Non-Small Cell Lung Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stages IIA and IIB NSCLC Treatment
Preoperative chemotherapy may, however, delay potentially curative surgery.
Evidence (neoadjuvant chemotherapy):
- The Cochrane Collaboration Review group reported a systematic review and meta-analysis of seven randomized controlled trials that included 988 patients and evaluated the addition of preoperative chemotherapy to surgery versus surgery alone. These trials evaluated patients with stages I, II, and IIIA NSCLC.
- Preoperative chemotherapy provided an absolute benefit in survival of 6% across all stages of disease, from 14% to 20% at 5 years (HR, 0.82; 95% CI, 0.69–0.97; P = .022).[Level of evidence: 1iiA]
- This analysis was unable to address questions such as whether particular types of patients may benefit more or less from preoperative chemotherapy.
- In the largest trial reported to date, 519 patients were randomly assigned to receive either surgery alone or three cycles of platinum-based chemotherapy followed by surgery. Most patients (61%) had clinical stage I disease; 31% had stage II disease; and 7% had stage III disease.
- No survival advantage was seen.
- Postoperative complications were similar between groups, and no impairment of quality of life was observed.
- There was no evidence of a benefit in terms of overall survival (OS) (HR, 1.02; 95% CI, 0.80–1.31; P = .86).
- Updating the systematic review by addition of the present result suggests a 12% relative survival benefit with the addition of neoadjuvant (preoperative) chemotherapy (1,507 patients; HR, 0.88; 95% CI, 0.76–1.01; P = .07), equivalent to an absolute improvement in survival of 5% at 5 years.
Adjuvant radiation therapy
The value of postoperative (adjuvant) radiation therapy (PORT) has been evaluated.
Evidence (adjuvant radiation therapy):
- 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.
The preponderance of evidence indicates that postoperative cisplatin combination chemotherapy provides a significant survival advantage to patients with resected stage II NSCLC. Preoperative chemotherapy may also provide survival benefit. The optimal sequence of surgery and chemotherapy and the benefits and risks of postoperative radiation therapy in patients with resectable NSCLC remain to be determined.