Beyond the calendar: A narrative review on chronobiological drivers of prognosis in resectable NSCLC

For decades, the surgical management of non-small cell lung cancer (NSCLC) has been predominantly guided by anatomical staging. However, this traditional approach often overlooks the “fourth dimension” of cancer biology: time. This narrative review explores how circadian and circannual rhythms act as silent drivers of oncological prognosis, deeply influencing the interaction between host immunity and tumor behavior. Evidence suggests that the integrity of the molecular clock, regulated by genes such as TIMELESS and RORA, is not merely a biochemical detail but a critical determinant of survival and metastatic potential. Furthermore, environmental cues like Vitamin D synthesis and photoperiodism introduce seasonal fluctuations in patient resilience, creating specific “windows of vulnerability” during surgical stress. Moving toward a “time-aware” oncology opens the possibility of synchronizing clinical interventions—from the hour/season of surgery to immunotherapy scheduling—with the patient’s biological rhythms. Such an approach represents a promising, cost-effective frontier to further personalize the therapeutic journey and optimize long-term outcomes in resectable NSCLC