Metastases from Renal Cell Carcinoma. Recurrence Patterns, Detection and Management.

This thesis provides novel insights into the detection, recurrence patterns and management of metastases from renal cell carcinoma (RCC). In paper I the role of metastasectomy and other local therapies were clarified in a robust systematic review. Studies included showed a benefit in performing complete metastasectomy in terms of overall survival (OS) and cancer-specific survival (CSS). Some evidence suggested benefits in reaching local or symptomatic control of metastases using radiotherapy. Evidence quality was low with overall high risk of bias and confounding. In paper II a population-based cohort was presented in regards to RCC demographics and treatments. Incidence of primary metastatic RCC decreased from 2005 (23%) to 2009 (18%). Treatments for asynchronous recurrences were shown to be systemic in 50%, observational in 27% and metastasectomy in 17% (68% with curative intent). For Study III and IV a multinational database (RECUR) with non-metastatic RCC patients was established to provide evidence on the impact of follow-up on recurrence detection and survival. In study III analysing clear cell RCC recurrence patterns and survival, the low-risk group recurrences according to Leibovich score were found to be infrequent at follow-up and occurred later. OS after recurrence management was disappointing especially in the Leibovich score high-risk group which harbored most patients with potentially curable recurrences. Symptomatic at recurrence meant poorer survival irrespective of metastatic burden. Competing risk analysis suggested age as an important factor in follow-up protocols. In paper IV imaging modality (cross-sectional vs. conventional) and more frequent follow-up imaging for detection of RCC recurrences did not impact OS. Finally, use of excessive follow-up imaging compared to frequencies recommended by the EAU guidelines was unlikely to increase OS after recurrence. Higher level of evidence is needed as well as novel markers in the molecular era of RCC to develop better follow-up protocols and prognostic models.