A controlled Study of Postoperative Radiotherapy for Patients with Completey Resected Non-Small Cell Lung Carcinoma

Reviewers: John Han-Chih Chang, MD
Source: Cancer 1999 Jul 15; Volume 86(Number 2): pages 265 - 273

Background/Critique/Discussion

Overall, non-small cell lung cancer (NSCLCa) comprises about 85% of the 171,000 newly diagnosed lung cancers each year. The rate of long-term survival has improved minimally over the past several years from 12% to 13 - 14%. Operable patients undergoing a complete surgical resection (CSR) have a long-term survival rate of nearly 30% - 40%. This is even higher in CSR patients with stage I - II disease (55% - 70%). Whether any treatment added adjuvantly in the postoperative setting improves this prognosis is the question. . Many nonrandomized trials have demonstrated the benefits of postoperative radiation therapy (PORT) for high-risk completely resected NSCLCa patients. However, a phase III randomized trial from Belgium (1) utilizing PORT for completely resected stage I NSCLCa demonstrated improved local control (LC), but decreased survival, likely related to treatment toxicity. The Lung Cancer Study Group 773 (2) randomized stage II and III squamous cell lung cancer patients post resection to PORT or no further adjuvant therapy. Five-year overall survival was similar (38% - 40%), but significantly improved LC was observed (60% for the no adjuvant therapy arm versus 97% for the PORT arm). A meta-analysis published recently in the Lancet (3) has cast doubt on the value of PORT for NSCLCa after complete resection. This article was one of the studies utilized in this meta analysis to counter PORT's utility.

Results suggest that PORT has a detrimental effect on NSCLCa patients. However, there is a very high proportion of patients with stage I - II disease, in which it has been shown that PORT can actually cause more toxicity than benefit. Including these patients, in whom we have extensive knowledge of the poor outcome with PORT, may bias the results in favor of no PORT. Of the patients included in this trial, only those with mediastinal disease (N2) were likely to have benefited from PORT. In fact, PORT did improve the distant and local recurrence and cancer related death rates in the N2 patients. This did not manifest itself in an improvement in survival because of the high 5-year intercurrent death rate with PORT (31% mostly treatment related). This may be associated with suboptimal radiotherapy technique as described in the article.This trial supports no PORT for completely resected NSCLCa. However, certain subsets of these patients may benefit. Whether PDRT may improve outcome for stage IIIA (N2 disease) or IIIB (T4 or N3 disease) patients who are completely resected remains a question. There have been subgroup analyses and retrospective reports supporting this.