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Minimum Playthroughs: A minimum of 4, but very unlikely.Does difficulty affect trophies?: Yes, hardcore difficulty is needed.
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You will be finishing the game multiple times anyway. Number of missable trophies: All trophies for defeating bosses in a certain time / way, trophies for Ada / Sherry specific tasks.Approximate amount of time to platinum: 30 Hours (can be done faster if you purchase the infinite weapons DLC for real money, which gives you infinite ammo from the beginning so you could rush through Hardcore difficulty in 1st playthrough).Estimated trophy difficulty: 6/10 (easier if you purchase the infinite weapons DLC for real money, which gives you infinite ammo from the beginning).