Survival and outcomes after nonoperative management of operable non-small cell lung cancer

The outcomes of patients with operable non-small cell lung cancer who forgo surgery remain poorly defined in the era of modern systemic and radiation therapies. This study evaluated the survival of untreated operable non-small cell lung cancer compared with nonsurgically treated patients using contemporary data.

Using the National Cancer Database (2018-2022), we identified patients with clinical stage I to IIIB non-small cell lung cancer considered operable. Patients were classified as untreated, treated nonoperatively (stereotactic body radiotherapy, radiotherapy, chemotherapy, immunotherapy, or combinations), or surgically treated with/without perioperative therapy. Baseline characteristics and overall survival were compared using chi-square, t tests, Kaplan-Meier, and Cox regression analyses. To further address selection bias, a 1:1 propensity score-matched analysis was performed comparing untreated operable patients with those treated nonsurgically. Matching was conducted using demographic, clinical, and facility-level variables, and survival was reevaluated in the matched cohort.

Among 155,693 operable patients, 149,686 (96%) underwent surgery, 4373 (3%) received nonoperative treatment, and 1634 (1%) were untreated. Untreated patients were younger (72.3 vs 73.2 years, P = .0015), more often White (79% vs 86%, P < .001), and more frequently treated at academic centers (29% vs 24%, P < .001). Median overall survival for untreated versus treated nonoperatively patients was 45 versus 64 months for stage I, 16 versus 37 months for stage II, and 9 versus 40 months for stage III disease. Five-year survival was 43%, 17%, and 14% for untreated patients versus 53%, 34%, and 40% for nonoperatively treated patients, respectively. Among patients with stage IIIB, median survival was 9 months for untreated versus 33 months with nonsurgical therapy (P < .001). On multivariable analysis, increasing age (hazard ratio, 1.04, 95% CI, 1.01-1.07, P = .02), squamous histology (hazard ratio, 2.24, 95% CI, 1.22-4.10, P = .01), and certain facility locations were independently associated with survival differences. After 1:1 propensity score matching, 1629 nonsurgically treated patients were matched to 1628 untreated patients with similar age, sex, comorbidity burden, and year of diagnosis. In the matched cohort, untreated patients continued to demonstrate significantly inferior overall survival compared with those receiving nonsurgical therapy across stages, confirming the robustness of the primary findings.

Patients with operable non-small cell lung cancer who undergo surgical treatment achieve the most favorable survival outcomes. Those treated nonoperatively in the modern era of precision oncology also experience a meaningful survival advantage. In contrast, untreated operable non-small cell lung cancer remains associated with poor prognosis, with median survival less than 1 year for stage III disease. These findings highlight the critical importance of offering active treatment, surgical or nonsurgical, whenever feasible.