van Zeijl MCT, Ismail RK, de Wreede LC, et al. - Researchers used nationwide population‐based registry to provide evidence on systemically treated patients with advanced melanoma not represented in phase III trials to support clinical decision‐making. Analysis were conducted on advanced melanoma individuals diagnosed between 2014 and 2017 in the Netherlands, treated with immune‐ or targeted therapy, who met ≥ 1 trial exclusion criteria. Of the 2,536 systemically treated patients with advanced melanoma, 1,004 (40%) patients were not eligible for Phase III trials. The conditional inference survival tree displayed the strongest prognostic covariate for survival was lactate dehydrogenase (LDH), followed by Eastern Cooperative Oncology Group Performance Score (ECOG PS). Patient prognosis with LDH of > 500 U/L is poor, but long‐term survival is possible. In real‐world, the prognosis of ineligible patients with advanced melanoma was very heterogeneous and highly dependent on LDH value, ECOG PS, and symptomatic BM.