Metastasis directed therapy in recurrent renal cell carcinoma - Retrospective analysis of a ten-year experience

Current guidelines provide a weak recommendation for metastasis directed therapy (MDT) in patients with recurrent renal cell carcinoma (RCC) and is focused on the goal of symptom control and potentially delaying systemic therapy. Especially in light of systemic treatment entailing targeted therapies for metastatic RCC, MDT's role remains undefined. Goal of our study was to evaluate which patients might benefit most from MDT. Our assessed endpoints were time to initiation of systemic therapy and progression-free survival (PFS).

We collected data retrospectively and exclusively at our centre; our study included patients with recurrent RCC after initial partial or radical nephrectomy, who subsequently underwent MDT at the University Hospital Freiburg and whose cases were discussed at our interdisciplinary urogenital tumour board between 2011 and 2021.

A total of 92 patients were included. Median follow up was 57.6 months (IQR 30.9-89.6). Median age was 65.1 (IQR 59.05-72.36) at the time of first MDT. Lung and lymph nodes were the most frequent locations of recurrence (40.2 % and 20.7 %, respectively). Median PFS after the first MDT was 392 days (IQR 100-855). Median time to the initiation of systemic therapy was 534 days (IQR 142-1707). In multivariate regression analysis, a higher T-stage in the initial pathology was associated with shorter PFS (HR 1.64, 95%-CI 0.98-2.66; p = 0.05). Furthermore, older age lowered the risk of progression after MDT (HR 0.97, 95%CI 0.94-1.00; p = 0.04). According to the non-parametrical log-rank test, patients with early recurrence (within 1 year after initial diagnosis) had significant shorter time to initiation of systemic therapy (p = 0.05). However, this effect was not apparent in multivariable regression analysis.

We report on a large cohort of patients who underwent MDT for recurrent RCC within the last ten years at our institution. Within the limitations of a retrospective single-centre analysis, our findings support the concept of MDT for recurrent disease in patients presenting a favourable initial tumour stage and rather late recurrence after initial therapy. However, as mRCC is a very heterogeneous disease, more investigation is needed to refine the definition of predictive parameters that facilitate patient-centred decision-making.