4.1 Treatment options for metastatic renal cell carcinoma (mRCC)

In recent years, there has been significant progress in the medical treatment of metastatic renal cell carcinoma (mRCC), and several different new treatment options have been developed. Several medicinal products are approved, and several new treatments are being tested.

Treatment options for mRCC

  1. Observation
  2. Metastasis surgery for 1 or few metastases
  3. Stereotactic radiotherapy for few metastases
  4. Cytoreductive nephrectomy (CN) followed by oncological treatment
  5. Participation in a clinical trial
  6. Targeted therapy (tyrosine kinase inhibitor (TKI), antibody to VEGF (Bevacizumab) or mammalian target of rapamycin (mTOR) inhibitor) (see oncology treatment section: Targeted therapy)
  7. Immunotherapy (checkpoint inhibitors, IL-2 based or T-cell therapy) (see section on oncological treatment: Immunotherapy)
  8. Palliative radiotherapy (see radiotherapy section)
  9. Supportive care (see section on supportive care)

1. Observation

Some patients with mRCC have only a limited disease burden (e.g., small lung metastases and/or slightly enlarged lymph nodes above or below the diaphragm) while being asymptomatic. In these patients, a shorter observation period without treatment can be considered, as the disease may remain stable or only grow very slowly for a shorter or longer period of time. Patients should be monitored regularly with blood tests, CT scans and clinical checks. If significant growth/emergence of new metastases, decreasing blood counts and/or the patient develops symptoms (advancing fatigue, weight loss, dyspnea and/or pain), the patient should begin treatment. 1

2. Metastasis surgery

Surgical resection of solitary metastases is associated with a 5-year survival of 35–50%. In solitary metastases, treatment should therefore be radical removal of the metastasis/metastases. 2

3. Stereotactic body radiotherapy (SBRT)

Stereotactic radiotherapy (SBRT) is high-dose, focused radiotherapy to one or few metastases given 1–5 times. The purpose of SBRT is to target the relevant metastasis(es) with high precision and with the least possible damage to the surrounding normal tissue.

If there are one or few metastases that cannot be removed surgically (cerebrum, lungs, lymph node, recurrent nephrectomy site, bone, etc.), stereotactic radiotherapy may be considered.

Decisions on stereotactic radiotherapy, whether cerebral or peripheral metastases, will be made at an MDT conference. See section on radiotherapy for details.

4. Cytoreductive nephrectomy (CN) followed by oncological treatment

Nephrectomy has been documented to cause regression of metastatic lesions in metastatic disease, although it is a rare (1%) phenomenon. 3

In the days when IL-2 based immunotherapy was used, cytoreductive nephrectomy (CN) was recommended for patients with good PS prior to treatment.

Since tyrosine kinase inhibitors (TKIs) have become standard treatment, two prospective studies have investigated the indication for CN before TKI. Both studies were closed early due to poor recruitment, but the conclusion from both studies was that there was no survival benefit with CN before TKI. There have been many criticisms of both studies, and according to EAU guidelines, data is only strong enough to conclude that patients belonging to a poor prognosis group according to IMDC (see section on prognostic stratification tools for patients with mRCC) should NOT be offered CN prior to TKI.4

Cytoreductive nephrectomy prior to systemic therapy can continue to be recommended:

  • in clinical trials
  • for patients in good AT (PS = 0–1) with large primary tumour and low metastatic volume that has not spread to CNS, bone or liver
  • for patients who have symptoms from their primary tumour in the form of haematuria or pain5

The decision on CN must always be taken at a multidisciplinary (MDT) conference. 5

5. Participation in clinical trials

The possibility of participating in a clinical trial, in which new medicines are tested, possibly in combination with already approved medicinal products, should always be considered.

References

  1. Active surveillance in metastatic renal-cell carcinoma: a prospective, phase 2 trial. Rini B et al. Lancet Oncol 2016; 17: 1317–24.
  2. DaRenCa guidelines
  3. Freed SZ, Halperin JP, Gordon M. Idiopathic regression of metastases from renal cell carcinoma. The Journal of urology. 977;118(4):538–42.
  4. Axel Bex et al. Updated European Association of Urology Guidelines for Cytoreductive Nephrectomy in Patients with Synchronous Metastatic Clear-cell Renal Cell Carcinoma. Eur Urol 2018; 74: 805-809
  5. DaRenCa guidelines, ESMO guideline og Bhindi et al. Systematic Review of the Role of Cytoreductive Nephrectomy in the Targeted Therapy Era and Beyond: An Individualized Approach to Metastatic Renal Cell Carcinoma. Eur Urol; 2019: 111-128

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