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Metastatic Renal Cell Carcinoma

Stage IV Renal Cell Cancer

Renal cell carcinoma is a malignancy originating from the kidney's tubular epithelium. The tumor is characterized by aggressive growth and propensity for metastatic spread. Patients often present with metastatic disease disease either at the time of diagnosis of the primary tumor or even several years after receiving treatment for the tumor.

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Presentation

RCC patients tend to remain asymptomatic until advanced stages of the disease. The classic symptom triad of flank pain, hematuria and a palpable abdominal mass is presented by less than 10% of affected individuals [10]. Symptoms associated with mRCC largely depend on the affected organ and involvement of adjacent tissue. As these symptoms are identical to symptoms triggered by other neoplasms affecting those organs, they cannot be ascribed to mRCC unless a histopathological analysis of fine-needle aspirates or biopsy specimens has been obtained.

Both RCC and mRCC may provoke symptoms consistent with paraneoplastic syndrome, and those may precede the onset of symptoms due to local mass effects mediated by the primary tumor and metastases. In this context, constitutive symptoms like fever, night sweats and weight loss may be accompanied by endocrine and electrolyte imbalances. Neoplastic tissue has been shown to release interleukins IL-1 and IL-6 as well as tumor necrosis factor-α, and these have been related to enhanced concentrations of acute phase markers like C-reactive protein. Moreover, tumor cells may release parathyroid hormone-related peptide and renin production by the affected kidneys may be increased. This results in hypercalcemia, possibly associated with fatigue, polyuria, polydipsia, and exsiccosis, nausea and vomiting, cardiac arrhythmia,hypertension and altered sensorium. Tumor cells may produce erythropoietin and provoke erythrocytosis. Polycythemia has also been described in mRCC patients. mRCC may be accompanied by amyloidosis, although its pathogenesis remains unclear.

Resection of a localized primary tumor and complete metastasectomy, in case of metastases, generally relieve symptoms of paraneoplastic syndrome. Otherwise, or upon recurrence of fever, night sweats, and weight loss, a thorough workup is required to detect metastases that may have been overlooked before.

