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Tractable tumors

Kidney cancer

Cancer cells attack the kidneys

Kidney cancer usually arises from an uncontrolled growth of the cells that line the inner tubules of the kidney, although it may also develop from other tissues or from the capsule that covers the outer surface of the kidney.

In 90% of cases, it is classified as renal cell carcinoma or adenocarcinoma.

In most cases, kidney cancer is fortuitously diagnosed by abdominal ultrasound performed for other reasons. The upside of this is that the disease is often detected at an early stage and can be successfully treated.

Historically, the preferred treatment for kidney cancer at an early stage is surgery. For the treatment of advanced disease both chemotherapy and radiation therapy have demonstrated to be poorly effective. Today, however, cancer immunotherapy may represent a new treatment opportunity for patients suffering from this disease.

Future perspectives: The results of the most recent studies reinforce the evidence of the efficacy of immunotherapy for this pathology, exploring its role in earlier stages of metastatic disease and in combination therapies.

Kidney cancer: what’s changed with Immunotherapy?

Camillo Porta Prof. Camillo Porta, Adjunct Professor of Medical Oncology at University of Pavia, Italy.

Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies, ranks 14th in incidence and is the 7th leading cause of death by cancer worldwide.

In 2006, 209,000 new cases of RCC and 102,000 RCC-related deaths were reported worldwide, while the estimated incidence in Europe was 29,600 new cases per years among men and 16,700 new cases per year among women.

About 30% of patients with RCC present with metastases at the time of diagnosis, while as many as 25% of patients who undergo radical surgery for localized or locally advanced cancer are bound to develop distant metastases within years or even decades. RCC is the most common type of kidney cancer in adult subjects and originates in the cells that line the inner tubules of the kidney, and is classified into three major types: clear cell tumors (25%), granular cell tumors (15%), and sarcomatoid cell tumors (10%); mixed forms of these three types can also be observed.

The treatment of kidney cancer

If there are no metastases and the tumor is organ-confined, surgical removal of the affected kidney is the most common strategy.

In the presence of metastases, the therapeutic approach until a few years ago was mainly based on chemotherapy, even though the results were only partially successful.

Since renal cell carcinoma is rich in blood vessels, another therapeutic strategy is based on the use of biological agents that inhibit the formation of new vessels that feed the tumor (angiogenesis; VEGF, vascular endothelial growth factor): in this setting, the so-called anti-angiogenic drugs (sorafenib, sunitinib, pazopanib, axitinib, cabozantinib) have gradually emerged as a therapeutic strategy for patients with advanced RCC, although with different indications (and lines of treatment). Likewise, molecules that inhibit the mTOR pathway (temsirolimus and everolimus) have been added to the current armamentarium for the treatment of this cancer.

More recently, the combination of a mTOR inhibitor, such as everolimus, with a multi-kinase inhibitor with anti-VEGFR action (among others), such as lenvatinib, has shown to provide anti-tumor activity in patients with metastatic RCC.

During the last few years, the peculiar immunogenicity of renal carcinoma (i.e. its propensity to be recognized and subsequently attacked by our immune system) has led to the development and use of immunotherapeutic agents (cytokines and, more recently, checkpoint inhibitors such as nivolumab), that have exhibited anti-tumor activity against clear cell RCC, initially as second-line therapy. Recently, the combination of two checkpoint inhibitors, ipilimumab and nivolumab, has shown to be highly active also as first-line treatment, to the point that it has been regarded as a new standard of care for patients with metastatic renal carcinoma, although mainly in a particular population of patients, i.e. those in the intermediate- or bad-risk groups.

After the age of targeted therapies, we are now witnessing the beginning of the age of immunotherapy for renal carcinoma, while expecting (and hoping) that the combination of two treatment strategies (immunotherapy and anti-angiogenic agents) will lead, if not to an actual cure, at least to the chronicization of this silent killer called renal carcinoma.

Radiation therapy and bone-targeting agents

For years, renal carcinoma has been considered as a radiation-resistant malignancy; however, the use of modern radiation therapy techniques has shown to be effective also against this type of cancer, although mainly in a palliative care setting.

RCC-related bone metastases may benefit not only from radiation therapy but also from the so-called bone-targeting agents, zoledronic acid and denosumab, the former having the potential of improving survival in addition to reducing the incidence of skeletal events (pathological fractures, medullary compression, pain, and the need for radiation therapy with pain-relieving and palliative purposes).

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