this presentation was done during clinical rotation to department of urosurgery during MS general surgery residency.

1. RENAL CELL
CARCINOMA
DR GAGAN ADHIKARI
MS RESIDENT

2. EMBRYOLOGY
Pronephros—week 4; then degenerates.
Mesonephros—functions as interim kidney for 1st trimester; later contributes to male genital system.
Metanephros—permanent; first appears in 5th week of gestation; nephrogenesis continues through
weeks 32–36 of gestation.
• Ureteric bud—derived from caudal end of mesonephric duct; gives rise to ureter, pelvises, calyces,
collecting ducts; fully canalized by 10th week
• Metanephric mesenchyme (ie, metanephric blastema)—ureteric bud interacts with this tissue;
interaction induces differentiation and formation of glomerulus through to distal convoluted tubule
(DCT)

3. EMBRYOLOGY

4. ANATOMY
Coverings of Kidney
1. The fibrous capsule: This is a thin membrane which closely invests the kidney and lines the renal sinus.
Normally it can be easily stripped off from the kidney, but in certain diseases it becomes adherent and cannot be
stripped.
2. Perirenal or perinephric fat: This is a layer of adipose tissue lying outside the fibrous capsule. It is thickest at
the borders of the kidney and fills up the extra space in the renal sinus.
3. Renal fascia: This is a fibroareolar sheath which surrounds the kidney and the perirenal fat called as the fascia
of Gerota. It consists of an anterior layer or (fascia of Toldt) and a posterior layer (or fascia of
Zuckerkandl or fascia retrorenalis). It is strongest near the lower pole connect the renal fascia to the fibrous
capsule across the perirenal fat.
4. Paranephric fat

5. ANATOMY
• Arterial Supply: Usually there is one renal artery on each side, arising from the
abdominal aorta. Accessory renal arteries are present in 30% of individuals; they arise
commonly from the aorta.
• Venous Drainage: Veins emerge at the renal sinus and join to form the renal vein which
drains into the inferior vena cava.

6. ANATOMY
• Lymphatic Drainage: The lymphatics of the kidney drain into the lateral aortic nodes
located at the level of origin of the renal arteries (L2).
• Nerve Supply: The kidney is supplied by the renal plexus, an offshoot of the coeliac
plexus. It contains sympathetic (T10-L1) fibres which are chiefly vasomotor. The afferent
nerves of the kidney belong to segments T10 toT12.

7. Epidemiology
• RCC accounts for roughly 2.8% of adult cancers
• constitutes approximately 85% of all primary malignant renal tumors.
• occurs most commonly in the fifth to sixth decade
• has a male–female ratio of 2:1.

8. Epidemiology
• The incidence of renal cancer may vary based on race, with black men
demonstrating a higher incidence than in men of all other races.
• Black men may also have a higher likelihood of a subsequent RCC in the contralateral kidney
(Rabbani et al, 2002).
• Asians appear to have the lowest incidence of RCC (Miller, 1996).

9. Etiology
• Cigarette smoking is the only risk factor consistently linked to RCC by both
epidemiologic case-control and cohort studies (La Vecchia et al, 1990)
• RCC occurs in two forms, inherited and sporadic.
• In 1979, Cohen and colleagues described a pedigree with hereditary RCC
• in which the pattern of inheritance was consistent with an autosomal dominant gene with a balanced
reciprocal translocation between the short arm of chromosome 3 and the long arm of chromosome 8.

10. Etiology
• Most significant risk factors are smoking and tobacco chewing
• Other risk factors are
• obesity,
• hypertension,
• exposure to Asbestos, petroleum products and cadmium,
• chronic renal failure(specially due to analgesic nephropathy)

11. Etiology
• Von Hippel-Lindau disease is a familial cancer syndrome
• in which affected individuals have a mutation of chromosome 3p
• predisposition to develop tumors in multiple organs, including cerebellar hemangioblastoma, retinal
angiomata, and bilateral clear cell RCC.
• In 1993, Latif and colleagues identified the von Hippel–Lindau gene, leading to the detection of a
germ line mutation in approximately 75% of families affected by von Hippel–Lindau disease (Chen
et al, 1995).
• It has also been recognized that at least 50% of cases of sporadic clear cell RCC has mutations in
VHL gene (Gnarra et al, 1994).

