Abstract
Simple SummaryIn resected lung cancer, adjuvant and neoadjuvant chemotherapy following surgery are currently mainly based on TNM classification. With the validation and ongoing trials of targeted therapies in this situation, the relapse risk evaluation needs to be improved to better discriminate patients who will really benefit from adjuvant therapies. The objective of this review is to put forth an update on the identified clinical, pathological and molecular prognostic factors and biomarkers in development that could change clinical practices in the near future.Lung cancer is the most common cause of cancer mortality worldwide, and non-small cell lung cancer (NSCLC) represents 80% of lung cancer subtypes. Patients with localized non-small cell lung cancer may be considered for upfront surgical treatment. However, the overall 5-year survival rate is 59%. To improve survival, adjuvant chemotherapy (ACT) was largely explored and showed an overall benefit of survival at 5 years < 7%. The evaluation of recurrence risk and subsequent need for ACT is only based on tumor stage (TNM classification); however, more than 25% of patients with stage IA/B tumors will relapse. Recently, adjuvant targeted therapy has been approved for EGFR-mutated resected NSCLC and trials are evaluating other targeted therapies and immunotherapies in adjuvant settings. Costs, treatment duration, emergence of resistant clones and side effects stress the need for a better selection of patients. The identification and validation of prognostic and theranostic markers to better stratify patients who could benefit from adjuvant therapies are needed. In this review, we report current validated clinical, pathological and molecular prognosis biomarkers that influence outcome in resected NSCLC, and we also describe molecular biomarkers under evaluation that could be available in daily practice to drive ACT in resected NSCLC.
Highlights
Based on GLOBOCAN estimates of lung cancer incidence and mortality in 2020, lung cancer represented 11.4% of the 19.3 million cases and remained the leading cause of cancer death with 1.8 million deaths [1]
We report current clinical, pathological and molecular markers used for prognosis assessment in localized
After adjusting for the period of study, age, sex, WHO performance status, comorbidities, side of tumor, extent of resection, histologic type and stage of disease, Alifano et al found that underweight was associated with lower survival (HRs 1.51, 95% (1.41–1.63)) compared to normal weight, whereas overweight and obesity were associated with improved survival (0.84, 95% (0.81–0.87) and 0.80, 95% (0.76–0.84), respectively) [23]
Summary
Based on GLOBOCAN estimates of lung cancer incidence and mortality in 2020, lung cancer represented 11.4% of the 19.3 million cases and remained the leading cause of cancer death with 1.8 million deaths [1]. ALCHEMIST-immunotherapy is ongoing (NCT02595944) for the evaluation of one-year nivolumab therapy after surgery and adjuvant chemotherapy for patients with stage IB-IIIA disease versus observation only. The role of immunotherapy in the neoadjuvant setting is being analyzed using the pathological response as primary endpoint in most cases This situation stresses the need for better prognosis stratification in localized NSCLC in order to identify patients with the highest risk of relapse and avoid unnecessary treatment for others. Last year, Sachs et al confirmed in a nationwide cohort of 6356 patients that women who were operated on for lung cancer had a significantly better prognosis than men (lower risk of death, HR = 0.73; 95% CI (0.67–0.79) and this survival advantage was found, regardless of age, common comorbidities, physical performance, tumor characteristics and stage of disease [15].
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