Who needs surgical removal of the bladder (radical cystectomy)? And who doesn’t need it? Unfortunately, that question is still very hard to answer. Some research groups have proposed that for certain patients with bladder cancer – people whose tumors contain specific mutations – a very favorable response to chemotherapy may be enough to justify leaving the bladder in place, and then following the patient closely.

Not so fast, say Brady scientists. “That’s a milestone we have not yet achieved,” says Trinity Bivalacqua, M.D., Ph.D., the R. Christian B. Evensen Professor in Urology and Director of Urologic Oncology. “The standard of care for localized, muscle-invasive bladder cancer is neoadjuvant chemotherapy, followed by radical cystectomy and urinary diversion. We don’t yet have reliable and accurate methods to identify who can safely avoid surgery.”

In a recent study, Bivalacqua and Alex Baras, M.D., Ph.D., Director of Pathology Informatics, studied data from more than 300 bladder cancer patients who received chemotherapy and radical cystectomy at Johns Hopkins, evaluating doctors’ accuracy in determining a patient’s response to chemotherapy before cystectomy. Their findings, published in European Urology, showed that current strategies to identify patients who can safely avoid cystectomy, including tumor sequencing for DNA mismatch repair mutations, were not useful in identifying patients who had responded well to chemotherapy. “Even repeated visual (cystoscopic) examinations of the bladder with repeat biopsies failed to identify residual high-stage cancer in nearly a third of patients,” says Baras.

“The idea that we could accurately pick out which patients have been cured by chemotherapy alone, and avoid surgery in those cases, is very intriguing,” says urology resident Russell Becker, M.D., Ph.D., one of two lead authors on the study, along with Brady resident Alexa Meyer, M.D. “But we just aren’t there yet. We have some work to do, to refine these techniques before they can safely be applied to guide management decisions – especially when the stakes are so high.” Several large, ongoing clinical trials are attempting to use tumor sequencing and post-chemotherapy clinical restaging to select patients to forego cystectomy. “Our work strongly suggests that those trials are misclassifying quite a few patients – who may, in fact, have residual muscle-invasive disease – and are shunting them into an experimental, conservative management strategy that may ultimately be more hazardous than the surgery they are trying to avoid.”