Treatment of kidney cancer: surgery, targeted therapy, immunotherapy

Causes and symptoms

The correct use of treatment methods for kidney cancer largely depends on understanding the reasons that led to the formation of the tumor. There are two main types of renal tumors:

• hereditary-congenital variant caused by a defect in kidney cells at the prenatal stage of development;
• acquired tumor caused by impaired immune defense and environmental factors.

It is very important to detect kidney cancer in time: when a small tumor-like formation is identified and surgery is performed, the prognosis for a person’s life is most optimal. You should immediately consult a doctor if the following symptoms appear:

• causeless weight loss;
• lumbar pain when problems with the spine are excluded;
• change in urine color (hematuria).

Treatment of other diseases starting with the letter - r

The information is for educational purposes only. Do not self-medicate; For all questions regarding the definition of the disease and methods of its treatment, consult your doctor. EUROLAB is not responsible for the consequences caused by the use of information posted on the portal.

Diagnosis of kidney cancer

At the first visit, the doctor will definitely conduct a full examination and prescribe tests. If there is significant suspicion of a tumor formation in the kidney area, an ultrasound examination is performed. When confirming the diagnosis, it will be necessary to clarify the location of the tumor and the degree of involvement of neighboring tissues and organs. It is extremely important to exclude the presence of metastases in the lungs and bones. To do this, you must go through the following procedures:

• survey, excretory and retrograde urography;
• tomographic examination (CT or MRI);
• angiographic examination (selective renal arteriography, renal venography);
• X-ray of the lungs;
• X-ray of the spine.

The need to take special medications after surgical removal of a tumor occurs when there is a pathological change in the vascular network in the area of ​​the tumor and with a high risk of metastasis.

Possibility of combination with other types of treatment

In accordance with the action of cytostatic agents, and the lack of sensitivity to them in malignant tumor cells, their simultaneous use with targeted drugs will not bring results.

In another way, we can talk about combining targeted agents with a similar, but slightly different mechanism of action. The simultaneous influence of drugs on various targets in the body helps to increase the effectiveness of treatment as a whole.

4 minutes to read

Kidney cancer is a common urological cancer. 210 thousand new cases of RP are diagnosed annually. Targeted therapy has been used since the 21st century. This treatment method is in great demand among doctors and patients. Targeted therapy is prescribed by an oncologist. It can act as both basic and complex treatment.

Possible complications

Kidney cancer can cause life-threatening conditions, including:

• metastasis of tumor cells to the bones, lungs, brain and liver, which will be manifested by a variety of symptoms of damage to these organs (hemoptysis, radiculitis pain, bone fractures, problems with stool and urination);
• vascular disorders in the form of varicocele, which is caused by compression of the veins by the tumor;
• internal bleeding due to the disintegration of the neoplasm;
• necrosis (necrosis) of part of the kidney tissue with a severe inflammatory reaction of the entire body.

The occurrence of any of these complicating conditions indicates a late stage of kidney cancer, which significantly worsens the prognosis of the disease. However, even in this case, a combination of surgery and drugs for targeted therapy can be used for therapeutic purposes.

What diseases can it be associated with?

Anemia is a condition in which there is low hemoglobin and/or red blood cells in the blood. In this case, it is a consequence of inhibition of the hematopoietic process by toxins.

Arterial hypertension is a persistent increase in blood pressure, which occurs with a tumor due to excessive production of renin. Renin, a blood pressure-regulating component, is produced in the walls of the arterioles of the glomeruli, from where it enters the blood and lymph. Kidney pathology affects the synthesis process and, as a consequence, pressure regulation.

Varicocele is an enlargement of the veins of the pampiniform plexus of the spermatic cord, the blood flow in which is largely determined by the renal veins and can be disrupted due to the formation of a tumor.

Hypercalcemia is an increase in the concentration of calcium in the blood plasma, in this case due to exposure to toxic substances produced by the tumor.

Hematuria is the content of blood in the urine due to damage to the renal vessels by the tumor mass.

Renal colic is a pain syndrome that occurs when there is an acute obstruction of the outflow of urine due to obstruction of the upper urinary tract by a calculus, a blood clot, mucus or pus, a conglomerate of uric salts, rejected necrotic tissue, etc.

Principles of treatment

Surgery is a prerequisite for effective treatment of kidney cancer. An operation to completely remove the affected organ (nephrectomy) is guaranteed to rid a person of the main focus of tumor growth. Partial removal of the kidney (resection) is performed only in cases where it is necessary to try to preserve urinary function.

An important factor in the radical treatment of renal cancer is the preoperative cessation of blood flow to the tumor. To do this, the doctor will perform embolization of the renal arteries using angiography. This method of preoperative therapy will help reduce the size of the tumor and reduce the risk of metastases spreading through the circulatory system.

The operation must be combined with therapeutic factors that will prevent metastasis or help get rid of existing cancer cells. The following treatment methods can be used:

• radiation therapy, prescribed when tumor cells enter the brain;
• immunotherapy, used in combination with targeted drugs;
• hormone therapy (used for some types of kidney tumors);
• targeted intracellular therapy.

