VHL and the Risk for Renal Cell Carcinoma — In the Clinic

When RCC is diagnosed on imaging, multi-disciplinary consultation with nephrologists, oncologists, and urologists is standard. Before considering surgery, it is important to note that patients with VHL have relatively high RCC recurrence rates and can have microscopic disease that is not yet evident on imaging.

In the past, the predominant surgical options included radical nephrectomy, which could predispose a patient to rapidly develop end-stage renal disease. To prevent this, there was a shift toward “nephron-sparing” treatments aimed at preserving the most kidney tissue possible.⁶ For example, the risk of metastasis in a patient with an RCC smaller than 3 cm is relatively low, so lesions of this size can be closely monitored and surgery can be deferred as long as the patient appears stable.⁷

If the decision made is not to operate, contrast enhanced imaging is used to follow suspicious renal lesions and track their growth. In one of the largest studies evaluating the growth characteristics of RCC in patients with VHL, Jilg et al found that the mean growth rate of 96 tumors was 4.4 mm/year and mean volume doubling time was 26 months.⁵ These data were, furthermore, similar to prior studies evaluating sporadic RCC.

Nephron-sparing treatments include radiofrequency ablation, cryotherapy, and partial nephrectomy. Although many of the studies are small, there are data supporting the notion that patients with VHL who undergo partial nephrectomy for RCC have similar outcomes to those undergoing total nephrectomy.

Bratslavsky et al evaluated a small cohort of patients with VHL who underwent partial nephrectomy and found no evidence of metastatic disease at a median of 25 months.⁶ Many patients undergoing partial nephrectomy did, however, develop major complications, though their renal function remained relatively preserved. Yet at 5 years post-RCC diagnosis, close to 30% of patients will develop new RCC lesions.

Radiofrequency ablation and cryoablation are options for patients who are not optimal surgical candidates, have peripheral lesions, and have lesions smaller than 3 to 4 cm. These options should not, however, be considered if there is evidence of metastasis, the lesions are larger than 4 to 5 cm, or if the patient’s life expectancy is less than one year.

References

1. Lonser RR, Glenn GM, Walther M, et al. von Hippel-Lindau disease. Lancet. 2003;361(9374):2059-67.
2. Chauveau D, Duvic C, Chretien Y, et al. Renal involvement in von Hippel-Lindau disease. Kidney Int. 1996;50(3):944-51.
3. Maher ER, Yates JR, Harries R, et al. Clinical features and natural history of von Hippel-Lindau disease. Q J Med. 1990;77(283):1151-63.
4. Rednam SP, Erez A, Druker H, et al. Von Hippel-Lindau and hereditary pheochromocytoma/paraganglioma syndromes: clinical features, genetics, and surveillance recommendations in childhood. Clin Cancer Res. 2017;23(12):e68-75.
5. Jilg CA, Neumann HP, Glasker S, et al. Growth kinetics in von Hippel-Lindau-associated renal cell carcinoma. Urol Int. 2012;88(1):71-8.
6. Bratslavsky G, Liu JJ, Johnson AD, et al. Salvage partial nephrectomy for hereditary renal cancer: feasibility and outcomes. J Urol. 2008;179(1):67-70.
7. Walther MM, Choyke PL, Glenn G, et al. Renal cancer in families with hereditary renal cancer: prospective analysis of a tumor size threshold for renal parenchymal sparing surgery. J Urol. 1999;161(5):1475-9.