with 4 weeks as a cycle and a total of 2 to 4 cycles. Radiotherapy and adjuvant chemotherapy are planned to be started synchronously, the patients whose intraoperative pathology showed no lymph node metastasis (N0) will receive prophylactic brain irradiation (PCI) treatment and adjuvant chemotherapy synchronously. Within 10 days, the patients will receive a total dose of 25 Gy of PCI, once a day, 2.5 Gy of brain irradiation each time. The patients whose intraoperative pathology show that there is lymph node metastasis (N1-2) are planned to receive PCI combined with mediastinal radiation therapy: namely the patient receive a total of 45 Gy within 3 weeks at the start of adjuvant chemotherapy, twice a day, 1.5 Gy of chest irradiation each time, and the PCI treatment is the same with patients whose intraoperative pathology show there is no lymph node metastasis (N0).