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The following module was designed following the objectives of the Oncology Goals and Objectives for Medical Students for kidney cancer. Information on epidemiology, risk factors, screening, presentation, diagnosis, and treatment for kidney cancer is provided. By the end of this module, the following objectives should be addressed:
The kidney is a retroperitoneal organ in the posterior abdominal area. It lies in close proximity to the duodenum, stomach, pancreas, liver, spleen, and colon. The kidneys are enveloped in a layer of perinephric fat. Further enclosing this is a layer of connective tissue known as the renal fascia, which also contains the adrenal glands. The renal fascia can be broken into the anterior portion, known as Gerota’s fascia, and a posterior portion, known as Zuckerkandl’s fascia. A final layer of paranephric fat surrounds the entire compartment (1).
The left and right renal arteries provide vascular supply to the kidneys. These arise inferior to the superior mesenteric artery and divide into anterior and posterior branches as they approach the kidney. The left and right renal veins, which sit just anterior to the renal arteries, provide venous drainage directly into the inferior vena cava. Of note, the left renal vein crosses posterior to the superior mesenteric artery and anterior to the abdominal aorta (1). Lymphatic drainage is via the hilar, abdominal para-aortic, and paracaval lymph nodes (2).
The functional unit of the kidney is known as the nephron. It contains a capillary network, known as the glomerulus, and a tubular network. The glomerulus acts to filter fluid from the blood. Thereafter, the filtrate travels through the tubular network which consists of the proximal tubule, loop of Henle, distal tubule, and collecting duct. The tubular network connects to the ureters, through which urine is excreted (3).
As filtrate travels through the renal system, there is selective reabsorption and secretion of electrolytes, water, and other metabolic substances based on the homeostatic demands of the body (3).
The kidney is responsible for the excretion of the body's metabolic waste products. These include urea, creatinine, uric acid, and products of hemoglobin and hormone breakdown (3).
The kidney contributes to the regulation of acid-base balance through selective secretion and resorption of hydrogen and bicarbonate (3).
The kidneys contribute to blood pressure regulation via selective reabsorption and secretion of sodium. Additionally, the kidney is responsible for release of renin, fundamental to the Renin-Aldosterone-Aldosterone System (RAAS), which results in blood pressure regulation (3).
Interstitial cells within the peritubular capillary bed of the renal cortex produce the hormone erythropoietin (EPO). EPO stimulates the differentiation of hematopoietic stem cells in the bone marrow into erythrocytes (red blood cells) (3).
The cells of the proximal tubule produce the enzyme 1-alpha-hydroxylase which converts 25-hydroxycholecalciferol (calcifediol) to 1,25-dihydroxycholecalciferol (calcitriol), which is the active form of the hormone Vitamin D (3).
Globally, there are 425 000 cases of kidney cancer diagnosed each year, and 137 000 mortalities. This corresponds to roughly 2% of malignancies (1,2,3). In 2019, there were an estimated 7200 Canadians diagnosed with kidney cancer: 4700 male and 2500 female, making up 4.2% and 2.3% of new cancer cases respectively. The lifetime incidence of kidney cancer is 1.9% for males and 1.1% of females (4).
The mortality rate of kidney cancer in Canada is 6.4% for males and 2.8% for females. In 2019 there were a projected 1250 male and 670 female deaths resulting from kidney and renal pelvis cancer (4).
Renal cell carcinoma (RCC) is associated with increasing age, with a median age at time of diagnosis of 64 (3). Additionally, RCC is more common among black, white, and non-hispanic populations, and less so amongst Asian and Pacific Islanders (3).
In adults, renal cell carcinoma (RCC) accounts for approximately 90-95% of kidney cancer (5). In contrast, there is a low incidence of RCC in children (2.6%). Instead, 95% of kidney cancer for those less than 15 years of age is a Wilms tumor (nephroblastoma) (6).
