Posted: Friday, July 8, 2022
Neoadjuvant cisplatin-based chemotherapy, followed by radical cystectomy, is the standard course of treatment for patients with muscle-invasive bladder cancer; however, up to 50% of patients experience a recurrence of metastatic disease. In an ongoing study presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract TPS4615), researchers discussed a bladder-sparing approach consisting of close cystoscopic and radiographic surveillance, avoiding the toxicities of definitive local therapy and complete bladder removal. Gopa Iyer, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues hypothesized that patients with somatic loss-of-function alterations within specific DNA damage response (DDR) genes and clinical responses to neoadjuvant cisplatin-based chemotherapy may benefit from such a bladder-sparing approach.
A total of 271 patients will be enrolled in this multicenter phase II trial. Patients must be diagnosed with muscle-invasive bladder cancer within 60 days of enrollment in the study. Additionally, only patients whose tumors contain deleterious alterations in any one of nine preselected DDR genes and who exhibit < T1 response on clinical restaging are eligible for organ-sparing management. Patients without deleterious gene alterations or with > T1 disease after cisplatin administration will undergo radical cystectomy or chemoradiation therapy.
The primary endpoint of this study is 3-year event-free survival in the gene-altered group. The secondary endpoints include clinical response rate (< cT1) in patients with deleterious gene alterations following cisplatin therapy, bladder-intact survival, overall survival, complete response rate in the gene-altered group who elect to undergo radical cystectomy, survival rate in patients without gene alterations, 3-year radical cystectomy rate in patients with DDR gene alterations, and intravesical management of in-bladder recurrences.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.