Renal Cell Carcinoma: 5 Things to Know

Kate M. O'Rourke


October 25, 2019

Renal cell carcinoma (RCC) is among the 10 most common cancers worldwide, accounting for approximately 2% of all cancer diagnosed.[1] As such, there is considerable research attention given to addressing RCC and its various histologic and molecular subtypes.

Here are five things that every physician treating RCC should know about the latest data regarding its epidemiology, contributing risk factors, and treatment.

1. Hereditary conditions underlie 3%-5% of all RCCs.[1]

Hereditary syndromes associated with RCC include von Hippel Lindau disease, BAPT1 mutant disease, succinate dehydrogenase–associated kidney cancer, hereditary leiomyomatosis, hereditary papillary kidney cancer, Birt-Hogg-Dubé syndrome, tuberous sclerosis complex, Cowden syndrome, and hyperparathyroidism jaw tumor syndrome.[1]

Onset of RCC in individuals age 46 years and younger should trigger consideration for genetic counseling.[1] Bilateral/multicentric tumors, in addition to young age, is a well-recognized feature of inherited RCC.[2]

2. Active surveillance is a reasonable initial treatment option in select patients.

For patients with small, solid or Bosniak 3/4 complex cystic renal masses, especially < 2 cm, active surveillance is an option for initial management.[3,4,5]

Physicians should prioritize active surveillance in such patients when the anticipated risk of intervention outweighs the potential oncologic benefits of active treatment.[5]For patients in whom the risk-benefit analysis for treatment is equivocal and who prefer active surveillance, physicians should repeat imaging in 3-6 months.[5]

In one study, 70% of patients on active surveillance were alive at 5 years.[3]

3. Combining targeted therapy and immunotherapy has clear value.

Traditionally, treatment for metastatic clear cell RCC has involved the use of a targeted therapy or immunotherapy, but new data support combining these two strategies.[6] RCC is refractory to conventional chemotherapy.[1]

Targeted therapy for RCC involves blocking signaling through the vascular endothelial growth factor receptor using such agents as axitinib, bevacizumab, cabozantinib, lenvatinib, pazopanib, sunitinib, and sorafenib, as well as those inhibiting the mechanistic target of rapamycin complex 1 (mTORC1), including everolimus and temsirolimus.[1,2]

Immunotherapy previously entailed dual therapy with nivolumab and ipilimumab for intermediate/poor International Metastatic RCC Database Consortium–risk disease patients, but within the past year, the use of the targeted agent axitinib combined with the anti-PD-L1 immunotherapies avelumab or pembrolizumab has been supported by clinical trial data.[6,7,8,9] Additionally, three recent trials of patients with sarcomatoid RCC compared sunitinib with three separate immunotherapy-containing regimens: axitinib plus pembrolizumab, atezolizumab plus bevacizumab, and ipilimumab plus nivolumab.[10,11,12] Sunitinib provided inferior progression-free survival in all trials.[10,11,12]

4. Folic acid may treat a common side effect.

Mucositis is common in patients with metastatic RCC treated with targeted therapies and immunotherapy, impairing quality of life and leading to dose reduction or discontinuation of treatment.[13]

Physicians often underestimate the severity of mucositis in patients.[14,15,16] Mucositis affects roughly 20% of patients treated with targeted therapies, and oral mucosal toxicities of targeted therapies differ from classic oral injuries observed with cytotoxic chemotherapy or radiotherapy.[17] Treatment for mucositis includes good daily oral hygiene and regular dental care.[17,18]

In a recent small study, folic acid significantly reduced mucositis in patients who had grade ≥2 mucositis from therapy with sunitinib, pazopanib, everolimus, axitinib, temsirolimus, interleukin-2/interferon-alpha, cabozantinib, bevacizumab, and nivolumab.[13] A double-blind, placebo-controlled prospective evaluation of folic acid is ongoing.[13]

5. Partial nephrectomy is recommended.

With more frequent diagnosis of smaller renal masses, particularly those < 7 cm, surgical approaches have evolved. Guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend partial nephrectomy whenever feasible.[19,20] Partial nephrectomies reduce ischemic time, and outcomes are comparable in terms of long-term disease control with reduced incidence of chronic renal failure, delayed cardiovascular disease, and improved survival.[21,22,23] Partial nephrectomy is the standard management for a cT1a renal mass, and recent data show that it should also be considered for larger cT1b and cT2 renal tumors.[21]

Kate O'Rourke is a freelance writer in Portland, Maine. She has covered the field of oncology for over 10 years. 

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