Hot topics in renal cancer pathology: implications for clinical management

References

• Marconi L, Sun M, Beisland C, et al. Prevalence, disease-free, and overall survival of contemporary patients with renal cell carcinoma eligible for adjuvant checkpoint inhibitor trials. Clin Genitourin Cancer. 2021;19(2):e92–e99.
   PubMed Web of Science ®Google Scholar
• Haas NB, Manola J, Dutcher JP, et al. Adjuvant treatment for high-risk clear cell renal cancer: updated results of a high-risk subset of the assure randomized trial. JAMA Oncol. 2017;3(9):1249–1252.
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Haas NB, Donskov F, et al. Randomized phase iii trial of adjuvant pazopanib versus placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma. J Clin Oncol. 2017;35(35):3916–3923.
   PubMed Web of Science ®Google Scholar
• Gross-Goupil M, Kwon TG, Eto M, et al. Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III, randomized ATLAS trial. Ann Oncol. 2018;29(12):2371–2378.
   PubMed Web of Science ®Google Scholar
• Ravaud A, Motzer RJ, Pandha HS, et al. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med. 2016;375(23):2246–2254.
   PubMed Web of Science ®Google Scholar
• Eisen T, Frangou E, Oza B, et al. Adjuvant Sorafenib for renal cell carcinoma at intermediate or high risk of relapse: results from the sorce randomized phase iii intergroup trial. J Clin Oncol. 2020;38(34):4064–4075.
   PubMed Web of Science ®Google Scholar
• Choueiri TK, Tomczak P, Park SH, et al. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021;385(8):683–694.
   PubMed Web of Science ®Google Scholar
• NCCN Guidelines Version 2022 https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1440 Accessed on 2022 Sept 12.
   Google Scholar
• EAU Guidelines. Edn. presented at the EAU Annual Congress Amsterdam 2022, Amsterdam. 2022.
   Google Scholar
• Powles T, Albiges L, Bex A, et al. ESMO Clinical Practice Guideline update on the use of immunotherapy in early stage and advanced renal cell carcinoma. Ann Oncol. 2021;32(12):1511–1519.
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Russo P, Gruenwald V, et al. Adjuvant nivolumab plus ipilimumab (NIVO+IPI) vs placebo (PBO) for localized renal cell carcinoma (RCC) at high risk of relapse after nephrectomy: results from the randomized, phase 3 CheckMate 914 trial. Ann Oncol. 2022;33(suppl_7):S808–S869.
   Google Scholar
• Pal SK, Uzzo R, Karam JA, et al., Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion010): a multicentre, randomised, double-blind, phase 3 trial, Lancet 2022 Sep 9 S0140-6736 22 1658.
   Google Scholar
• Allaf M, Kim SE, Harshman LC, et al. LBA67 - Phase III randomized study comparing perioperative nivolumab (nivo) versus observation in patients (Pts) with renal cell carcinoma (RCC) undergoing nephrectomy (PROSPER, ECOG-ACRIN EA8143), a national clinical trials network trial. Ann Oncol. 2022;33(suppl_7):S808–S869.
   Google Scholar
• Magee DE, Kutikov A. Re: adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. Eur Urol. 2022;81(3):317–318.
   PubMed Web of Science ®Google Scholar
• Ghisoni E, Wicky A, Bouchaab H, et al. Late-onset and long-lasting immune-related adverse events from immune checkpoint-inhibitors: an overlooked aspect in immunotherapy. Eur J Cancer. 2021;149:153–164.
   PubMed Web of Science ®Google Scholar
• Thompson RH, Blute ML, Krambeck AE, et al. Patients with pT1 renal cell carcinoma who die from disease after nephrectomy may have unrecognized renal sinus fat invasion. Am J Surg Pathol. 2007;31:1089–1093.
   PubMed Web of Science ®Google Scholar
• Williamson SR, Rao P, Hes O, et al. Challenges in pathologic staging of renal cell carcinoma: a study of interobserver variability among urologic pathologists. Am J Surg Pathol. 2018;42(9):1253–1261.
   PubMed Web of Science ®Google Scholar
• Cimadamore A, Gasparrini S, Santoni M, et al. Biomarkers of aggressiveness in genitourinary tumors with emphasis on kidney, bladder, and prostate cancer. Expert Rev Mol Diagn. 2018;18(7):645–655.
   PubMed Web of Science ®Google Scholar
• Delahunt B, Cheville JC, Martignoni G, et al. Members of the ISUP renal tumor panel. the international society of urological pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters. Am J Surg Pathol. 2013;37(10):1490–1504.
