CLINICAL, SURGICAL, PATHOLOGICAL AND FOLLOW-UP FEATURES OF KIDNEY CANCER IN PATIENTS WITH VON HIPPEL-LINDAU SYNDROME: NOVEL INSIGHTS FROM A LARGE EUROPEAN CONSORTIUM

Von Hippel-Lindau (VHL) syndrome is a relatively rare hereditary condition leading to renal and extrarenal manifestations. Although physiopathology and involved molecular pathways have been extensively analyzed, few data are available regarding the natural history, clinical and surgical aspects, complications and follow-up after renal surgery in this specific cohort of kidney cancer patients. A multi-institutional European consortium was built including Caucasian patients with VHL syndrome and kidney cancer treated at 8 referral institutions. Descriptive and survival analyses were performed. Overall, 78 patients were included. Of these, 40 were males (51.3%). Mean (median) age at VHL diagnosis was 34.2 (34) years. Mean (median) patient's age at renal management was 41.1 (38) years. Only 2 patients (2.6%) showed only renal manifestations at VHL diagnosis. Concomitant involvement of Central Nervous System (CNS) vs. pancreas vs. eyes vs. adrenal gland vs. others were present in 61.5 vs. 62.8 vs. 29.5 vs. 14.1 vs. 16.7% of patients, respectively. Forty-two percent of patients had both CNS and pancreatic disease alongside kidney. Mean tumor size of the index lesion which led to a treatment was 42 mm. The proportion of patients with preoperative vs. postoperative chronic kidney disease (CKD, any grade) resulted 16.5% vs. 25.3%. At final pathology, 52.4% harbored low-grade tumors (G1-2) and tumor size <4 cm (T1a). Conversely, the proportion of patients with low-grade larger tumors (>4 cm and G1-2) was 22.6%. Finally, 11.9% and 13.1% of the resected tumors were either high-grade and small (G3-4 and <4 cm) or high-grade and larger (G3-4 and >4 cm). With a mean follow-up of 123 months (median 83) after the first renal treatment, clinical progression rate resulted 15% and 36.6% at 5 and 10 years, respectively. All-cause mortality was 5.2% and 7.6% at 5 and 10 years, respectively. Cancer-specific mortality rates were 3.4% and 5.8% at 5 and 10 years, respectively. In the context of VHL patients, virtually all patients with renal tumors already have manifestations in other organs at first presentation. In candidates for renal treatment, CNS and pancreas are the most frequent extra-renal VHL localizations. Although the majority of tumors are small and of a low grade, cancer-specific mortality is not negligible.