Second Primary Lung Cancer – An Emerging Issue in Lung Cancer Survivors

As a result of an increased focus on early detection including lung cancer screening, combined with more curative treatment options, the 5-year survival rates for lung cancer are improving. Welcome though this is, it brings new, hitherto unseen challenges. As more patients are cured and survive longer, they are at risk of developing second primary cancers, particularly lung cancer. In this review, we examine the challenges that surveillance, diagnosis, and management of second primary lung cancer (SPLC) bring and how these can be addressed. Recent data from prospective follow-up studies suggests that the incidence of SPLC may be higher than previously appreciated, partly due to an increase in multi-focal adenocarcinoma spectrum disease. Over 5 years, up to 1 in 6 long-term lung cancer survivors may develop a SPLC. Although not routinely used in clinical practice at present, genomic approaches for differentiating SPLC from intrapulmonary metastases of the first primary are emerging, and we highlight how this could be used to help differentiate lesions. An accurate distinction between SPLC and the recurrence of the first primary is of paramount importance due to the very different management strategies that may be required. Wrongly classifying an SPLC as a recurrence of the first primary may have significant consequences for patient management and overall survival. Updated approaches to the classification of SPLC combining clinical history, histopathological assessment, and genomic profiling are needed. Finally, we review the potential role of early detection biomarkers in the identification of SPLC, focusing in particular on blood-based biomarkers that are being examined in a multi-center prospective study recruiting lung cancer survivors.