12. Etiology
• Hereditary papillary renal carcinoma was described in 1994 and is characterized by a
predisposition to develop multiple bilateral renal tumors with a papillary histologic
appearance (Zbar et al, 1994).
• Acquired cystic disease of the kidneys is a well-recognized entity of multiple
bilateral cysts in the native kidneys of uremic patients (Reichard et al, 1998).
• The risk of developing RCC has been estimated to be >30 times higher in patients
receiving dialysis who have cystic changes in their kidney than in the general
population (Brennan et al, 1991).

13. Types
1. Clear cell carcinoma
2. Papillary carcinoma
3. Chromophobe renal carcinoma
4. Collecting duct (bellini duct) carcinoma
5. Medullary cell carcinoma

14. Clear cell carcinoma
• MC type of RCC, mainly sporadic
• Both sporadic and familial cases are associated
with loss of sequence on chromosome 3
either by translocation (3:6, 3:8, 3:11) or deletion
• This region harbors the VHL gene

15. Clear cell carcinoma
• Arise from proximal tubular epithelial cells
particularly of cortex
• Occurs as solitary unilateral lesion, often a
pseudocapsule is formed around tumor by
compression of surrounding tissue.
• Tumor cells are clear and contain glycogen & lipids
• Most are well differentiated.

16. Papillary carcinoma
• Characterized by papillary growth pattern.
• MC cytogenetic abnormalities are trisomies 7,
16, and 17.
• This is due to mutated MET gene on
chromosome 7.

17. Papillary carcinoma
−− Arise from DCT, can be multifocal and
bilateral
−− Typically hemorrhagic and cystic.
−− Papillary carcinoma is the MC type of RCC
in patients with dialysis associated cystic disease.
−− Composed of cuboidal and low columnar
cells.
−− Psammoma bodies may be present.

18. Chromophobe renal carcinoma
• Represent 5% of RCC, composed of cells with prominent
cell membrane and eosinophilic cytoplasm with a halo
around nucleus.
• Relative transparent cytoplasm with a fine reticular
pattern described as ‘Plant cell’ appearance.
• Associated with best prognosis

19. Chromophobe renal carcinoma
• These tumors exhibit multiple chromosome loss and
extreme hypodiploidy
• Loss of multiple chromosomes 1, 2, 6, 10, 13, 17, 21 and
Y.
• Arises from intercalated cells of collecting duct.
• Composed of pale eosinophilic cells often with a
perinuclear halo

20. Collecting duct (bellini duct) carcinoma
• Rarest type of RCC, composed of malignant cells enmeshed within a prominent fibrotic
stroma typically in medullary location.
• Arise from collecting duct cells in the medulla.
• Has got very aggressive course.

21. Medullary cell carcinoma
• is seen almost exclusively in association with sickle cell trait.

22. Pathogenesis
• RCCs are vascular tumors that tend to spread
• either by direct invasion through the renal capsule into perinephric fat and adjacent visceral structures
• or by direct extension into the renal vein.
• Approximately 25–30% of patients have evidence of metastatic disease at presentation.
• The most common site of distant metastases is the lung.
• However, liver, bone (osteolytic), ipsilateral adjacent lymph nodes and adrenal gland,
brain, the opposite kidney, and subcutaneous tissue are frequent sites of disease spread.

23. Symptoms and Signs
• The classically described triad of
• gross hematuria, flank pain, and a palpable mass
• occurs in only 7–10% of patients and
• is frequently a manifestation of advanced disease.
• Patients may also present with
• hematuria, dyspnea, cough, and bone pain that are typically
symptoms secondary to metastases.
• With the routine use of CT scanning for evaluation of
nonspecific findings, asymptomatic renal tumors are
increasingly detected incidentally (>50%).

24. Paraneoplastic Syndromes
• RCC is associated with a wide spectrum of paraneoplastic syndromes
including
• erythrocytosis,
• hypercalcemia,
• hypertension, and
• nonmetastatic hepatic dysfunction.
• Overall, these manifestations can occur in 10–40% of patients with RCC.

