New and contemporary markers of prognosis in nonmuscle invasive urothelial cancer

Abstract

Nonmuscle invasive (NMI) urothelial cancer (UC) is associated with varied biological potential. It is characterized by frequent recurrence and progression, which thus worsens the oncological outcome. Nearly three-quarters of NMI UCs recur within 5 years, whereas half can progress during follow-up. Progression is particularly seen in T1 and carcinoma in situ (CIS). Undoubtedly, NMI UC is one of the most expensive cancers to manage. The European Organisation for Research and Treatment of Cancer (EORTC) risk calculator is a commonly used tool for assessing the recurrence and progression potential of a newly diagnosed cancer. The parameters used in the assessment are tumor size and number, pathological stage and grade of the cancer, presence of CIS, and prior recurrence rate. The main advantages of the EORTC tool are its ease of use and the lack of need to run expensive molecular tests. However, reproducibility of pathologic stage and grade is modest, which is a concern to clinicians. Molecular markers have potential for predicting the clinical outcome of NMI UC, given that clinico-pathologic variables are not sufficient for prediction of prognosis in an individual. Significant work has been done in the past 2 decades in understanding the molecular biology of bladder cancer; however, the translational value of this knowledge remains poor. The role for molecular markers in predicting recurrence seems limited because multifocal disease and incomplete treatment are probably more important for recurrence than the molecular features of a resected tumor. Urinary markers have very limited value in prognostication of bladder cancer and are used (mainly as an adjunct to cytology) for detection and surveillance of urothelial cell cancer recurrence. Prediction of progression with molecular markers holds considerable promise. Nevertheless, the contemporary value of molecular markers over clinico-pathologic indexes is limited.

Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis

“…Each year, approximately 110 500 men and 70 000 women are diagnosed with the disease and 38 200 patients in the European Union and 17 000 patients in the US die from UC 1 . Approximately 75% of bladder cancer is non-muscle invasive (NMI) UC at the time of diagnosis, of which 70% present as noninvasive, papillary tumors confined to the mucosa (pTa), 20% as tumors invading the subepithelial tissue (pT1), and 10% as flat dysplastic (carcinoma in situ , or CIS) lesions 2 . High grade (HG) tumors carry a worse prognosis than low-grade (LG) tumors.…”

Potential role of miR-139-5p in cancer diagnosis, prognosis and therapy

“…Pathological features including tumor size, stage, grade, lymph-node metastasis, vascular invasion and metastasis are prognotic factors, but do not reflect the status of tumor progression and treatment efficacy (49). Therefore, a number of studies have indicated that the expression of miR-139 may act as an independent prognostic factor that is significantly associated with overall survival rates of cancer patients.…”

“…Enhancement of migration and invasion, as phenotypes of cell transformation, are involved in the process of metastasis of cancer cells ( 48 ), thus making it essential for improved stratification of cancer patients to predict disease recurrence risk and to guide therapy ( 17 ). Pathological features including tumor size, stage, grade, lymph-node metastasis, vascular invasion and metastasis are prognotic factors, but do not reflect the status of tumor progression and treatment efficacy ( 49 ). Therefore, a number of studies have indicated that the expression of miR-139 may act as an independent prognostic factor that is significantly associated with overall survival rates of cancer patients.…”

Fruit and vegetable intake and the risk of recurrence in patients with non-muscle invasive bladder cancer: a prospective cohort study

“…Confounders were considered a priori as factors known or suspected to be related with cancer recurrence and/or fruit and vegetables and were included in the multivariate regression models. Confounders included: age at diagnosis (continuous) [ 8 ], sex (male/female) [ 9 ], smoking status (never/former/current smoker) [ 10 ], and tumor characteristics including stage (pTa/pTis/pT1), grade (1/2/3), size of largest tumor (< 3 mm/≥ 3 mm), and tumor multiplicity (1/> 1) [ 11 – 13 ]. Multivariate time to multiple recurrences regression models were additionally corrected for re-resection of a bladder tumor as second-line treatment (yes/no).…”