Nephrectomy in a patient with known metastatic disease, with the aim of achieving an oncological benefit, usually as an adjunct to systemic treatment.
Its current role is changing and evidence in the immunotherapy era is lacking, with current available data from TKIs and interferon treatments which are quickly being replaced.
The rationale for CN comes from:
- Rare but described reports of regression of metastatic disease following CN
- Pre-clinical data suggesting large tumours inhibited systemic T cell responses
- The inability of older agents to induce any local response in the primary
- These theoretical benefits were then backed up by data in the interferon era showing a survival benefit
Palliative nephrectomy is different – removal of a kidney in a metastatic patient with symptomatic concerns (haematuria, pain etc) aiming to relieve symptoms – no aim to improve oncological control or benefit.
What is the available evidence regarding cytoreductive nephrectomy?
- Survival benefit demonstrated with interferon treatment
Combined analysis in 2004 of 2 x RCTs showed median survival of 13.6 months cf. 7.8 months for interferon treatment alone.
But… “IFN-based immunotherapy is no longer relevant in contemporary clinical practice” (EAU)
- TKI era – questionable benefit
SURTIME:
- Looked at sequence of CN and TKI (i.e. surgery first or second)
- No effect on progression free survival
- Poor accrual and did not meet targets
- Analysis has shown that there was a strong OS benefit in the deferred CN arm – 32 vs 15 months – appearing to “select out” patients with inherent resistance to systemic therapy
CARMENA:
- Included only intermediate and poor risk patients
- CN then sunitinib, versus sunitinib alone
- Overall survival was non inferior (18 vs 13 months) for sunitinib alone vs CN
Criticisms of CARMENA:
- Large proportion of poor risk patients
- Reasonable proportion of crossover (didn’t receive nephrectomy and were meant to, or did receive nephrectomy and weren’t supposed to)
- Excluded patients with low metastatic burden
- Median survival best 18 months – compared to > 2 years in most modern trials
What can be surmised from these trials:
Patients who require systemic therapy benefit from immediate drug treatment
Intermediate and poor risk patients should not have upfront CN followed by sunitinib
- The immunotherapy era – data to come, but likely promising
Trials addressing cytoreductive nephrectomy in metastatic disease treated with immunotherapy are underway.
The trials showing the efficacy of checkpoint inhibitors and combination therapy contained a good proportion (up to 30 %) of patients with kidney still in situ, and these patients responded better to checkpoint inhibitors cf. sunitinib.
There is a proportion of patients in the metastatic trials (around 5 – 10 %) with complete radiological response of disease. These patients would theoretically seem to benefit from cytoreductive nephrectomy.
Who is not a good candidate for cytoreductive nephrectomy?
- Poor risk group
- Poor performance status
- High volume of metastatic disease
- Unresectable / locally advanced primary
- Brain or liver metastases
- Progression on systemic treatment
Who is a good candidate for cytoreductive nephrectomy?
- Excellent performance status
- Resectable primary
- Resectable metastases / oligometastatic disease – potential for R0 resection
- Symptomatic
- “favourable” intermediate risk
- Good responders to upfront systemic therapy
