Age, Pneumonectomy Linked to Poor NSCLC Surgery Outcomes

In the process of their investigation to identify candidates who may be most appropriate for surgical resection of their stage IIIA-N2 non–small cell lung cancer (NSCLC), experts have landed on age older than 70 years and pneumonectomy—a process that involves complete removal of the lung¹—as high-risk factors for poor outcomes.

Publishing their findings in Journal of Chest Surgery, investigators noted that this group of patients were predisposed to less favorable outcomes even after receiving neoadjuvant concurrent chemoradiation therapy (nCCRT).² Optimal treatment of this NSCLC subtype remains up in the air, they continued, with chemotherapy, chemoradiotherapy, a combination of those modalities, and surgical resection all employed.

The investigators' analysis involved 574 patients who received care between 1997 and 2013 | Image Credit: Samsung Medical Center

For this analysis, postop complications had to occur in the 30 days after surgery or before hospital discharge. The authors considered morbidity and mortality outcomes following NSCLC surgery to clarify those factors that put patients at higher risk for poor outcomes. All patients (N = 574; mean [SD] age, 60 [23-76] years; 77.4%, male patients) received treatment at Samsung Medical Center between August 1997 and December 2013. The center employs a trimodal approach to treat and potentially cure NSCLC, which encompasses preoperative CCRT and surgical resection.

As part of their pretreatment staging, all patients underwent pulmonary function tests, CT scans, brain MRI, 18F-fluorodeoxyglucose PET, and nodal staging. Radiation was administered at 45 Gy over 5 weeks (1.8 Gy/fraction/day) from May 1997 to 2008 and then at 44 Gy over 4.5 weeks (2.0 Gy/fraction/day); chemotherapy consisted of weekly paclitaxel or docetaxel plus carboplatin or cisplatin for 5 weeks. Surgery followed within 4 to 6 weeks of CCRT.

No patient had an ECOG performance status (PS) above 1; 98.6% were at ECOG PS 0 and 1.4%, ECOG PS 1. Also, 3.1% had comorbid chronic obstructive pulmonary disease, 59.1% had ever smoked, 28.4% had hypertension, and 11.7% had diabetes. The most common type of lung cancer was adenocarcinoma (56.1%), and clinical T stage distribution, T2 (67.2%). Also, patients received a median (IQR) radiation dose of 45 Gy (44-45), 97.4% of patients had a partial response to CCRT, and a median 33 days elapsed between CCRT and surgery.

The most common types of surgical resection were lobectomy (76.7%), pheumonectomy (12.7%), and bilobectomy (9.9%). Ninety-five percent of patients had a complete resection 5.4% had an incomplete resection, and 57% required adjuvant treatment (30.3%, radiotherapy alone; 13.1%, chemotherapy alone; and 13.6%, CCRT). After treatment, 47% of patients had persistent N2 disease.

Comparing early and late postop mortality—within 30 or 90 days, respectively—1.4% and 7.1% or patients had this outcome, with the investigators seeing a correlation with extent of surgical resection. Also, 4.4% died within 60 days. Complications from surgery were seen in 34.7% of the patients, and the top 3 were arrhythmia (20.2%), prolonged air leak (6.1%), and pneumonia (5.6%).

The investigators incorporated univariate analyses to help them identify risk factors for morbidity and mortality. Male sex, being older than 70 years, smoking history, and pneumonectomy were all associated with worse morbidity and mortality. Additionally, nonadenocarcinoma histology and having a body mass index (BMI) below 18.5 kg/m² were linked to increased morbidity and 5 weeks between completion of CCRT and surgery with worse mortality.

Multivariate analysis then found 82% (OR, 1.82; P = .040), 162% (OR, 2.62; P = .022), and 80% (OR, 1.8; P = .026) predictability of morbidity from age older than 70 years, BMI below 18.5 kg/m², and pneumonectomy, respectively, and 82% (OR, 1.82; P = .022) and 226% (OR, 3.256; P = .003) predictability of mortality from age older than 70 years and pneumonectomy, respectively.

“It is crucial to carefully select patients for surgery who are likely to achieve complete resection with minimal morbidity and mortality following induction chemoradiation therapy,” the authors wrote. “However, there is scant literature on the risk factors associated with morbidity and mortality in surgical treatment for patients with stage IIIA-N2 NSCLC after induction therapy.”

Their findings echo previous research on connections between older age and long-term outcomes,^3,4 elevated mortality rates from pneumonectomy,^5,6 and postop complications irrespective of induction treatment.^7-9

In light of these results, they recommend that future studies examine alternative treatments among older high-risk patients who have “diminished lung function,” including definitive CCRT.

References

1.Pneumonectomy. Johns Hopkins Medicine. Accessed July 9, 2024. https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/pneumonectomy

2. Jeong GH, Lee J, Jeon YJ, et al. Risk factor analysis of morbidity and 90-day mortality of curative resection in patients with stage IIIA-N2 non-small cell lung cancer after induction concurrent chemoradiation therapy. J Chest Surg. 2024;57(4):351-359. doi:10.5090/jcs.23.165

3. Birim O, Kappetein AP, Bogers AJ. Charlson comorbidity index as a predictor of long-term outcome after surgery for nonsmall cell lung cancer. Eur J Cardiothorac Surg. 2005;28(5):759-762. doi:10.1016/j.ejcts.2005.06.046

4. Balducci L. ESH-SIOG International Conference on Haematological Malignancies in the Elderly. Expert Rev Hematol. 2010;3(6):675-677. doi:10.1586/ehm.10.72

5. Van Raemdonck DE, Schneider A, Ginsberg RJ. Surgical treatment for higher stage non-small cell lung cancer. Ann Thorac Surg. 1992;54(5):999-1013. doi:10.1016/0003-4975(92)90677-v 20

6. Mansour Z, Kochetkova EA, Santelmo N, et al. Risk factors for early mortality and morbidity after pneumonectomy: a reappraisal. Ann Thorac Surg. 2009;88(6):1737-1743. doi:10.1016/j.athoracsur.2009.07.016

7. Duque JL, Ramos G, Castrodeza J, et al. Early complications in surgical treatment of lung cancer: a prospective, multicenter study. Grupo Cooperativo de Carcinoma Broncogenico de la Sociedad Espanola de Neumología y Cirugia Toracica. Ann Thorac Surg. 1997;63(4):944-950. doi:10.1016/s0003-4975(97)00051-9

8. Albain KS, Rusch VW, Crowley JJ, et al. Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group phase II study 8805. J Clin Oncol. 1995;13(8):1880-1892. doi:10.1200/JCO.1995.13.8.1880

9. Deslauriers J, Ginsberg RJ, Piantadosi S, Fournier B. Prospective assessment of 30-day operative morbidity for surgical resections in lung cancer. Chest. 1994;106(suppl 6):329S-330S. doi:10.1378/chest.106.6_supplement.329s