Fatigue
  • The dose of sorafenib was reduced and temporarily discontinued because adverse events, including fatigue and cardiac infarction, occurred.[ncbi.nlm.nih.gov]
  • The patient described in this case did not have any symptoms commonly seen in RCC, such as painless hematuria, weight loss, anorexia, fatigue, or anemia, despite the bulk of his disease.[ncbi.nlm.nih.gov]
  • Of several adverse events, only anemia and fatigue were significantly more frequently observed in older than younger patients.[ncbi.nlm.nih.gov]
  • The presence of fatigue, pain, dyspnoea, and the application of radiotherapy were associated with significantly lower EQ-5D utilities. CONCLUSIONS: Key drivers for reduced HRQoL in mRCC are disease symptoms.[ncbi.nlm.nih.gov]
  • Toxicities of TKIs were Grade 1 or 2 in 13 patients and Grade 3 or 4 in 9 patients; the most common being fatigue, followed by hand-foot syndrome, skin rash, mucositis, and hypertension.[ncbi.nlm.nih.gov]
Weight Loss
  • Abstract An 81-year-old South Asian man normally resident in the UK presented with night sweats for over 2 months on a background of weight loss of 4 kg in 6 months.[ncbi.nlm.nih.gov]
  • The patient described in this case did not have any symptoms commonly seen in RCC, such as painless hematuria, weight loss, anorexia, fatigue, or anemia, despite the bulk of his disease.[ncbi.nlm.nih.gov]
  • Symptoms typically include: blood in the urine pain on one side of the lower back lump in the back or side weight loss fatigue fever swelling of the ankles night sweats A physical exam and a review of your medical history may prompt further testing to[healthline.com]
  • In this context, constitutive symptoms like fever, night sweats and weight loss may be accompanied by endocrine and electrolyte imbalances.[symptoma.com]
  • Lifestyle measures such as exercise, weight loss and diet changes can help. Some people may need to add medications to lower their blood pressure. Discuss your options with your doctor.[mayoclinic.org]
Anemia
  • The patient described in this case did not have any symptoms commonly seen in RCC, such as painless hematuria, weight loss, anorexia, fatigue, or anemia, despite the bulk of his disease.[ncbi.nlm.nih.gov]
  • Of several adverse events, only anemia and fatigue were significantly more frequently observed in older than younger patients.[ncbi.nlm.nih.gov]
  • A grade 3 microangiopathic hemolytic anemia syndrome was observed in four (16%) patients. Five (22%) patients achieved a partial response.[ncbi.nlm.nih.gov]
  • The adverse event profile of two treatments was quite different: hypertension, hypothyroidism, and fatigue were observed only with pazopanib, whereas anemia and metabolic disorders were commonly reported with everolimus.[journal.frontiersin.org]
  • Available at: Colorectal Cancer Colorectal Cancer Screening Genetic/Familial High-Risk Assessment: Colorectal Prostate Cancer Early Detection NCCN GUIDELINES FOR SUPPORTIVE CARE Cancer- and Chemotherapy-Induced Anemia Cancer-Associated Venous Thromboembolic[nccn.org]
Fever
  • High fevers unresponsive to antimicrobial therapy, cytopenias, disseminated intravascular coagulation, and progressive multiorgan failure led to intubation and intensive care unit stay.[ncbi.nlm.nih.gov]
  • Symptoms typically include: blood in the urine pain on one side of the lower back lump in the back or side weight loss fatigue fever swelling of the ankles night sweats A physical exam and a review of your medical history may prompt further testing to[healthline.com]
  • In this context, constitutive symptoms like fever, night sweats and weight loss may be accompanied by endocrine and electrolyte imbalances.[symptoma.com]
  • Call your health care provider if you experience fever; cold symptoms, such as runny nose or a sore throat that does not go away; flu symptoms, such as cough, feeling tired, and body aches; pain when urinating; or cuts, scrapes, or wounds that are red[us.votrient.com]
  • In the later stages, kidney cancer signs and symptoms may include: Blood in your urine, which may appear pink, red or cola colored Pain in your back or side that doesn't go away Loss of appetite Unexplained weight loss Tiredness Fever, which usually comes[mayoclinic.org]
Swelling
  • We report the case of a 64-year-old otherwise healthy woman who presented with left facial swelling. Imaging of the neck revealed multiple masses in the salivary and thyroid glands.[ncbi.nlm.nih.gov]
  • Preoperatively US of the swelling and head-neck CT scan with 3D rendering ( Figure 2 ). Figure 2: 3D rendering showing dimension and position of the submandibular swelling.[omicsonline.org]
  • Symptoms typically include: blood in the urine pain on one side of the lower back lump in the back or side weight loss fatigue fever swelling of the ankles night sweats A physical exam and a review of your medical history may prompt further testing to[healthline.com]
  • Call your health care provider if you experience pain or swelling in the stomach area, vomiting blood, or black sticky stools. VOTRIENT may cause lung problems that may lead to death.[us.votrient.com]
  • Rare case of renal cell carcinoma with mandibular swelling as primary presentation. Case Rep Urol 2013;2013:806192. 22. Miah MS, White SJ, Oommen G, Birney E, Majumdar S.[e-ultrasonography.org]
Cough
