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Grade 1 Clear Cell Renal Cell Carcinoma

MedGen UID:
232245
•Concept ID:
C1333829
•
Neoplastic Process
Synonym: Grade 1 Conventional (Clear Cell) Renal Cell Carcinoma

Definition

A clear cell renal cell carcinoma characterized by absent or inconspicuous and basophilic nucleoli at x 400 magnification. (WHO 1982 /ISUP 2014) [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGrade 1 Clear Cell Renal Cell Carcinoma

Professional guidelines

PubMed

New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia.
Trpkov K, Hes O, Williamson SR, Adeniran AJ, Agaimy A, Alaghehbandan R, Amin MB, Argani P, Chen YB, Cheng L, Epstein JI, Cheville JC, Comperat E, da Cunha IW, Gordetsky JB, Gupta S, He H, Hirsch MS, Humphrey PA, Kapur P, Kojima F, Lopez JI, Maclean F, Magi-Galluzzi C, McKenney JK, Mehra R, Menon S, Netto GJ, Przybycin CG, Rao P, Rao Q, Reuter VE, Saleeb RM, Shah RB, Smith SC, Tickoo S, Tretiakova MS, True L, Verkarre V, Wobker SE, Zhou M, Gill AJ
Mod Pathol 2021 Jul;34(7):1392-1424. Epub 2021 Mar 4 doi: 10.1038/s41379-021-00779-w. PMID: 33664427
Novel, emerging and provisional renal entities: The Genitourinary Pathology Society (GUPS) update on renal neoplasia.
Trpkov K, Williamson SR, Gill AJ, Adeniran AJ, Agaimy A, Alaghehbandan R, Amin MB, Argani P, Chen YB, Cheng L, Epstein JI, Cheville JC, Comperat E, da Cunha IW, Gordetsky JB, Gupta S, He H, Hirsch MS, Humphrey PA, Kapur P, Kojima F, Lopez JI, Maclean F, Magi-Galluzzi C, McKenney JK, Mehra R, Menon S, Netto GJ, Przybycin CG, Rao P, Rao Q, Reuter VE, Saleeb RM, Shah RB, Smith SC, Tickoo S, Tretiakova MS, True L, Verkarre V, Wobker SE, Zhou M, Hes O
Mod Pathol 2021 Jun;34(6):1167-1184. Epub 2021 Feb 1 doi: 10.1038/s41379-021-00737-6. PMID: 33526874
Management of toxicities of immune checkpoint inhibitors.
Spain L, Diem S, Larkin J
Cancer Treat Rev 2016 Mar;44:51-60. Epub 2016 Feb 6 doi: 10.1016/j.ctrv.2016.02.001. PMID: 26874776

Recent clinical studies

Etiology

Deep learning-based multi-model prediction for disease-free survival status of patients with clear cell renal cell carcinoma after surgery: a multicenter cohort study.
Chen S, Gao F, Guo T, Jiang L, Zhang N, Wang X, Zheng J
Int J Surg 2024 May 1;110(5):2970-2977. doi: 10.1097/JS9.0000000000001222. PMID: 38445478Free PMC Article
Phase I LITESPARK-001 study of belzutifan for advanced solid tumors: Extended 41-month follow-up in the clear cell renal cell carcinoma cohort.
Jonasch E, Bauer TM, Papadopoulos KP, Plimack ER, Merchan JR, McDermott DF, Dror Michaelson M, Appleman LJ, Roy A, Perini RF, Liu Y, Choueiri TK
Eur J Cancer 2024 Jan;196:113434. Epub 2023 Nov 15 doi: 10.1016/j.ejca.2023.113434. PMID: 38008031
Multimodal recurrence scoring system for prediction of clear cell renal cell carcinoma outcome: a discovery and validation study.
Gui CP, Chen YH, Zhao HW, Cao JZ, Liu TJ, Xiong SW, Yu YF, Liao B, Cao Y, Li JY, Huang KB, Han H, Zhang ZL, Chen WF, Jiang ZY, Gao Y, Han GP, Tang Q, Ouyang K, Qu GM, Wu JT, Guo JP, Li CX, Li PX, Liu ZP, Hsieh JT, Cai MY, Li XS, Wei JH, Luo JH
Lancet Digit Health 2023 Aug;5(8):e515-e524. Epub 2023 Jun 29 doi: 10.1016/S2589-7500(23)00095-X. PMID: 37393162
Machine learning-based pathomics signature could act as a novel prognostic marker for patients with clear cell renal cell carcinoma.
Chen S, Jiang L, Gao F, Zhang E, Wang T, Zhang N, Wang X, Zheng J
Br J Cancer 2022 Mar;126(5):771-777. Epub 2021 Nov 25 doi: 10.1038/s41416-021-01640-2. PMID: 34824449Free PMC Article
Management of Atypical Renal Cell Carcinomas.
Liaw BC, Mehrazin R, Baker C, Sfakianos JP, Tsao CK
Curr Treat Options Oncol 2017 Sep 14;18(10):61. doi: 10.1007/s11864-017-0501-1. PMID: 28913767