25. Paraneoplastic Syndromes
• In patients with RCC, the elevated erythrocyte mass is physiologically inappropriate
• Which may result either from enhanced production of erythropoietin from the tumor
• Or as a consequence of regional renal hypoxia promoting erythropoietin production from nonneoplastic
renal tissue (Hocking, 1987).

26. Paraneoplastic Syndromes
• Hypercalcemia has been reported to occur in up to 20% of patients with RCC (Muggia,
1990).
• Hypercalcemia may be due to production of a parathyroid hormone-related peptide that mimics the
function of parathyroid hormone (Strewler et al, 1987) or
• other humoral factors such as osteoclast-activating factor, tumor necrosis factor, and transforming growth
factor-alpha (Muggia, 1990).

27. Paraneoplastic Syndromes
• Hypertension associated with RCC has been reported in up to 40% of patients (Sufrin et
al, 1989)
• Renin production by the neoplasm has been documented in 37%.
• These typically refractory to antihypertensive therapy
• but may respond after nephrectomy (Gold et al, 1996).

28. Paraneoplastic Syndromes
• In 1961, Stauffer described a reversible syndrome of hepatic dysfunction in the absence
of hepatic metastases associated with RCC.
• Hepatic function abnormalities include elevation of alkaline phosphatase and bilirubin, hypoalbuminemia,
prolonged prothrombin time, and hypergammaglobulinemia.
• Stauffer’s syndrome tends to occur in association with fever, fatigue, and weight loss
• typically resolves after nephrectomy.
• The reported incidence of Stauffer’s syndrome varies from 3% to 20% (Gold et al, 1996).
• It may be due to overproduction of granulocyte macrophage colony stimulating factor by
the tumor (Chang et al, 1992).

29. Paraneoplastic Syndromes
• RCC is known to produce a multitude of other biologically active products that result in
clinically significant syndromes, including
• adrenocorticotropic hormone (Cushing’s syndrome),
• enteroglucagon (protein enteropathy),
• prolactin (galactorrhea),
• insulin (hypoglycemia), and
• gonadotropins (gynecomastia and decreased libido; or hirsutism, amenorrhea, and male
pattern balding) (Sufrin et al, 1986).

30. Paraneoplastic Syndromes
• The patients whose paraneoplastic metabolic disturbances fail to
normalize after nephrectomy
• suggests the presence of clinically undetectable metastatic disease
• these have very poor prognoses (Hanash, 1982).

31. Laboratory Findings
• laboratory abnormalities are
• lab findings of the various RCC paraneoplastic syndromes,
• anemia,
• hematuria, and
• an elevated sedimentation rate
• Anemia occurs in about 30% of RCC patients.
• Gross or microscopic hematuria can be seen in up to 60% of patients presenting
with RCC

32. Laboratory Findings
• The anemia in RCC
• is not secondary to blood loss or hemolysis
• is commonly normochromic.
• The serum iron and total iron binding capacity are usually low, as in the anemia of chronic
disease.
• Iron therapy is usually ineffective
• however, surgical removal of early-stage tumors usually leads to physiologic correction of the
anemia.
• The potential role of recombinant erythropoietin for patients with unresectable disease
represents an option.

33. Laboratory Findings
• complete cell blood count
• erythrocyte sedimentation rate
• serum creatinine
• glomerular filtration rate (GFR)
• liver function study, alkaline phosphatase, lactate dehydrogenase (LDH)

34. Laboratory Findings
• serum corrected calcium,
• coagulation study
• urinalysis.
• urinary cytology and possibly endoscopic assessment should be
considered
• for central renal masses abutting or invading the collecting system
• in order to exclude urothelial cancer

35. Ultrasonography
• able to further delineate a renal mass.
• It is approximately 98% accurate in
distinguishing simple cysts from solid
lesions.
• ultrasonographic criteria for a simple
cyst include
• through transmission,
• a well-circumscribed mass without internal
echoes
• and adequate visualization of strong
posterior wall .

