It has always been the aim of the Kidney Cancer Journal to cover the broadest spectrum of topics related to all aspects of managing renal cell carcinoma (RCC). When I was asked to serve as Guest Editor, I knew that this issue of the journal would be no exception. The assortment of articles attests to how our field is rapidly evolving—whether it is new information emerging from the 2017 meeting of the European Society of Medical Oncology (ESMO) or updates from our authors on changing standards in clinical practice or new results from the bench with translational impact.
This year’s ESMO scientific sessions presented some pivotal information on key issues with potential translational impact, including the combination of immunotherapy and targeted therapy, and the sequence of sunitinib and nephrectomy. These findings, notably an update on the Checkmate 214 trial and the SURTIME trial, are reviewed in this issue of the Kidney Cancer Journal, in addition to other results from ESMO.
If you follow the medical literature as closely as I do, you may be surprised at how the latest studies have not only more pointedly addressed long-standing controversies in RCC but go further—approaching a consensus that tends to debunk some of the myths surrounding practice standards. A case in point—our content on the safety and efficacy of stereotactic body radiation therapy (SBRT) for RCC, both primary and metastatic.
In terms of our knowledge about and application of this technique, we are light years away from the 1950s when a Swedish neurosurgeon first described single-dose ablative radiotherapy delivered to brain lesions. The revolutionary development concerns the way this principle has been extrapolated to the stereotactic delivery of severely hypofractionated treatments to body targets, including kidney, either primary or metastatic, cranial and extracranial. And yet, the myth has lingered that such application in RCC is limited by perceived radioresistance to conventional fractionation. If this is still your perception (a misconception, I might add) then review the article by Raquib Hannan, MD, on how such resistance can be overcome in many clinical settings, thus sparing many patients from nephrectomy, especially those who are poor surgical candidates.
One of the areas that has long been a focus of my research is the optimal dosing schedule for sunitinib and efforts to prolong exposure to the drug while limiting the adverse effects that often stand in the way of continuing with the 4 weeks on and 2 weeks off strategy. So here, too, an intriguing and significant evolution in the standard of care is taking place with regards to the relative merits of the 4/2 dosing schedule vs the 2/1 schedule. The particularly interesting aspect of this evolution is the apparent initiative on the part of many of our colleagues in community practice to stay ahead of the curve or integrate novel approaches that enable them to prolong exposure to sunitinib or at least mitigate the impact of adverse effects through various drug-free interval strategies.
There are skeptics, however, who may ask whether it is appropriate to expend more resources prospectively testing (data we need to verify appropriate dosing schedules) a new schedule of an older targeted agent in lieu of the excitement over the latest generation of immune-oncologics in RCC. There are two reasons for continuing to investigate VEGF blockade in this context. First, not all RCCs respond to immunotherapy, as Lauren C. Harshman, MD reminds us in an Editorial in the Journal of Clinical Oncology (2017;35(16) 1755-1757. This is true of even the modern and more tolerable PD-1 pathway antibodies. Also, VEGF-pathway blockade remains the backbone of many ongoing, first-line PD-1 combination studies. These considerations remain essential in view of the new agents recently approved and the implications for the treatment paradigm. The article in this issue by Pavlos Msaouel, MD, and Nizar Tannir, MD, not only delineates these issues but suggests state-of-the-art thinking on tailoring sunitinib schedules to achieve maximum benefit.
Bernard J. Escudier, MD