The role for potential neoadjuvant and adjuvant treatments in RCC are evolving and currently under significant investigation.
In terms of adjuvant TKI treatments:
- Trials have failed to show a survival benefit for any TKIs
- In one trial, there was improved DFS for sunitinib, but no benefit for overall survival
- Therefore, EAU guidelines recommend against any adjuvant TKI therapy following surgical resection.
Immunotherapy and immune checkpoint inhibitors have shown impressive results in the metastatic setting, and early results have shown some promise in the adjuvant setting:
The Keynote-564 RCT:
- Pembrolizumab (Keytruda) vs placebo
- pT2 grade 4, or pT3+, N1, or resected M1
- Improved DFS (77 vs 68 %) at 2 years, trend towards overall survival improvement but not significant yet, ongoing results to follow.
- Update Oct 2022 at 30 months – 75 % vs 65 %
EAU guidelines – weak recommendation to offer adjuvant pembro to high risk patients following curative intent surgery.
Currently, not available in Australia unless in trial.
Checkmate-914 published 2023:
- Adjuvant ipi/nivo
- No difference in progression free survival at 2 years (75 % each group)
- 4 deaths in ipi/nivo group attributed to treatment (out of 405 patients)
- 33 % discontinuation in ipi/nivo group (may be related to lack of effect)
There is no role for neoadjuvant therapy in organ-confined disease. There may be a role in oligometastatic or metastatic disease prior to cytoreductive nephrectomy.