Proposed hypothetical pathway for clinical high risk (IPI 3-5) patients with DLBCL in future. An ideal workup should include molecular subtyping, functional imaging with radiomic risk assessment, and ctDNA measurements at the baseline and during treatment. Therapies should be adjusted for the various risk factors. Patients without other than clinical risk factors and with a good response to therapy might not need additional treatment other than standard (PV)R-CHOP. Notably, the addition of PV to R-CHOP requires the omission of vincristine (PV-R-CHP).