  • Tell your health care provider right away if you develop a cough that will not go away or have shortness of breath. Reversible posterior leukoencephalopathy syndrome is a condition that can happen while taking VOTRIENT that may cause death.[us.votrient.com]
  • For example, cancer that spreads to the lungs may cause coughing and shortness of breath. Cancer that spreads to the bones may cause bone pain. Exams and Tests To see if you may have kidney cancer, your doctor will do a physical exam.[northshore.org]
  • Fatigue 65 9 35 2 50 8 Arthralgia/myalgia 11 (11–21) (0) 25 0 Decreased appetite 48 2 12 58 4 Vomiting 34 2 (15–17) (0) 39 4 Nausea 54 4 14 62 8 Stomatitis 24 2 2 0 25 2 Hypertension 52 15 Not defined Not defined 48 17 Peripheral edema 9 0 4 0 15 0 Cough[jhoonline.biomedcentral.com]
  • […] tumors, hence slowing growth and in some cases reducing the size of the tumors. [97] Side effects unfortunately are quite common with these treatments and include: [98] Gastrointestinal effects – nausea, vomiting, diarrhea, anorexia Respiratory effects – coughing[en.wikipedia.org]
Nausea
  • The majority, 68 percent, experienced some adverse effects — fatigue, nausea and diarrhea — but nothing life-threatening. One patient died due to disease progression.[consultqd.clevelandclinic.org]
  • Tell your health care provider right away if you have yellow eyes or skin, dark urine, tiredness, nausea or vomiting, loss of appetite, pain in the right upper side of your stomach area, or if you bruise easily.[us.votrient.com]
  • Adverse Effects In the AXIS trial, treatment with axitinib was associated with diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome, decrease in weight, vomiting asthenia, and constipation.[cancertherapyadvisor.com]
  • This results in hypercalcemia, possibly associated with fatigue, polyuria, polydipsia, and exsiccosis, nausea and vomiting, cardiac arrhythmia,hypertension and altered sensorium. Tumor cells may produce erythropoietin and provoke erythrocytosis.[symptoma.com]
  • The maximum tolerated dose (MTD) was defined as 25 mg, and the most prevalent toxicities were diarrhea (45% ), hypertension (40% ), nausea (37% ), stomatitis (32% ) and proteinuria (26% ).[content.iospress.com]
Vomiting
  • Call your health care provider if you experience pain or swelling in the stomach area, vomiting blood, or black sticky stools. VOTRIENT may cause lung problems that may lead to death.[us.votrient.com]
  • Adverse Effects In the AXIS trial, treatment with axitinib was associated with diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome, decrease in weight, vomiting asthenia, and constipation.[cancertherapyadvisor.com]
  • This results in hypercalcemia, possibly associated with fatigue, polyuria, polydipsia, and exsiccosis, nausea and vomiting, cardiac arrhythmia,hypertension and altered sensorium. Tumor cells may produce erythropoietin and provoke erythrocytosis.[symptoma.com]
  • The most important toxicities of any grade reported in all cohorts were fatigue (60% ), mucositis (50% ), proteinuria, diarrhea, vomiting, hypertension and nausea (40% each). Rates of PR and SD were 33% and 50%, respectively [ 27 ].[content.iospress.com]
  • Home treatment for nausea or vomiting includes watching for and treating early signs of dehydration , such as having a dry mouth or feeling lightheaded when you stand up. Eating smaller meals may help.[northshore.org]
Loss of Appetite
  • Tell your health care provider right away if you have yellow eyes or skin, dark urine, tiredness, nausea or vomiting, loss of appetite, pain in the right upper side of your stomach area, or if you bruise easily.[us.votrient.com]
  • In the later stages, kidney cancer signs and symptoms may include: Blood in your urine, which may appear pink, red or cola colored Pain in your back or side that doesn't go away Loss of appetite Unexplained weight loss Tiredness Fever, which usually comes[mayoclinic.org]
  • Loss of appetite . Weight loss for no known reason. Anemia . Tests that examine the abdomen and kidneys are used to detect (find) and diagnose renal cell cancer.[cancer.gov]
  • The main side effects cited by the patients that contributed to patient preference were diarrhea, health-related QOL, fatigue, loss of appetite, taste changes, nausea and vomiting, hand and foot soreness, stomach pain, and mouth and throat soreness.[cancer.gov]
  • […] of appetite; [10] anaemia resulting from depression of erythropoietin ; [8] erythrocytosis (increased production of red blood cells ) due to increased erythropoietin secretion; [8] varicocele , which is seen in males as an enlargement of the pampiniform[en.wikipedia.org]
Constipation
  • Adverse Effects In the AXIS trial, treatment with axitinib was associated with diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome, decrease in weight, vomiting asthenia, and constipation.[cancertherapyadvisor.com]
  • These most common grade 3 and 4 treatment-emergent adverse events from the dual-therapy patient group include constipation (37%), diarrhea (20%), fatigue (14%), and hypertension (14%).[jhoonline.biomedcentral.com]
  • Rates of grade 3 and 4 AEs were seen in 71% of patients on the combination and described as follows: constipation (37% ), diarrhea (20% ), fatigue (14% ) and hypertension (14% ).[content.iospress.com]
Abdominal Mass
