There are many options.
If you really just want a 3D box, then you can use Annotation ROI node (select it on the toolbar and initialize it with two clicks in an axial slice):
It is often enough to just mark points. You can use Markups Fiducial points (you can select it from the same toolbar as ROI).
If you prefer a custom shape (for example, sphere) then you can follow this example: Documentation/Nightly/ScriptRepository - Slicer Wiki
If you want some more flexibility then you can use Segment Editor module. For example, you can paint strokes corresponding to “definitely tumor” and “definitely not tumor”. Or, you can quickly create arbitrary shapes using Surface Cut effect (in SegmentEditorExtraEffects extension).
You can customize and automate everything using Python scripts. So, if you need to annotate thousands of images then you don’t need to make a single unnecessary click.