NIEUWEGEIN, THE NETHERLANDS--Five-year survival of patients with non-small-cell lung cancer (NSCLC) is now 41.4%, a new study of more than 2,000 patients indicates.[1] This study also provides evidence that advanced age may not have as adverse an impact on the prognosis for NSCLC as had been thought.

These findings come from a retrospective Dutch study of 2,361 lung cancer patients. This cohort represents all patients with stage I, II, or IIIA primary NSCLC given initial treatment at one institution between 1970 and 1992. The primary objective of the study was to investigate the validity of 1997 changes to staging criteria for NSCLC.

The overall five-year survival rate was 41.4%, van Rens et al found. Not surprisingly, outcome correlated with the severity of the tumor; the survival rate ranged from 63% for patients with stage IA tumors to 19% for those with stage IIIA (Figure 1).

Figure 1 Survival After Surgery for Non-Small-Cell Lung Cancer

Data extracted from van Rens et al. Chest. 2000.[1]

However, some surprises were found. For example, when clinical staging data were augmented by surgical findings and ranked according to the tumor-node-metastasis (TNM) classification, survival rates for patients in clinical stages IB (pT2 N0 M0) and IA (pT1 N1 M0) were found not to be different.

Clinical staging is an inexact science because "understaging" is demonstrated in a considerable number of patients once surgical data become available.

Among the patients who underwent complete resection, 44.3% survived for five or more years, compared with only 16.2% of patients who had incomplete resections. The type of cancer influenced outcome only among patients in the pT2 N1 M0 group, the researchers reported. In this subset, survival was significantly better among patients with squamous-cell lung carcinoma than among those patients with non-squamous-cell carcinoma.

Overall five-year survival was 44% in those under 65 years of age and 38% in those age 65 years or older. However, the authors noted that their study did not differentiate between deaths from cancer and deaths from other causes; therefore, a higher death rate would be expected in the elderly. Furthermore, they found that outcome was worse among elderly patients only in those pTNM subsets that have a better prognosis.

Therefore, van Rens et al suggested that the reduced survival in elderly persons may reflect the fact that these patients are dying from comorbid conditions, not cancer. This suggestion is corroborated by the finding that survival rates were similar in elderly persons and younger patients during the first four years after surgery. A more aggressive approach to treatment may therefore be warranted in elderly patients, the authors noted.

STAGING REFINEMENTS

Based on their results, van Rens et al concluded that the TNM staging system accurately reflects prognosis for many patients with primary NSCLC; however, refinements in some of the stage definitions (such as stage IB and stage IIA) may be needed. Furthermore, the authors suggested that T3 N1 M0 tumors could be reclassified as stage IIB, rather than stage IIIA, disease. However, patients with T3 tumors invading the thoracic wall have better survival rates than do T3 patients with central localization.

--Robert McCarthy

Reference
1. van Rens MThM, Brutel de la Rivière A, Elbers HRJ, van den Bosch JMM. Prognostic assessment of 2,361 patients who underwent pulmonary resection for non-small cell lung cancer, stage I, II, and IIIA. Chest. 2000;117:374-379.

IS COMBINED THERAPY SUPERIOR FOR NON-SMALL-CELL LUNG CANCER?

SALT LAKE CITY--Findings from a phase III clinical trial suggest that chemotherapy followed by irradiation improves survival in patients with advanced, inoperable non-small-cell lung cancer (NSCLC).[1] Although the relative increase in survival is small, the pool of potential patients--particularly, younger patients--who may benefit is significant. In this large, multicenter clinical trial, which included 458 patients with stage II, IIIA, or IIIB NSCLC, Sause et al compared standard radiation therapy with chemotherapy followed by irradiation and, in a third arm, hyperfractionated irradiation, a technique that delivers radiation more than once daily but at a cumulative dose equal to standard irradiation. To be eligible for inclusion in the trial, patients had to have a Karnofsky Performance Status of at least 70 and a weight loss of less than 5% within the three months before study entry. Those eligible were randomized into three equal groups receiving either: 2.0 Gy per fraction once daily, five days a week, up to a total dose level of 60 Gy. 1.2 Gy per fraction twice daily, five days per week, for a total dose of 69.6 Gy. Two months of cisplatin and vinblastine chemotherapy, with radiation therapy beginning on day 50. (In this group, subsequent irradiation was given at a dosage and delivery similar to that in the first irradiation-only group.) The investigators found that median survival rates for the chemotherapy/irradiation group were slightly better than for the two irradiation-only groups. Patients receiving standard irradiation survived, on average, for 11.4 months, with a five-year survival rate of 5%; the hyperfractionated irradiation group survived an average of 12 months, with a five-year survival rate of 6%; and the chemotherapy/irradiation group survived for an average of 13.2 months and had a five-year survival rate of 8%. Survival rates were at least partially a function of age. For patients younger than age 60 years, median survival after chemotherapy and irradiation was 15.4 months, compared with 11.7 months after standard irradiation and 11.5 months after hyperfractionated irradiation therapy. Patients older than age 70 years, however, showed the highest median survival with standard radiation therapy alone (13.1 months). Part of the reason is that all deaths secondary to chemotherapy occurred in those over age 70 years. Sause et al also found that the combination of chemotherapy and irradiation was most effective for non-squamous-cell cancers: median survival was 15.6 months with this form of treatment versus 11.4 months with standard irradiation. Among those with squamous-cell carcinoma, the best outcome was seen with hyperfractionated irradiation, but the differences in survival in this group were not statistically significant. Despite the small size of the benefit shown by the combination of chemotherapy and irradiation, the researchers believe that this large, phase III trial confirms "our ability to alter the natural history of regionally advanced non-small-cell lung cancer with aggressively applied nonsurgical therapy."

Reference 1. Sause W, Kolesar P, Taylor S, et al. Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer. Chest. 2000;117:358-364.

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