Localised non‐metastatic sarcomatoid renal cell carcinoma: a 31‐year externally verified study

Objective To evaluate post‐nephrectomy outcomes and predictors of cancer‐specific survival (CSS) between patients with localised sarcomatoid renal cell carcinoma (sRCC) and those with Grade 4 RCC (non‐sRCC), as most sRCC research focuses on advanced or metastatic disease with limited studies analysing outcomes of patients with localised non‐metastatic sRCC. Patients and Methods A total of 564 patients with localised RCC underwent partial or radical nephrectomy between June 1988 to March 2019 for sRCC ( n = 204) or World Health Organization/International Society of Urological Pathology Grade 4 non‐sRCC ( n = 360). The CSS at every stage between groups was assessed. Phase III ASSURE clinical trial data were used to externally validate the CSS findings. The Mann–Whitney U ‐test and chi‐squared test compared outcomes and the Kaplan–Meier method evaluated CSS, overall survival (OS) and recurrence‐free survival. Clinicopathological features associated with RCC death were evaluated using Cox proportional hazards regression. Results The median follow‐up was 31.5 months. The median OS and CSS between the sRCC and Grade 4 non‐sRCC groups was 45 vs 102 months and 49 vs 152 months, respectively ( P < 0.001). At every stage, sRCC had worse CSS compared to Grade 4 non‐sRCC. Notably, pT1 sRCC had worse CSS than pT3 Grade 4 non‐sRCC. Negative predictors of CSS were sarcomatoid features, non‐clear cell histology, positive margins, higher stage (pT3/pT4), and use of minimally invasive surgery (MIS). ASSURE external verification showed worse CSS in patients with sRCC (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.12–2.36; P = 0.01), but not worse outcomes in MIS surgery (HR 1.39, 95% CI 0.75–2.56; P = 0.30). Conclusions Localised sRCC had worse CSS compared to Grade 4 non‐sRCC at every stage. Negative survival predictors included positive margins, higher pathological stage, use of MIS, and non‐clear cell histology. sRCC is an aggressive variant even at low stages requiring vigilant surveillance and possible inclusion in adjuvant therapy trials.