37. CT Scanning
• more sensitive than USG for detection of renal masses.
• A typical finding of RCC on CT is a mass that becomes
enhanced with the use of intravenous contrast media.
• exhibits an overall decreased density in Hounsfield units compared
with normal renal parenchyma
• but shows either a homogeneous or heterogeneous pattern of
enhancement (increase in density of >15 Hounsfield units)
following contrast administration.

38. CT Scanning
• In addition to defining the primary lesion, CT
scanning is also the method of choice in staging the
patient
• by visualizing the renal hilum, perinephric space, renal vein
and vena cava, adrenals, regional lymphatics, and adjacent
organs.
• In patients with equivocal chest x-ray findings
• a CT scan of the chest is indicated.
• Patients who present with symptoms consistent
with brain metastases
• should be evaluated with either head CT or MRI.

39. CT Scanning
• Spiral CT with 3-dimensional reconstruction has become useful for evaluating
tumors
• before nephron-sparing surgery
• to delineate the 3-dimensional extent of the tumor
• and precisely outline the vasculature,
• which can aid the surgeon in preventing positive surgical margins (Holmes et al, 1997).
• Intraoperative ultrasonography is also often used
• to confirm the extent and number of masses in the kidney at the time of performing a partial
nephrectomy.

40. Renal Angiography
• With availability of CT scanners, the role of renal angiography in the
diagnostic evaluation of RCC has markedly diminished and is now
very limited.
• There remain a very few specific clinical situations in which
angiography may be useful
• for example, guiding the operative approach in a patient with an RCC in a solitary
kidney when attempting to perform a partial nephrectomy
• However, CT angiography or MR angiography can give better
information with less risk to the patient.

41. Radionuclide Imaging
• Determination of metastases to bones is most accurate by radionuclide bone scan
• although the study is nonspecific and requires confirmation with bone x-rays of
identified abnormalities
• to verify the presence of the typical osteolytic lesions.
• There is evidence that patients without bone pain and with a normal alkaline
phosphatase level
• have a very low incidence of bone metastases (Henriksson et al, 1992)
• thus a routine bone scan is not necessary in such patients.

42. Magnetic Resonance Imaging
• MRI is equivalent to CT for staging of RCC (Hricak et al, 1988).
• Its primary advantage is in the evaluation of patients with suspected
vascular extension.
• Prospective trials have demonstrated that MRI
• is superior to CT in assessing inferior vena caval involvement (Kabala et al, 1991) and
• is at least as accurate as venacavography (Horan et al, 1989).

43. Magnetic Resonance Imaging
• Recent studies using MRI angiography with
gadolinium or CT angiography have improved
vascular evaluation of renal neoplasms (Bluemke and
Chambers, 1995).
• MR angiography can also be used
• to delineate the vascular supply before planned
nephron-sparing surgery.

44. Positron Emission Tomography (PET)
• This technique allows the measurement of systemically administered
biochemical agents such as 18-fluoro-2- deoxyglucose (FDG), which can
accumulate in the kidney.
• Although FDG-PET scanning can yield false-positive results in some
patients with RCC (Bachor et al, 1996),
• it may be useful in monitoring response to systemic therapy in those with metastatic disease
(Hoh et al, 1998).

45. Positron Emission Tomography (PET)
• FDG-PET may also be more accurate than routine CT scanning in
detecting disease recurrence or progression,
• which may alter treatment decisions in up to 50% of cases (Ramdave et al, 2001).
• However, most recent studies suggest that FDG-PET is of insufficient
sensitivity to be useful for staging RCC.

46. Targeted Imaging
• The enzyme carbonic anhydrase IX (CA IX) is expressed at high levels in clear cell RCC.
• CA IX is expressed at low levels in the gastrointestinal mucosa, and biliary tract but not
in other normal tissues.
• CA IX is regulated by the VHL gene
• with loss of the VHL tumor suppressor gene (being very common in clear cell RCC)
• there is loss of regulation of CA IX expression
• CA IX expression is significantly increased.

