Fox Chase Cancer Center is conducting a clinical trial, named the "RETAIN Bladder" study, to determine if active surveillance can be a safe alternative to radical cystectomy for patients with muscle-invasive bladder cancer (MIBC) who have undergone chemotherapy. The study employs a risk-adapted approach, integrating clinical and genetic data to predict the likelihood of successful bladder preservation without recurrence or metastasis.
The trial is based on the observation that the standard treatment for MIBC, radical cystectomy, significantly impacts patients' quality of life. Daniel M. Geynisman, MD, the lead researcher, stated, "Removing the bladder, which is the standard of care for MIBC, has many quality-of-life ramifications. If we can develop predictive biomarkers to figure out who responds to chemotherapy and who doesn’t, we can apply our recommendations in a more nuanced way."
Risk-Adapted Treatment Approach
The RETAIN Bladder study uses a decision tree based on pre-chemotherapy biopsy results and post-chemotherapy imaging and cystoscopy. Patients whose biopsies show specific genetic mutations and who exhibit no evidence of disease after chemotherapy may be eligible for active surveillance. Conversely, patients with residual disease or lacking the key mutations will be considered for additional intravesical therapy, chemoradiation, or cystectomy. Patients with stage 3 disease are recommended to undergo cystectomy.
Prior Research and Rationale
Previous studies, including research led by Fox Chase's Alexander Kutikov, MD, FACS, and David Y.T. Chen, MD, FACS, have indicated that approximately 30% of cystectomy patients show no evidence of MIBC following AMVAC chemotherapy (methotrexate, vinblastine, adriamycin, and cisplatin). Furthermore, studies suggest that mutations in DNA damage repair/response genes can predict pathologic response to neoadjuvant chemotherapy, with patients achieving pT0 disease (no cancer remaining at bladder removal) demonstrating favorable long-term survival.
Study Objectives and Endpoints
The primary objective of the RETAIN Bladder study is to evaluate metastasis-free survival at two years. Secondary objectives include assessing the rate of urothelial carcinoma recurrence in active surveillance patients, bladder preservation rates, feasibility of an Endoscopic Tumor Quantification System, quality of life, genomic correlates in urinary cell-free DNA, and treatment-related toxicity.
Rosalia Viterbo, MD, FACS, a participating surgeon, emphasized the potential benefits for patients: "Although about 70 percent of patients will probably need a cystectomy eventually, this gives patients a bit more time before that and it preserves the bladder for the 30 percent whose disease responds well to the chemotherapy."
The research is funded by Fox Chase/Temple Health and Caris Life Sciences, which is responsible for the genetic sequencing. Collaborators also include researchers from Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and the Sidney Kimmel Cancer Center at Thomas Jefferson University.
Geynisman highlighted the collaborative nature of the research: "Together, we are combining clinical data with molecular or genomic data to see if we can make a smarter decision with our patients about cystectomies and bladder cancer care in general."