Diagnosis

Upregulation of serine metabolism enzyme PSAT1 predicts poor prognosis and promotes proliferation, metastasis and drug resistance of clear cell renal cell carcinoma.
Ye J, Huang X, Tian S, Wang J, Wang H, Feng H, Zhao X, Cao S, Xuan Y, Li X, Ma X, Huang Y, Zhang X
Exp Cell Res 2024 Apr 1;437(1):113977. Epub 2024 Feb 17 doi: 10.1016/j.yexcr.2024.113977. PMID: 38373588
Multimodal recurrence scoring system for prediction of clear cell renal cell carcinoma outcome: a discovery and validation study.
Gui CP, Chen YH, Zhao HW, Cao JZ, Liu TJ, Xiong SW, Yu YF, Liao B, Cao Y, Li JY, Huang KB, Han H, Zhang ZL, Chen WF, Jiang ZY, Gao Y, Han GP, Tang Q, Ouyang K, Qu GM, Wu JT, Guo JP, Li CX, Li PX, Liu ZP, Hsieh JT, Cai MY, Li XS, Wei JH, Luo JH
Lancet Digit Health 2023 Aug;5(8):e515-e524. Epub 2023 Jun 29 doi: 10.1016/S2589-7500(23)00095-X. PMID: 37393162
BAP1-Mutated Clear Cell Renal Cell Carcinoma.
Gallan AJ, Parilla M, Segal J, Ritterhouse L, Antic T
Am J Clin Pathol 2021 Apr 26;155(5):718-728. doi: 10.1093/ajcp/aqaa176. PMID: 33210135
Grading of renal cell carcinoma.
Delahunt B, Eble JN, Egevad L, Samaratunga H
Histopathology 2019 Jan;74(1):4-17. doi: 10.1111/his.13735. PMID: 30565310
The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters.
Delahunt B, Cheville JC, Martignoni G, Humphrey PA, Magi-Galluzzi C, McKenney J, Egevad L, Algaba F, Moch H, Grignon DJ, Montironi R, Srigley JR; Members of the ISUP Renal Tumor Panel
Am J Surg Pathol 2013 Oct;37(10):1490-504. doi: 10.1097/PAS.0b013e318299f0fb. PMID: 24025520