Smoking is an independent risk factor for Renal Cell Carcinoma (RCC). The relative risk (RR) is 1.31 for all smokers, 1.36 for current smokers, and 1.16 for those who have quit. In addition, increasing frequency of tobacco use is associated with more advanced disease (1).
Hypertension is an independent risk factor for RCC. A meta-analysis demonstrated a RR of 1.67, notably most of the studies included were done in males. In addition, they observed the following trend: every 10 mmHg increase in SBP and DBP was associated with a 10-22% increased risk of RCC regardless of sex (2).
Obesity is an independent risk factor for RCC. A prospective study of over 300 000 individuals demonstrated an increasing association between BMI and risk of RCC in both males and females: RR was 1.15 for those with a BMI of 22.5 - 25, 1.50 for those with a BMI of 25 - 27.4, 1.72 for those with a BMI of 27.5 - 29.9, 2.06 for those with a BMI of 30 - 34.9, and 2.56 for those with a BMI of > 35.In addition, they observed that any degree of obesity during an older age conferred an increased risk relative to the same degree of obesity at a younger age (3).
Renal disease has been tied to the development of various cancers through several suggested mechanisms: DNA damage, release of cytokines during dialysis, accumulation of carcinogenic agents, and chronic infections and inflammatory status (4). GFR less than 30 results in a 2 fold increased risk of renal cell cancer compared to GFR 60-89 (5). Progression to ESRD and dependence on dialysis increase the risk of developing ACKD, which confers 30 fold increased risk for RCC (6).
An international study on the association between occupational exposures and RCC demonstrated the following associations: Blast-furnace / coke-oven industry, RR: 1.7, Iron and Steel industries, RR: 1.6, Asbestos exposure, RR: 1.4, Cadmium, RR: 2.0, Dry-cleaning Solvents, RR: 1.4, Gasoline, RR: 1.6, and other petroleum products, RR: 1.6. Notably, they observed the duration of employment in the industry increased the risk of development (7).
Some analgesics have been shown to be independent risk factors for RCC. A prospective study on over 100 000 individuals demonstrated the following increasing association between regular use of nonaspirin NSAIDS (defined as >2 / week): RR was 0.81 for those using aspirin regularly for less than 4 years, 1.36 for those using aspirin regularly for between 4 and 10 years, and 2.92 for those using aspirin regularly for more than 10 years (8).
Case studies have demonstrated association between a rare subtype of RCC, MiTF/TFE translocation RCC, and prior exposure to cytotoxic chemotherapy regimens that included Cyclophosphamide, Cytarabine, Tioguanine, Etoposide, Daunorubicin, Dactinomycin, Vincristine, Doxorubicin, or Carboplatin (9).
There are several familial syndromes associated with development of RCC, which appear to account for 4-6% of cases of RCC (10). One of the most well known is Von Hippel-Lindau, an autosomal dominant syndrome that predisposes to RCC, pheochromocytoma, hemangiomas, and pancreatic cysts and tumours, and affects about 1 in 36 000 individuals (11,12). 25-45% of those with VHL will develop RCC, and often develop it in the second to fourth decade of life (12).
Other familial syndromes associated with RCC include: hereditary papillary RCC, hereditary leiomyomatosis and RCC, succinate dehydrogenase deficiency RCC, Birt-Hogg-Dube syndrome, tuberous sclerosis complex, and Cowden syndrome (10,12).
In a large retrospective analysis, chronic infection with Hepatitis C was demonstrated to be an independent risk factor for RCC with a hazard ratio of 1.77. (13).
Kidney stones may be an independent risk factor for RCC and Transitional Cell Carcinoma (TCC). In a large meta-analysis and systematic review, a history of kidney stones was shown to confer a RR of 1.76 of RCC and 2.14 for TCC. However, the authors note that the studies used in the meta-analysis varied highly in their methods and definitions (14).
