Objectives

Adjuvant pembrolizumab has improved overall survival after surgery for clear cell renal cell carcinoma (ccRCC) with an intermediate-high and high risk of recurrence according to the inclusion criteria of Keynote-564 study, but non-RCC mortality is common during postoperative follow-up. We aimed to evaluate the competing risk of death after surgery in patients with ccRCC stratified according to the risk of recurrence with Keynote-564, Three-feature and Leibovich models.

Material and Methods

A total of 1108 patients with ccRCC operated with curative intent between 2005 and 2021 before the use of adjuvant immunotherapy were identified from two academic centres in Finland and Sweden. Patients with cytoreductive nephrectomy, multiple kidney tumours or non-ccRCC were excluded. Baseline characteristics and survival outcomes were described, and the Kaplan-Meier method was used to estimate overall survival.

Results

During the median postoperative follow-up of 5.0 years, 134 (12%) patients had died from RCC with a median time to death of 3.7 years (IQR 1.6-6.6) while for 220 (20%) patients the cause of death was other than RCC, most commonly other cancers (n = 59, 5%) and cardiovascular diseases (n = 54, 5%). According to the Keynote-564 criteria, 34 (3%) patients were classified as having high risk of recurrence, 336 (30%) patients intermediate-high risk and 738 (67%) patients low risk of recurrence with 41% of RCC deaths observed in this subgroup. Limitations of this study include the lack of information on performance status, comorbidities and systemic treatments for recurrent RCC.

Conclusions

In addition to deaths from RCC, deaths from other cancers and cardiovascular diseases were common after surgery for ccRCC. As 41% of RCC deaths were observed among patients currently excluded from adjuvant therapy, more research on patient selection for perioperative immunotherapy is needed as well as interventions improving the treatment of comorbidities and lifestyle after nephrectomy.