By many criteria, prior radiotherapy and non-clear cell histology are marked as poor prognostic factors for patients with renal cell carcinoma (RCC). However, radiosurgery for brain metastases or other painful bone metastasis does not interfere with the ability to administer targeted therapy, believes Brian I. Rini, MD. In most cases, patient outcomes following radiotherapy mirror the overall population in terms of response to treatment, states Janice P. Dutcher, MD.

Differentiating between clear cell and non-clear cell histology is useful in the confines of ascertaining a patient's prognosis, believes Daniel Heng, MD, MPH. However, when it comes to determining treatment, histology has less value. Subgroup analyses suggested that the mTOR inhibitor temsirolimus is beneficial in patients with non-clear cell histology when compared with sunitinib. However, in the phase II ESPN trial, this same benefit was not seen with the mTOR inhibitor everolimus.

In this study, 73 patients with non-clear cell histology were randomized to sunitinib or everolimus. In the first-line setting, the median progression-free survival (PFS) was 6.1 months with sunitinib compared with 4.1 months with everolimus (P = 0.25). The median PFS in the second-line with sunitinib was 1.8 versus 4.3 months with everolimus.

This divide from one trial to another suggests a greater understanding of the biology of non-clear cell RCC is required, notes Rini. Clinical trials are underway exploring the various subtypes using next-generation sequencing. A recent study demonstrated that multiple genetic subtypes existed within the papillary type 2 histologic subtypes, suggesting that more study is needed in this area, Rini believes.