47. Targeted Imaging
• This can be used to detect clear cell RCC using a radiolabeled monoclonal antibody scan
using the antibody G250 which targets carbonic anhydrase IX (Stillebroer et al, 2010).
• Up to 80% of clear cell RCC are found to express G250 antigen and in nearly imaging studies
(Oosterwijnk et al, 1993).
• Other renal tumors such as chromophobe and papillary RCC demonstrate very little CA IX expression.
• More recently an immuno-PET approach has been used combining the monoclonal
antibody to CA IX and a PET scan to better visualize renal lesions.
• In early studies, 94% of renal tumors were correctly identified using this approach (Divgi et al, 2007).

48. Fine-Needle Aspiration
• diagnostic approach of choice in those patients with clinically apparent
metastatic disease who may be candidates for nonsurgical therapy.
• Indications
• establishing a diagnosis in patients who are not surgical candidates,
• differentiating a primary RCC from a renal metastasis in patients with known primary cancers
of nonrenal origin, and
• evaluating some radiographically indeterminate lesions.
• to confirm the diagnosis of a neoplasm particularly in patients who may undergo observation
or percutaneous ablative therapy (Shah et al, 2005).

49. Fine-Needle Aspiration
• While core needle biopsies may be able to accurately diagnose malignancy in up to 100%
of cases >4 cm and 95% of cases <4 cm,
• this may require multiple cores for accuracy (Wunderlich et al, 2005).
• Rare reports of seeding of the needle tract have been reported but the risk of seeding is
reported to be <0.01% (Volpe et al, 2007).
• Recently, core biopsies of the primary renal mass have been more commonly utilized in
patients with metastatic disease (when biopsy of a metastatic site is not feasible),

50. Fine-Needle Aspiration
• The accuracy of needle core biopsies is reported to be >90% with sensitivity ranging
between 70–100% and specificity of 100% (Volpe et al, 2007).
• The accuracy of fine needle aspiration cytology of renal masses is reported to be slightly
lower mainly because of lower sensitivity. Specificity can still be high and close to 100%.

51. Instrumental and Cytologic Examination
• Patients presenting with hematuria should also be evaluated with cystoscopy.
• Blood effluxing from the ureteral orifice identifies the origin of bleeding from the upper
tract.
• Most renal pelvis tumors can be distinguished radiographically from RCC
• however, endoscopic evaluation of the bladder, ureters, and renal pelvis is occasionally helpful in making
a diagnosis.
• Urine cytologic study is rarely helpful in the diagnosis of RCC
• Cytologic study of urine with renal pelvis washing is frequently diagnostic in renal pelvis
tumors.

54. Tumor grade
• Histological grade is an independent factor correlating with
survival.
• Can be used for Clear cell, Chromophobe and papillary variety.
• Fuhrman’s system
• is the most widely used,
• generally adopted and
• is now recognized as the independent prognostic factor
for RCC generally and for clear cell RCC in particular.

55. MANAGEMENT
1. Localized RCC
2. Locally advanced RCC
3. Advanced/metastatic RCC
4. Recurrent RCC

56. Localised disease

57. Radical nephrectomy
• The prognoses of patients with stages T1–T3a disease are similar following radical nephrectomy.
• The goal is to achieve the removal of tumor and to take a wide margin of normal tissue.
• Radical nephrectomy includes
• en bloc removal of the kidney and its enveloping fascia (Gerota’s) including
• the ipsilateral adrenal,
• proximal one-half of the ureter, and
• lymph nodes up to the area of transection of the renal vessels

58. Radical nephrectomy
• Various open incisions provide optimal access for the
radical nephrectomy
• an anterior subcostal (unilateral chevron) or
• thoracoabdominal incision, and,
• occasionally, a midline incision or
• the classic flank incision.
• The likelihood of local recurrence after radical
nephrectomy is 2–3% (Itano et al, 2000).

59. Radical nephrectomy
• Gold standard treatment for localized RCC with contralateral normal kidney, adequate surgical margin
and is the preferred treatment if the tumor extends into the inferior vena cava.
• A radical nephrectomy includes a perifascial resection of the kidney, perirenal fat, regional lymph nodes,
and ipsilateral adrenal gland.
• Principles of Surgery
– Early ligation of renal artery and vein,
– removal of kidney including Gerota’s fascia,
– removal of ipsilateral adrenal gland,
– regional lymphadenectomy from crus of diaphragm to aortic
bifurcation.

