Reviewer: John J. Wilson, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: August 23, 2002
Authors: Keller SM, Adak S, et al.
Source: New England Journal of Medicine 2000; 343(17): 1217-22.
In patients with surgically resected NSCLC (non-small-cell lung cancer), spread of the tumor to intrathoracic lymph nodes significantly worsens the prognosis for patients. Therefore, many of these patients receive post-operative therapy. The Lung Cancer Study Group found that radiotherapy, combined chemotherapy (cyclophosphamide, doxorubicin, and cisplatin), or both improve local control and disease-free survival, but not overall survival. Radiotherapy is considered to be standard therapy in patients with intrathoracic lymph-node metastases, but many physicians question the efficacy of postoperative chemotherapy. Therefore, the study authors investigated the benefits of postoperative chemotherapy by comparing radiation and chemotherapy compared to radiation alone after surgery in patients with Stage II and IIIa NSCLC.
This study reports on a randomized trial investigating the benefits of adding concurrent chemotherapy onto postoperative radiotherapy for stage II and IIIA N1 or N2 NSCLC. There was no appreciable benefit in survival or recurrence with concurrent treatment, and there were more serious side effects as well. Over the past 20 years, nine phase three trials have been performed looking at adjuvant therapy (chemo, rads, or chemo/rads) in stage II or IIIA NSCLC patients. Six trials showed some benefit in disease free survival, but no benefit in overall survival. The other three trials used cisplatin followed by 6-12 months of a daily oral chemotherapeutic drug, and showed a survival benefit in the treatment group. These findings are of great interest but require validation before they are standard therapy. Also, since there is no clear evidence of a benefit with adjuvant chemotherapy in this group of patients, its use should be restricted to clinical trials. Of note, the median survival of both patient groups (38-39 months) was considerably longer than earlier studies in patients with similar stage cancers. This could be due to more accurate staging and/or better care of patients currently as compared to earlier. Survival seemed to be strongly associated with the type of lymph node dissection patients received, but there were no guidelines or explanations for who received what. Complete dissection was associated with improved survival, which could be due to better removal of metastatic lymph nodes, or it could be a marker for a more experienced/more thorough surgeon.