   PubMed Web of Science ®Google Scholar
• Browning L, Colling R, Verrill C. WHO/ISUP grading of clear cell renal cell carcinoma and papillary renal cell carcinoma; validation of grading on the digital pathology platform and perspectives on reproducibility of grade. Diagn Pathol. 2021;16(1):75.
   PubMed Web of Science ®Google Scholar
• Cheville JC, Lohse CM, Zincke H, et al. Sarcomatoid renal cell carcinoma: an examination of underlying histologic subtype and an analysis of associations with patient outcome. Am J Surg Pathol. 2004;28(4):435–441.
   PubMed Web of Science ®Google Scholar
• Dagher J, Delahunt B, Rioux-Leclercq N, et al. Clear cell renal cell carcinoma: validation of World Health Organization/International Society of Urological Pathology grading. Histopathology. 2017;71(6):918–925.
   PubMed Web of Science ®Google Scholar
• Delahunt B, McKenney JK, Lohse CM, et al. A novel grading system for clear cell renal cell carcinoma incorporating tumor necrosis. Am J Surg Pathol. 2013;37(3):311–322.
   PubMed Web of Science ®Google Scholar
• Fenstermaker M, Tomlins SA, Singh K, et al. Development and validation of a deep-learning model to assist with renal cell carcinoma histopathologic interpretation. Urology. 2020;144:152–157.
   PubMed Web of Science ®Google Scholar
• Jones TD, Eble JN, Wang M, et al. Clonal divergence and genetic heterogeneity in clear cell renal cell carcinomas with sarcomatoid transformation. Cancer. 2005;104(6):1195–1203.
   PubMed Web of Science ®Google Scholar
• Peralta-Venturina M D, Moch H, Amin M, et al. Sarcomatoid differentiation in renal cell carcinoma: a study of 101 cases. Am J Surg Pathol. 2001;25(3):275–284.
   PubMed Web of Science ®Google Scholar
• Amin MB, Paner GP, Alvarado-Cabrero I, et al. Chromophobe renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 145 cases. Am J Surg Pathol. 2008;32(12):1822–1834.
   PubMed Web of Science ®Google Scholar
• Mian BM, Bhadkamkar N, Slaton JW, et al. Prognostic factors and survival of patients with sarcomatoid renal cell carcinoma. J Urol. 2002;167(1):65–70.
   PubMed Web of Science ®Google Scholar
• Merrill MM, Wood CG, Tannir NM, et al. Clinically nonmetastatic renal cell carcinoma with sarcomatoid dedifferentiation: natural history and outcomes after surgical resection with curative intent. Urol Oncol. 2015;33:166.e21–9.
   PubMed Web of Science ®Google Scholar
• Zhang BY, Thompson RH, Lohse CM, et al. A novel prognostic model for patients with sarcomatoid renal cell carcinoma. BJU Int. 2015;115:405–441.
   PubMed Web of Science ®Google Scholar
• Kim T, Zargar-Shoshtari K, Dhillon J, et al. Using percentage of sarcomatoid differentiation as a prognostic factor in renal cell carcinoma. Clin Genitourin Cancer. 2015;13:225–230.
   PubMed Web of Science ®Google Scholar
• Malouf GG, Ali SM, Wang K, et al. Genomic characterization of renal cell carcinoma with sarcomatoid dedifferentiation pinpoints recurrent genomic alterations. Eur Urol. 2016;70(2):348–357.
   PubMed Web of Science ®Google Scholar
• Bakouny Z, Braun DA, Shukla SA, et al. Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma. Nat Commun. 2021;12(1):808.
   PubMed Web of Science ®Google Scholar
• Gokden N, Nappi O, Swanson PE, et al. Renal cell carcinoma with rhabdoid features. Am J Surg Pathol. 2000;24(10):1329–1338.
   PubMed Web of Science ®Google Scholar
• Leroy X, Zini L, Buob L, et al. Renal cell carcinoma with rhabdoid features: an aggressive neoplasm with overexpression of p53. Arch Pathol Lab Med. 2007;31(1):102–108.
   Google Scholar
• Williamson SR, Kum JB, Goheen MP, et al. Clear cell renal cell carcinoma with a syncytial-type multinucleated giant tumor cell component: implications for differential diagnosis. Hum Pathol. 2014;45(4):735–744.
   PubMed Web of Science ®Google Scholar
• Berzal Cantalejo F, Sabater Marco V, Alonso Hernández S, et al. Syncytial giant cell component. Review of 55 renal cell carcinomas. Histol Histopathol. 2004;19(1):113–118.
