Renal Cell Carcinoma is Treatable and Curable
Early diagnosis, surgery while cancer is confined to kidney are key, but pharmacological agents are used for Stage IV.
The National Cancer Institute estimates that by the end of 2020, there will be 73,750 new cases of kidney and renal pelvis cancer, representing 4.1% of all new cancer diagnoses, with 14,830 new deaths.1
The 5-year relative survival rate has slowly increased each year for the past 4 decades. Figure 11 shows the rates for relative 5-year survival by stage at diagnosis.
In addition to the risk factors listed in Figure 21-4, unmodifiable factors, such as age, gender, and race are also associated with an increased risk for renal cancer. African Americans, men, and older individuals have a higher risk.2 Older patients also have a higher rate of death from kidney and renal pelvis cancer.1
Renal carcinomas can present in many ways, with the most common form being renal cell carcinoma (RCC), representing about 85% of diagnoses. RCC develops in the epithelium of the proximal renal tubules and can occur in a hereditary or nonhereditary manner. Regardless of the disease’s etiology, a structural alteration in the short arm of chromosome 3 is responsible for the development of cancer.3 Common hereditary syndromes are also summarized in Figure 2.1-4
Diagnosis and Screening
The National Comprehensive Cancer Network (NCCN) does not offer screening recommendations for RCC. For patients presenting with symptoms or those with a family history of RCC, clinicians can perform an abdominal CT scan, as well as a renal ultrasound, for diagnosis.5 Table 1 outlines common symptoms of RCC.2 Patients can also undergo other tests, such as a bone scan, chest x-ray, cranial MRI, and needle biopsy to aid in tumor staging.
Determining histology subtype is important for choosing an appropriate systemic therapy regimen, as well as for establishing a risk group using a prognostic factor model discussed in the guidelines.5
The role of systemic therapy is primarily in stage IV, or metastatic disease, according to the NCCN guidelines. For patients with stage I through III RCC, the preferred treatment is a partial or radical nephrectomy. For patients with stage IV RCC, the recommended algorithm is outlined in Online Figure 3.5 The first-line preferred systemic therapies are summarized in Online Table 2.5 For those with clear cell histology, clinicians determine treatment based on the patient’s risk group, either favorable risk or intermediate or poor risk.5
Recently, investigators reported significant results in the setting of metastatic or advanced clear-cell RCC in the CheckMate 9ER phase 3 trial (NCT03141177). The trial compared cabozantinib plus nivolumab to sunitinib, an active comparator. The investigators looked at objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and safety, finding that all these measures were statistically significant favoring cabozantinib plus nivolumab versus sunitinib with an acceptable safety profile. The ORR and PFS were both doubled in the intervention group versus sunitinib. The effects on OS and PFS were consistent among each risk group. The follow-up time for this trial was 18 months, which may not be long enough to determine the lasting effects of this regimen, but the results have been promising thus far.6
The methodology of treating RCC has evolved rapidly in the past few years, leaning more toward combination therapies and less toward monotherapy, particularly in the setting of metastatic clear-cell RCC.7 A vast number of clinical trials are continuing, some of which are outlined in Online Table 3. Investigators anticipate that results will be released in the next few years, which could greatly affect how clinicians treat metastatic RCC.
In addition to newer drug therapies, there has been an increasing interest surrounding the role of genetic biomarkers in predicting a patient’s response to targeted therapy. A recent study presented at the European Society for Medical Oncology Virtual Congress 2020 analyzed the relationship between the expression of effector T cell and angiogenesis signatures and response to treatment with nivolumab in patients with metastatic RCC. The authors recognized that patients with a high-effector T cell and low angiogenesis expression had a higher response rate and median PFS, whereas patients with low-effector T cell and low angiogenesis expression had a poor response rate. They also recognized that patients with low numbers of stromal cells had a higher response rate and longer median PFS.17
RCC can often be cured if it is diagnosed and treated surgically while still confined to the kidney and the immediately surrounding tissue. The probability of a cure is commensurate with the degree or stage of tumor dissemination. Even when regional lymphatics or blood vessels are involved, a high percentage of patients can attain prolonged survival and a probable cure. However, once the tumor has metastasized to stage IV status, surgical cure is improbable and reliance is placed upon pharmacological agents, such as immunological and targeted therapies, but disease-free survival is poor. Because most patients receive their diagnosis when the tumor is still relatively localized and amenable to surgical resection, about three-fourths of all patients with RCC survive for 5 years. As with most solid malignancies, early surgical intervention confers the best benefit.18
Jerry A. Barbee Jr, PharmD, BCPS, CPh, and Glenn Schulman, PharmD, MS, BCPS, BCACP, BCGP, BCIDP, are clinical pharmacists in Pensacola, Florida. Taylor A. VandenBerg is a PharmD candidate at the University of Florida College of Pharmacy in Gainesville.