Pharmacotherapy

Targeted therapy

Targeted therapy for kidney cancer (from English target) is treatment with drugs that block the function of malignant cells at the level of specific molecular mechanisms that exist only in altered structures and ensure the development of carcinoma. Unlike traditional chemotherapy drugs, which suppress all actively dividing cells, targeted drugs are more selective.

Tools used:

• Sorafenib (Nexavar): 400 mg twice daily;
• Sunitinib (Sutent): 50 mg/day;
• Pazopanib (Votrient): 800 mg once daily;
• Axitinib: initial dosage 5 mg/day, with normal tolerability within 2 weeks - dose escalation to 7 mg 2 times a day, with normal tolerability after another 2 weeks - up to 10 mg 2 times a day;
• Bevacizumab (Avastin): 10 mg/kg once every 2 weeks;
• Nivalumab: 3 mg/kg every 2 weeks;
• Temsirolimus (Torisel): 25 mg once a week;
• Everolimus (Afinitor): 10 mg once daily.

The specific combination of drugs and treatment regimen is selected by the oncologist based on the patient’s general condition, prognostic markers, tolerability of a particular drug, and tumor response to treatment.

Immunotherapy

Immunotherapy for kidney cancer was one of the earliest treatments for metastatic cancer. It is aimed at restoring the immune response against the tumor. Like any foreign agents, atypical cells produce antigen proteins that are not found in a healthy body. But the tumor learns to “hide” these antigens from the immune system. Immunotherapy makes cancer cells “visible” and then the body fights on its own.

Alpha interferon drugs make cancer cells recognizable to lymphocytes. At the same time, they enhance the activity of natural killer cells: a special type of lymphocytes responsible for the destruction of tumor cells and cells affected by viruses. In addition, interferon-based agents slow down the division of cancer cells and activate their apoptosis (natural death).

As monotherapy, recombinant interferons are effective in the early stages of kidney cancer in combination with radical nephrectomy. In disseminated forms (multiple metastases), they help slow down the process, but the probability of cure is 15–20%.

Interferons are used in combination either with targeted therapy drugs or in combination with interleukin-2, which does not directly affect tumor cells, but stimulates the activity of T and B lymphocytes, natural killer cells, and regulates the production of interferon gamma. Thus, it suppresses the activity of atypical cells indirectly, through activation of the immune system.

Chemotherapy

Chemotherapy for kidney cancer is used extremely rarely, since this tumor is insensitive to chemotherapy. Therefore, it is prescribed only to patients who are insensitive to immuno- and targeted therapy. Drugs used:

• Capecibin;
• Gemcitabine;
• Cisplatin;
• Doxorubicin;
• 5-fluorouracil.

Targeted therapy

An extremely unfavorable factor for the growth and spread of tumor cells is an increase in the number of vessels in a malignant neoplasm. A branched and extensive vascular network provides the tumor with nutrition and oxygen, which significantly increases the risk of a rapid increase in the size of the tumor. And, most importantly, it promotes the metastatic spread of cancer throughout the human body. Often it is pathological angiogenesis (pronounced intracellular activation of the construction of a new vascular network near the tumor) that becomes the cause of complications and rapid deterioration of the patient’s condition.

The essence of the targeted treatment method is targeted intracellular exposure to drugs that prevent the formation of new vessels, reduce the severity of tumor tissue growth (proliferation) and do not allow tumor cells to spread throughout the body. In the fight against metastasis and angiogenesis, the best results are shown by drugs for targeted therapy of metastatic kidney cancer, which include:

• Sunitinib;
• Nexavar;
• Torisel;
• Avastin.

Each of these drugs is used strictly according to indications and only under the supervision of a physician. In some cases, a combination of drugs is necessary, when a specialist prescribes the drug along with an immunomodulator. An important factor in targeted therapy will be long-term medication use.

Side effects

The therapeutic effect of a targeted technique may be accompanied by a number of unpleasant side effects, which include:

• bowel dysfunction in the form of diarrhea;
• nausea and vomiting;
• skin dermatitis on the palms and soles;
• focal hair loss (alopecia);
• increased blood pressure.

Side effects when taking targeted drugs do not always occur and are not so pronounced that one should refuse to use this highly effective method of treatment.

Combination therapy: new research and drugs

The past decade has seen the emergence of an impressive arsenal of experimental drugs for the treatment of renal cell carcinoma.
Today, it is common to prescribe immunotherapy and targeted drugs sequentially. But companies in the US and other Western countries are conducting clinical trials of new combination therapy regimens. These efforts allow scientists to combine multiple, complementary drug mechanisms to overcome cancer resistance, restore functional immune control, and improve patient survival.

Unfortunately, immunotherapy for kidney cancer is just beginning to develop. Current results are far from optimal, so participation in clinical trials of new drugs and combinations is often a real chance of survival.

