Sarcomatoid bladder cancer (SBC) is rare – affecting fewer than five percent of patients with bladder cancer – but aggressive. It had been considered resistant to chemotherapy – until several years ago, when medical oncologist Noah Hahn, M.D., Deputy Director of the GBCI, tried something new in collaboration with Brady urologists.

“A sarcomatoid bladder cancer patient with bulky, unresectable (inoperable) disease was referred to the GBCI Multidisciplinary Bladder Cancer Clinic,” says Hahn. He gave the patient a triple-drug combination of cisplatin, gemcitabine, and docetaxel (CGD), and the result was a shocker: “Surprisingly, the patient’s tumor shrank dramatically, making cystectomy (removal of the bladder) possible. Once removed and examined under the microscope, the bladder tissue showed a pathologic complete response – no evidence of tumor – at the time of surgery!” says Hahn’s colleague and mentee, medical oncologist Burles “Rusty” Johnson III, M.D., Ph.D.

Encouraged, over the next eight years, Hahn and other GBCI investigators gave CGD to 16 more patients with muscle-invasive SBC before cystectomy. “We found that 38 percent of these patients had a complete response – again, no tumor found – when surgery was performed to remove the bladder.”

Their findings were published in Bladder Cancer in June 2024, and due to their results and the work of others, SBC is no longer considered a chemotherapy-resistant form of bladder cancer. “These results dispelled the longstanding dogma that chemotherapy does not work in this disease,” says Johnson.

“While our cohort is small, this study represents the first data generated in SBC patients who were treated with a uniform and consistent treatment regimen. This has provided the bladder cancer community with valuable insights,” and may lead to larger studies and new therapeutic approaches. But wait, there’s more! Johnson and Hahn went deeper to learn about SBC, and the drugs that might kill it, on a molecular level. “Our team investigated the gene expression patterns of SBC tumor tissue by performing whole transcriptome RNA sequencing on patient samples before treatment,” says Johnson.

And once again, they obtained results they didn’t expect: “We found that SBC is heterogeneous, and thus does not represent a disease completely distinct from traditional muscle-invasive bladder cancer,” says Johnson. They also discovered that immunotherapy drugs might work here: “It turns out that SBC tumors have high expression of multiple immune-related genes, such as PD-L1, whose expression in tumor samples often correlates with benefit to immune checkpoint inhibitors. We are planning clinical and laboratory-based studies to investigate this possibility.”