Some controversies continue even in the recent literature about the intrinsic prognostic value of the IVC invasion. One could summarise these debates by saying that renal tumours with IVC invasion are more likely to be larger, have higher Fuhrman grades, and contain sarcomatoid features. It probably explains their aggressive behaviour. It is not a contradiction with the fact that in localised tumours the presence or the extent of IVC invasion is often identified as a prognostic factor in univariate analysis. However, in metastatic disease it is clear that IVC invasion is no longer a prognostic parameter [8].

3. Therapeutic considerations

Two distinct groups of patients should be considered: those with and without distant metastases. Although patients with localised or locally advanced renal tumours with IVC invasion cancer should be considered at high risk of dying from cancer, there is no doubt that radical surgery is the preferred option in this setting. However, as stressed by the paper from Rigaud et al., morbidity and perioperative mortality risks are not negligible and have to be taken into account when considering this type of surgery in aged people or in patients with important comorbidities. After completion of surgery, 5-yr probability of survival in patients with N0M0 tumours is between 35% and 56% [8]. Such a poor outcome is undoubtedly a strong argument for adding medical treatments after surgery. No adjuvant treatment has proven effective so far, but there is a great hope that in these type of tumours associated with a particular vascular phenotype, antiangiogenic drugs could be effective for improving survival [9]. Finally, in locally advanced tumors including T4 or N1N2 tumors with extensive local or nodal invasion rendering primary surgery difficult or impossible a neoadjuvant approach should also be tested.

Although advocated by many authors [3], [8], [10], surgery in patients with metastatic RCC invading the vena cava is much more debatable due to the absence of controlled studies proving the benefit of surgery in this setting. So far, the benefit of radical nephrectomy in the setting of metastases has only been proven in selected patients and it is not clear that such a strategy is applicable to all or some patients with IVC invasion. Particularly, it is not obvious that immunotherapy alone or palliative care would have done worse than a 10.7 mo median survival time, which is obtained in some recent series combining surgery and immunotherapy in patients having metastatic RCC and IVC invasion [3]. Additionally, patients with IVC invasion are more likely to have poor performance status [8] and to be subjected to surgical complications that could alter their chance to benefit from a systemic treatment. As noted in the paper of Rigaud et al., a significant number of patients will not be amenable to systemic therapy although they have experienced a potential life-threatening surgery without any proven long-term survival benefit. On the other hand, some arguments plead for combining aggressive surgery and systemic treatment when possible. First, it is clear that the presence of IVC invasion is not a prognostic factor when metastases are present. Second, surgery seems to have the same complication rate when IVC is present regardless of the presence of metastases [10]. Third, some authors have reported that patients with distant metastases and IVC invasion had a significantly better response to immunotherapy than those treated nonoperatively [8]. The truth is probably between two extreme unreasonable attitudes and the good way to proceed is to try to select those patients who could benefit from such an aggressive strategy. However, we will probably never know whether patients with RCC with IVC thrombus could benefit from combined surgery and immunotherapy because it is likely that randomised studies answering these questions will never be performed.

As mentioned, a new era is now open with targeted therapies based on the results that were obtained in metastatic disease. Therefore, many concepts have to be revisited. Specifically in case of metastatic RCC with IVC invasion, the role of first-line nephrectomy should be addressed as well as the potential risks of antiangiogenic treatments when tumour and thrombus are left in place. Similarly the potential haemorrhagic risk of surgery after antiangiogenic therapy should be addressed and consequently guidelines for appropriated timing between treatment and surgery should be determined. It can be expected that thanks to these new therapeutic approaches patients with RCC and IVC invasion will be proposed for specially designed clinical trials, including smart translational research.