‘Intriguing’ data may advance more personalized approach to muscle-invasive bladder cancer
Click Here to Manage Email Alerts
SAN FRANCISCO — Transurethral resection of bladder tumor followed by systemic therapy induced stringently defined clinical complete response among more than 40% of patients with muscle-invasive bladder cancer, according to phase 2 study results.
Most patients who met clinical complete response criteria achieved at least 2 years of bladder-intact survival, findings presented at ASCO Genitourinary Cancers Symposium showed.
The results show the potential of this approach to identify patients with particularly favorable outcomes and facilitate bladder sparing, according to researcher Matt D. Galsky, MD, professor of medicine (hematology and medical oncology) and professor of urology at Icahn School of Medicine at Mount Sinai.
“The findings are quite intriguing — and perhaps even better than expected,” Galsky told Healio.
Background and methodology
Cisplatin-based neoadjuvant chemotherapy induces pathologic complete response for an estimated 30% to 40% of patients with muscle-invasive bladder cancer.
“Paradoxically, a pathologic complete response can only be determined after the bladder has already been surgically removed,” Galsky said during a presentation.
Since the 1980s, there have been reports of patients who received systemic treatment and opted not to have their bladders removed.
“The problem is, most of the data are anecdotal or single-center experiences,” Galsky told Healio. “This hasn’t been embraced as a standard treatment strategy, and one of the reasons is the paucity of prospective studies testing this approach.”
Another challenge has been the lack of uniform definition of clinical complete response.
“We should feel confident we’re defining it uniformly if we’re going to try to measure its performance as a biomarker to guide treatment decisions,” Galsky said. “That was the genesis of this study — trying to define clinical complete response as a biomarker to determine whether there is a population of patients who do not have to have their bladders removed surgically.”
The phase 2 HCRN GU16-257 study assessed the use of gemcitabine, cisplatin and nivolumab (Opdivo, Bristol Myers Squibb) with selective bladder sparing for patients with muscle-invasive bladder cancer.
The trial included 76 cisplatin-eligible patients (median age, 69 years; 79% men) with cT2-T4aN0M0 urothelial bladder cancer (cT2, 56%; cT3, 32%; cT4, 12%).
Patients received four cycles of gemcitabine, cisplatin and nivolumab, followed by clinical restaging, which included cystoscopy, biopsies of any visible tumor, urine cytology and MRI of the bladder unless contraindicated.
Patients determined to have normal assessments on clinical restaging were deemed to have achieved clinical complete response. They had the option to proceed without cystectomy and receive eight cycles of maintenance nivolumab. Patients who did not achieve clinical complete response were recommended for cystectomy.
Co-primary endpoints included clinical complete response rate and the performance of clinical complete response in predicting treatment benefit, defined as 2-year metastasis-free survival for those who did not undergo cystectomy and pathologic complete response for those who underwent immediate cystectomy.
Results
After median follow-up of 27 months, 72 patients underwent clinical restaging.
Thirty-three patients (43%; 95% CI, 32-55) achieved clinical complete response. One of those patients opted for immediate cystectomy. Among those who did not achieve clinical complete response, the majority proceeded with protocol-recommended cystectomy, Galsky said.
Median follow-up for patients who achieved clinical complete response was 30 months (range, 18-42).
Clinical complete response predicted treatment benefit with a positive predictive value of 0.96 (95% CI, 0.89-1). At the time of landmark analysis, clinical complete response appeared significantly associated with improved metastasis-free survival (P = .007) and improved OS (P = .003).
At 2 years, patients who achieved clinical complete response appeared more likely than those without clinical complete response to remain alive (100% vs. 75.8%), and to be alive and metastasis-free (96.6% vs. 74.6%).
The majority (72.2%) of patients who achieved clinical complete response remained alive with intact bladder at 2 years.
Higher tumor mutational burden ( 10 mutations/megabase) appeared significantly associated with higher likelihood for bladder-intact metastasis-free survival (P = .02).
Next steps
The findings may help advance a more personalized approach to management of muscle-invasive bladder cancer, Galsky and colleagues concluded.
“The major question is where we go from here, because it is a nonstandard approach,” Galsky told Healio. “There are two ways to think about it. One is that transurethral resection of the bladder tumor plus systemic therapy as a treatment strategy for bladder cancer — I believe — has legs, particularly with some emerging technologies, but it certainly requires further investigation.
“Second is a larger potential paradigm shift,” Galsky added. “Even if we’re not ready to not remove patients’ bladders or not deliver definitive local therapy, maybe we should be doing personalized risk-adapted treatment based on clinical response assessment if it is such a powerful biomarker.”
Collapse
Galsky MD, et al. Abstract 447. Presented at: ASCO Genitourinary Cancers Symposium; Feb. 16-18, 2023; San Francisco.
Click Here to Manage Email Alerts