Stage 4 Kidney Cancer

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Kidney Cancer or Renal Cell Carcinoma is among the 10 most common cancers in the world. It is more commonly seen in men and its risk increases with an advancing age, with peak of incidence being 64 years as per data obtained from National Institute of Health.

While kidney cancer does account for a significant rate of mortality, you must know that early diagnosis of kidney cancer massively improves your chances of survival. A UK – based study found that early diagnosis improves survival rates by 70 to 94 % because the tumor is diagnosed at a stage when it is only localised.

Here we will discuss about stage 4 or metastatic kidney cancer, which has spread to distant sites.

Symptoms of Stage 4 Kidney Cancer

Stage 4 kidney cancer may present with local symptoms due to locoregional involvement of nearby structures, symtoms due to spread to distant sites and constitutional symptoms. We have discussed them below in detail.

Hematuria

Hematuria or the presence of blood in the urine is one of the most common symptoms of kidney cancer. Almost 18 % of all patients with renal cancer complain of hematuria at some point of their disease.

Hematuria may be seen as a drop of blood in your urine, but, most likely, it is manifested as an orange or pinkish discoloration of the urine. In some individuals, even a dark red colour may be noted.

Loin Pain

Loin is the area between your lower ribs and hips. Loin pain or flank pain is commonly reported by patients of kidney cancer. Some may also complain of chronic pain in the lower back generally on one side.

If you are suffering from kidney stones, it is possible that you may associate this type of pain with the one experienced due to stones. But the pain due to stones is acute and colicky in nature and that associated with cancer is mostly dull-aching. So, if you feel unbearable pain in this region, it is advisable to seek medical attention regardless of your diagnosis of kidney stones.

Abdominal Mass

In addition to pain, a peculiar loin mass may be present on physical examination. It may be felt as a small, soft lump or mass in the region of lower back or loin.

Urinary Tract Infections

Urinary tract infections are noted in approximately 11 % of patients with kidney cancer. The signs and symptoms of UTI include frequent micturition, pain or burning sensation while urinating, inability or pain while holding urine during urgent situations.

Breathlessness or Cough

Spread or metastasis of kidney cancer to lungs may cause symptoms such as breathlessness or cough. It may be associated with chest pain or discomfort.

Symptoms usually depend on the site and extent of lung metastasis, presence of pleural effusion, etc.

Bony Pain

Bone is also one of the common site of spread from kidney cancer. Pain at one or more bony sites like lower back pain, rib pain or other sites may be due to spread of kidney cancer to bones.

Other Symptoms

Nausea and constipation are reported by approximately 5 to 6 % of the patients.

Anemia, manifested as pale skin, fatigue, difficulty in concentration and frequent headaches, is complained by another 23 % of the patients, making it a commoner symptom than hematuria; however, the latter is more specific.

What is Stage 4 Kidney Cancer?

When kidney cancer spreads to distant sites, it is called as stage 4 or metastatic disease.

Like in the image below, it has spread to liver as multiple tumor deposits.

This figure shows multiple metastatic deposits in the liver.
metastasis to liver And here cancer has spread to the lungs in form of multiple nodular deposits.
metastasis to lungs It may also spread to the peritoneum in the form of peritoneal deposits, as you can see in this figure.
metastasis to peritoneum Metastatic deposits in the adrenal gland without direct extension of a tumor may also be seen.
Metastatic deposits in the adrenal gland Sometimes, it may also spread to the brain or bones.

Treatment of Stage 4 Kidney Cancer

Treatment of metastatic or stage 4 kidney cancer depends on the site, number and extent of metastasis.

If the primary tumor and metastatic disease both are resectable, surgical resection of primary and sites of metastasis is preferred.
If the metastatic disease is not completely resectable, cytoreductive surgery followed by systemic therapy (targeted therapy or immunotherapy) may be done if feasible. or else, primary systemic therapy may be given.
If the disease is unresectable, systemic therapy in the form of targeted therapy and/or immunotherapy is the treatment of choice.
stage 4 kidney cancer treatment
But the final decision whether to start chemotherapy or to do surgery is taken by oncologists on an individual patient basis, after assessing the exact conditions of the patient, comorbidities, performance status, along with other factors.

