Circulating tumor cells detection has independent prognostic impact in high-risk non-muscle invasive bladder cancer

TY - JOUR

T1 - Circulating tumor cells detection has independent prognostic impact in high-risk non-muscle invasive bladder cancer

AU - Gazzaniga, Paola

AU - de Berardinis, Ettore

AU - Raimondi, Cristina

AU - Gradilone, Angela

AU - Busetto, Gian Maria

AU - De Falco, Elena

AU - Nicolazzo, Chiara

AU - Giovannone, Riccardo

AU - Gentile, Vincenzo

AU - Cortesi, Enrico

AU - Pantel, Klaus

N1 - © 2014 UICC.

PY - 2014/10/15

Y1 - 2014/10/15

N2 - High-risk non-muscle invasive bladder cancer (NMIBC) progresses to metastatic disease in 10-15% of cases, suggesting that micrometastases may be present at first diagnosis. The prediction of risks of progression relies upon EORTC scoring systems, based on clinical and pathological parameters, which do not accurately identify which patients will progress. Aim of the study was to investigate whether the presence of CTC may improve prognostication in a large population of patients with Stage I bladder cancer who were all candidate to conservative surgery. A prospective single center trial was designed to correlate the presence of CTC to local recurrence and progression of disease in high-risk T1G3 bladder cancer. One hundred two patients were found eligible, all candidate to transurethral resection of the tumor followed by endovesical adjuvant immunotherapy with BCG. Median follow-up was 24.3 months (minimum-maximum: 4-36). The FDA-approved CellSearch System was used to enumerate CTC. Kaplan-Meier methods, log-rank test and multivariable Cox proportional hazard analysis was applied to establish the association of circulating tumor cells with time to first recurrence (TFR) and progression-free survival. CTC were detected in 20% of patients and predicted both decreased TFR (log-rank p < 0.001; multivariable adjusted hazard ratio [HR] 2.92 [95% confidence interval: 1.38-6.18], p = 0.005), and time to progression (log-rank p < 0.001; HR 7.17 [1.89-27.21], p = 0.004). The present findings provide evidence that CTC analyses can identify patients with Stage I bladder cancer who have already a systemic disease at diagnosis and might, therefore, potentially benefit from systemic treatment.

AB - High-risk non-muscle invasive bladder cancer (NMIBC) progresses to metastatic disease in 10-15% of cases, suggesting that micrometastases may be present at first diagnosis. The prediction of risks of progression relies upon EORTC scoring systems, based on clinical and pathological parameters, which do not accurately identify which patients will progress. Aim of the study was to investigate whether the presence of CTC may improve prognostication in a large population of patients with Stage I bladder cancer who were all candidate to conservative surgery. A prospective single center trial was designed to correlate the presence of CTC to local recurrence and progression of disease in high-risk T1G3 bladder cancer. One hundred two patients were found eligible, all candidate to transurethral resection of the tumor followed by endovesical adjuvant immunotherapy with BCG. Median follow-up was 24.3 months (minimum-maximum: 4-36). The FDA-approved CellSearch System was used to enumerate CTC. Kaplan-Meier methods, log-rank test and multivariable Cox proportional hazard analysis was applied to establish the association of circulating tumor cells with time to first recurrence (TFR) and progression-free survival. CTC were detected in 20% of patients and predicted both decreased TFR (log-rank p < 0.001; multivariable adjusted hazard ratio [HR] 2.92 [95% confidence interval: 1.38-6.18], p = 0.005), and time to progression (log-rank p < 0.001; HR 7.17 [1.89-27.21], p = 0.004). The present findings provide evidence that CTC analyses can identify patients with Stage I bladder cancer who have already a systemic disease at diagnosis and might, therefore, potentially benefit from systemic treatment.

KW - Bone Neoplasms

KW - Carcinoma, Transitional Cell

KW - Disease-Free Survival

KW - Female

KW - Humans

KW - Kaplan-Meier Estimate

KW - Lymphatic Metastasis

KW - Male

KW - Neoplasm Invasiveness

KW - Neoplasm Recurrence, Local

KW - Neoplastic Cells, Circulating

KW - Prognosis

KW - Proportional Hazards Models

KW - Prospective Studies

KW - Risk

KW - Treatment Outcome

KW - Urinary Bladder Neoplasms

U2 - 10.1002/ijc.28830

DO - 10.1002/ijc.28830

M3 - SCORING: Journal article

C2 - 24599551

VL - 135

SP - 1978

EP - 1982

JO - INT J CANCER

JF - INT J CANCER

SN - 0020-7136

IS - 8

ER -