Dataset Information

Competing-risks nomogram for predicting cancer-specific death in upper tract urothelial carcinoma: a population-based analysis.

ABSTRACT:

Objective

This study aimed to use a competing-risks model to establish a nomogram to accurately analyse the prognostic factors for upper tract urothelial carcinoma (UTUC) cancer-specific death (CSD).

Design

Retrospective observational cohort study.

Setting

The programme has yielded a database of all patients with cancer in 18 defined geographical regions of the USA.

Participants

We selected patients with UTUC from the latest edition of the Surveillance, Epidemiology, and End Results database from 1975 to 2016. After excluding patients with unknown histological grade, tumour size and lymph node status, 2576 patients were finally selected.

Primary and secondary outcome measures

We used the Fine-Gray proportional subdistribution hazards model for multivariate analysis and compared the results with cause-specific hazards model. We finally constructed a nomogram for 3-year, 5-year and 8-year CSD rates and tested these rates in a validation cohort.

Results

The proportional subdistribution hazards model showed that sex, tumour size, distant metastasis, surgery status, number of lymph nodes positive (LNP) and lymph nodes ratio (LNR) were independent prognostic factors for CSD. All significant factors associated with CSD were included in the nomogram. The 3-year, 5-year and 8-year concordance indexes were 0.719, 0.702 and 0.692 in the training cohort and 0.701, 0.675 and 0.668 in the validation cohort, respectively.

Conclusions

The competing-risks model showed that sex, tumour size, distant metastasis, surgery status, LNP and LNR were associated with CSD. The nomogram predicts the probability of CSD in patients with UTUC at 3, 5 and 8 years, which may help clinicians in predicting survival probabilities in individual patients.

SUBMITTER: Li C

PROVIDER: S-EPMC8291317 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Very few studies have been published on the causes of death of upper tract urothelial carcinoma (UTUC). We sought to explore the mortality patterns of contemporary UTUC survivors. Methods We performed a retrospective cohort study involving patients with upper urinary tract carcinoma from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database (2000 and 2015). We used standardized mortality ratios (SMRs) to compare death rates among patients with UTUC in the general population and excess absolute risks (EARs) to quantify the disease-specific death burden. Results A total of 10,179 patients with UTUC, including 7,133 who died, were included in our study. In total, 302 (17.17%) patients with the localized disease died of UTUC; however, patients who died from other causes were 4.8 times more likely to die from UTUC (n = 1,457 [82.83%]). Cardiovascular disease was the most common non-cancer cause of death (n = 393 [22.34% of all deaths]); SMR, 1.22; 95% confidence intervals [CI], 1.1–1.35; EAR, 35.96). A total of 4,046 (69.99%) patients with regional stage died within their follow-up, 1,413 (34.92%) of whom died from UTUC and 1,082 (26.74%) of whom died from non-cancer causes. UTUC was the main cause of death (SMR, 242.48; 95% CI, 230–255.47; EAR, 542.47), followed by non-tumor causes (SMR, 1.18; 95% CI, 1.11–1.25; EAR, 63.74). Most patients (94.94%) with distant stage died within 3 years of initial diagnosis. Although UTUC was the leading cause of death (n = 721 [54.29%]), these patients also had a higher risk of death from non-cancer than the general population (SMR, 2.08; 95% CI, 1.67–2.56; EAR, 288.26). Conclusions Non-UTUC deaths accounted for 82.48% of UTUC survivors among those with localized disease. Patients with regional/distant stages were most likely to die of UTUC; however, there is an increased risk of dying from non-cancer causes that cannot be ignored. These data provide the latest and most comprehensive assessment of the causes of death in patients with UTUC.

Project description:Despite a similar histologic appearance, upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) tumors have distinct epidemiologic and clinicopathologic differences.To investigate whether the differences between UTUC and UCB result from intrinsic biological diversity.Tumor and germline DNA from patients with UTUC (n=83) and UCB (n=102) were analyzed using a custom next-generation sequencing assay to identify somatic mutations and copy number alterations in 300 cancer-associated genes.We described co-mutation patterns and copy number alterations in UTUC. We also compared mutation frequencies in high-grade UTUC (n=59) and high-grade UCB (n=102).Comparison of high-grade UTUC and UCB revealed significant differences in the prevalence of somatic alterations. Genes altered more commonly in high-grade UTUC included FGFR3 (35.6% vs 21.6%; p=0.065), HRAS (13.6% vs 1.0%; p=0.001), and CDKN2B (15.3% vs 3.9%; p=0.016). Genes less frequently mutated in high-grade UTUC included TP53 (25.4% vs 57.8%; p<0.001), RB1 (0.0% vs 18.6%; p<0.001), and ARID1A (13.6% vs 27.5%; p=0.050). Because our assay was restricted to genomic alterations in a targeted panel, rare mutations and epigenetic changes were not analyzed.High-grade UTUC tumors display a spectrum of genetic alterations similar to high-grade UCB. However, there were significant differences in the prevalence of several recurrently mutated genes including HRAS, TP53, and RB1. As relevant targeted inhibitors are being developed and tested, these results may have important implications for the site-specific management of patients with urothelial carcinoma.Comparison of next-generation sequencing of upper tract urothelial carcinoma (UTUC) with urothelial bladder cancer identified that similar mutations were present in both cancer types but at different frequencies, indicating a potential need for unique management strategies. UTUC tumors were found to have a high rate of mutations that could be targeted with novel therapies.

Project description:BackgroundDifferent genomic characterization in urothelial carcinoma (UC) by site of origin may imply contrasting therapeutic opportunities and pathogenetic mechanisms. The aim of this study was to investigate whether differences between upper tract UC (UTUC) and UC of the bladder (UCB) result from intrinsic biological diversity.Materials and methodsWe prospectively sequenced 118 tumors and matched blood DNA from Chinese patients with UC using next-generation sequencing techniques, including 45 UTUC and 73 UCB. Two hundred twenty-six patients with UTUC and 350 patients with UCB for The Cancer Genome Atlas were acquired from the cbioportal.ResultsThere were marked disparities in the mutational landscape for UC according to race and site of origin. Signature 22 for exposure to aristolochic acid was only observed in the UTUC cohort. Conversely, signature 6 for defective DNA mismatch repair only existed in the UCB cohort. Compared with UCB, UTUC had higher clonal and subclonal mutation numbers. TP53, PIK3CA, and FGFR3 mutations may be the driver genes for UTUC, whereas for UCB, the driver gene may be BRCA1. Patients with UTUC had lower PD-L1 than those with UCB. There was no significant difference in the number of DDR mutations, copy number variation counts, and tumor mutational burden between UTUC and UCB.ConclusionUTUC and UCB exhibit significant differences in the prevalence of genomic landscape and carcinogenesis. Consequently, molecular subtypes differ according to location, and these results may imply the site-specific management of patients with urothelial carcinoma. Mutational signature may be used as a screening tool to assist clinical differential diagnosis between UTUC and UCB.Implications for practiceThis study's findings lay the foundation for a deeper understanding of distinct molecular mechanisms and similar treatment opportunities between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) and had important implications for the site-specific management of patients with urothelial carcinoma. A comprehensive understanding of the biology of UTUC and UCB is needed to identify new drug targets in order to improve clinical outcomes.