  • The classic symptom triad of flank pain, hematuria and a palpable abdominal mass is presented by less than 10% of affected individuals. Symptoms associated with mRCC largely depend on the affected organ and involvement of adjacent tissue.[symptoma.com]
  • This classic triad [8] is 1: haematuria , which is when there is blood present in the urine, 2: flank pain, which is pain on the side of the body between the hip and ribs, and 3: an abdominal mass, similar to bloating but larger.[en.wikipedia.org]
Hypertension
  • During the treatment with everolimus and lenvatinib combined, 42% of the patients developed hypertension, while 10% of the patients treated with everolimus alone and 48% of the of the lenvatinib only treated patients developed hypertension.[ncbi.nlm.nih.gov]
  • On-treatment hypertension, diarrhea, and hand foot syndrome were associated with longer OS (P 0.0004, 0.0036 and 0.0115, respectively).[ncbi.nlm.nih.gov]
  • The condition of hypertension as an adverse event markedly depended on whether or not axitinib was administered.[ncbi.nlm.nih.gov]
  • Additionally, adherence to a healthy diet lowers the individual risk of overweight/obesity and related pathologies like diabetes mellitus and hypertension.[symptoma.com]
  • A meta-analysis that included data from 10 trials evaluating axitinib showed an overall incidence of all-grade and high hypertension of 40.1% and 13.1%, respectively. 3 Risk for all-grade hypertension with axitinib was significantly higher compared with[cancertherapyadvisor.com]
Back Pain
  • They also may reduce chronic low back pain, joint pain, headaches, and pain from treatments. Before you try a complementary treatment, talk to your doctor about the possible value and potential side effects.[northshore.org]
  • Primary symptoms were intractable back pain and/or radicular pain in 16 cases and lower limb weakness, spasticity, or sensory changes due to cord or nerve root compression in five cases (20.8%).[ajnr.org]
Night Sweats
  • Abstract An 81-year-old South Asian man normally resident in the UK presented with night sweats for over 2 months on a background of weight loss of 4 kg in 6 months.[ncbi.nlm.nih.gov]
  • Symptoms typically include: blood in the urine pain on one side of the lower back lump in the back or side weight loss fatigue fever swelling of the ankles night sweats A physical exam and a review of your medical history may prompt further testing to[healthline.com]
  • In this context, constitutive symptoms like fever, night sweats and weight loss may be accompanied by endocrine and electrolyte imbalances.[symptoma.com]
  • sweats and generally feeling unwell . [1] When RCC metastasises, it most commonly spreads to the lymph nodes , lungs , liver , adrenal glands , brain or bones. [5] Immunotherapy and targeted therapy have improved the outlook for metastatic RCC. [6] [[en.wikipedia.org]
Hematuria
  • The patient described in this case did not have any symptoms commonly seen in RCC, such as painless hematuria, weight loss, anorexia, fatigue, or anemia, despite the bulk of his disease.[ncbi.nlm.nih.gov]
  • The classic symptom triad of flank pain, hematuria and a palpable abdominal mass is presented by less than 10% of affected individuals. Symptoms associated with mRCC largely depend on the affected organ and involvement of adjacent tissue.[symptoma.com]
  • Case History A 56-year-old woman came to our clinic with gross hematuria and left flank pain. Computed tomographic (CT) scan showed a large inhomogeneous mass arising from the left kidney for which she underwent open radical nephrectomy.[gotoper.com]
  • They usually occur in 50-70-year old patients and macroscopic hematuria occurs in 60% of the cases.[radiopaedia.org]
  • The benefits of CN include decreasing the total tumor burden and palliation of local symptoms (such as hematuria or pain) or paraneoplastic symptoms (such as anemia or hypercalciuria).[hematologyandoncology.net]
Flank Pain
  • The classic symptom triad of flank pain, hematuria and a palpable abdominal mass is presented by less than 10% of affected individuals. Symptoms associated with mRCC largely depend on the affected organ and involvement of adjacent tissue.[symptoma.com]
  • Case History A 56-year-old woman came to our clinic with gross hematuria and left flank pain. Computed tomographic (CT) scan showed a large inhomogeneous mass arising from the left kidney for which she underwent open radical nephrectomy.[gotoper.com]
  • Risk factors cigarette smoking 2 dialysis-related cystic disease 2 obesity treatment with cyclophosphamide (chemotherapy agent) 14 hypertension 26 Presentation is classically described as the triad of: macroscopic hematuria: 60% flank pain: 40% palpable[radiopaedia.org]
  • This classic triad [8] is 1: haematuria , which is when there is blood present in the urine, 2: flank pain, which is pain on the side of the body between the hip and ribs, and 3: an abdominal mass, similar to bloating but larger.[en.wikipedia.org]
Macroscopic Hematuria
  • They usually occur in 50-70-year old patients and macroscopic hematuria occurs in 60% of the cases.[radiopaedia.org]
Polyuria
  • This results in hypercalcemia, possibly associated with fatigue, polyuria, polydipsia, and exsiccosis, nausea and vomiting, cardiac arrhythmia,hypertension and altered sensorium. Tumor cells may produce erythropoietin and provoke erythrocytosis.[symptoma.com]

