Presentation Authors: Florian Janisch*, Constantin Fühner, Christian P. Meyer, Tobias Hillemacher, Thomas Klotzbücher, Christina Kienapfel, Phillip Marks, Roland Dahlem, Hamburg, Germany, Shahrokh F. Shariat, Vienna, Austria, Margit Fisch, Michael Rink, Hamburg, Germany
Introduction: The introduction of tyrosine-kinase inhibitors (TKI) fundamentally changed the natural history and outcomes of patients with metastatic renal-cell cancer (mRCC). Clear cell RCC (ccRCC) is the most common histological subtype. Sarcomatoid variant histology (sRCC) is associated with aggressive tumor biology. However, distribution patterns and outcomes in the TKI era is scarcely investigated. To analyze clinical behavior of mRCC with or without sRCC features in a real-world setting.
Methods: We collected complete patient, treatment and outcome data of 262 mRCC patients from our institutional tertiary care center database. All patients were treated with TKI as single or multimodal treatment approach. Patients were stratified according to sRCC histology. Descriptive statistics as well as uni- and multivariable outcome metrics including progression-free (PFS) and overall survival (OS) were performed.
Results: The entire cohort had a median age of 62 yrs. and 193 patients were male (74%). Overall, 18 (6.9%) pts. had sRCC variant histology. Of these, 15 (83.3%), 1 (5.6%) and 2 (11.2%) had clear cell, papillary or mixed baseline histology, respectively. Patients with sRCC differentiation had more frequently advanced disease stages >/=pT3 (p=0.011) and received more often cytoreductive surgery (p < 0.001). There were no other differences in baseline characteristics. Most common first line TKIs in the entire cohort were Sunitinib (65.6%), Sorafenib (19.5%) and Pazopanib (10.3%), respectively. sRCC pts. received most commonly Sutinib (72.2%) for 1st line treatment. There was no difference in the number of therapy lines between sRCC and non-sRCC pts. At a mean follow-up of 32 months, Kaplan-Meier estimates demonstrated a significant reduced median PFS (3.7 vs 13.2 months, p=0.002) and OS (7.6 vs 29.0 months, p=0.001) in sRCC compared to non-sRCC pts. In multivariable analyses that adjusted for standard mRCC outcome prognosticators, sRCC was an independent predictor for inferior PFS (HR= 2.51; CI: 1.15-5.46; p=0.039) and OS (HR= 2.51; CI: 1.15-5.46; p=0.020), respectively. In subgroup analyses of only sRCC pts., there was no difference in PFS or OS according to the administered drug in 1st or 2nd line therapy.
Conclusions: Despite its rare occurrence, our findings confirm sRCC variant histology being a strong predictor for inferior outcomes in mRCC treated with targeted therapies. Our findings support the thesis of a reduced response to antiangiogenic therapies due to an increased resistance in sRCC compared to ccRCC.