Predicting Outcomes in NSCLC: Staging or Biology or Both?

The clinical and pathological TNM classification system is the gold standard for estimating survival for patients diagnosed with cancer, including non-small cell lung cancer. For patients with early stage NSCLC, surgical resection, when possible, is considered optimal treatment with improved survival benefit compared to radiation therapy or chemotherapy. Long-term survival for patients with NSCLC remains disappointing, however, and is difficult to predict. Accurate cancer staging remains an invaluable tool to guide treatment and inform patients; something is missing however. In the accompanying article, Li et al. propose that the use of a patient specific systemic inflammatory score provides additional prognostic information for patients undergoing surgical resection for NSCLC.

Cancer alters immunologic and hematologic processes and impacts baseline nutritional status. The Systemic Inflammatory Score (SIS) consists of common laboratory values (serum albumin and lymphocyte-to-monocyte ratio) related to patient nutritional and immune status. For patients with intra-abdominal cancers, the SIS provides predictive information regarding patient survival. In this article, the authors demonstrate for the first time that the SIS predicts survival for patients with NSCLC who undergo VATS lobectomy and reinforces the utility of inflammatory and nutritional markers in predicting outcomes in patients with cancer.

It should not be surprising that the SIS provides important prognostic information for patients with NSCLC. Over the last decade, nutrition has been shown to be increasingly important in lung cancer patients. Poor nutritional status and decrease in body mass accurately predict adverse outcomes in NSCLC patients undergoing targeted immunotherapy [1, 2]. For patients selected for operative resection of NSCLC, preoperative optimization of nutrition decreased postoperative complications and time to chest tube removal and there is a direct correlation with decrease in serum albumin and overall survival [3, 4]. Avoidance of malnourished states before surgery improves outcomes.

Similarly, inflammation portends worse outcomes for patients with cancer. Inflammation is an essential element in the growth and development of most tumors due to exposure to environmental elements and mutations leading to tumor development [5]. Anti-inflammatory drugs have been proven to reduce tumor growth. Studies examining this relationship have quantified inflammation by measuring platelet, neutrophil, and lymphocyte counts, as well as CRP, and these levels have been shown to successfully prognosticate outcomes in NSCLC [6].

Previous studies have also examined various biological markers and their relationship to outcomes in NSCLC patients. Albumin, prealbumin, vitamin precursors, and interleukins have been associated with outcomes in patients with NSCLC [7, 8]. While these markers may be prognostic, it is unclear if a single marker is widely applicable to NSCLC patients regardless of chemotherapy or surgical intervention. Combinations of these nutritional and inflammatory markers have also been used to risk stratify patients [4]. The Glasgow Prognostic Score (GPS) and modified GPS, as well as the comorbidity scoring system (SCSS) have shown promise in predicting outcomes in lung cancer patients [8, 9]. These markers serve as a surrogate for inflammation and immune response, and although the markers verify the relationship between immunosuppression and poor nutritional reserve and poor outcomes, which marker is most predictive is unclear. Forrest et al., considered combinations of albumin and CRP with outcomes for NSCLC patients with inoperable tumors, then, compared this to conventional consideration of performance status and stage [10]. Data showed these two combinations had similar prognostic value. The present study implies that the SIS should be considered as a risk stratification tool as well, which begs the question: which scoring system should be used?

Comparison of different scoring systems as predictive tools for patients with NSCLC undergoing resection would be informative. The SIS is useful in that is predictive and provides the means for intervention for patients at increased risk. Conceptually, preoperative nutritional support is possible, but questions remain as to the duration, means, and end goal of such support. Reducing the role of inflammation also provides potential targets for pharmacotherapy; whether this will improve outcomes will require future prospective randomized study.

The addition of a scoring system to improve prediction of long-term outcomes in individual patient is important for individual patients as well as for cohort comparison within clinical studies. The appeal of the SIS is its simplicity and effectiveness. Whether it is the final answer is unclear, but using the SIS in patients to assess risk and intervene when appropriate makes it an attractive tool that allows for translation into practice immediately. Further validation and adjustment in the SIS and other risk scores with further data may potentially improve outcomes for patients with NSCLC undergoing curative resection.

Declaration of Interest

The authors report no conflict of interest.