Upgrade ubuntu release from 16.04 to 18.04 on ec2 instance safely

It depends on what your definition is of "safely".

If you define safely as zero downtime for your app, it may be better to reinstall the app in a new ec2 that uses 18.04 as a base and migrate traffic to the new instance.

If you define safely as an in-place upgrade with expected downtime, then it may be better to create an AMI of your instance, spin up a new ec2 and try the upgrade. If the upgrade works then you can deprecate the old instance.

Instead of 18.04 (Apr 2018), if possible, I would recommend using the latest Ubuntu which is 22.04 (Apr 2022) today. Both are LTS releases which have support for 5 years. The former will have support until 2023 and the latter will have support until 2027.