The combat radius is dictated by the mission ( escort, in which optimal cruise speed is tailored either by flight path (i.e Essing) or modified cruise settings to match bomber speeds - or a compromise.
For a WWII conventional bomber (B-17, Lancaster, He 177, Ju 88) in which a typical mission is defined by trading payload (fuel, crew, bomb load, ammo load) is traded for range a set of parameters need to be assessed. That said,
typical combat radius planning charts are conceptualized and then refined by flight tests so that specific fuel consumption as a function of MP, RPM and altitude charts can be documented along with a set of assumptions.
Internal fuel for the mission, payload, external drag items, cruise speeds as a function of GW and engine settings are key calculation parameters.
During the design phase, mission profiles are often stipulated as a spec and could be described as "Start engines, taxi/take off/climb to altitude, cruise to target, bomb - for the max Gross take off condition for a bomber; then return cruise at a specific altitude calculated at a lower gross weight and even engine settings, loiter for 30 minutes, descend for landing and land with X minutes of internal fuel remaining".
The universal key to mission planning was the mission characteristics which could be expected at the extreme of the planning horizon. For an escort fighter it could be "Drop external fuel tanks/go 100% internal, fight for 5 minutes at WEP, 15 minutes at MP, cruise at 25,000 feet at optimal cruise settings for range at specific altitudes, loiter for 30 minutes, and land with 15 minutes internal fuel remaining".
Then operational and planning details can alter the mission Profile. If a Mustang Group is tasked to go straight to the target and pick up their assigned bombers on the IP, escort them over the target, escort them halfway home - thaey may be cruising at 300mph TAS but because the bombers are doing 210mph TAS, the fighters are not traveling nearly as far in the direction of home because they are Essing around and over the bombers to keep pace - so the planner has to take that factor into account.