- Cancer stat facts: kidney and renal pelvis cancer. National Cancer Institute. Accessed October 1, 2020. https://seer.cancer.gov/statfacts/html/kidrp.html
- Kidney cancer. Cancer.Net. March 27, 2019. Accessed October 1, 2020. https://www.cancer.net/cancer-types/kidney-cancer
- Sachdeva K. Renal cell carcinoma. Updated June 8, 2020. Accessed October 1, 2020. https://emedicine.medscape.com/article/281340-overview
- World Cancer Research Fund. Worldwide cancer data. American Institute for Cancer Research. Accessed October 1, 2020. https://www.wcrf.org/dietandcancer/cancer-trends/worldwide-cancer-data
- Motzer RJ, Jonasch E, Agarwal N, et al. Kidney cancer, version 1.2021 NCCN Clinical Practice Guidelines in Oncology. July 15, 2020. Accessed October 1, 2020. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf
- New first-line treatment option for metastatic kidney cancer, according to results of phase 3 study [news release]. Lugano, Switzerland; September 19, 2020: European Society for Medical Oncology. September 19, 2020. Accessed October 1, 2020. https://www.esmo.org/meetings/esmo-virtual-congress-2020/meeting-resources/news/esmo2020-metastatic-kidney-cancer-nivolumab-cabozantinib-checkmate9er
- Khetani VV, Portal DE, Shah MR, Mayer T, Singer EA. Combination drug regimens for metastatic clear cell renal cell carcinoma. World J Clin Oncol. 2020;11(8):541-562.doi:10.5306/wjco.v11.i8.541
- US National Library of Medicine. S0931, everolimus in treating patients with kidney cancer who have undergone surgery. ClinicalTrials.gov. Updated June 25, 2020. Accessed October 1, 2020. https://clinicaltrials.gov/ct2/show/NCT01120249?recrs=ad
- US National Library of Medicine. Study of cabozantinib in combination with nivolumab and ipilimumab in patients with previously untreated advanced or metastatic renal cell carcinoma. ClinicalTrials.gov. Updated August 28, 2020. Accessed October 1, 2020. https://clinicaltrials.gov/ct2/show/NCT03937219?recrs=ad.
- US National Library of Medicine. Immunotherapy with nivolumab and ipilimumab followed by nivolumab or nivolumab with cabozantinib for patients with advanced kidney cancer, the PDIGREE study. ClinicalTrials.gov. Updated October 23, 2020. Accessed October 28, 2020. https://clinicaltrials.gov/ct2/show/study/NCT03793166
- US National Library of Medicine. Lenvatinib/everolimus or lenvatinib/pembrolizumab versus sunitinib alone as treatment of advanced renal cell carcinoma. ClinicalTrials.gov. Updated July 31, 2020. Accessed October 1, 2020. https://clinicaltrials.gov/ct2/show/NCT02811861?recrs=ad
- US National Library of Medicine. A study of TQB2450 injection combined with anlotinib hydrochloride capsule versus sunitinib in subjects with advanced renal cancer. ClinicalTrials.gov. Updated July 31, 2020. Accessed October 1, 2020. https://clinicaltrials.gov/ct2/show/NCT04523272?recrs=ad
- US National Library of Medicine. A study of bempegaldesleukin (NKTR-214: BEMPEG) in combination with nivolumab compared with the investigator's choice of a tyrosine kinase inhibitor (TKI) therapy (either sunitinib or cabozantinib monotherapy) for advanced metastatic renal cell carcinoma (RCC). ClinicalTrials.gov. Updated September 30, 2020. Accessed October 1, 2020. https://clinicaltrials.gov/ct2/show/study/NCT03729245
- US National Library of Medicine. A study of pazopanib with or without abexinostat in patients with locally advanced or metastatic renal cell carcinoma (RENAVIV). ClinicalTrials.gov. Updated January 7, 2020. Accessed October 1, 2020. https://clinicaltrials.gov/ct2/show/NCT03592472
- A study of TQB2450 injection combined with anlotinib hydrochloride capsule versus sunitinib in subjects with advanced renal cancer. ICH-GCP. Accessed October 1, 2020. https://ichgcp.net/clinical-trials-registry/NCT04523272
- Bempegaldesleukin (NKTR-214). Nektar. Accessed October 1, 2020. https://www.nektar.com/pipeline/rd-pipeline/nktr-214
- Indicators of outcome are identified for nivolumab treatment of patients with metastatic clear cell renal cell carcinoma. European Society of Medical Oncology. September 21, 2020. Accessed October 1, 2020. https://www.esmo.org/meetings/esmo-virtual-congress-2020/meeting-resources/scientific-news/indicators-of-outcome-are-identified-for-nivolumab-treatment-of-patients-with-metastatic-clear-cell-renal-cell-carcinoma
- National Institutes of Health. Renal Cell Cancer Treatment (PDQ®)-Health Professional Version. National Cancer Institute. Accessed October 5, 2020. https://www.cancer.gov/types/kidney/hp/kidney-treatment-pdq