Role of Targeted Therapy

targeted therapy for kidney cancer Targeted drug therapy has become the standard of care for the management of advanced-stage renal cancers owing to their improved efficacy and safety compared to conventional cytotoxic chemotherapy. Targeted drugs that have been approved for the treatment of renal cancer:

Sunitinib

sunitinib It is a multi-functional kinase inhibitor targeting several tyrosine kinases, the intracellular enzymes that trigger the growth and proliferation of cells. It is considered the preferred first-line treatment of patients with advanced-stage clear cell renal cancer.

Sorafenib

sorafenib It is a small molecule inhibitor of multiple kinases involved in the growth and proliferation of cancer cells. It can be employed as second-line therapy in patients with clear cell renal cancer who had previously received cytokines, sunitinib, or bevacizumab. It is reported to have a reduced efficacy in the treatment of patients with advanced-stage renal cancer with non-clear cell histologies.

Pazopanib

pazopanib It is an oral angiogenesis (formation of blood vessels) inhibitor that inhibits multiple factors responsible for tumor cell growth and proliferation. It is considered the preferred first-line treatment of patients with advanced-stage clear cell renal cancer. It can also be employed as second-line therapy for patients with advanced-stage clear cell renal cancer.

Axitinib

axitinib It is a selective, second-generation angiogenesis inhibitor. It has been approved as the first-line and subsequent line therapy (preferred option) for patients with advanced-stage clear cell renal cancer.

Temsirolimus

temsirolimus It is an inhibitor of the mammalian target of rapamycin (mTOR) protein that regulates cell growth, angiogenesis, and apoptosis (programmed cell death). It is recommended as the preferred first-line treatment for advanced-stage clear cell renal cancer in poor-risk patients and with a non-clear cell histologies and poor prognostic features.

Everolimus

everolimus It is an oral mTOR inhibitor. It is generally employed as subsequent therapy for patients with advanced-stage clear cell renal cancer and as first-line therapy for patients with advanced-stage renal cancer and non-clear cell histologies.

Bevacizumab

Bevacizumab It is a monoclonal antibody that inhibits angiogenesis. Bevacizumab in combination with Interferon (IFN)-alpha is considered a good option for first-line treatment of patients with advanced-stage clear cell renal cancer. It can also be given as single-agent therapy for the treatment of both clear cell and non-clear cell renal cancer.

Cabozantinib

cabozantinib It is a small-molecule inhibitor of multiple tyrosine kinases responsible for growth and proliferation of cancer cells. It is considered as the preferred subsequent-line treatment of patients with advanced-stage clear cell renal cancer.

Lenvatinib

lenvatinib It a multi-targeted tyrosine kinase inhibitor, in combination with everolimus is recommended as the preferred subsequent-line therapy for advanced-stage clear cell renal cancer.

Role of Immunotherapy

immunotherapy for kidney cancer

Interleukin-2 and INF-alfa

The utility of Interleukin-2 is limited due to the associated serious side-effects, which include low blood pressure, pleural effusion, extreme fatigue, difficulty in breathing, raised heartbeat, high fever, chills, kidney damage, heart attack, gastrointestinal bleeding, and psychological changes. INF-alpha is commonly used in combination with bevacizumab (a targeted drug).

Nivolumab

It selectively blocks the interaction of programmed death receptor-1 (PD-1) expressed on activated T cells with its ligands (PD-L1 and similar) expressed on normal cells and tumor cells. It is approved after failure of first line treatment.

Ipilimumab

It blocks the interaction of cytotoxic T-lymphocyte antigen 4 (CTLA-4), a negative regulator expressed on activated T cells, with its ligands CD80/CD86 expressed on the tumor/normal cells. The combination of nivolumab and ipilimumab is recommended as the preferred first-line treatment for intermediate- and poor-risk patients with advanced-stage clear cell renal cancer.

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