To elucidate which patients with clear cell renal cell carcinoma have the highest risk for disease relapse after curative nephrectomy is challenging but is acutely relevant in the era of approved adjuvant therapies. Pathological and genetic markers were used to improve the University of California Los Angeles Integrated Staging System (UISS) for the risk stratification and prognostication of recurrence free survival (RFS).
Necrosis, sarcomatoid features, Rhabdoid features, chromosomal loss 9p, combined chromosomal loss 3p14q and microvascular invasion (MVI) were tested in univariable and multivariable analyses for their ability to improve the discriminatory ability of the UISS.
In the development cohort, during the median follow-up time of 43.4 months (±SD 54.1 months), 50/240 (21%) patients developed disease recurrence. MVI (HR: 2.22; p = 0.013) and the combined loss of chromosome 3p/14q (HR: 2.89; p = 0.004) demonstrated independent association with RFS and were used to improve the assignment to the UISS risk category. In the current UISS high-risk group, only 7/50 (14%) recurrence cases were correctly identified; while in the improved system, 23/50 (45%) were correctly prognosticated. The concordance index meaningfully improved from 0.55 to 0.68 to distinguish patients at intermediate risk versus high risk. Internal validation demonstrated a robust prognostication of RFS. In the external validation cohort, there was no case with disease recurrence in the low-risk group, and the mean RFS times were 13.2 (±1.8) and 8.2 (±0.8) years in the intermediate and high-risk groups, respectively.
Adding MVI and combined chromosomal loss3p/14q to the UISS improves the ability to define the patient group with clear cell renal cell carcinomawho are at the highest risk for disease relapse after surgical treatment.
European journal of cancer (Oxford, England : 1990). 2022 Apr 20 [Epub ahead of print]
Nils Kroeger, Cédric Lebacle, Justine Hein, P N Rao, Reza Nejati, Shuanzeng Wei, Martin Burchardt, Alexandra Drakaki, Marshall Strother, Alexander Kutikov, Robert Uzzo, Allan J Pantuck
Institute of Urologic Oncology at the Department of Urology, David Geffen School of Medicine at University of California, Los Angeles, USA; Department of Urology, University of Greifswald, Germany. Electronic address: ., Institute of Urologic Oncology at the Department of Urology, David Geffen School of Medicine at University of California, Los Angeles, USA; Department of Urology, University Hospital Bicetre, APHP, University Paris-Saclay, Le Kremlin Bicetre, France., Department of Urology, Hospital Magdeburg, Germany., Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, USA., Department of Pathology at the Fox Chase Cancer Center, Philadelphia, USA., Department of Urology, University of Greifswald, Germany., Institute of Urologic Oncology at the Department of Urology, David Geffen School of Medicine at University of California, Los Angeles, USA; Department of Hematology and Oncology, David Geffen School of Medicine at University of California, Los Angeles, USA., Department of Urology, Fox Chase Cancer Center, Philadelphia, USA., Institute of Urologic Oncology at the Department of Urology, David Geffen School of Medicine at University of California, Los Angeles, USA.