Medjedovic stood to lose all of the ETH he was paying in transaction fees (which could have easily been 3 ETH) if someone decided to frontrun his transaction. If that was most of his ETH, that does sound "significant" to me.
The transaction bundle will fail if the success criteria is not reached (often a certain level of profit), so the worst that happens is that the profit margin falls to that level or the transaction is not included with zero cost to the sender