For more than 130 years, Johns Hopkins has provided expertise in treating difficult and rare diseases that doctors at some hospitals might never even come across: diseases like UTUC.

“UTUC is a rare and challenging cancer to manage, accounting for only 5 to 10 percent of all urothelial tumors,” says Nirmish Singla, M.D., M.SC., “Treatment approaches have traditionally been extrapolated from bladder cancer, but mounting evidence suggests that UTUC and bladder cancers are actually disparate entities.”

For example: tobacco exposure is the most common risk factor for developing either UTUC or bladder cancer, but UTUC also has other risk factors, including Lynch syndrome (an inherited condition that raises the risk of many types of cancer) and exposure to aristolochic acid (found in some Chinese herbal medicines and also sold as weight-loss aids).

Furthermore, Singla continues, “UTUC is inherently subject to diagnostic and staging challenges, including both the technical challenges of biopsying tumors in the upper urinary tract and the limitations of conventional cross-sectional imaging.

The gold standard approach to surgically treating UTUC, radical nephroureterectomy (removal of the renal pelvis, kidney, ureter, and bladder cuff), is not without consequences, either, as it places patients at risk of chronic kidney disease.” Given the rarity of UTUC and the complexities of its management, very few centers nationwide have expertise in caring for patients with UTUC.

Recent clinical trials have shown a benefit to integrating systemic therapy with surgery in treating high-risk UTUC. “Thus, access to a multidisciplinary care team that includes an experienced urologic surgeon and genitourinary medical oncologist is paramount to optimizing outcomes in patients with UTUC,” says medical oncologist Jean Hoffman-Censits, M.D., Co-Director of the Women’s Bladder Cancer Program at the Sidney Kimmel Cancer Center.

Recognizing this critical need, as of June 2021, Johns Hopkins offers such a team, co-directed by Hoffman-Censits and Singla. The Clinic, held twice per month, offers streamlined, “one-stop,” personalized care from multiple specialists for patients with this rare and complex disease. Patients will also be able to take part in clinical trials andresearch studies. The clinic will be expanding to include specialists from other disciplines, including nephrology and genetics. 

Same Patient, Different Types of Bladder Cancer

Some patients with cancer in one part of the bladder develop cancer in another part – and these cancers may be made up of different cells, have different biomarkers, and may require different treatment.

“Upper tract and lower tract bladder cancers often arise in the same patients, but the biological relationships between them are not clear,” says David McConkey, Ph.D., the Erwin and Stephanie Greenberg Professor of Urology and Director of the Greenberg Bladder Cancer Institute.

Recently, McConkey and colleagues performed RNA sequencing on upper tract urothelial carcinoma (UTUC) and bladder cancers and examined the tumors’ biological properties. “We found that the tumors could be grouped into two subsets: one that was enriched with biomarkers characteristic of bladder cancer luminal subtypes, and the other that was enriched with basal-like biomarkers. Interestingly, most of the bladder-then-upper tract cancers were concentrated in the basal-like subset, whereas most of the other cancers were luminal, and the basal-like cancers were associated with increased invasion and shorter disease-specific survival.”

“In addition, as is being appreciated in patients with lower-tract cancers, patients with UTUC basal-like cancers may benefit more from immunotherapy, whereas patients with luminal cancers might benefit more from targeted therapies, such as FGFR inhibitors (drugs that slow cell growth) or antibody-drug conjugates.” This work was published in the Journal of Urology.