Abstract
We previously showed that ERCC1 19007 C>T polymorphism was associated with cancer-specific survival (CSS) after platinum-based chemotherapy in patients with advanced urothelial cancer (aUC). We aimed to confirm this association in a different cohort of patients. Genotyping of the 19007C>T polymorphism was carried out by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) in 98 aUC patients, treated with platinum-based chemotherapy. Median age of the patients was 68.8, 13.3% of them were female, 90.8% had ECOG PS of 0 or 1, and 48% received cisplatin-based chemotherapy. In addition to chemotherapy, 32.7% of the patients received immunotherapy, and 19.4% vinflunine. Eighty-one patients (82.7%) were carriers of the 19007T polymorphic allele: 46 (46.9%) were heterozygotes, and 35 (35.7%) were homozygotes. The ERCC1 polymorphism was not associated with CSS, progression-free (PFS), or overall (OS) survival in the total population. Nevertheless, there was a significant interaction between the prognostic significance of ERCC1 polymorphism and the use of modern immunotherapy: the T allele was associated with worse outcome in patients who received chemotherapy only, while this association was lost in patients who received both chemotherapy and immune checkpoint inhibitors. Our study suggests that novel therapies may influence the significance of ERCC1 polymorphism in patients with aUC. Its determination may be useful in the changing treatment landscape of the disease.
Highlights
Urothelial cancer (UC) is a common malignancy in Greece
We identified 115 patients with histologically confirmed UC from whom pre-treatment blood samples were available
Seventeen patients were excluded from further analyses due to lack of clinical information (n = 1), no evidence of advanced or metastatic disease (n = 11), and no treatment with platinum-based chemotherapy (n = 5)
Summary
Urothelial cancer (UC) is a common malignancy in Greece. With an age-standardized rate of 21.2 cases/100,000, Greece rates second in the world for both sexes and first for men, with a rate of 40.4 [1]. Most cases present as superficial cancers, requiring only local treatment. 25% of UCs are muscle invasive (MIUC), while 5% present with locally advanced (inoperable) or metastatic disease, usually referred to as advanced urothelial cancer (aUC). Muscle invasion is a decisive prognostic factor associated with increased risk of death from UC. Approximately half of the patients undergoing surgery for invasive disease will relapse. Such a development is associated with unfavorable prognosis
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