Background: Pts with aPDAC often have general health impairment due to high symptom burden at diagnosis. We investigated prospectively the clinical benefit (CB) of an EISCP followed by CTx as early as suspicion of aPDAC in pts with ECOG performance status (PS)≥2. Methods: In this multicenter study, PS≥2 pts with pathologically confirmed or suspected aPDAC on imaging were included at first oncology visit (V1) in a personalized 14-d EISCP including pain, nutritional, diagnostic/stenting procedures. Post-EISCP PS≤1 pts received mFOLFIRINOX or gemcitabine(Gem)/Nab-paclitaxel(NP), PS≥2 received mFOLFOX7 or investigator choice CTx or best supportive care (BSC). The primary endpoint was the 14-EISCP success on both feasibility of procedures within 14-d±2 and CB defined by post-EISCP PS≤1, ≥5 points improvement of either fatigue/pain/global health EORTC QLQ-C15-PAL quality of life (QOL) scores, or CTx start ≤30d, aiming 59% success for clinical relevance. Secondary endpoint included uni/multivariate median overall survival (mOS) analyses. Results: As of 07/2022, 106 pts were included; 93 pts were evaluable for primary endpoint: male 46%, mean age 74 yrs, PS2/3 79%/21%, metastases (M1) 62%, pathological diagnosis needed 53%, biliary stenting 16%. V1 mean QOL global health score was 48±23. mOS was 4.1 months (IC95 2.8-5.7). The 14-d feasibility was achieved in 71%. Post-EISCP CB was observed in 82% of pts: 13%, PS improvement to 0/1, 23% QOL improvement and/or 73% CTx start ≤30-d. Eight pts (9%) died during the EISCP. The primary endpoint was achieved in 59% of pts (n=55). Overall, 17 pts (16%) received mFOLFIRINOX/GemNP, 32 (30%) FOLFOX, 29 (27%) Gem or 5FU alone, and 28 (27%) BSC. OS analyses are shown. At d30, pts receiving CTx had a mean change of QOL global health score from 51±23 to 60±23. Conclusions: In PS≥2 pts with aPDAC, a personalized 14-EISCP is feasible and lead to a meaningful CB allowing the administration of doublet/triplet CTx in nearly half of the pts. Pts starting CTx within 30d had improved OS. Clinical trial information: NCT02979483.