   PubMed Web of Science ®Google Scholar
• Lloreta J, Bielsa O, Munné A, et al. Renal cell carcinoma with syncytial giant cell component. Virchows Arch. 2002;440(3):330–333.
   PubMed Web of Science ®Google Scholar
• Bonsib SM. Renal lymphatics, and lymphatic involvement in sinus vein invasive (pT3b) clear cell renal cell carcinoma: a study of 40 cases. Mod Pathol. 2006;19(5):746–753.
   PubMed Web of Science ®Google Scholar
• Bonsib SM, Gibson D, Mhoon M, et al. Renal sinus involvement in renal cell carcinomas. Am J Surg Pathol. 2000;24(3):451–458.
   PubMed Web of Science ®Google Scholar
• Taneja K, Arora S, Rogers CG, et al. Pathologic staging of renal cell carcinoma: a review of 300 consecutive cases with emphasis on retrograde venous invasion. Histopathology. 2018;73(4):681–691.
   PubMed Web of Science ®Google Scholar
• Guo P, Wang Y, Han Y, et al. Oncological outcomes of patients with different pathological features of pT3a renal tumor: a systematic review and quantitative synthesis. Front Oncol. 2021;11:678459.
   PubMed Web of Science ®Google Scholar
• Williamson SR, Taneja K, Cheng L. Renal cell carcinoma staging: pitfalls, challenges, and updates. Histopathology. 2019;74(1):18–30.
   PubMed Web of Science ®Google Scholar
• Sorbellini M, Kattan MW, Snyder ME, et al. A postoperative prognostic nomogram predicting recurrence for patients with conventional clear cell renal cell carcinoma. J Urol. 2005;173:48–51.
   PubMed Web of Science ®Google Scholar
• Isbarn H, Patard JJ, Lughezzani G, et al. Limited prognostic value of tumor necrosis in patients with renal cell carcinoma. Urology. 2010;75:1378–1384.
   PubMed Web of Science ®Google Scholar
• Brinker DA, Amin MB, de Peralta-Venturina M, et al. Extensively necrotic cystic renal cell carcinoma: a clinicopathologic study with comparison to other cystic and necrotic renal cancers. Am J Surg Pathol. 2000;24:988–995.
   PubMed Web of Science ®Google Scholar
• Faria V, Surendra T, Poller DN. Prognostic relevance of extensive necrosis in renal cell carcinoma. J Clin Pathol. 2005;58:39–43.
   PubMed Web of Science ®Google Scholar
• Samaratunga H, Delahunt B, Srigley JR, et al. Granular necrosis: a distinctive form of cell death in malignant tumours. Pathology. 2020;52(5):507–514.
   PubMed Web of Science ®Google Scholar
• Katz MD, Serrano MF, Grubb RL. Percent microscopic tumor necrosis and survival after curative surgery for renal cell carcinoma. J Urol. 2010;183(3):909–914. 3rd.
   PubMed Web of Science ®Google Scholar
• Khor LY, Dhakal HP, Jia X, et al. Tumor necrosis adds prognostically significant information to grade in clear cell renal cell carcinoma: a study of 842 consecutive cases from a single institution. Am J Surg Pathol. 2016;40(9):1224–1231.
   PubMed Web of Science ®Google Scholar
• Stühler V, Rausch S, Kroll K, et al. The prognostic value of fat invasion and tumor expansion in the hilar veins in pT3a renal cell carcinoma. World J Urol. 2021;39(9):3367–3376.
   PubMed Web of Science ®Google Scholar
• Volpe A, Patard JJ. Prognostic factors in renal cell carcinoma. World J Urol. 2010;28(3):319–327.
   PubMed Web of Science ®Google Scholar
• Hu C, Sun J, Zhang Z, et al. Parallel comparison of R.E.N.A.L., Padua, and C-index scoring systems in predicting outcomes after partial nephrectomy: a systematic review and meta-analysis. Cancer Med. 2021;10(15):5062–5077.
   PubMed Web of Science ®Google Scholar
• Campi R, Kutikov A. Predictive models for patients with a renal mass in the clinical trenches continue to be a muddy proposition. Eur Urol. 2022;S0302-2838(22):4–74.
   Google Scholar
• Karakiewicz PI, Briganti A, Chun FK, et al. Multi-institutional validation of a new renal cancer-specific survival nomogram. J Clin Oncol. 2007;25(11):1316–1322.