Therapy

Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma.
Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Chang YH, Lee JL, Sarwar N, Haas NB, Gurney H, Sawrycki P, Mahave M, Gross-Goupil M, Zhang T, Burke JM, Doshi G, Melichar B, Kopyltsov E, Alva A, Oudard S, Topart D, Hammers H, Kitamura H, McDermott DF, Silva A, Winquist E, Cornell J, Elfiky A, Burgents JE, Perini RF, Powles T; KEYNOTE-564 Investigators
N Engl J Med 2024 Apr 18;390(15):1359-1371. doi: 10.1056/NEJMoa2312695. PMID: 38631003
Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.
Powles T, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Gurney H, Chang YH, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Burgents JE, Xu L, Imai K, Quinn DI, Choueiri TK; KEYNOTE-564 Investigators
Lancet Oncol 2022 Sep;23(9):1133-1144. doi: 10.1016/S1470-2045(22)00487-9. PMID: 36055304
Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma.
Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Chang YH, Hajek J, Symeonides SN, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Gurney H, Chevreau C, Melichar B, Kopyltsov E, Alva A, Burke JM, Doshi G, Topart D, Oudard S, Hammers H, Kitamura H, Bedke J, Perini RF, Zhang P, Imai K, Willemann-Rogerio J, Quinn DI, Powles T; KEYNOTE-564 Investigators
N Engl J Med 2021 Aug 19;385(8):683-694. doi: 10.1056/NEJMoa2106391. PMID: 34407342
Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma.
Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, Oyervides Juárez VM, Hsieh JJ, Basso U, Shah AY, Suárez C, Hamzaj A, Goh JC, Barrios C, Richardet M, Porta C, Kowalyszyn R, Feregrino JP, Żołnierek J, Pook D, Kessler ER, Tomita Y, Mizuno R, Bedke J, Zhang J, Maurer MA, Simsek B, Ejzykowicz F, Schwab GM, Apolo AB, Motzer RJ; CheckMate 9ER Investigators
N Engl J Med 2021 Mar 4;384(9):829-841. doi: 10.1056/NEJMoa2026982. PMID: 33657295Free PMC Article
Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma.
Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthélémy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B; CheckMate 214 Investigators
N Engl J Med 2018 Apr 5;378(14):1277-1290. Epub 2018 Mar 21 doi: 10.1056/NEJMoa1712126. PMID: 29562145Free PMC Article

Prognosis

Metabolic heterogeneity in clear cell renal cell carcinoma revealed by single-cell RNA sequencing and spatial transcriptomics.
Yang G, Cheng J, Xu J, Shen C, Lu X, He C, Huang J, He M, Cheng J, Wang H
J Transl Med 2024 Feb 27;22(1):210. doi: 10.1186/s12967-024-04848-x. PMID: 38414015Free PMC Article
Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.
Powles T, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Gurney H, Chang YH, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Burgents JE, Xu L, Imai K, Quinn DI, Choueiri TK; KEYNOTE-564 Investigators
Lancet Oncol 2022 Sep;23(9):1133-1144. doi: 10.1016/S1470-2045(22)00487-9. PMID: 36055304
Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): long-term follow-up results from an open-label, randomised, phase 3 trial.
Motzer RJ, Powles T, Burotto M, Escudier B, Bourlon MT, Shah AY, Suárez C, Hamzaj A, Porta C, Hocking CM, Kessler ER, Gurney H, Tomita Y, Bedke J, Zhang J, Simsek B, Scheffold C, Apolo AB, Choueiri TK
Lancet Oncol 2022 Jul;23(7):888-898. Epub 2022 Jun 7 doi: 10.1016/S1470-2045(22)00290-X. PMID: 35688173Free PMC Article
Grading of renal cell carcinoma.
Delahunt B, Eble JN, Egevad L, Samaratunga H
Histopathology 2019 Jan;74(1):4-17. doi: 10.1111/his.13735. PMID: 30565310
Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial.
Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, Hammers HJ, Donskov F, Roth BJ, Peltola K, Lee JL, Heng DYC, Schmidinger M, Agarwal N, Sternberg CN, McDermott DF, Aftab DT, Hessel C, Scheffold C, Schwab G, Hutson TE, Pal S, Motzer RJ; METEOR investigators
Lancet Oncol 2016 Jul;17(7):917-927. Epub 2016 Jun 5 doi: 10.1016/S1470-2045(16)30107-3. PMID: 27279544