60. Radical nephrectomy
• Open, laparoscopic, or robotic surgical techniques may be used to perform
radical nephrectomy.
• A laparoscopic approach to RN is now an established standard and should
be considered
• because it is associated with a more rapid recovery.
• Long-term outcomes data indicate that laparoscopic and open radical
nephrectomies have equivalent cancer-free survival rates.

61. Partial Nephrectomy (Nephron Sparing
Surgery)
Indications
• Bilateral RCC
• RCC in a solitary functioning kidney
• Unilateral RCC with contralateral kidney under threat of its future function
– Renal artery stenosis
– Chronic pyelonephritis
– Hydronephrosis
– Ureteral reflux
– Calculus disease
– Systemic disease such as diabetes
• Tumor less than 4cms with normal opposite kidney.
 Local tumor recurrence of 10% is reported.

62. Partial Nephrectomy
Advantages
• preserved renal function
• decreased overall mortality
• reduced frequency of cardiovascular events
• hereditary form of RCC, such as VHL disease, should also be considered for nephron-sparing therapy.
• in patients with T1a and T1b renal tumors (ie, up to 7 cm in greatest dimension) and a normal contralateral kidney
• partial rather than radical nephrectomy was associated with improved survival
Goals
• optimal locoregional tumor control while minimizing ischemia time to ideally less than 30 minutes.

63. Partial Nephrectomy
Essential steps in partial nephrectomy:
A. Temporary occlusion of the vascular pedicle and excision of the tumor with a rim of normal
parenchyma
B. Closure of the collecting system and ligation of transected vessels
C. Capsular reconstruction

64. Adrenalectomy
• Ipsilateral adrenal gland resection should be considered for patients with
• large upper pole tumors or
• abnormal-appearing adrenal glands on CT.
• Removal of the adrenal is unnecessary if the tumor is not in the upper pole, because adrenal involvement
is uncommon in this instance.
• Adrenalectomy is not indicated when imaging shows
• a normal adrenal gland or
• if the tumor is not high risk, based on size and location.

65. Radical lymphadenectomy
• Lymph node dissection for clinically negative lymph nodes (cN0) : Controversial
• Randomized study of lymphadenectomy versus controls at the time of renal surgery failed to show a
distinct advantage
• The clinical assessment of LN status is based on the detection of an enlargement of LNs either by
CT/MRI or intraoperative palpability of enlarged nodes.
• Less than 20% of suspected metastatic nodes (cN+) are positive for metastatic disease at
histopathological examination (pN+).

66. Radical lymphadenectomy
• Both CT and MRI are unsuitable for detecting malignant disease in nodes of normal
shape and size
• More recent studies including a randomized prospective study as well as a population-
based study failed to show any survival benefit that could be obtained by routinely
performing regional lymphadenectomy especially in patients with organ-confined disease
(Blom et al, 1999; Joslyn et al, 2005).

67. Embolisation
• In patients unfit for surgery, or with non-resectable disease, embolisation can control
symptoms, including visible haematuria or flank pain
• Preoperative renal artery embolization (angioinfarction) has been used in the past as a surgical
adjunct to facilitate radical nephrectomy
• there is no conclusive evidence that preoperative embolization actually decreases blood
loss or facilitates surgery,
• its use should be limited to patients with very large tumors in which the renal artery may
be difficult to reach early in the procedure.
• In addition, this technique may be useful to palliate patients with nonresectable tumors
and significant symptoms such as hemorrhage, flank pain, or paraneoplastic syndromes.

68. Active surveillance
• Elderly and comorbid patients with incidental small renal masses have a low RCC-specific mortality
• Active surveillance is defined as the initial monitoring of tumour size by serial abdominal imaging (US,
CT, or MRI) with delayed intervention reserved for tumours showing clinical progression during follow-
up.
• The concept of AS differs from the concept of watchful waiting;
• watchful waiting is reserved for patients whose comorbidities contraindicate any subsequent active
treatment
• and do not require follow-up imaging, unless clinically indicated.

