Outcome of patients with metastatic, papillary renal cell carcinoma

Szabados, Bernadett (2024): Outcome of patients with metastatic, papillary renal cell carcinoma: 10- year single centre experience. Dissertation, LMU München: Medizinische Fakultät

Abstract

Background: Targeted therapies such as VEGF-, mTOR- inhibitors and immune checkpoint inhibitors (ICIs) are established treatment strategies in metastatic clear cell renal cell carcinoma (RCC), however level 1 evidence is lacking in papillary RCC (papRCC). Evidence is derived from single-arm trials, expanded access schemes and subgroup analysis of larger RCC studies. Currently the most effective treatment approach for patients with papRCC represents an unmet therapeutic need. Objective: The aim of this dissertation was to analyse the outcome of patients with metastatic, papRCC who received treatment between 2005 – 2015, in the Department of Urology, University Hospital Munich Grosshadern, Ludwig-Maximilians University. We aimed to compare the effectiveness of different systemic therapies used and describe outcomes such as response to therapy, progression free survival (PFS), and overall survival (OS). We also analysed baseline clinical and pathological features which may influence patient outcomes. Furthermore, we aimed to review the relevant literature comparing the oncological outcomes of different systemic therapies in patients with metastatic papRCC in order to put this research into relevant context. Results and limitations: This is a retrospective, single centre audit with data collected over a period of 10 years. The median follow-up for this patient population was 71 months (95%CI, 24-118) which is the longest reported in the current literature. Baseline patient and tumour characteristics are similar to those previously described in the literature. The median disease-free survival (DFS) postsurgery was 14.9 months (95% CI, 2.5 – 27.3) and 43% of patients developed metastatic disease after initial surgery with curative intent. There was no statistical difference in OS in patients undergoing cytoreductive nephrectomy compared to those who didn’t (9.8 vs 7.7 months, p=0.777). All patients received front-line therapy, however only 48% received second line, 21% received third line and 5% received fourth line, subsequent therapies. The median OS was 10.5 months (95%CI, 5.4 – 15.7). The percentage of patients who were alive at 1 year, 2 years and 5 years were 41%, 31% and 5%, respectively. Sunitinib was the most frequently used first line therapy agent in 74% of patients. The overall response rate in these patients was 26% with 10% achieving complete response. Based on the results of the recent PAPMET trial (NCT02761057), cabozantinib is currently the recommended front-line therapy agent due to higher response rate (23% vs. 4%) and more favourable PFS (HR 0.60 [0.37–0.97], p = 0.019) compared to sunitinib. The combination of ICI and VEGF inhibitors have changed the therapy landscape of clear cell RCC, and it is likely that these agents will be adopted in papRCC as well. Limitations of this work include the retrospective nature of the data collection, and small number of patients. Furthermore, there were no cabozantinib treated patients as this therapy option was not approved at the time. The relatively long survival in some of the patients is attributed to the heavy selection bias. Conclusions: This retrospective, single centre cohort analysis showed that VEGF-inhibitors are effective and have superior outcomes with regards to response rate and survival when compared to mTOR inhibitors. Together with the robust summary of currently available data, this work contributes towards the establishment of evidence-based therapy of metastatic papRCC.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 14. November 2024
• 1. Bericht­erstatter:in: Staehler, Michael