Stage I NSCLC Treatment
Limitations of evidence:
Conclusions about the efficacy of surgery for patients with local and locoregional NSCLC are limited by the small number of participants studied to date and the potential methodological weaknesses of the trials.
Many patients treated surgically subsequently develop regional or distant metastases. Such patients are candidates for entry into clinical trials evaluating postoperative treatment with chemotherapy or radiation therapy following surgery. At present, neither chemotherapy nor radiation therapy has been found to improve the outcome of patients with stage I NSCLC that has been completely resected.
Adjuvant radiation therapy
The value of postoperative (adjuvant) radiation therapy (PORT) has been evaluated.
- A meta-analysis, based on the results of ten randomized controlled trials and 2,232 individuals, reported the following:
- An 18% relative increase in the risk of death for patients who received PORT compared with surgery alone (HR = 1.18; P = .002). This is equivalent to an absolute detriment of 6% at 2 years (95% CI, 2%-9%), reducing OS from 58% to 52%. Exploratory subgroup analyses suggested that this detrimental effect was most pronounced for patients with stage I/II, N0-N1 disease, whereas for patients with stage III, N2 disease, there was no clear evidence of an adverse effect.
- Results for local (HR = 1.13; P = .02), distant (HR = 1.14; P = .02), and overall (HR = 1.10; P = .06) recurrence-free survival similarly showed a detriment of PORT.[Level of evidence: 1iiA]
Further analysis is needed to determine whether these outcomes can potentially be modified with technical improvements, better definitions of target volumes, and limitation of cardiac volume in the radiation portals.
Based on a meta-analysis, postoperative chemotherapy is not recommended outside of a clinical trial for patients with completely resected stage I NSCLC.[9,10][Level of evidence: 1iiA]
- Data on individual patient outcomes were collected and pooled into a meta-analysis from the five largest trials (4,584 patients) that were conducted after 1995 of cisplatin-based chemotherapy in patients with completely resected NSCLC.
- With a median follow-up time of 5.2 years, the overall HR of death was 0.89 (95% CI, 0.82-0.96; P = .005), corresponding to a 5-year absolute benefit of 5.4% from chemotherapy.
- The benefit varied with stage (test for trend, P = .04; HR for stage IA = 1.40; 95% CI, 0.95-2.06; HR for stage IB = 0.93; 95% CI, 0.78-1.10; HR for stage II = 0.83; 95% CI, 0.73-0.95; and HR for stage III = 0.83; 95% CI, 0.72-0.94).
- The effect of chemotherapy did not vary significantly (test for interaction, P = .11) with the associated drugs, including vinorelbine (HR = 0.80; 95% CI, 0.70-0.91), etoposide or vinca alkaloid (HR = 0.92; 95% CI, 0.80-1.07), or other drugs (HR = 0.97; 95% CI, 0.84-1.13).
- The apparent greater benefit seen with vinorelbine should be interpreted cautiously as vinorelbine and cisplatin combinations generally required that a higher dose of cisplatin be given. Chemotherapy effect was higher in patients with a better performance status.
- There was no interaction between chemotherapy effect and any of the following:
- Type of surgery.
- Planned radiation therapy.
- Planned total dose of cisplatin.
- Several other randomized controlled trials and meta-analyses have evaluated the use of postoperative chemotherapy in patients with stage I, II, and IIIA NSCLC.[11,12,13,14,15,16,17]