   PubMed Web of Science ®Google Scholar
• Cindolo L, Chiodini P, Brookman-May S, et al. Assessing the accuracy and generalizability of the preoperative and postoperative Karakiewicz nomograms for renal cell carcinoma: results from a multicentre European and US study. BJU Int. 2013;112(5):578–584.
   PubMedGoogle Scholar
• Russo GI, Di Rosa A, Favilla V, et al. Accuracy capabilities comparisons between karakiewicz, kattan and cindolo nomograms in predicting outcomes for renal cancer carcinoma: a systematic review and meta-analysis. Can Urol Assoc J. 2015;9(5–6):E359–66.
   PubMed Web of Science ®Google Scholar
• Ljungberg B, Albiges L, Abu-Ghanem Y, et al. European Association of urology guidelines on renal cell carcinoma: the 2022 Update. Eur Urol. 2022;S0302-2838(22):1–1676.
   Google Scholar
• Rosiello G, Palumbo C, Knipper S, et al. Histotype predicts the rate of lymph node invasion at nephrectomy in patients with nonmetastatic renal cell carcinoma. Urol Oncol. 2020;38(5):537–544.
   PubMed Web of Science ®Google Scholar
• European Association of Urology (EAU)-Young Academic Urologists (YAU) Renal Cancer Working Group, Erdem S, Capitanio U, Campi R, et al. External validation of the VENUSS prognostic model to predict recurrence after surgery in non-metastatic papillary renal cell carcinoma: a multi-institutional analysis. Urol Oncol 2022;S1078-1439(22):00005–9.
   Google Scholar
• Marchioni M, Amparore D, Ingels A, et al. european association of urology (EAU) young academic urologists (YAU) Renal Cancer Working Group. Renal tumors ablation. Minerva Urol Nephrol. 2021;73(4): 549–551
   Google Scholar
• Marchioni M, Cheaib JG, Takagi T, et al. Active surveillance for small renal masses in elderly patients does not increase overall mortality rates compared to primary intervention: a propensity score weighted analysis. Minerva Urol Nephrol. 2021;73(6): 781–788
   Google Scholar
• Psutka SP, Gulati R, Jewett MAS, et al. A clinical decision aid to support personalized treatment selection for patients with clinical T1 Renal masses: results from a multi-institutional Competing-risks Analysis. Eur Urol. 2021;S0302-2838(21):2144–2148.
   Google Scholar
• Montorsi F, Capitanio U, Rosiello G, et al. A clinical decision aid to support personalized treatment selection for patients with clinical t1 renal masses: results from a multi-institutional competing-risks analysis. Eur Urol. 2022;S0302-2838(22):2–1668.
   Google Scholar
• Heng DY, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol. 2009;27(34):5794–5799.
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Mazumdar M, Bacik J, et al. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol. 1999;17(8):2530–2540.
   PubMed Web of Science ®Google Scholar
• Méjean A, Ravaud A, Thezenas S, et al. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma. N Engl J Med. 2018;379(5):417–427.
   PubMed Web of Science ®Google Scholar
• Bex A, Mulders P, Jewett M, et al. Comparison of Immediate vs deferred cytoreductive nephrectomy in patients with synchronous metastatic renal cell carcinoma receiving sunitinib: the surtime randomized clinical trial. JAMA Oncol. 2019;5(2):164–170.
   PubMed Web of Science ®Google Scholar
• EAU-Young Academic Urologist Kidney Cancer Group, Marchioni M, Kriegmair M, Heck M, et al. Development of a novel risk score to select the optimal candidate for cytoreductive nephrectomy among patients with metastatic renal cell carcinoma. results from a multi-institutional registry (REMARCC). Eur Urol Oncol. 2021; 4(2):256–263.
   PubMed Web of Science ®Google Scholar
• Okita K, Hatakeyama S, Naito S, et al. External validation of the REMARCC model for the selection of cytoreductive nephrectomy in patients with primary metastatic renal cell carcinoma: a multicenter retrospective study. Urol Oncol. 2021;39(12):836.e11–836.e17.
   PubMed Web of Science ®Google Scholar
• Fasanella D, Antonaci A, Esperto F, et al. Potential prognostic value of miRNAs as biomarker for progression and recurrence after nephrectomy in renal cell carcinoma: a literature review. Diagnosis (Berl). 2021. 10.1515/dx-2021-0080.
   PubMedGoogle Scholar
• Zisman A, Pantuck AJ, Wieder J, et al. Risk group assessment and clinical outcome algorithm to predict the natural history of patients with surgically resected renal cell carcinoma. J Clin Oncol. 2002;20(23):4559.