69. Active surveillance
• One recent study noted a growth rate of 0–1.3 cm/year in 40 patients followed up for a mean
of 3.5 years (Bosniak, 1995),
• indicating that with careful follow-up, watchful waiting may be appropriate in selected
patients.
• Only one-third of small (<4 cm) renal masses are observed to increase in size over 2 years
with none experiencing disease progression (Volpe et al, 2004).
• This further suggests that at least initially observation is a reasonable option particularly for
older patients with comorbidities who may not be amenable to surgery.

70. Cryoablation and Radiofrequency ablation
• Additional therapeutic approaches being increasingly applied for the treatment of small, incidentally discovered renal lesions
include the use of
• cryoablation,
• high-intensity focused US, and radiofrequency ablation (Murphy and Gill, 2001).
• Cryoablation with liquid nitrogen or argon gas, either percutaneously using MRI guidance or via laparoscopic probes, has
proved to be feasible and effective in selected patients (Gill et al, 2000; Shingleton and Sewell, 2002).
• Radiofrequency ablation has also been accomplished via the percutaneous approach with minimal morbidity in small groups of
patients (Pavlovich et al, 2002).
• These approaches are particularly attractive in patients with single or multiple small lesions or older individuals with many
comorbidities.

71. Cryoablation and Radiofrequency ablation
• The long-term effectiveness of both radiofrequency ablation as well as cryoablation
appears to be acceptable (Kimura et al, 2010).
• It appears that cryoablation is superior to radiofrequency ablation in terms of long-term
cancer control.
• Bleeding, scarring of renal pelvis, and urine leak are among the commonly reported
complications with the ablative therapies.

72. EAU recommendations for the treatment of
localised RCC

73. Locally advanced RCC
Patients with locally advanced RCC usually present with pain, generally from invasion of the posterior
abdominal wall, nerve roots, or paraspinous muscles.
Surgical therapy like extended operations with en-bloc resection of adjacent organs are occasionally
indicated.
Complete excision of the tumor, including resection of the involved bowel, spleen, or abdominal wall muscles,
is the aim of therapy

74. Clinically positive lymph nodes (cN+)
• In the presence of clinically positive LNs (cN+), LND is always justified.
• However, the extent of LND remains controversial.
• A systematic review and meta-analysis attempted to evaluate the role of retroperitoneal LND in non-metastatic and mRCC
[334].
• The review included several studies which recruited patients at high risk of LN metastases, including cN1 patients.
• Lymph node dissection was not associated with any survival benefit.
• However, LND may provide additional staging information.
• A recent analysis also indicates that LND is not associated with improved oncologic outcomes in patients with radiographic
lymphadenopathy (cN1) and across increasing probability thresholds of pN1 disease

75. RCC with venous tumour thrombus
• Involvement of the venous system occurs in 4% to 10% of patients with RCC
• 45-70 % of patients with RCC and IVC thrombus can be cured with an aggressive surgical approach
including radical nephrectomy and IVC thrombectomy
• The risk of morbidity can be substantial for thrombi extending above the diaphragm and mortality rates
associated with radical nephrectomy and IVC thrombectomy have been reported to be as high as 5% to
10%.
• High-quality preoperative imaging (CT or MRI) should be obtained close to the anticipated surgery to
plan for and achieve intraoperative success.

76. RCC with venous tumour thrombus
Staging of the level of IVC thrombus is as follows:
I. adjacent to the ostium of renal vein;
II. extending up to the lower aspect of the liver;
III. involving the intrahepatic portion of the IVC but below the diaphragm;
IV. extending above the diaphragm.
• Level IV IVC thrombi have traditionally been managed with cardiopulmonary bypass and
hypothermic circulatory arrest, and this is still the preferred approach.

77. RCC with venous tumour thrombus
• significant adverse prognostic factor.
• Traditionally, patients with venous tumour thrombus undergo surgery to remove the kidney and
tumour thrombus.
• Aggressive surgical resection is widely accepted as the default management option for patients
with venous tumour thrombus.

