On the contrary, SMAD4 loss was statistically significantly associated with a worse prognosis (33.3% in PP vs 7.4% in GP), and this is the first consistent evidence in lung cancer, in line with other diseases where this alteration was more widely explored.28 In light of the suggested increased sensitivity to DNA topoisomerase inhibitors in lung cancer, this prognostic implication is highly intriguing for further investigations.29 This evidence concerns the gene SMAD4 and lung cancer.