Researchers have found that following chemotherapy, 46% of patients with muscle-invasive urothelial carcinoma were able to avoid a cystectomy and achieve a 2-year metastasis-free survival, according to new findings presented by Daniel M. Geynisman, MD, and colleagues at the 2023 ASCO Genitourinary Cancers Symposium (Abstract 438). Although the researchers did not meet their overall benchmark for 2-year metastasis-free survival in the entire group of patients, the results will inform future clinical trials.
Daniel M. Geynisman, MD
Background
“Whether it’s in the next trial or the trial after that, we’re continuously trying to, in an iterative process, improve upon the way we treat patients, preserve quality of life, and provide some options for organ preservation,” emphasized lead study author Dr. Geynisman, Associate Professor of Hematology and Oncology and Chief of the Division of Genitourinary Medical Oncology at the Fox Chase Cancer Center.
Researchers noted that the intent behind the new study was to identify whether certain patients with muscle-invasive urothelial carcinoma could ultimately undergo bladder-sparing treatment. Currently, the standard of care is to treat these patients with chemotherapy and surgically remove their bladders. However, for some patients, the chemotherapy successfully wipes out the cancer—in which case, they may not need a subsequent cystectomy.
Study Methods and Results
In the RETAIN BLADDER phase II clinical trial, the researchers compared the outcomes of an active surveillance group of 26 patients with muscle-invasive urothelial carcinoma who showed no evidence of cancer following chemotherapy and were spared a cystectomy with a control group of 45 patients who received standard-of-care chemotherapy followed by a cystectomy. The endpoint for the trial was 2-year metastasis-free survival.
“Whether patients have surgery or don’t have surgery to remove their bladders, you expect a certain proportion of patients to unfortunately develop metastatic disease,” explained Dr. Geynisman. “The question was, if we do this approach where we allow some [patients] not to go on to surgery, will we be doing at least as good in regards to this very important endpoint of metastatic disease? Because if we are, then we’ve saved some [patients] a big surgery, they have their bladder, and that by itself is a win,” he added.
After 2 years posttreatment with chemotherapy, 12 (46%) of the 26 patients in the active surveillance group had survived without developing metastatic disease and retained their bladders with no radiation. However, 10 (38%) of the patients in the active surveillance group developed metastatic disease—a statistically similar proportion as was seen in the control group, where 14 (31%) of the 45 patients who participated in the trial developed metastasis (P = .6). The 2-year metastasis-free survival—77% among the patients in the active surveillance group and 67% among the patients in the control group (P = .82)—was also statistically similar between the two groups.
“Our question as we look at these data is this: would [an] earlier cystectomy have cured the 10 patients in the observation cohort who later developed metastatic disease, and if so, how can we better find out who they are to route them to earlier surgery while sparing cystectomy for those who can safely keep their native bladders?” said study coauthor Elizabeth Plimack, MD, MS, Professor of Hematology and Oncology, Director of Genitourinary Clinical Research, and Deputy Director of the Fox Chase Cancer Center.
Further, the researchers learned that when patients in the active surveillance group developed recurrent localized urothelial carcinoma, it was a good indicator that it was time to remove the bladder rather than continuing with local therapies. Of the 10 patients in the active surveillance group who developed metastatic disease, 90% of them experienced localized recurrence first.
“You can imagine patients who went on this trial and who got to go on surveillance were really excited and committed to not having their bladder removed, as were their physicians. I think we need to be very mindful of this as we counsel patients in ongoing and future trials of this approach,” concluded Dr. Geynisman.
The results of the new study will inform how the researchers will move forward with subsequent trials. In the next iteration, the RETAIN BLADDER II trial, patients with muscle-invasive urothelial carcinoma will receive an initial combination of chemotherapy and immunotherapy, instead of chemotherapy alone. The researchers plan to examine whether this combination better eradicates the cancer and improves 2-year metastasis-free survival in patients who retain their bladder.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