Examples of experimental combination therapy regimens

Immunotherapy + immunotherapy:
• Nivolumab (anti-PD-1) + ipilimumab (anti-CTLA-4) • Atezolizumab (anti-PD-L1) + varilimumab (anti-CD-27) • Pembrolizumab (anti-PD-1) + ipilimumab (anti-CTLA-4) • Pidilizumab (anti-PD-1) + tumor vaccine • Tremelimumab (anti-CTLA-4) + durvalumab (anti-PD-1)

Immunotherapy + targeted therapy:

• Pembrolizumab (anti-PD-1) + pazopanib (TKI) • Nivolumab (anti-PD-1) + bevacizumab (anti-VEGF) • Atezolizumab (anti-PD-L1) + bevacizumab (anti-VEGF) • Nivolumab (anti-VEGF) -PD-1) + multikinase inhibitors • Sunitinib (TKI) + tumor vaccine

Forecast

Preserving the life and health of a patient with kidney cancer depends on the following prognostic factors:

• age (the chances of recovery are greater in people over 40 years old);
• stage and type of tumor process (the earlier renal cancer is detected, the greater the chance of recovery);
• general condition of the body (immune defense, the presence of blood diseases and chronic pathologies are important);
• detection and number of metastases (metastasis to the brain, liver and lungs is extremely unfavorable);
• performing a surgical operation to remove the primary tumor focus (if nephrectomy is not performed, then there is no possibility of recovery);
• mandatory and long-term use of therapy with special medications.

At the first stage of treatment for kidney cancer, surgical intervention is always used to completely remove the tumor formation in the organ. After nephrectomy, medications are prescribed to prevent the spread of metastases. If there are already metastatic foci in the lungs, bones and liver, the targeted use of special drugs will become a real and highly effective method of getting rid of tumor cells. The chances of recovery increase significantly with proper, consistent implementation of the doctor’s recommendations and constant monitoring by a specialist.

Effect of treatment and its toxic effects

Targeted treatment prevents the proliferation and spread of tumor cells, so its toxic effect on healthy cells in the human body is much less compared to cytotoxic therapy.
The frequency of identification of serious negative impacts remains relatively low. There is neutropenia, thrombocytopenia, impaired digestive functions - stomach upset and increased amylase concentrations. Damage to the skin epithelium will manifest as hand-foot syndrome in 5% of cases. In some cases, hypertension develops, and most complications are easily controlled by reducing the dosage of medications.

Duration of treatment and dosages used:

The standard prescribed dose is 50 mg of the drug per day for four weeks. Then a break is taken for two weeks. If serious side effects develop, the dosage is reduced to 37.% or 25 mg, and a subsequent dose reduction does not make sense.

First line drugs

This type of medication is used to reduce or control the course of the disease in common tumor formations. The results of the study and patient responses indicate the effectiveness of targeted therapy.

The development of cancer cells is slowed down for several months, and sometimes years.

Systematic medication intake controls the progression of the disease. Throughout the entire therapeutic process, the patient visits the doctor every 2-3 weeks.

Once every 90 days, a specialist orders a scan. Based on the results, the effectiveness of treatment is determined.

Sunitinib

The drug is prescribed for secondary lesions, at stages 3–4 of the pathology. Belongs to the group of inhibitors. Acts as a blocker of intracellular proteins (tyrosine kinases) in tumor cells, stopping their growth and division. The composition of the medication interferes with blood supply, the cells are deprived of nutrients and oxygen composition.

Undesirable complications of taking Sunitinib include: fatigue, anemia, modification of taste, rashes. Possible dysfunction of the thyroid gland. Therefore, a systematic blood test is prescribed.

Pazopanib

The drug is prescribed both for primary therapy of a developing tumor process, and secondary after the use of interferon. Considered a common cancer growth inhibitor. Available in tablet form, taken daily.

Consequences: vomiting, itching, rash, diarrhea.

The drugs have a targeted effect on cancer cells. Advantage: preservation of healthy cells, easy tolerability (compared to chemotherapy).

Second line drugs

If the drugs of the first group do not cope with the disease and the cancer cells begin to grow again, second-line drugs are prescribed.

Avastin

The medication acts as a monoclonal antibody and slows down the development of blood vessels in tumor formations. The drug is taken in combination with interferon. Avastin - every 14 days, interferon - 3 times every 7 days.

Taking the drug is accompanied by flu-like symptoms. To avoid cold symptoms, take paracetamol 30 minutes before the injection. Other consequences include: melancholy, nausea and the development of hypertension.

Temsirolimus

It is prescribed intravenously, once every seven days. It belongs to the class of MTOR inhibitors and prevents the growth of malignant cell structures. Prescribed for common tumor processes.

Undesirable symptomatic manifestations: redness and rashes on the skin, inflammatory conditions in the oral cavity.

Despite the effectiveness of medications, they all have side effects. Before prescribing targeted therapy, the doctor consults the patient and explains how to more easily overcome the consequences.

Description

Targeted therapy is a treatment tactic that destroys diseased cells without harming healthy ones. Traditional chemotherapy is difficult and painful for patients. Targeted drugs improve the patient's health, significantly extending life years. The doctor prescribes medications for stages 3-4 of the disease.

In English, targeted is translated as target. Therefore, the second name for targeted therapy is targeted. The drugs specifically target malignant cells, preventing the production of necessary substances. As a result, their existence and reproduction is interrupted. The immune system begins to distinguish healthy cells from sick ones. The destruction of malignant cells occurs.