Primary carcinomas with rhabdoid features have been reported in various anatomical sites including the bladder,3,4
the central nervous system12–16
and the vulva.17,18
In the kidney, pure rhabdoid carcinomas are usually found in the pediatric population, in which they account for 2% of pediatric renal tumours.19,20
Pure rhabdoid carcinomas in the pediatric population were first described as a variant of Wilms tumour by Beckwith and Palmer in 1978;21
however, it is now clear that they are a distinct malignancy.22
Conversely, in adults, pure rhabdoid variant RCC is exceedingly rare, with only 5 reports in the literature.23–27
Gokden and colleagues1
proposed that in several of these cases, partial examination may have missed a mixed RCC. Renal cell carcinoma with rhabdoid features are more commonly found alongside clear-cell carcinoma in adults and, in one recent report, alongside chromophobe carcinoma.28
In 4 retrospective series of RCC patients, encompassing a total of 1131 patients, the incidence of rhabdoid features ranged from 3% to 7% of RCC cases. In Gokden and colleagues’1
review of 480 patients, 23 had rhabdoid features mixed with clear-cell carcinoma. Leroy and coauthors29
found 14 rhabdoid tumours in 310 cases. Shannon and colleagues’27
series of 68 RCC cases yielded 5 rhabdoid tumours. Kuroiwa and coauthors2
found 8 cases among 253 cases of RCC.
Whether alone or in combination, rhabdoid features are a marker of poor prognosis. These tumours are more likely to present at higher grades, twice as likely to show extrarenal invasion and more likely to metastasize.1
It is thought that this malignant behaviour results from high cellproliferative activity.2
Median patient survival was found to be only 8 months in some studies.2,29
It remains unclear whether rhabdoid features arise de novo
or from other histological types of RCC. Some propose that they represent divergent differentiation of established pathological subtypes, much like sarcomatoid change, which also carries poor prognostic implications. Others suggest these features represent the end point of clonal evolution on a continuum beginning with clear-cell carcinoma.2
Although our case does not clarify the pathogenesis of this disease, it certainly adds to the growing body of literature confirming the aggressive nature of rhaboid RCC in adults.
Sorafenib is an oral multikinase inhibitor that was originally identified as a Raf kinase inhibitor. It was also found to inhibit other receptors, including vascular endothelial growth factor receptor 1, 2 and 3. The recent Treatment Approaches in Renal Cancer Global Evaluation Trial30
was an international phase 3 study, in which 903 patients who were resistant to prior systemic therapy were randomized to oral sorafenib at a dose of 400 mg twice daily continuously, or placebo. The primary end point of the study was overall survival and the main secondary end point was progression-free survival (PFS). Most patients had clear-cell histology. Ninety-three percent of patients had had nephrectomy and 82% had received cytokine therapy as their prior systemic treatment. The median duration of treatment was 23 weeks in the sorafenib group and 12 weeks in the placebo group.
The first analysis of overall survival was performed immediately before crossover was allowed, when 220 deaths (41% of the protocol-defined 540 deaths) had occurred. With a median follow-up of 6.6 months, the median actuarial overall survival was 14.7 months in the placebo group but had not been reached in the sorafenib arm, for a hazard ratio (HR) of 0.72 (95% confidence interval [CI] 0.54–0.94, p = 0.02). When survival was assessed 6 months later, 216 of 452 patients receiving placebo had switched to sorafenib and 367 deaths had occurred. Median overall survival was 19.3 months in the sorafenib group and 15.9 months in the placebo group, with an HR of 0.77 (95% CI 0.63–0.95, p = 0.02). For both analyses, p value was 0.02, which was less than the prespecified O’Brien–Fleming values for statistical significance for preliminary analyses.
The first analysis of PFS observed a median PFS of 5.5 months in the sorafenib arm, compared with 2.8 months in the placebo arm, with an HR of 0.44 (95% CI 0.35–0.55, p < 0.001). Best radiological response was assessed by independent reviewers. Among the 451 patients in the sorafenib group, 1 patient had a complete response and 43 patients (10%) had a partial response; 333 (74%) had stable disease. In the placebo group of 452 patients, no patients had a complete response, 8 patients (2%) had a partial response and 239 patients (53%) had stable disease. Among the 44 patients with a complete or partial response on sorafenib, the median time to response was 80 (range 35–275) days and the median duration of response was 182 (range 36–378) days.
The results of this phase 3 trial have demonstrated that sorafenib has a significantly better PFS compared with placebo in patients with advanced RCC who have received prior systemic therapy. The trial reports a large PFS benefit with a high stable-disease rate but a low objective response rate. Whether similar outcomes can be achieved in patients with non–clear-cell histology remains unclear. This report details response to sorafenib with overall stable disease in a patient with adult rhabdoid RCC. Other reasonable agents to treat this patient would have been sunitinib or temsirolimus, although there is a lack of data of the potential efficacy of these agents in rhabdoid RCC patients. Further study and larger case series are needed to fully clarify the natural history and ideal treatment regimen for these aggressive tumours.