Systems and methods for minimally invasive treatment of target tissue among one or more passageways include a flexible elongate device, a tool including a first tubular member, and an instrument to perform treatment on target tissue around the target location. The flexible elongate device includes a proximal end, a distal end, and a lumen therebetween. The tool is configured for deployment within the lumen to a passageway exit site, puncturing a passageway wall at the passageway exit site, and deployment to a target location. The instrument is sized to be deployed within the tool. In some embodiments, the systems and methods further include an anchor configured to stabilize the tool. In some embodiments, the first tubular member is a first hollow sheath configured to be deployed past the distal end of the flexible elongate device to the passageway exit site.