Sarcomatoid dedifferentiation as a predictor of overall mortality in surgically treated metastatic renal cell carcinoma

In metastatic clear-cell renal cell carcinoma (ccmRCC), sarcomatoid dedifferentiation is routinely reported in G4 patients, but routine reporting is not recommended in G3 patients. We tested independent predictor status of sarcomatoid dedifferentiation in G4 ccmRCC. Additionally, we explored whether sarcomatoid dedifferentiation may have a role in overall mortality (OM) prediction in G3 ccmRCC.

Within the Surveillance, Epidemiology, and End Results database, univariable and multivariable Cox-regression models assessed cytoreductive nephrectomy (CN)-treated ccmRCC patients (2010-2020).

Of 2644 CN-treated ccmRCC patients, 1336 (51 %) harbored G4, of whom 528 (40 %) harbored sarcomatoid dedifferentiation. In G4, median overall survival (OS) according to presence vs. absence of sarcomatoid dedifferentiation was 20 vs. 21 months (p = 0.6) and sarcomatoid dedifferentiation was not independent predictor in multivariable analyses. Of all, 1308 (49 %) harbored G3, of whom 79 (6 %) harbored sarcomatoid dedifferentiation. In G3, median OS according to presence vs. absence of sarcomatoid dedifferentiation was 22 vs. 38 months (p < 0.001) and sarcomatoid dedifferentiation independently predicted higher OM in multivariable analyses (hazard ratio 1.7, p < 0.001).

Reporting of sarcomatoid dedifferentiation in G4 RCC is routinely recommended. However, in G4 ccmRCC, presence of sarcomatoid dedifferentiation does not independently predict higher OM and its inclusion is not essential in multivariable considerations in G4 patients. Conversely, despite absence of standard reporting recommendation for sarcomatoid dedifferentiation in G3, presence of sarcomatoid dedifferentiation is associated with significantly higher mortality and achieved independent predictor status. Therefore, it possibly should be routinely reported and routinely included in multivariable analyses addressing G3 ccmRCC patients.