Patients with sickle cell trait can develop a rare, and aggressive subtype of RCC known as renal medullary carcinoma. The mean age of diagnosis is 19 years, and prognosis is generally 12 months at most (10, 15).
Historically, kidney cancer had been suspected on the basis of the classic triad of palpable mass, gross hematuria, and flank pain. However, this triad is a marker of advanced disease, and carries a dismal prognosis, thus the nickname the “too late triad” (1). Due to recent advances in imaging, kidney cancer is more often diagnosed incidentally. Notably, incidental diagnosis of RCC between 1971 - 2010 increased from 7% to 57% (2).
Invasion of the kidney cancer into the collecting system may result in hematuria. Likewise, RCC can invade into the venous system, of which the estimated prevalence is 4-10% (1). Obstruction of the gonadal vein can result in varicocele, while invasion into the IVC can produce a variety of symptoms including: edema, ascites, hepatic dysfunction (thought to be from budd-chiari syndrome), and pulmonary embolism (3).
Paraneoplastic syndromes are estimated to be found in 10-20% of patients with RCC. They are diverse and numerous and on occasion may be the only presenting symptom of a patient with a RCC (1). Several of the paraneoplastic syndromes are the result of pathological activation of normal kidney functions. The following are the most common examples:
Anemia occurs with surprising frequency in RCC, estimates placing the rates at between 29-88%, with increasing rates as the disease progresses (4). The anemia is suspected to be secondary to poor nutritional status and the presence of chronic disease rather than abnormalities in red blood cells or bone marrow (5).
Stauffer’s Syndrome is an observed phenomenon occurring in 3-20% of those with RCC. In Stauffer’s syndrome there are serum elevations in liver enzymes and abnormal levels of hepatic synthesis products in the absence of hepatic metastasis. Clinically, there may be hepatomegaly (5).
Hypercalcemia is estimated to be present in between 13%-20% of patients with RCC (1,5). RCC is thought to be one of the malignancies with the greatest incidence of hypercalcemia (6). It can result from either a paraneoplastic phenomena, or from osteolytic bone metastases. The paraneoplastic phenomena arises from tumor production of parathyroid hormone related protein (PTHrP). PTHrP binds to the PTH receptor and results in increased calcium reabsorption from the bone and increased reabsorption of calcium from the kidneys (5,6).
Polycythemia, specifically “absolute polycythemia,” refers to an increase in the number of red blood cells (RBC) in blood. This phenomenon occurs in approximately 1 - 8% of patients with RCC. It is thought to be mediated by neoplastic tumor production of erythropoietin (EPO). Interestingly, ectopic EPO is found in 66% of cases of RCC, but it may be produced in an inactive form, hence the lower rates of actual absolute polycythemia (5).
Hypertension is another paraneoplastic syndrome commonly associated with RCC. Age matched controls showed an incidence of about 20% (5). There are several purported mechanisms for hypertension in RCC. These include increased renin production, ureteral or parenchymal compression, presence of an AV fistula within the tumor, and eventual renal artery stenosis from compression of the renal artery (1,5).
Constitutional symptoms refer to a cluster of symptoms affecting a diverse range of body systems, and are seen in approximately 33% of those with RCC. These symptoms commonly include fever, weight loss, anorexia, and fatigue. In particular, fever has been highlighted as a relatively frequent occurrence in those with RCC with rates of between 20-30%. In RCC constitutional symptoms are suspected to be mediated by elevated levels of cytokines, namely TNF-alpha and IL-6 (5).
Although early diagnosis optimizes patient care, there are currently no established screening guidelines for the general population. This is due to the low incidence of kidney cancer and the high cost of imaging (1,2). However, screening is recommended for target populations. These include groups such as ESRD with ARCD, patients with genetic syndromes such as VHL, HNPCC, and Birt-Hogg Dube, and patients with tuberous sclerosis (1,2). Further prediction models based on established risk factors need to be created to identify the individuals who would benefit most (3).
There are two commonly used classification systems to classify a Renal Mass.
