The benefit of deferred Cytoreductive Nephrectomy (CN) has to be re-assessed in the context of IO +IO and IO + TKI systemic treatment. Given the benefit of CN in the setting of first generation immunotherapy, it is conceivable that both trials underestimated the benefit of CN, in absence of immunotherapy.

In past years, much research has been done into the beneficial effects of cytoreductive nephrectomy in patients with metastatic renal cancer receiving systemic therapy with positive results. In the meantime systhemic therapy, and in particular immunotherapy, have changed. Patients with metastatic renal cancer are increasingly treated with immunocheckpoint inhibitors, but the effect of adding cytoreductive nephrectomy in this group of patients has not yet been investigated. The aim of this study is to investigate whether performing a cytoreductive nephrectomy has a beneficial effect on overall survival in patients with metastatic renal cancer receiving systemic therapy using immunocheckpoint inhibitors.

A randomized controlled trial. All eligible patients have already been enrolled in the PRO-RCC registry, a registry that collects prospective observational data, and have also given consent to be included in other studies as a control cohort. This design is called a TWiC (trial within cohort). After randomization, patients who are randomized into the therapy arm will receive a patient information via their treating physician. Upon participation, an informed consent will be signed and the patient will be scheduled for surgery.

Inclusion Criteria:

1. Male or female patients age ≥ 18 years
2. Signed and written informed consent Note: Written and signed informed consent will be obtained before any study procedures, including study-specific-screening procedures, has been performed.
3. Informed consent obtained for being offered future experimental interventions within the PRO-RCC project.
4. Histologically confirmed diagnosis of metastatic clear cell, papillary or chromophobe renal cell carcinoma of intermediate to poor risk, including sarcomatoid features, with
5. World Health Organization (WHO) performance status of 0-1.
6. Surgical candidates based on surgeon and anesthetist assessment
7. Treatment with an IO combination (IO+IO or IO+TKI) as standard of care for metastatic RCC
8. Absence of progression at metastatic sites at time of identification (6month after start of systemic first line treatment). 9) Primary tumor in situ 10) Participation in the PRO-RCC prospective cohort.

Exclusion Criteria:

NA