In principle, urothelial cancer at all stages can metastasize to other organs. The most malignant (grade 3) metastasize earlier than grade ≤ 2. An advanced stage local tumor (T ≥ 2) metastasizes more frequently than superfical tumors (T ≤ 1).
WHO grade 1 tumors can become large and infiltrate locally. They have a great tendency for recurrence, but almost never metastasize to other organs.
WHO grade 2 tumors grow slowly locally, but infiltrating into mucosa (T1) and further through the basal membrans and into the bladder muscle, through this and out into adipose tissue or into neighboring organs (T ≥ 2). A grade 2 tumor can cause spread when it becomes infiltrating (T ≥ 1), but the risk of metastases usually increases only when it infiltrates muscle. The deeper infiltration of the local tumor, the higher frequency of metastases.
A WHO grade 3 tumor is the most aggresive tumor type and almost always infiltrates (T ≥ 1) at the time of diagnosis. This tumor does not necessarily become very large, but quickly infiltrates the bladder wall and neighboring organs. It spreads early to both regional lymph nodes and distant metastases. Metastases occur hematogenously to pelvic and retroperitoneal lymph nodes with distant spread to the lungs, bone, and liver.
Metastasis occurs hematogenously to all organs, most frequently the lungs, liver, bone, or lymphatically to regional lymph nodes in the pelvis, or further to retroperitoneal lymph nodes.