Pushing the Limits of Metastasis-Directed Treatment in Metastatic Renal Cell Carcinoma in the Era of Targeted Therapy - Beyond the Abstract

In this article, we describe the survival of patients with metastatic renal cell carcinoma (mRCC), initially managed with surgical removal of metastasis or metastasectomy (MxT). Over a period of time ranging from 1989 to 2015, patients presenting with metastasis thought to be amenable to complete resection and no evidence of disease (NED) status, fit enough to undergo surgery were considered primarily for MxT. A total of 138 patients were included, of which 127 (92%) reached NED status. No patient was International Metastatic RCC Database Consortium (IMDC) poor risk and interestingly, chronology, synchronous metastasis or not, as well as disease free interval between primary tumor removal and MxT of less than one year, had no impact on survival. Median overall survival (OS) and cancer specific survival (CSS) were 88 and 93 months respectively. Except for lung-only metastasis, location of metastasis had no impact on OS.

101 patients experienced recurrence during follow-up. Upon recurrence, a broader range of metastasis-directed therapies (MDT) was considered, including MxT, radiofrequency ablation, radiotherapy, and combinations. MDT aiming NED was again attempted in 58 patients with recurrence and NED was reached in 56 of which 16 remained NED up to end of follow up.  MDT was considered a third time in 18 patients, NED reached in 15 and remained in 5. Thus of 127 patients reaching NED the first time, 47 (37%) patients are still considered NED without any kind of oncological treatment at the end of follow-up. Median systemic progression-free survival (SPFS) was 40.9 (36.0 – 60.1) month with no difference between patients treated with first MxT before and after the advent of tyrosine kinase inhibitors (TKI), year 2006 (fig. 1). SPFS is the time between first MxT to progression not manageable by MDT or simple observation, where systemic or palliative therapies are needed.


In the evolving field of mRCC, new drugs complement the therapeutic armamentarium almost every year. Agents such as immune checkpoint inhibitors show promising results and could become real game-changers in the long term, but those results are still lacking. In the future, MxT needs to be evaluated against and combined with these new agents. To assess the real impact on OS, MxT should also be compared to simple observation, especially in very low burden disease, such as lung-only metastasis, which are the patients with the best OS, but probably carrying less aggressive disease.

MxT or more largely MDT is up to date the only treatment modality that can lead mRCC patients to median-term NED status without having to take any kind of oncologic treatment. This is probably the closest to cure one can get in mRCC at the current state of the art. MxT furthermore has the advantage of providing unequivocal histologic diagnosis and biological material to study tumoral behaviour.

Acknowledging the fact that primary extrarenal tumor (>pT2) and sarcomatoid dedifferentiation are factors that independently worsen OS, MxT should always be considered as the primary treatment of mRCC in patients fit enough to undergo surgery and where NED is thought achievable, even if several procedures are needed.

Written by: Serge Holz, Lorenzo Tosco, Murat Akand, Annelies Verbiest, Benoit Beuselinck, Maarten Albersen, Eduard Roussel, Hein Van Poppel, Steven Joniau

University Hospitals Leuven, Department of Urology, Leuven, Belgium; University Hospital Ambroise Pare, Department of Urology, Mons, Belgium. Electronic address: ., University Hospitals Leuven, Department of Urology, Leuven, Belgium; Humanitas University, Department of Biomedical Sciences, Milan, Italy; Humanitas Gradenigo Hospital, Department of Urology, Turin, Italy., University Hospitals Leuven, Department of Urology, Leuven, Belgium., University Hospitals Leuven, Department of Oncology, Leuven, Belgium.

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