title: Prognostic Significance of VEGF after Twenty-Year Follow-up in a Randomized Trial of Fenretinide in Non-Muscle-Invasive Bladder Cancer.
abstract: Non-muscle-invasive bladder cancer (NMIBC) may progress to muscle-invasive disease, but no effective preventive treatments are available. In addition, no reliable prognostic biomarkers have been identified. We assessed the long-term effect of the oral retinoid fenretinide and the prognostic value of circulating VEGF levels. We updated through the Tumor Registry the vital status of 99 patients with resected Ta/T1 bladder tumors who were recruited in a randomized trial of 2 years of fenretinide or no treatment in 1993-1994. Serum VEGF levels measured at baseline and 12 months were available in a subgroup of 62 patients. After a median of 20.5 years, 54 subjects died, 35 of any cancer and 14 of bladder cancer. Neither overall survival (OS), nor cancer survival (CS) or bladder cancer survival (BCS) was affected by fenretinide (log-rank P ≥ 0.2). DNA aneuploidy in bladder washing was associated with shorter OS (P = 0.02), CS (P = 0.05), and BCS (P = 0.09). Subjects with baseline VEGF levels in the top quintile (≥350 pg/mL) had a significantly shorter OS (P = 0.01), CS (P = 0.02), and BCS (P = 0.008). The trend across quintiles of VEGF was significant for BCS (P = 0.007). Multivariate analyses showed that, in addition to smoking status, VEGF level in the top quintile was an independent prognostic factor for OS (HR = 2.7; 95% CI, 1.1-6.5), CS (HR = 3.3; 95% CI, 1.1-9.4) and BCS (HR = 8.9; 95% CI,1.3-61). Fenretinide did not affect the long-term outcome of patients with NMIBC. High serum VEGF level was a significant predictor of overall and cancer death and may help to identify high-risk subjects who may benefit from a preventive therapy. Cancer Prev Res; 9(6); 437-44. ©2016 AACR.
authors.affiliation: Clinical Trial Unit, Scientific Direction, E.O. Ospedali Galliera, Genoa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Puntoni
authors.affiliation: Medical Oncology Unit, E.O. Ospedali Galliera, Genoa, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Petrera
authors.affiliation: Medical Oncology Unit, E.O. Ospedali Galliera, Genoa, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Campora
authors.affiliation: Liguria Region Mortality Registry, IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Elsa
authors.initials: E
authors.lastname: Garrone
authors.affiliation: Medical Oncology Unit, E.O. Ospedali Galliera, Genoa, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Defferrari
authors.affiliation: Department of Oncology and Hematology, Humanitas Cancer Center, Humanitas Clinical and Research Hospital, Rozzano (Milan), Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Torrisi
authors.affiliation: Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy.
authors.forename: Harriet
authors.initials: H
authors.lastname: Johansson
authors.affiliation: Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bruno
authors.affiliation: University Urology Clinic, IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Curotto
authors.affiliation: Medical Oncology Unit, E.O. Ospedali Galliera, Genoa, Italy. Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy. Wolfson Institute of Preventive Medicine, Queen Mary University of London, UK. andrea.decensi@galliera.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: DeCensi
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017313:Fenretinide / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012042:Registries; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017313:Fenretinide