Really, this whole category (also the whole game) is RNG Hell. One mistake and you are basically done. It doesn't matter that you just started the run, it's over.

So, to get the best possible time, there are two ways. One way is to move when you see a lot people at one place, then just use the rocket launcher to kill the enemies faster and if you want a faster approach, bomb jump to that place.

However, the enemies can just kill eachother when you arrive, so sometimes it's useless.

The second way was done in my best time (which is a WR) was done since the enemies only had their spawns at the top, so when they respawned i immediately killed them. In other words, the enemies need to have a spawn closer to the top for the best time save.

This guide also applies to the 100 Kills category.

You can only lose a run if you die or just bad RNG. That's about it. I hope this helps.