Prognostic impact and genomic backgrounds of renal parenchymal infiltration or micronodular spread in clear cell renal cell carcinoma

You have accessJournal of UrologyCME1 Apr 2023MP41-14 PROGNOSTIC IMPACT AND GENOMIC BACKGROUNDS OF RENAL PARENCHYMAL INFILTRATION OR MICRONODULAR SPREAD IN CLEAR CELL RENAL CELL CARCINOMA Hajime Tanaka, Yuki Fukawa, Kouhei Yamamoto, Kousuke Tanimoto, Akira Takemoto, Hisashi Hasumi, Akihiro Hirakawa, Yudai Ishikawa, Shohei Fukuda, Yuma Waseda, Soichiro Yoshida, Minato Yokoyama, Steven C. Campbell, and Yasuhisa Fujii Hajime TanakaHajime Tanaka More articles by this author , Yuki FukawaYuki Fukawa More articles by this author , Kouhei YamamotoKouhei Yamamoto More articles by this author , Kousuke TanimotoKousuke Tanimoto More articles by this author , Akira TakemotoAkira Takemoto More articles by this author , Hisashi HasumiHisashi Hasumi More articles by this author , Akihiro HirakawaAkihiro Hirakawa More articles by this author , Yudai IshikawaYudai Ishikawa More articles by this author , Shohei FukudaShohei Fukuda More articles by this author , Yuma WasedaYuma Waseda More articles by this author , Soichiro YoshidaSoichiro Yoshida More articles by this author , Minato YokoyamaMinato Yokoyama More articles by this author , Steven C. CampbellSteven C. Campbell More articles by this author , and Yasuhisa FujiiYasuhisa Fujii More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003279.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The efficacy of adjuvant immune checkpoint inhibition has been reported recently for locally advanced clear cell renal carcinoma (ccRCC); however, further exploration is required to define optimal candidates for this strategy, who are at high risk for recurrence. In this study, we defined renal parenchymal infiltration or micronodular spread (RPI/MNS) in ccRCC and investigated its prognostic impact and genomic backgrounds. METHODS: We retrospectively analyzed 333 M0 ccRCC patients treated with radical nephrectomy (approval # M2019-172 and M2021-272). Two pathologists evaluated the whole tissue sections of surgical specimens and performed the focused analysis on the tumor interface with normal renal parenchyma. Recurrence-free survival (RFS) was analyzed as an endpoint. Genomic DNA was extracted from tumor tissue in eligible cases (n=51), and variants were screened using a panel of 440 cancer-related genes. RESULTS: Overall, ≥pT3a, WHO/ISUP grade 3-4, and microvascular invasion were observed in 107 (32%), 138 (41%), and 199 (60%) patients, respectively. Histological assessment revealed the variations of the tumor interface with normal renal parenchyma and identified the specific pattern at high risk for recurrence. This finding was defined as RPI/MNS, in whichcancer cells infiltrated or spread into the renal parenchyma by involving normal renal tissue and/or by forming micronodules. RPI/MNS was finally identified in 40 patients (12%). During the median follow-up of 6.0 years, 67 patients (20%) developed recurrence. On multivariable analysis, ≥pT3a, grade 3-4, and RPI/MNS were independently associated with shorter RFS; RPI/MNS showed the highest hazard ratio (4.63) followed by grade 3-4 (2.03) and ≥pT3a(1.99). 2y-RFS rates were 38% and 95% in patients with and without RPI/MNS, respectively. The genomic analysis revealed significantly different patterns of representative gene mutations in ccRCC (figure). Patients with RPI/MNS (n=18) had significantly more frequent mutations in SETD2 (28% vs. 6%) and TSC1 (17% vs. 0%) in comparison to those without RPI/MNS (n=33). CONCLUSIONS: RPI/MNS had a strong impact on recurrence after surgery with the background of aggressive genomic features in ccRCC. Adjuvant therapy may be recommended for patients showing RPI/MNS. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e560 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hajime Tanaka More articles by this author Yuki Fukawa More articles by this author Kouhei Yamamoto More articles by this author Kousuke Tanimoto More articles by this author Akira Takemoto More articles by this author Hisashi Hasumi More articles by this author Akihiro Hirakawa More articles by this author Yudai Ishikawa More articles by this author Shohei Fukuda More articles by this author Yuma Waseda More articles by this author Soichiro Yoshida More articles by this author Minato Yokoyama More articles by this author Steven C. Campbell More articles by this author Yasuhisa Fujii More articles by this author Expand All Advertisement PDF downloadLoading ...