For purposes of this overview renal masses have been divided into benign and malignant, with some mention of their radiographic features. Several tree diagrams are included which indicate a potential approach.
The most common benign renal lesions are renal cysts, which may represent approximately 65% of renal masses (1,2). The prevalence of renal cysts is estimated at about 10%, with risk factors for developing including increasing age, male sex, hypertension, and renal dysfunction (1,3). Importantly, though frequently asymptomatic, renal cysts can present with abdominal and flank pain, palpable mass, and hematuria which are symptoms identical to malignant lesions (4).
While often benign, renal cysts can be malignant, and so they are often distinguished using the Bosniak renal cyst classification system into five separate categories (I, II, IIF, III, IV). A benign simple cyst (categories I and II) is one with a thin wall without septa, calcifications, or solid components. On radiologic evaluation it does not enhance and has the density of water. Benign simple cysts do not require follow up (5). In contrast, complex renal cysts (categories IIF, III, and IV) do require follow up. Indicators of malignancy are: septa with measurable enhancement, calcifications, and soft-tissue components of the cyst (5).
Angiomyolipoma is a benign solid tumor that consists of blood vessels, smooth muscle tissue, and adipose tissue. Angiomyolipomas arise sporadically 80% of the time, with the other 20% associated with genetic disease - most commonly tuberous sclerosis. Overall prevalence is estimated somewhere between 0.2% to 0.6%, and they are more commonly seen in female populations (6,7).
Unlike many other benign renal masses, angiomyolipoma can frequently be diagnosed via CT or MRI imaging on the basis of macroscopic fat (1). Commonly, these can be followed with active surveillance, however if greater than 4cm they have an increased risk of spontaneous bleeding so treatment may be considered (8).
Oncocytoma is a benign solid tumor. It makes up to 25% of renal masses below 3cm, and roughly 75% of all benign renal tumors (9,10). They can represent a diagnostic challenge as they can be difficult to differentiate from a RCC.
On pathological analysis, due to their high eosinophilic appearance they are hardest to distinguish from a eosinophilic chromophobe version of RCC (9). Radiographically, oncocytomas may have a characteristic central stellate scar; however, they cannot always be reliably distinguished from RCC (11). As a result oncocytomas are most often surgically removed, though there is some evidence that active surveillance for lesions less than 4cm may be an option (10).
Renal adenomas can be considered papillary or metanephric.
By definition papillary adenomas are small lesions less than 0.5cm (12). However, there is some thought that it may represent a premalignant lesion for papillary RCC (1). As a result, they should be carefully observed.
Metanephric Adenomas are rare epithelial neoplasms measuring between 3cm - 6cm with a female predisposition (1,12). Though frequently asymptomatic, these too can present with similar features to RCC such as hematuria, flank pain, palpable mass, and polycythemia (1). Radiographically there are not always enough features to establish a diagnosis so a biopsy is sometimes performed, which can help distinguish from the similar appearing Wilms tumour and papillary RCC. If the diagnosis is made, nephron sparing surgery can often be considered (1).
Malignant diagnoses of a renal mass include RCC, urothelium based cancers, sarcomas, nephroblastic tumours, carcinoma associated with neuroblastoma, and metastases. By far, the vast majority of malignant renal masses in adults are RCC (90-95%), which can be further subdivided based on histology. In contrast, RCC makes up a small percentage of childhood tumors with the majority being Wilms or neuroblastoma (1). The focus of this article will be primarily on renal cell carcinoma and the various subtypes.
Clear cell RCC is estimated to represent 70-80% of all RCC. This malignancy arises from the lining of the proximal convoluted tubule and is composed of cells with clear or granular cytoplasm, hence the name (13).
