Outcomes of Patients with Renal Carcinoma and Sarcomatoid Dedifferentiation Treated with Nephrectomy and Systemic Therapies: Comparison between the Cytokine and Targeted Therapy Eras: Expert Commentary

Though nephrectomy is the gold standard treatment for renal cell carcinoma, 20%-40% of patients have a recurrence and 20-30% of patients present with metastatic disease1. Sarcomatoid dedifferentiation is found in approximately 5% of all RCC and can be an associated feature with any RCC histological subtype. But they are historically associated with a poor prognosis and a median overall survival of 4 to 9 months2-4. The objective of this study was to then analyze the outcome of patients with metastatic sRCC in different therapeutic eras and explore factors associated with patient survival.

This was a retrospective study that identified patients with sarcomatoid renal cell carcinoma who underwent nephrectomy and received systemic therapy from 1987 – 2005. Demographics, clinical features, performance status, symptoms at diagnosis, laboratory values, operative notes, pathological features, postoperative evaluation, systemic therapies and follow-up were recorded for CCI calculations.  Systemic therapies were grouped as targeted, immunotherapy chemotherapy, or combinations (combination group consisted of 2 subgroups). For statistical analysis, multivariate regression models were used to determine the association with survival.

In total, 199 patients with sRCC were identified (mean age, 57). 92% of patients were symptomatic at initial diagnosis, and 69% presented with metastatic disease at initial diagnosis. 167 patients (83.9%) of the study population died, with mean overall survival of 16.5 months. The researchers found that survival of patients with clear histology was significantly longer vs those with non clear cell histology, and patients with synchronous metastatic disease had significantly shorter survival than patients with metachronous metastatic disease. Significant improvement in survival rate was observed in first year patients treated in targeted therapy era, but disappeared at years 3 to 5 after diagnosis and was not evident in patients with poor risk features.

The authors noted that some limitations in the study include retrospective nature and heterogenous systemic therapies that patients received during the years. However, they controlled for several clinical and pathological variables known to influence survival outcomes. In conclusion, the survival of patients with advanced sRCC without poor risk features who underwent nephrectomy steadily improves; however, survival does not extend beyond the first 2 years. Thus, there is still a poor prognosis for sRCC with no clear long-term benefit of target therapy. Future studies need to be done to develop more effective systemic therapies for these patients.

Written by: Zhamshid Okhunov, University of CA, Irvine

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