   PubMed Web of Science ®Google Scholar
• Leibovich BC, Blute ML, Cheville JC, et al. Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: a stratification tool for prospective clinical trials. Cancer. 2003;97(7):1663.
   PubMed Web of Science ®Google Scholar
• Leibovich BC, Lohse CM, Cheville JC, et al. Predicting oncologic outcomes in renal cell carcinoma after surgery. Eur Urol. 2018;73(5):772–780.
   PubMed Web of Science ®Google Scholar
• Klatte T, Gallagher KM, Afferi L, et al. The VENUSS prognostic model to predict disease recurrence following surgery for non-metastatic papillary renal cell carcinoma: development and evaluation using the ASSURE prospective clinical trial cohort. BMC Med. 2019;17(1):182.
   PubMed Web of Science ®Google Scholar
• Buti S, Puligandla M, Bersanelli M, et al. Validation of a new prognostic model to easily predict outcome in renal cell carcinoma: the GRANT score applied to the ASSURE trial population. Ann Oncol. 2017;28(11):2747–2753.
   PubMed Web of Science ®Google Scholar
• Heng DY, Xie W, Regan MM, et al. External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol. 2013;14(2):141–8.
   PubMed Web of Science ®Google Scholar
• Kotecha RR, Motzer RJ, Voss MH. Towards individualized therapy for metastatic renal cell carcinoma. Nat Rev Clin Oncol. 2019;16:621–633.
   PubMed Web of Science ®Google Scholar
• Joseph RW, Kapur P, Serie DJ, et al. Clear cell renal cell carcinoma subtypes identified by BAP1 and PBRM1 Expression. J Urol. 2016;195:180–187.
   PubMed Web of Science ®Google Scholar
• Voss MH, Reising A, Cheng Y, et al. Genomically annotated risk model for advanced renal-cell carcinoma: a retrospective cohort study. Lancet Oncol. 2018;19:1688–1698.
   PubMed Web of Science ®Google Scholar
• Brooks SA, Brannon AR, Parker JS, et al. ClearCode34: a prognostic risk predictor for localized clear cell renal cell carcinoma. Eur Urol. 2014;66:77–84.
   PubMed Web of Science ®Google Scholar
• Rini B, Goddard A, Knezevic D, et al. A 16-gene assay to predict recurrence after surgery in localised renal cell carcinoma: development and validation studies. Lancet Oncol. 2015;16:676–685.
   PubMed Web of Science ®Google Scholar
• Wei JH, Feng ZH, Cao Y, et al. Predictive value of single-nucleotide polymorphism signature for recurrence in localised renal cell carcinoma: a retrospective analysis and multicentre validation study. Lancet Oncol. 2019;20:591–600.
   PubMed Web of Science ®Google Scholar
• Ahn T, Roberts MJ, Abduljabar A, et al. a review of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in renal cell carcinoma (RCC). Mol Imaging Biol. 2019;21(5):799–807.
   PubMed Web of Science ®Google Scholar
• Rhee H, Blazak J, Tham CM, et al. Pilot study: use of gallium-68 PSMA PET for detection of metastatic lesions in patients with renal tumour. EJNMMI Res. 2016;6(1):76.
   PubMedGoogle Scholar
• Tariq A, Kwok M, Pearce A, et al. The role of dual tracer PSMA and FDG PET/CT in renal cell carcinoma (RCC) compared to conventional imaging: a multi-institutional case series with intra-individual comparison. Urol Oncol. 2022;40(2):66.e1–66.e9.
   PubMed Web of Science ®Google Scholar
• Tariq A, McGeorge S, Pearce A, et al. Characterization of tumor thrombus in renal cell carcinoma with prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT). Urol Oncol. 2022;40(6):276.e1–276.e9.
   PubMed Web of Science ®Google Scholar
• Morgantetti G, Ng KL, Samaratunga H, et al. Prostate specific membrane antigen (PSMA) expression in vena cava tumour thrombi of clear cell renal cell carcinoma suggests a role for PSMA-driven tumour neoangiogenesis. Transl Androl Urol. 2019;8(Suppl 2):S147–S155.
   PubMedGoogle Scholar
• Spatz S, Tolkach Y, Jung K, et al. Comprehensive evaluation of prostate specific membrane antigen expression in the vasculature of renal tumors: implications for imaging studies and prognostic role. J Urol. 2018;199(2):370–377.
   PubMed Web of Science ®Google Scholar
• Telix Granted FDA Breakthrough Therapy Designation for Renal Cancer Imaging Product. Published online July 1, 2020. Accessed January 25, 2021. https://bit.ly/39hkIpT.
   Google Scholar