Clear cell RCC occurrence patterns include: sporadic and hereditary. The most common is sporadic, accounting for 95% of cases (13). The remaining 5% of clear cell RCC have associations with inherited, genetic mutations. The most common amongst these is von Hippel-Lindau disease (VHL). VHL is an autosomal dominant multisystem neoplasm disorder that arises secondary to the deletion of the VHL gene, a tumor suppressor gene on chromosome 3 (14). Approximately two thirds of patients with VHL develop clear cell RCC (15). Interestingly, 98% of all cases of clear cell RCC, independent of occurrence pattern, arise secondary to loss of sequences on chromosome 3, and 92% of sporadic clear cell RCC have mutations to the VHL gene (14).
With respect to radiographic characteristics, clear cell RCC tends to have the following characteristics: heterogeneous appearance (92%), poorly marginated (>50%), and high T2 weighted signal (>89%) (16). In addition, they may possess calcifications (1).
Papillary RCC is estimated to represent 5-10% of all malignant renal masses. This malignancy arises from renal tubular epithelium and is characterised by papillary and tubulopapillary architecture (17). There are two subtypes of papillary RCC (type 1 and type 2) which can be distinguished based on histologic appearance, occurrence patterns, and prognosis (14).
The majority of cases of Type 1 Papillary RCC occur sporadically, but a hereditary form does exist called hereditary papillary RCC syndrome that has been linked to an abnormality with the MET proto-oncogene on chromosome 7. Type 1 papillary RCC is known to confer a more favorable prognosis (14).
Type 2 Papillary RCC is more commonly associated with hereditary syndromes and patterns of occurrence. Specifically, Type 2 Papillary RCC is associated with Hereditary Leiomyomatosis, and mutations of the FH tumor suppressor gene. It can also occur sporadically but less often. Type 2 Papillary RCC is known to confer a worse prognosis (14).
Papillary RCC may have the following imaging characteristics: homogenous appearance (67%), well marginated (84%), and low T2 weighted signal (92%) (16).
Chromophobe RCC is estimated to represent 3-5% of all malignant renal masses. This malignancy arises from intercalated cells of the collecting system. Chromophobe RCC occurrence patterns include: sporadic and hereditary. It is most commonly associated with Birt-Hogg-Dube syndrome, an autosomal dominant inherited cancer syndrome characterised by mutations in the FLCN gene. Chromophobe RCC tends to confer an excellent prognosis (14).
Chromophobe RCC may have the following imaging characteristics: a central stellate scar, exclusive to chromophobe RCC and oncocytoma, well marginated (84%) (16).
Unlike adults, where RCC is the most predominant kidney cancer, a nephroblastoma (known colloquially as a Wilms tumor) accounts for the majority of pediatric kidney cancer. For children less than 15 years of age, Wilms tumor represent 95% of all kidney cancer, with RCC only accounting for 2.6%. Most commonly this tumor is diagnosed within the first 5 years of life (19).
The genetics of Wilms tumor has been thoroughly studied, and it appears that it arises primarily from somatic mutations as well as from some germline mutations, many of which affect tumor suppressor genes. There are several congenital syndromes associated with a Wilms tumor including WAGR (wilms tumor, aniridia, genital abnormalities, mental retardation), Beckwith-Wiedman syndrome, and Denys Drash syndrome among others (1).
Clinically, a Wilms tumor is most often incidentally found as an asymptomatic mass. However, children can present with abdominal pain, fever, hematuria, and/or hypertension. There are several prognostic factors for a Wilms tumor, with tumor histology being the more important; however, younger age tends to have a better outcome as well. Treatment is often multimodal, involving a combination of chemotherapy, radiation, and surgery. Overall prognosis can vary based on the prognostic determinants (20).
While key malignant and benign renal masses have been identified, it is important to consider some of the other differentials which can present with similar symptoms. These include, but are not limited to, hydronephrosis, nephrolithiasis, and neuroblastoma for pediatrics.
The following classification based on radiographic features provides a broad overview of imaging characteristics. There is detailed information pertaining to individual lesion characteristics available elsewhere.
