Circulating tumor cell-driven use of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer.

Abstract

4523 Background: International guidelines for the treatment of non-metastatic muscle-invasive bladder cancer (MIBC) recommend neoadjuvant chemotherapy (NAC), which, however, is underutilized in practice. We hypothesized that the absence of circulating tumour cells (CTCs), an established prognostic marker in MIBC, may identify patients with such a favourable prognosis that NAC may be withheld. Methods: The CirGuidance study included adults with clinical stage T2-T4aN0-N1M0 muscle-invasive urothelial carcinoma of the bladder who were fit to undergo radical cystectomy. CTCs were enumerated using the CellSearch system. CTC-negative patients (no CTCs detectable) underwent radical surgery without NAC; CTC-positive patients (≥1 detectable CTCs) were advised to receive NAC followed by radical surgery, but NAC could be withheld at the discretion of the treating physician. The primary endpoint was the two-year overall survival (OS) in the CTC-negative group, analysed in the intention-to-treat population. The prespecified criterion for trial success was a two-year OS of minimally 75% (95% confidence interval (CI) ±5%) in the CTC-negative group. Results: Of 315 patients screened for eligibility, 273 were enrolled in the study. The median age was 69 years; the median follow-up was 36 months. The two-year OS in the CTC-negative group was 69.5% (n = 203; 95% CI 62.6%-75.5%); in the CTC-positive group it was 58.2% (n = 70; 95% CI 45.5%-68.9%). CTC-positive patients had a higher rate of cancer-related mortality (hazard ratio (HR) 1.61, 95% CI 1.05-2.45, p = 0.03) and disease relapse (HR 1.87, 95% CI 1.28-2.73, p = 0.001) than CTC-negative patients. Explorative analyses suggested that CTC-positive patients who had received NAC (n = 22) survived longer than CTC-positive patients who had not (n = 48), with a two-year OS of 74.8% (95%CI 49.5%-88.8%) versus 52.0% (95% CI 37.2%-65.0%), respectively. Conclusions: The two-year OS in the CTC-negative group did not meet the prespecified criterion for trial success. However, given the trial population’s advanced age and high rate of non-cancer related mortality, the benefit of NAC is likely to be limited in CTC-negative MIBC patients. CTC enumeration at the moment of diagnosis could aid in the decision to prescribe neoadjuvant chemotherapy for a muscle-invasive bladder cancer patient as a criterion in addition to clinical characteristics. Clinical trial information: NL3954.

Patients with Muscle-Invasive Bladder Cancer with Nonluminal Subtype Derive Greatest Benefit from Platinum Based Neoadjuvant Chemotherapy

“…We combined 4 cohorts of patients with bladder cancer who underwent RC and had genomic data available from transurethral resection of bladder tumor samples: 1) NAC I—neoadjuvant chemotherapy cohort I (82), which consisted of patients with clinical T2-4aN0-3M0 bladder cancer treated with NAC followed by RC; 11 only the validation cohort was used in this study, as the model being tested here was trained on the discovery cohort; 2) NAC II—neoadjuvant chemotherapy cohort II (244), which consisted of patients with clinical T2-4N0-3M0 or TanyN1-3M0 bladder cancer treated with NAC followed by RC; 16 3) CirGuidance study—bladder cancer cohort (292), which consisted of patients with clinical T2-4aN0-1M0 MIBC treated with NAC and RC or RC alone; 17 and 4) MOL—molecular upstaging cohort (210), which consisted of patients with clinical T1-2N0 bladder cancer who underwent RC without NAC. 6 Only tumors with muscle-invasive disease were included (see below).…”

Molecular Subtypes as a Basis for Stratified Use of Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer—A Narrative Review

“…The percentage of each GSC subtype that was given NAC was 35% for GSC-luminal, 45% for GSC-luminal-infiltrated, 40% for GSC-basal, and 54% for GSC-claudin-low. Furthermore, patients from one of the four cohorts had undergone circulating tumor cell (CTC) analysis, as part of a trial protocol where the CTC-positive patients were selectively recommended NAC, whereas CTC-negative patients were not [ 42 ]. The adherence to this recommendation was not included in the abstract, meaning that it is not known to what extent CTC-positive patients, unlikely to be cured by surgery alone [ 43 , 44 ], were selectively included in the NAC-cohort and CTC-negative patients in the non-NAC cohort.…”