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The answer to your question is pretty editor agnostic. Yes, you can remove the Prologue file (both the html file and any entries pointing to it in the opf file). You'd probably want to remove any links from other html files to the now non-existent prologue file as well.
Some editors may automatically take care of the opf changes for you. I'd ask your question in the calibre editor forum for the specifics of how to do so with that editor.
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