Notably, within the radiographic features diagram a mass may fall under multiple categories. For example, an Angiomyolipoma can be: multifocal, fat containing, and strongly enhancing.
In patients who present with clinical signs and symptoms suggestive of a RCC discussed above, diagnostic evaluation may include a CBC, urinalysis, comprehensive metabolic panel, imaging studies, and biopsy (1).
In all patients in whom the diagnosis of a renal mass, such as RCC, is suspected imaging is highly relied on.
CT is better diagnostically, however sometimes a renal US is performed first to differentiate a simple cyst from a complex cyst or other solid renal mass. Any complex cyst or solid renal mass requires CT imaging (1). The specific type of CT imaging may influence the diagnostic accuracy (abdominal CT versus dedicated renal CT). CT has been found to be about 90% sensitive for the diagnosis of a small renal mass (2). In the event that the CT is inconclusive or the patient has contraindications to CT,,an MRI is an appropriate alternative. MRI may be better for small renal tumors less than 2cm, or analysis of local invasion into adjacent structures (2,3).
For patients with a confirmed renal mass, a biopsy may be indicated, which provides a histological diagnosis in 80-90 % of cases (4). The standard approach is a percutaneous renal biopsy, which can be guided via imaging such as ultrasound, fluoroscopy, or CT. Notably, a biopsy of the kidney is quite invasive and requires a high degree of precision and operator skill and confers a risk of complications associated with the procedure (5). Further, since renal biopsies are not always diagnostic they should be used judiciously and only considered if they will alter subsequent management. Some potential considerations for renal biopsy are as follows (1,6,7)
Of note, a renal mass biopsy is not indicated for young health patients who do not want to accept the limitations of a biopsy, and for older frail patients who will be managed the same regardless of biopsy findings (1,7).
The following is the current staging system used to describe all variants of RCC.
When considering the treatment options for RCC, the first distinction that has to be made is between localized and advanced RCC.
A general definition used for “localized cancer” is one that is limited to the tissue or organ where it began and has not spread to nearby lymph nodes or other organs (1). This equates to overall stage I-II.
A general definition used for “advanced cancer” is one that is unlikely to be cured or controlled by treatment secondary to features such as: spread to surrounding lymph nodes, tissues, or other organs (1). This equates to overall stage III-IV.
See Table 6 below for treatment options on the basis of stage.
For patients who present with localized kidney cancer, there are several available modalities of treatment, which include surgical, thermal ablation, and active surveillance. Treatment modalities are recommended on the basis of patient and tumor factors (2).
Historically, an open radical nephrectomy included ligation of the renal artery and vein, removal of the kidney including gerota's fascia, ipsilateral adrenalectomy, and extended lymph node dissection. However, in modern practices this procedure typically omits an ipsilateral adrenalectomy and there is some discussion on the requirement of a lymph node dissection (1,2).
The main indications for an open radical nephrectomy include: a larger tumor (greater than 12cm), local advancement of the tumor, bulky adenopathy, and a tumor thrombus. Advantages include effective removal of the tumor and surrounding tissue, while disadvantages include surgical morbidity and reduction in renal function (35 % decrease in GFR) (1).
Laparoscopic approaches are able to include all the essential steps of an open nephrectomy, with the advantages of decreased pain and morbidity as well as a quicker recovery time. Like an open nephrectomy, minimally invasive nephrectomy also results in a reduction in renal function (35% decrease in GFR). Primarily, this approach is used for tumors 10-12cm in size (1).
An open partial nephrectomy removes the tumor with the aim of preserving normal functioning kidney tissue. The main benefit is preservation of renal function. This is especially important for individuals with diabetes, hypertension, baseline CKD, an abnormal contralateral kidney, solitary kidney, bilateral RCC, or any other conditions which may portend future renal dysfunction. Disadvantages include surgical morbidity and a greater risk of local recurrence. Indications are for small to medium sized tumors (around 7cm) where nephron sparing is important (1).