Workup

As has been mentioned above, RCC does not necessarily provoke clinical symptoms until advanced stages of the disease and the formation of metastases. Nevertheless, RCC may be detected during early stages, incidentally in patients undergoing routine imaging procedures. Due to the tumor's propensity for metastatic spread, diagnostic measures should be taken to rule out the presence of mRCC in these patients. For this computed tomography scans of the thoracic cavity are usually carried out. This technique allows for the visualization of lung metastases and enlarged mediastinal lymph nodes. Similarly, abdomen and pelvis are examined. Here, spread to regional lymph nodes and to hepatic tissue may be observed. Neuroimaging and bone scans are not routinely performed unless clinical symptoms suggest metastases to the brain/bones. With regards to the latter, 18F-NaF-positron emission tomography/computed tomography has recently been proven significantly more sensitive than 99mTc-MDP bone scintigraphy [11]. Essentially, these same techniques are employed to assess the extension of mRCC. Additionally, tumor thrombi may be visualized using sonography or magnetic resonance imaging. As is the case with non-metastatic RCC, confirmation of the tumor type requires histopathological analyses with fine-needle aspirates or biopsy samples.

A thorough physical examination as well as laboratory analyses of blood samples are recommended to identify hematological and biochemical anomalies consistent with paraneoplastic syndrome. Hypercalcemia, hypertension and thromboembolism may contribute to mRCC-related morbidity and may thus require additional, symptomatic therapy. Urine sample analysis may reveal signs of urinary tract infection or hemorrhages.

Multiple Pulmonary Nodules
  • Multiple pulmonary nodules as described. Figure 5. Axial HASTE image showing apical and distal lateral involvement of the myocardium with the mass as well as juxtaposed precordial ECG leads representing ST-segment changes as they relate to the mass.[scmr.org]
Erythrocytosis
  • Tumor cells may produce erythropoietin and provoke erythrocytosis. Polycythemia has also been described in mRCC patients. mRCC may be accompanied by amyloidosis, although its pathogenesis remains unclear.[symptoma.com]
  • . [9] Other signs and symptom may include haematuria ; [8] loin pain; [8] abdominal mass; [9] malaise , which is a general feeling of unwellness; [9] weight loss and/or loss of appetite; [10] anaemia resulting from depression of erythropoietin ; [8] erythrocytosis[en.wikipedia.org]

Treatment

While partial or total nephrectomy is the treatment of choice for patients diagnosed with non-metastatic RCC, this procedure is not generally recommended for individuals suffering from mRCC. Here, systemic therapy preceded by cytoreductive nephrectomy or followed by resection of any residual tumors should be considered. There are no published guidelines and thus, the choice of an appropriate approach to treatment should be based on the number, location and resectability of metastases as well as on the patient's general condition [12].

With regards to systemic therapy, mRCC are usually resistant to cytotoxic chemotherapy, and cytokines IL-2 and interferon-α have been the mainstays of mRCC treatment for about two decades. Although use of these drugs has been associated with prolonging median survival times, response rates have remained below 20% [13]. Nowadays, monotherapy with IL-2 or interferon-α is no longer recommended for mRCC treatment, unless patient has pulmonary mRCC, clear cell subtype. [10].

More recently, kinase inhibitors axitinib, pazopanib, sorafenib, sunitinib, everolimus, lenvatinib plus everolimus and temsirolimus as well as bevacizumab plus interferon have been approved for mRCC treatment. These compounds are used for targeted cancer therapy if other therapeutic regimens fail to induce a satisfactory response. Sequential application of several compounds has repeatedly been carried out, and the interested reader is referred to an excellent review published recently.[14]. Similarly, the European Association of Urology emphasizes the need for sequential treatment due to insufficient efficacy of monotherapies and reduced tolerability of combined therapy. In general, treatment recommendations are based on prior risk assessment and determination of the histological subtype of RCC. Current guidelines may be revised elsewhere [10], but are likely to be updated in the near future.

Standard therapies are indicated to relieve symptoms associated with paraneoplastic syndrome.

Regular follow-ups are indispensable for an early diagnosis of recurrence.

