Search

Background: Guidelines recommend neoadjuvant chemotherapy (NAC) for the treatment of nonmetastatic muscle-invasive bladder cancer (MIBC). NAC is, however, underutilized in practice because of its associated limited overall survival (OS) benefit and significant treatment-related toxicity. We hypothesized that the absence of circulating tumour cells (CTCs) identifies MIBC patients with such a favourable prognosis that NAC may be withheld. Patients and methods: The CirGuidance study was an open-label, multicentre trial that included patients with clinical stage T2-T4aN0-N1M0 MIBC, scheduled for radical cystectomy. CTC-negative patients (no CTCs detectable using the CELLSEARCH system) underwent radical surgery without NAC; CTC-positive patients (≥1 detectable CTCs) were advised to receive NAC, followed by radical surgery. The primary endpoint was the 2-year OS in the CTC-negative group with a prespecified criterion for trial success of ≥75% (95% confidence interval (CI) ±5%). Results: A total of 273 patients were enrolled. Median age was 69 years; median follow-up was 36 months. The primary endpoint of 2-year OS in the CTC-negative group was 69.5% (N = 203; 95% CI 62.6%-75.5%). Two-year OS was 58.2% in the CTC-positive group (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). Conclusion: The absence of CTCs in MIBC patients was associated with improved cancer-related mortality and a lower risk of disease relapse after cystectomy; however, their absence alone does not justify to withhold NAC. Exploratory analyses suggested that CTC-positive MIBC patients might derive more benefit from NAC. Trial registration: Netherlands Trial Register

Background: Cisplatin (cDDP) has regained interest for metastatic breast cancer (MBC) patients, given the platinum sensitivity in subtypes and better manageable toxicity. Here, the primary aim was to determine whether molecular characteristics of circulating tumor cells (CTCs) could identify patients responding to cDDP and to describe the outcomes to cDDP monotherapy in a large group of MBC patients pretreated with anthracycline- and taxane-based treatments.Methods: Based on cell line data, a CTC-cDDP-sensitivity profile was generated. Applying an A'Herns single-stage phase II design, further investigation was considered worthwhile if 5/10 patients with a favorable profile responded to cDDP. Patients received 70mg/m 2 cDDP every three weeks, CTCs were enumerated and the CTC-cDDP-sensitivity profile was determined. In total, 65 heavily pretreated MBC patients (77% received ≥2 lines of previous chemotherapy for MBC) were eligible for the per-protocol analysis. Primary endpoint was response rate, secondary endpoints included best observed response, progression-free survival (PFS) and overall survival (OS). Results: The best observed response during cDDP therapy was a partial response in 7% and stable disease in 56% of the patients. None of the patients with a favorable CTC-cDDP-sensitivity profile had a response. The median baseline CTC count was 8 (range 0-3254). Patients with <5 CTCs had a better PFS and OS than patients with ≥5 CTCs (median PFS 4.5 months (95%CI 2.38-6.62) vs. 2.1 months [(95%CI 1.34-2.80)( p=0.009)] and median OS 13.1 months (95%CI 9.89-16.33) vs. 5.6 months [(95%CI 3.60-7.64)( p=0.003)]. No other factors than CTC count were associated with outcome to cDDP therapy, including triple-negative breast cancer versus ER-positive tumors. Conclusions: The CTC-cDDP-sensitivity profile was unable to select patients responding to cDDP monotherapy. In an unselected group of heavily pretreated MBC patients, cDDP yields outcomes compar