Two Chemo/RT Regimens Provide Bladder-Sparing Options in Bladder Cancer

Two bladder-sparing regimens involving chemotherapy plus radiotherapy yielded good distant metastasis–free survival rates at 3 years (DMF3) in patients with muscle-invasive bladder cancer (MIBC), according to a new phase II study. A regimen involving gemcitabine and once-daily radiation may offer more convenience and less toxicity than a cisplatin-based regimen with twice-daily radiation.

“Selective bladder preservation using trimodality therapy is an established treatment of MIBC with outcomes that are comparable to those of radical cystectomy,” wrote study authors led by John J. Coen, MD, of 21st Century Oncology in Providence, Rhode Island. Previous research has incorporated cisplatin-based chemotherapy along with twice-a-day radiation, and subsequently a regimen involving gemcitabine and radiation only once per day has also been shown to be effective. The new study compared these two approaches with regard to DMF3.

The trial included a total of 66 patients with cT2-4a MIBC, randomized to receive either fluorouracil plus cisplatin and radiation twice per day or gemcitabine plus radiation once per day (33 patients in each group). Half the cohort was aged 60 to 69 years, with 33.3% older than that and 16.6% aged 59 or younger. Most of the patients were male (75.8%), and most were white (89.4%). The median follow-up period was 4.3 years; results were published in the Journal of Clinical Oncology.

The DMF3 rate in the cisplatin-based regimen group was 77.8%, compared with 84.0% in the gemcitabine and once-daily radiation group. A post-hoc analysis showed no significant difference between these groups (P = .73), and both regimens met the prespecified benchmark of 75%.

There were similar rates of treatment completion in the 2 groups, with 56% of the cisplatin group and 55% of the gemcitabine group completing the adjuvant chemotherapy treatment following induction and consolidation therapy. A cystectomy was performed in three of four patients without a complete response in the cisplatin group, and in five of seven such patients in the gemcitabine group.

In the cisplatin/fluorouracil and twice-daily radiation group, 64% of patients had a treatment-related grade 3 or 4 toxicity during the treatment; there was one death due to an intracranial hemorrhage likely related to the treatment in that group. In the gemcitabine and once-daily radiation group, 55% had treatment-related grade 3 or 4 adverse events, and fewer patients experienced hematologic events than in the other group (42% vs 55%).

“Both [regimens] could be considered for additional study,” the authors concluded. “Concurrent low-dose gemcitabine is a reasonable alternative to a cisplatin-based regimen. Once-per-day radiation is a reasonable alternative to accelerated twice-a-day radiation, which may allow for the wider adoption of bladder preservation.”

Michael Glodé, MD, of the University of Colorado School of Medicine in Denver, who was not involved in the research, called this “an important step in the ongoing efforts … to develop bladder-sparing chemotherapy/radiotherapy protocols.” He noted that the trial was not designed to directly compare the two regimens, though both clearing the prespecified benchmark is encouraging. “The gemcitabine plus once-daily radiotherapy regimen is more convenient for patients and less toxic, providing a basis on which to incorporate versions of this treatment into future immunologic approaches with checkpoint inhibitors,” he told Cancer Network.