Biopsy-confirmed de novo renal cell carcinoma (RCC) in renal grafts: a single-centre management experience in a 2396 recipient cohort

15590 Background: 5-Fluorouracil ( 5-FU ) is an anticancer agent clinically used against various cancers including renal cell carcinoma ( RCC ). 5-FU is a prodrug and orotate phosphoribosyltransferase ( OPRT ) is the principal enzyme which directly converts 5-FU to an active anticancer metabolite, 5-fluoro-2’-deoxyuridine 5’-monophosphate. Furthermore, OPRT is the key enzyme in the de novo DNA and RNA synthetic process, which converts orotic acid to orotidine 5’-phosphate. Little is known about the significance of OPRT in a variety of cancers including RCC. We investigated OPRT activity in 83 RCC and evaluated the association between OPRT activity and the stage/grade of RCC. The relationship between OPRT activity in RCC cells and their sensitivity to 5-FU was also examined. Methods: OPRT activity in non-fixed fresh frozen RCC and normal kidney were determined enzymatically by the 5-FU phosphorylation assay. The sensitivity of RCC cells to 5-FU was assessed by the microculture tetrazolium dye assay. Results: OPRT activity was approximately 8.5-fold higher in RCC compared to normal kidney. OPRT activity in T3/4 RCC was 3-fold higher than that in T1/2 RCC. OPRT activity in M1 RCC was 2.5-fold higher than that in M0 RCC. In addition, OPRT activity in Stage III/IV RCC was 3-fold higher than that in Stage I/II RCC. The level of OPRT activity in Grade 3 RCC was 3-fold higher than that in Grade 1/2 cancer. Patients with RCC with low OPRT activity had a longer postoperative disease-specific survival than those with high activity in the 5-year follow-up. OPRT activity in RCC cells positively correlated with their sensitivity to 5-FU. Conclusions: The present study has demonstrated that OPRT activity in RCC was higher than that in normal kidney, and that OPRT activity positively correlated with the stage/grade of RCC. Moreover, higher OPRT activity in RCC predicted worse prognosis and higher sensitivity to 5-FU. These results suggest that OPRT activity may be used as both a prognostic parameter and a predictive indicator for 5-FU efficacy in RCC. No significant financial relationships to disclose.

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Impact of diabetes mellitus on functional and survival outcomes in renal cell carcinoma: An international multicenter study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.666 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 666-666

Author(s):

Raksha Dutt ◽

Margaret Frances Meagher ◽

Dattatraya Patil ◽

Kazutaka Saito ◽

Devin Patel ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Risk Factor ◽

Cell Carcinoma ◽

Kidney Function ◽

Tumor Size ◽

Renal Cell ◽

Independent Risk Factor ◽

De Novo ◽

Functional Decline ◽

Increased Risk

666 Background: Functional decline is an important consideration in the surgical treatment of renal cell carcinoma (RCC). While radical nephrectomy (RN) may be associated with increased risk of functional decline compared to partial nephrectomy (PN), the modifying effect of DM, an independent risk factor of chronic kidney disease (CKD), is not completely understood. We investigated the relationship between DM and decline in kidney function following surgery for RCC, and impact on overall survival (OS) in patients with RCC. Methods: A multicenter dataset of RCC patients undergoing PN and RN was utilized. The cohort was divided based on DM status [DM vs No DM (NDM)]. Multivariable analysis (MVA) elucidated potential variables associated with decline in kidney function [de novo estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73m2 and de novo eGFR < 30 ml/min/1.73m2] and worse all-cause mortality (ACM). Kaplan-Meier analysis (KMA) was used to investigate OS rates in DM and NDM patients undergoing RN and PN. Results: 2928 patients were analyzed (DM = 406, NDM = 2522). On MVA, independent risk factors associated with eGFR < 45 included age (OR = 1.07, p < 0.001), DM (OR = 1.88, p < 0.001), tumor size (OR = 1.03, p = 0.032), and RN (OR = 1.54, p < 0.001). Variables associated with eGFR < 30 included age (OR = 1.05, p < 0.001), African American race (OR = 2.18, p < 0.001), and DM (OR = 2.09, p < 0.001). MVA for ACM revealed age (OR = 1.02, p = 0.002), HTN (OR = 2.47, p < 0.001), tumor size (OR = 1.12, p < 0.001), tumor grade (OR = 1.87, p < 0.001), RN (OR = 1.55, p = 0.011), eGFR < 45 (OR = 1.40, p = 0.03), and eGFR < 30 (OR = 1.87, p = 0.026) to be independently associated. On KMA, 5-year OS stratified by DM status showed that DM is associated with worse OS for RN patients (p = 0.047), but not for PN patients (p = 0.944). Conclusions: Presence of DM is an independent risk factor for renal functional decline and development of worsening CKD is a risk factor for worsening ACM. Furthermore, decreased survival in DM patients was associated with RN recipients but not with PN recipients. Presence of DM may be considered a strong indicator for nephron preservation management strategies when safe and feasible in RCC patients.

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