Prognosis

Despite considerable advances in mRCC therapy, the disease is still associated with high morbidity and mortality. In 2003, median survival times of less than one year have been reported for mRCC patients [8]. According to that same study, less than 20% of affected individuals remained alive two years after diagnosis. However, the outcome varies depending on the organ affected by metastatic spread of RCC and on the resectability of tumors that don't respond to other therapeutic regimens. In this context, complete metastasectomy may increase median survival times to almost five years [9]. Renewed tumor growth is likely after incomplete resection of mRCC and while patients with recurrent pulmonary metastases are often able to undergo another surgery, this does not apply to those suffering from bone metastases [1]. Furthermore, survival times of patients diagnosed with clear cell carcinoma are shorter than those of individuals suffering from papillary and chromophobic neoplasms [3]. To summarize, RCC and mRCC account for about 100,000 deaths each year [4].

Etiology

Renal cell carcinoma (RCC) originates from proximal renal tubular epithelium. The etiology of the tumor is still largely unknown, but a series of risk factors have been identified [2]:

  • Cigarette smoking
  • Western-style diet
  • Overweight/obesity
  • Lack of exercise
  • Diabetes mellitus
  • Hypertension
  • Medical history of urinary tract infection
  • In women, parity and oophorectomy
  • Occupational and environmental exposure to chloroacetate, trichloroethylene, vinyl chloride
  • Mutations of genes encoding for glutathione S-transferases
  • Von Hippel–Lindau Disease, Birt-Hogg-Dubé syndrome

Some of these factors are mutually dependent, e.g., people adhering to a Western-style diet may be more prone to obesity. Evidence regarding the etiological role of gene variants is scarce, but patients carrying certain gene defects may be more susceptible to RCC after exposure to carcinogenic agents. To date, it is not known whether individual risk factors predispose for certain subtypes of RCC, namely clear cell, papillary, chromophobic and collecting duct RCC. Clear cell RCC are associated with a worse prognosis than papillary and chromophobic RCC, and this fact may be due to an increased propensity for metastatic spread in the former [3].

Epidemiology

RCC accounts for more than 90% of kidney tumors and approximately 3% of malignancies detected in adult patients [4]. The worldwide incidence of RCC has been estimated to 209,000 in 2006, while more than 300,000 new cases have been diagnosed in 2012 [5]. Although these values do not necessarily indicate a drastic increase in case numbers - disagreements may merely be owing to methodological differences - worldwide incidence rates have been reported to have increased by up to 3% per decade [4]. Higher incidence rates in developed countries may be ascribed to the aforementioned risk factors being more prevalent in the respective geographical regions [5]. People of all races and both genders may develop mRCC, although men are affected about twice as often as women. The disease is most commonly diagnosed in patients aged 40-60 years. Development of mRCC by young patients is often related to hereditary disorders predisposing for tumor growth.

Sex distribution
Age distribution

Pathophysiology

About a fourth of affected individuals present with metastatic renal cancer at the time of diagnosis.Distant metastases are most commonly located in the lungs (in more than 50% of mRCC cases), bones and liver (each more than 30%), and brain (about 5% of mRCC). Furthermore, mRCC may affect adrenal glands,thyroid, pancreas, skin and spinal cord as well as other tissues. These values imply that majority of mRCC patients suffer from multiple sites of mRCC. In fact, solitary metastases are encountered in only 5% of individuals diagnosed with mRCC [4].

RCC tumor cells may spread through blood vessels - primarily through renal veins and inferior vena cava - as well as the lymphatic system. Tumor thrombi may form within those vessels and in fact, such complications may be observed in up to 10% of mRCC patients [6]. mRCC have been shown to invade venous walls, although case reports on metastatic spread to venous vessels are rare. Nevertheless, tumor thrombi constitute reservoirs of tumor cells that may induce recurrence after treatment of mRCC. Administration of sunitinib may further increase the likelihood of thromboembolic events [7].

Prevention

Because smoking is a major risk factor for kidney cancer and mRCC, patients should be advised to stop tobacco consumption. Additionally, adherence to a healthy diet lowers the individual risk of overweight/obesity and related pathologies like diabetes mellitus and hypertension. If dietary adjustments are combined with regular exercise, patients may not only prevent renal neoplasms, but also a wide variety of other disease entities. Exposure to carcinogens should be reduced as much as possible, although evidence regarding a direct correlation between such substances and mRCC has not yet been provided.

People diagnosed with von Hippel-Lindau disease or other disorders known to predispose for tumor growth should be offered regular examinations. This may help to detect RCC in the early stages prior to metastatic spread.