Clinical prediction guides

Deep learning-based multi-model prediction for disease-free survival status of patients with clear cell renal cell carcinoma after surgery: a multicenter cohort study.
Chen S, Gao F, Guo T, Jiang L, Zhang N, Wang X, Zheng J
Int J Surg 2024 May 1;110(5):2970-2977. doi: 10.1097/JS9.0000000000001222. PMID: 38445478Free PMC Article
Multimodal recurrence scoring system for prediction of clear cell renal cell carcinoma outcome: a discovery and validation study.
Gui CP, Chen YH, Zhao HW, Cao JZ, Liu TJ, Xiong SW, Yu YF, Liao B, Cao Y, Li JY, Huang KB, Han H, Zhang ZL, Chen WF, Jiang ZY, Gao Y, Han GP, Tang Q, Ouyang K, Qu GM, Wu JT, Guo JP, Li CX, Li PX, Liu ZP, Hsieh JT, Cai MY, Li XS, Wei JH, Luo JH
Lancet Digit Health 2023 Aug;5(8):e515-e524. Epub 2023 Jun 29 doi: 10.1016/S2589-7500(23)00095-X. PMID: 37393162
Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates.
Lee CH, Voss MH, Carlo MI, Chen YB, Zucker M, Knezevic A, Lefkowitz RA, Shapnik N, Dadoun C, Reznik E, Shah NJ, Owens CN, McHugh DJ, Aggen DH, Laccetti AL, Kotecha R, Feldman DR, Motzer RJ
J Clin Oncol 2022 Jul 20;40(21):2333-2341. Epub 2022 Mar 17 doi: 10.1200/JCO.21.01944. PMID: 35298296Free PMC Article
Machine learning-based pathomics signature could act as a novel prognostic marker for patients with clear cell renal cell carcinoma.
Chen S, Jiang L, Gao F, Zhang E, Wang T, Zhang N, Wang X, Zheng J
Br J Cancer 2022 Mar;126(5):771-777. Epub 2021 Nov 25 doi: 10.1038/s41416-021-01640-2. PMID: 34824449Free PMC Article
Grading of renal cell carcinoma.
Delahunt B, Eble JN, Egevad L, Samaratunga H
Histopathology 2019 Jan;74(1):4-17. doi: 10.1111/his.13735. PMID: 30565310

Recent systematic reviews

Adverse Events of Immune Checkpoint Inhibitors Therapy for Urologic Cancer Patients in Clinical Trials: A Collaborative Systematic Review and Meta-analysis.
Wu Z, Chen Q, Qu L, Li M, Wang L, Mir MC, Carbonara U, Pandolfo SD, Black PC, Paul AK, Di Lorenzo G, Porpiglia F, Mari A, Necchi A, Rouprêt M, Psutka SP, Autorino R
Eur Urol 2022 Apr;81(4):414-425. Epub 2022 Jan 31 doi: 10.1016/j.eururo.2022.01.028. PMID: 35101302
Association between immune-related side effects and efficacy and benefit of immune checkpoint inhibitors - A systematic review and meta-analysis.
Hussaini S, Chehade R, Boldt RG, Raphael J, Blanchette P, Maleki Vareki S, Fernandes R
Cancer Treat Rev 2021 Jan;92:102134. Epub 2020 Dec 3 doi: 10.1016/j.ctrv.2020.102134. PMID: 33302134
Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review.
Khoja L, Day D, Wei-Wu Chen T, Siu LL, Hansen AR
Ann Oncol 2017 Oct 1;28(10):2377-2385. doi: 10.1093/annonc/mdx286. PMID: 28945858
Incidence of Programmed Cell Death 1 Inhibitor-Related Pneumonitis in Patients With Advanced Cancer: A Systematic Review and Meta-analysis.
Nishino M, Giobbie-Hurder A, Hatabu H, Ramaiya NH, Hodi FS
JAMA Oncol 2016 Dec 1;2(12):1607-1616. doi: 10.1001/jamaoncol.2016.2453. PMID: 27540850
Management of Renal Masses and Localized Renal Cancer: Systematic Review and Meta-Analysis.
Pierorazio PM, Johnson MH, Patel HD, Sozio SM, Sharma R, Iyoha E, Bass EB, Allaf ME
J Urol 2016 Oct;196(4):989-99. Epub 2016 May 6 doi: 10.1016/j.juro.2016.04.081. PMID: 27157369Free PMC Article

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