585 HEREDITARY PAPILLARY RENAL CELL CARCINOMA: A 20-YEAR EXPERIENCE IN MANAGEMENT OF A UNIQUE HEREDITARY CANCER SYNDROME

INTRODUCTION AND OBJECTIVES: In 1994 we described a novel hereditary cancer syndrome, Hereditary Papillary Renal Cell Carcinoma (HPRC). HPRC is an autosomal dominant hereditary cancer syndrome in which affected individuals are at risk for the development of bilateral, multifocal, type 1 papillary kidney cancer. In 1997 we identified the proto-oncogene MET as the HPRC gene. HPRC patients are characterized by germline activating missense mutation in tyrosine kinase domain of MET and have a lifelong risk for the development of bilateral multifocal kidney tumors. Here we present our near-20-year experience on management of these patients. METHODS: From May 1992 to October 2011, 12 families with known germline MET mutation were followed with careful, periodic screening for development, growth, recurrence and metastasis of their renal tumors. Surgical removal was recommended when the largest kidney tumor reached a 3-cm cutoff size, and preference was given to nephron-sparing surgery. Median follow up was 65 months (range 1 month to 20 years). RESULTS: A total of 56 patients underwent periodic surveillance. Of these patients, 34 developed renal tumors: bilateral in 17, unilateral multiple in 13 and single in 4 patients. The average age at onset was 42 years (range 19 to 66). Twenty-nine patients underwent 42 kidney surgeries, of which 23 were performed at the National Cancer Institute: 17 were partial nephrectomies, of which 1 was a simultaneous bilateral partial nephrectomy, 2 were radical nephrectomies and 4 were radiofrequency ablation of renal tumors. Up to 59 tumors were removed from each renal unit. None of the patients required renal replacement therapy, with 22/23 patients maintaining postoperative eGFR 60. Metastatic disease developed in 5 patients all of whom presented with large or very rapidly growing lesions. CONCLUSIONS: In the largest reported experience worldwide with HPRC, patients affected by hereditary papillary renal cancer can be safely managed by expectant management, with nephron-sparing surgery triggered by tumors reaching a 3 cm size threshold. This management optimizes the renal function of these patients without compromising their oncologic outcomes.