At Kanazawa University Hospital, Dr. Hiroshi Kotani and his team have done something that seemed impossible just months ago: they've successfully treated urachal cancer, an ultra-rare malignancy so uncommon it strikes fewer than one person in five million people globally. For patients living with this disease, the breakthrough arrived like a door opening in a wall that had seemed solid for decades.
Urachal cancer is a peculiar disease. It grows in the upper portion of the bladder and accounts for less than one percent of all bladder cancers—so rare that until now, no approved drug treatments existed anywhere in the world for cases where surgery wasn't possible. Compounding the challenge, it behaves differently than typical bladder cancer, instead resembling gastric and colorectal malignancies. That observation proved crucial to the Kanazawa team's insight.
Rather than treating urachal cancer as a bladder disease, the physicians reasoned, why not use the proven treatment regimen for the cancers it actually resembled? They designed a multidisciplinary approach, coordinating specialists from medical oncology, urology, thoracic surgery, and respiratory medicine across their hospital. The treatment they selected—a combination of three drugs: S-1 and oxaliplatin (chemotherapy agents) plus nivolumab (an immune checkpoint inhibitor)—is already the standard therapy for gastric cancer. This chemoimmunotherapy combination delivered remarkable results.
Four patients received the treatment. All four showed clear therapeutic effects. One patient had a tumor so advanced it couldn't be surgically removed; after chemoimmunotherapy, it shrank enough to become operable. Another experienced complete disappearance of their lesions. That patient stopped treatment after two years and remains disease-free today. These aren't incremental improvements—they're transformative outcomes for people who faced a diagnosis with virtually no options.
But how does it work? That's where the Kanazawa team's reverse translational research answered a deeper question. They studied urachal cancer cells in the laboratory to understand the mechanism driving these clinical successes. They confirmed that the platinum-fluorouracil chemotherapy combination inhibited cancer cell growth. More intriguingly, they discovered that this same chemotherapy increased expression of calreticulin, a cellular molecule that flags cancer cells for destruction by the immune system. In other words, the chemotherapy was essentially preparing cancer cells to be recognized and killed by the body's own immunity—which is precisely what nivolumab, an immune checkpoint inhibitor, amplifies.
"These findings not only demonstrate the clinical promise of chemoimmunotherapy for urachal cancer but also elucidate its underlying mechanism of action," Dr. Kotani said. The implications extend beyond these four patients. This research, published in the journal MedComm, is expected to pave the way for the first-ever officially approved drug treatment for urachal cancer—a disease that has lacked any effective systemic therapy worldwide. For an ultra-rare cancer, that's not just progress. It's hope made tangible.