A partial nephrectomy can also be performed laparoscopically. Like the open approach, this maximizes preservation of renal function. Additionally, there is the added benefit of less pain, morbidity, and a quicker recovery time. The primary disadvantage is there may be increased urologic complications for high complexity tumors, and further there may be higher recurrence rates. This approach is used for small tumors (less than 5cm) that are of low to moderate complexity (1).
Thermal ablation has emerged as a new kidney sparing approach for small tumors (less than 3cm). The main indications are for patients who are poor surgical candidates but don’t want active surveillance, patients with multifocal disease, and patients with local recurrence of disease. Its main disadvantage is a higher rate of local recurrence (1).
Some data suggests that small masses exhibit linear growth and have a low rate of metastasis. Further, since surgery isn’t a benign intervention the role of active surveillance has emerged as a viable option for some patients. This approach is primarily used for patients with renal masses less than 2cm, complex cysts, and poor surgical candidates with limited life expectancy (1). These patients are followed closely with serial imaging (1).
The management of advanced renal cell carcinoma is complex and differs based on the subtype. However, due to advances in pharmaceutical treatment, median survival of metastatic disease has increased (3). Some potential modalities will be briefly discussed below.
Prior to development of targeted therapies, immunotherapy with interferon-alpha and high dose IL2 were the standards of treatment of metastatic disease. However, these treatments alone only benefited a small population of patients and are quite toxic (1,3).
More recent immunotherapy options include programmed cell death 1 (PD-1) inhibitors such as Nivolumab, which is a checkpoint inhibitor that acts by stimulating antitumor immunity. It has been shown to be effective and has a relatively benign toxicity profile which may be beneficial for combination approaches (1). Notably, a recent trial combining Nivolumab and Ipilimumab (a monoclonal antibody approved for treatment of metastatic melanoma) found favourable results when compared against first line Anti-VEGF drug Sunitinib (4).
The vascular endothelial growth factor pathway has emerged as a targeted pathway option for treatment of RCC. A large number of RCC’s have a mutation in the VHL gene which results in up regulation of VEGF, thus promoting angiogenesis. Currently, there are two anti-VEGF approaches: tyrosine kinase inhibitors (sunitinib, pazopanib, sorafenib, and axitinib) and monoclonal antibodies (bevacizumab). These treatment modalities work well for clear cell RCC (1).
In addition to targeting the VEGF receptor, multi-targeted TK inhibitors (cabozantinib and lenvatinib) also target other proteins such as ME and AXL (1). A 2017 clinical trial comparing cabozantinib to sunitinib for patients of poor or intermediate risk metastatic RCC showed some benefit with cabozantinib (5).
Mammalian Target of Rapamycin (mTOR) is a molecule involved in tumor promoting pathways, one of which is VEGF.. The mTOR inhibitors (temsirolimus and everolimus) are used for poor-risk patients. It appears that VEGF targeted therapy is superior to the mTor inhibiting agents (1).
While RCC was previously considered to be a “Radio-resistant” malignancy, new techniques in the delivery of radiation have begun to change this. Stereotactic Body Radiotherapy (SBRT) also known as Stereotactic Ablative Radiotherapy (SABR) is a radiation therapy technique in which radiation therapy can be delivered at very high doses in very precise locations achieving in many cases permanent tumor control. In the context of RCC SBRT the research thus far has shown promising results particularly for advanced stage malignancy (7). Trials are now taking place widely to gain a better understanding of the long term benefits of this treatment. Results have been promising (8).
The prognosis of kidney cancer is quite variable and depends on the patient risk factors, subtype, and stage at presentation.
Routine follow-up is recommended at all stages of kidney cancer. The stage of the cancer and type of treatment is used to determine the types and the frequency of assessments. Follow up typically includes history, physical, metabolic panel, renal function, and forms of imaging.
The following tables are adapted from the NCCN Physician guidelines for Kidney Cancer.
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