about renal cell carcinoma

Renal cell carcinoma (RCC) is the most common malignant kidney tumour and is responsible for approx. 85% of all malignancies in this organ. The incidence, i.e. the annual number of new cases in Switzerland, is around 1,000 per year; however, men are almost twice as likely as women to fall ill with the disease. Renal cell carcinoma is responsible for around 2% of all cancer-related deaths in Switzerland.[1] The incidence rate is increasing in Western countries by 2–3 per cent every year. The disease occurs predominantly in older people (between 50 and 70). The most significant risk factors include nicotine, obesity, chronic renal insufficiency as well as exposure to halogenated hydrocarbons and x-rays.

With the increasing number of radiological examinations, renal cell carcinoma is often discovered by chance in an early stage.[2] The classic triad of pain, palpable flank tumour and macrohaematuria is becoming increasingly rare. The disease only manifests in pre-existing metastases in some patients.

The following histological subtypes of renal cell carcinoma are clinically significant: clear-cell renal cell carcinoma (80–90%), papillary renal cell carcinoma (10–15%) and chromophobe renal cell carcinoma (3–5%); 1% of renal carcinomas are urothelial carcinomas.[3] All subgroups can also display sarcomatoid differentiation. The TNM system is used for staging.
Based on the prognostic models, various risk factors must be established and therapy-relevant scores collated. The Motzer score (Tables 1 and 2) was established in patients treated with Interferon.[4] A revised version (IMDC/Heng criteria) contains additional values of neutrophil granulocytes and thrombocytes.[5]

Table 1

Motzer-Criteria IMDC/Heng-Criteria
Karnofsky Performance Status Scale < 80% Karnofsky Performance Status Scale < 80%/td>
Hb < sex-specific normal value Hb < sex-specific normal value
Calcium corrected > 10 mg/dl (> 2.5 mmol/L) Calcium corrected > 10 mg/dl (> 2.5 mmol/L)
Time from diagnosis to treatment < 12 months Time from diagnosis to treatment < 12 months
LDH > 1.5 of the upper normal value Neutrophil granulocytes > normal value
Thrombocytes > normal value

Table 2

Number of
risk factors
Prognosis Median OS
(Motzer-Criteria)
Median OS
(IMDC/Heng-Criteria)
0 Favourable 29.6 months 37 months
1-2 Intermediate 13.8 months 28.5 months
3-5 Unfavourable 4.9 months 9.4 months

Surgical resection is the first-line treatment for early or localised tumours; however, depending on the size and location of the tumour, a nephrectomy or a tumour resection during a partial nephrectomy is carried out. The surgery is now frequently carried out as a laparoscopic procedure, and robotic-assisted technology is also being used more often. Percutaneous ablation of kidney tumours (using cold or heat) has become an established alternative to surgical resection for localised findings in the last few years. In selected cases, transarterial treatment, such as for poly morbid patients, may be an alternative to undergoing a tumour nephrectomy.

Increasing advances have been made in the area of advanced and metastasised renal cell carcinoma through the introduction of numerous new substances. According to the results of the CARMENA study, a prior tumour nephrectomy for patients who require systemic therapy and have an intermediate or unfavourable risk are no longer standard.[6]

Metastatic surgery or ablation still has its place, in particular when resection/ablation of all metastases is possible with limited risk.

At the beginning of the 2000s, immune therapy with Interferon-alpha (IFN-α) and also with Interleukin-2 (IL-2) were standard treatment; however, with response rates of 10–20%, the efficacy was rather low in this case as well.[7] The new drugs can be essentially classified into three substance groups: Tyrosinase inhibitors (TKI: Sunitinib, Pazopanib, Sorafenib, Axitinib, Cabozantinib, Lenvatinib), inhibitors of the mammalian target of Rapamycin (mTOR) (Everolimus, Temsirolimus) and immune checkpoint inhibitors (Nivolumab, Ipilimumab). However, mTOR inhibitors are now less important than immunotherapy.

In addition, the antibody Bevacizumab is used together with IFN-α to combat the vascular endothelial growth factor receptor (VEGF). Table 3 provides an overview of all substances approved in Switzerland.[6]

Table 3

Drug Approval status
Axitinib
(Inlyta)
Advanced renal cell carcinoma after failure of previous systemic treatment
Bevacizumab
(Avastin)
First-line therapy for nephrectomy patients with advanced and/or metastasised renal cell carcinoma in combination with Interferon alfa-2a
Cabozantinib
(Cabometyx)
Treatment of advanced renal cell carcinoma (renal cell carcinoma, RCC) in adults after previous targeted treatment against VEGF (vascular endothelial growth factor)
Everolimus
(Afinitor)
Advanced renal cell carcinoma after failure of treatment with Sunitinib or Sorafenib
Ipilimumab
(Yervoy)
In combination with Nivolumab for the treatment of advanced (unresectable or metastasised) renal cell carcinoma in previously untreated adult patients with an intermediate/unfavourable risk profile
Lenvatinib
(Kisplyx)
Used in combination with Everolimus to treat adult patients with advanced renal cell carcinoma (RCC) after previous targeted treatment against vascular endothelial growth factor (VEGF)
Nivolumab
(Opdivo)
In combination with Ipilimumab for the treatment of advanced (unresectable or metastasised) renal cell carcinoma in previously untreated adult patients with an intermediate/unfavourable risk profile and for the treatment of adult patients with advanced renal cell carcinoma after previous antiangiogenic therapy
Pazopanib
(Votrient)
Advanced and/or metastasised renal cell carcinoma
Sorafenib
(Nexavar)
Metastasised, inoperable renal cell carcinoma
Sunitinib
(Sutent)
Advanced and/or metastasised renal cell carcinoma
Temsirolimus
(Torisel)
For first-line treatment of advanced renal cell carcinoma in patients who present with at least three of six unfavourable prognostic risk factors

 

  1. Nicer. Foundation National Institute for Cancer Epidemiology and Registration. 2018.
  2. Ljungberg B, Albiges L, Abu-Ghanem Y, et al. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2019 Update. Eur Urol 2019;75:799-810.
  3. Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. Eur Urol 2016;70:93-105.
  4. Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 1999;17:2530-40.
  5. Heng DY, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 2009;27:5794-9.
  6. Escudier B, Porta C, Schmidinger M, et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol 2019;30:706-20.
  7. Baaten G, Voogd AC, Wagstaff J. A systematic review of the relation between interleukin-2 schedule and outcome in patients with metastatic renal cell cancer. Eur J Cancer 2004;40:1127-44.