Renal cell carcinoma (RCC) develops in 25-60% of patients von Hippel-Lindau (VHL), which is characterized by germline mutations in the VHL gene. Our institution practice has been to perform active surveillance for renal lesions less than 3 cm and surgical resection for lesions greater than 3 cm, based on early observations of low metastatic potential of small lesions. However, patients who are referred with larger tumors or who are lost to follow-up may not be managed exclusively by this guideline. We sought to evaluate the oncologic efficacy of the 3 cm size threshold with in a large cohort with long-term follow-up.

From a prospective registry of 764 patients with VHL, a subset of patients with solid renal masses was identified. The diameter of the largest solid tumor, length of follow-up, and development of metastatic disease was abstracted from imaging reports and the medical record. Patients were further subdivided into those who were managed exclusively by the 3 cm threshold and those who were not. The proportion of patients who developed metastatic disease at size thresholds beyond 3 cm was assessed in 1 cm increments. Follow-up was defined as the interval from initial screening at institution to last clinic visit or progression. Metastasis-free survival (MFS) was defined as the interval from initial screening to development of distant metastatic disease.

A total of 440 patients (57.5%) developed solid kidney tumors. Of these 417 (94.7%) had prior imaging reports available. Median follow-up was 103 months. Metastatic disease developed in 42 patients (10.1%). No patients developed metastatic disease when the size of their largest tumor was < 3 cm. Table 1 lists the proportion of patients who developed metastases by size of their largest tumor. MFS for patients managed with the 3 cm threshold was significantly longer compared to those who were not (p=0.007). The 5, 10 and 20-year MFS for patients who were not managed by the 3 cm threshold was 95.7%, 91.1%, and 69.5%, respectively.

In a large cohort of patients with VHL, adherence to the 3 cm guideline was associated with superior MFS compared to those who were not. We advocate the use of this guideline in conjunction with other patient characteristics and surgical judgement.