Summary

Renal cell carcinoma (RCC) is the most common type of malignant tumor affecting the kidneys. RCC accounts for about 3% of malignancies diagnosed in adult patients and it has been estimated that more than 200,000 people develop RCC each year. About half of those patients develop metastatic renal cell carcinoma (mRCC). This condition may either be diagnosed at the time of detection of the primary tumor or at any time later, possibly after an apparently successful treatment of kidney cancer [1]. RCC most commonly metastasizes to regional lymph nodes, lungs, bones, liver and adrenal glands, but occasional metastasis to other organs has also been reported. While bone and brain metastases usually provoke clinical symptoms, this does not apply to the primary tumor, lymph node or pulmonary metastases. Patients suffering from RCC remain asymptomatic until advanced stages of the disease and the initial spread to lymph nodes or lungs may not be noted either. Consequently, wide-spread mRCC is more commonly detected than solitary metastases, and this condition negatively affects the patient's response to therapy, the resectability of tumor tissue and the associated prognosis.

Patient Information

Renal cell carcinoma is the most common malignancy originating from the kidney's tubular epithelium. The tumor is characterized by aggressive growth and propensity for metastatic spread. Additionally, patients do not typically develop any symptoms until advanced stages of the disease and thus, many suffer from metastatic renal cell carcinoma (mRCC) at the time of diagnosis. mRCC most commonly affects lymph nodes, lungs, bones, liver and brain, but may also be encountered in other organs. While non-metastatic tumors may be resected, surgical removal of tumor tissue is a major challenge if multiple organs are compromised. Consequently, mRCC patients often have to undergo systemic therapy. The prognosis of an individual patient depends on a variety of factors, namely on the organ(s) compromised by mRCC, the resectability of tumors that do not respond to other therapeutic regimens and on the tumor's histopathological properties. Recently, several compounds have been approved for mRCC treatment, and they may prolong survival times.

References

Article

  1. Ljungberg B. The role of metastasectomy in renal cell carcinoma in the era of targeted therapy. Curr Urol Rep. 2013; 14(1):19-25.
  2. Murai M, Oya M. Renal cell carcinoma: etiology, incidence and epidemiology. Curr Opin Urol. 2004; 14(4):229-233.
  3. Cheville JC, Lohse CM, Zincke H, Weaver AL, Blute ML. Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma. Am J Surg Pathol. 2003; 27(5):612-624.
  4. Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C. Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev. 2008; (3):193-205.
  5. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136(5):E359-386.
  6. Loh-Doyle JC, Patil MB, Daneshmand S. Renal cell carcinoma with inferior vena cava tumor thrombus and metastatic caval wall invasion. Urology. 2012; 79(2):e6-8.
  7. Lonergan MT, Kellehar F, McDermott R, Collins R. Ischaemic stroke in a patient on sunitinib. BMJ Case Rep. 2010; 2010.
  8. Flanigan RC, Campbell SC, Clark JI, Picken MM. Metastatic renal cell carcinoma. Curr Treat Options Oncol. 2003; 4(5):385-390.
  9. Alt AL, Boorjian SA, Lohse CM, Costello BA, Leibovich BC, Blute ML. Survival after complete surgical resection of multiple metastases from renal cell carcinoma. Cancer. 2011; 117(13):2873-2882.
  10. Ljungberg B, Bensalah K, Canfield S, et al. EAU guidelines on renal cell carcinoma: 2014 update. Eur Urol. 2015; 67(5):913-924.
  11. Gerety EL, Lawrence EM, Wason J, et al. Prospective study evaluating the relative sensitivity of 18F-NaF PET/CT for detecting skeletal metastases from renal cell carcinoma in comparison to multidetector CT and 99mTc-MDP bone scintigraphy, using an adaptive trial design. Ann Oncol. 2015; 26(10):2113-2118.
  12. Swanson DA. Surgery for metastases of renal cell carcinoma. Scand J Surg. 2004; 93(2):150-155.
  13. Curtis SA, Cohen JV, Kluger HM. Evolving Immunotherapy Approaches for Renal Cell Carcinoma. Curr Oncol Rep. 2016; 18(9):57.
  14. Albiges L, Choueiri T, Escudier B, et al. A systematic review of sequencing and combinations of systemic therapy in metastatic renal cancer. Eur Urol. 2015; 67(1):100-110.

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Last updated: 2018-06-21 18:44