The prognostic impact of tumor necrosis in non-muscle invasive bladder cancer

SUMMARY OBJECTIVE: We aimed to investigate the impact of tumor necrosis in non-muscle invasive bladder cancer on patients’ recurrence and progression rates and survival outcomes. METHODS: This study was conducted retrospectively in a single tertiary center in Turkey. Medical records of patients who underwent transurethral resection of the bladder tumor between January 2016 and January 2021 were reviewed. Patients with pTa and pT1 non-muscle invasive bladder cancer who had undergone complete resection were included in our study. All pathological specimens were reevaluated for the presence of tumor necrosis. RESULTS: A total of 287 patients (244 males and 43 females) were included in our study. Of them, 33 (11.5%) patients had tumor necrosis. The rates of multiple and large tumors (>3 cm) were higher in patients with tumor necrosis (p=0.002 and p<0.001, respectively). Tumor necrosis was associated with higher rates of pT1 diseases (p<0.001), high-grade tumors (p<0.001), and the presence of lymphovascular invasion (p=0.007). The mean recurrence-free survival of patients with tumor necrosis was 42.3 (4.6) months, and the recurrence-free survival of patients without tumor necrosis was 43.5 (1.8) months (p=0.720). The mean progression-free survival of patients with tumor necrosis was 43.1 (4.6) months, and the progression-free survival of patients without tumor necrosis was 58.4 (0.9) months. In log-rank analysis, there was a statistically significant difference between patients with and without tumor necrosis in terms of progression-free survival (p<0.001). CONCLUSION: In this study, we demonstrated that patients with non-muscle invasive bladder cancer and tumor necrosis in pathological specimens have shorter progression-free survival and more adverse pathological features.

[1]  A. Jemal,et al.  Cancer statistics, 2022 , 2022, CA: a cancer journal for clinicians.

[2]  A. Masson-Lecomte,et al.  European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ). , 2021, European urology.

[3]  Wen‐Horng Yang,et al.  Tumor Necrosis with Adjunction of Preoperative Monocyte-to-Lymphocyte Ratio as a New Risk Stratification Marker Can Independently Predict Poor Outcomes in Upper Tract Urothelial Carcinoma , 2021, Journal of clinical medicine.

[4]  L. Kiemeney,et al.  European Association of Urology (EAU) Prognostic Factor Risk Groups for Non-muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel. , 2021, European urology.

[5]  B. Delahunt,et al.  Granular necrosis: a distinctive form of cell death in malignant tumours. , 2020, Pathology.

[6]  E. Çakır,et al.  8-armed octopus: Evaluation of clinicopathologic prognostic factors of urothelial carcinoma of the upper urinary system , 2019, Turkish journal of medical sciences.

[7]  A. Yıldırım,et al.  Assessment of transurethral resection of the bladder specimens with pT1 high-grade urothelial carcinoma for the predictor features of muscularis propria invasion on radical cystectomy specimens. , 2018, Annals of diagnostic pathology.

[8]  Bin Xu,et al.  Tumour front inflammation and necrosis are independent prognostic predictors in high-grade urothelial carcinoma of the bladder , 2017, Journal of Clinical Pathology.

[9]  J. Yun,et al.  Tumor necrosis predicts poor clinical outcomes in patients with node-negative upper urinary tract urothelial carcinoma. , 2015, Japanese journal of clinical oncology.

[10]  S. Minner,et al.  The Impact of Tumor Diameter and Tumor Necrosis on Oncologic Outcomes in Patients With Urothelial Carcinoma of the Bladder Treated With Radical Cystectomy. , 2015, Urology.

[11]  K. Bensalah,et al.  Tumour necrosis is an indicator of aggressive biology in patients with urothelial carcinoma of the upper urinary tract. , 2010, European urology.

[12]  M. Gallucci,et al.  Independent prognostic value of tumour diameter and tumour necrosis in upper urinary tract urothelial carcinoma , 2009, BJU international.

[13]  Deng-Chyang Wu,et al.  Overexpression of hypoxia‐inducible factor‐1α predicts an unfavorable outcome in urothelial carcinoma of the upper urinary tract , 2008, International journal of urology : official journal of the Japanese Urological Association.

[14]  T. Thamboo,et al.  An investigation into the prognostic significance of necrosis and hypoxia in high grade and invasive bladder cancer. , 2007, The Journal of urology.

[15]  P. Rehak,et al.  Tumor necrosis as prognostic indicator in transitional cell carcinoma of the upper urinary tract. , 2006, The Journal of urology.

[16]  S. Horvath,et al.  Clinicopathologic and molecular correlations of necrosis in the primary tumor of patients with renal cell carcinoma , 2005, Cancer.

[17]  A. Lazaris,et al.  Hypoxia-inducible factor 1 alpha expression correlates with angiogenesis and unfavorable prognosis in bladder cancer. , 2004, European urology.

[18]  P. Carmeliet.  Angiogenesis in health and disease , 2003, Nature Medicine.

[19]  Donna Richardson,et al.  Tumour necrosis is an independent prognostic marker in non-small cell lung cancer: correlation with biological variables. , 2002, Lung cancer.

[20]  G. Semenza,et al.  Oncogenic alterations of metabolism. , 1999, Trends in biochemical sciences.

[21]  A. Harris,et al.  Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast , 1999, British Journal of Cancer.

[22]  Ji Hyung Yu,et al.  Prognostic significance of tumor necrosis in primary transitional cell carcinoma of upper urinary tract. , 2007, Japanese journal of clinical oncology.