78. Neo-adjuvant radiotherapy
• Rotterdam study
– Radical nephrectomy vs neo-adjuvant RT (30Gy/15# APPA) plus nephrectomy
– No overall survival or metastasis-free survival advantage (both 50% 5- year survival)
– No improvement in resectability
– Further study to 40Gy - still no advantage
• Swedish study
– Poorer 5-year survival with pre-op RT (47% vs 63%)

79. Adjuvant radiotherapy
• currently no evidence from randomised phase III trials that adjuvant therapy offers a survival benefit.
• Some early studies suggested advantage to post-op RT but poorly designed and reported
• Newcastle (UK) study
– Poorer survival with adjuvant RT (55Gy) vs surgery alone
• Copenhagen study
– Stage II/III disease
– No difference in RCC relapse
– Significantly more GI complications (44%) in RT group
– 19% of deaths attributed to RT complications

80. Advanced/metastatic RCC

81. Cytoreductive nephrectomy
• Indicated in patients with
– Severe hemorrhage,
– Severe pain,
– Paraneoplastic syndrome or compression of adjacent viscera
– Solitary metastasis can be resected and may show some survival advantage
• Therapeutic:
– Not curative but produce some long-term survivors.
– The possibility of disease-free survival increases after resection of primary tumor and isolated metastasis excision.
– to decrease tumor burden in preparation for subsequent therapy

82. Cytoreductive nephrectomy

84. Local therapy of metastases in metastatic RCC
• Resection of metastasis
– in pt. not relieved from palliative RT
– In solitary metastasis
• Spontaneous regression of metastasis
– < 1 % of cases
– only 4 (0.8%) of 474 patients in 9 series who underwent nephrectomy experienced regression of metastatic foci

85. Immunotherapy
• Interferon (IFN)
• Interleukin (IL -2)
• Systemic type of treatment used to improve the body’s natural defenses.
• Boosts the immune system and slows down the cancer growth
• Clinical response to immunotherapy seen in patients with
– Good performance status
– Had a prior nephrectomy
– Non bulky pulmonary or soft tissue metastasis
– Asymptomatic patient

86. Immunotherapy in metastatic RCC

87. Targeted Molecular Therapy
• In renal cell carcinoma patients, this type of therapy uses drugs that stop the new blood vessels from growing, and targets certain factors that
cause the cells to grow.
• Tyrosine kinase (TK) inhibitors block the intracellular domain of the VGEF receptor
– Sunitinib (Sutent)
– Sorafenib (Nexavar)
• Monoclonal antibody that binds circulating VEGF preventing the activation of the VEGF receptor
– Bevacizumab (Avastin)
• Mammalian target of rapamycin (mTor) inhibitors
– Temsirolimus (TMSR), Everolimus

88. Targeted Molecular Therapy
• Anti-VEGF TKIs are small molecules that are orally bioavailable.
• Currently FDA approved are sorafenib, sunitinib, and pazopanib.
• Anti-VEGF TKI administration requires significant expertise in managing toxicities, which for instance
include hypertension, diarrhea, rash, hand foot skin reactions, cardiac abnormalities, and many others.
• mTOR inhibitors(Temsirolimus, Everolimus) are another important class of agents with activity against
RCC. The mTOR pathway interacts with the VEGF pathway at the molecular level and is another
contributor of angiogenesis in RCC
• mTOR inhibitors can cause mouth sores, fatigue, pneumonitis, and hypertriglyceridemia among other
side effects

89. Targeted Molecular Therapy

90. Targeted Molecular Therapy

91. Follow up
• The sensitivity of chest radiography and US for small metastases is poor.
• The sensitivity of chest radiography is significantly lower than CT-scans, as proven in histology controlled
comparative trials.
• In low-risk tumours, surveillance intervals should be adapted taking into account radiation exposure and
benefit..
• When the risk of relapse is intermediate or high, CT of the chest, abdomen and pelvis should be performed.
• Surveillance should also include evaluation of renal function and cardiovascular risk factors.

92. Follow up
• Positron-emission tomography and PET-CT as well as bone scintigraphy should not be used in RCC surveillance, due to their
limited specificity and sensitivity.
• After injection of contrast medium, the risk of acute renal failure seems to be negligible in patients with a GFR > 20 mL/min
and chronic renal impairment.
• Stage T1 disease- yearly chest x-rays and liver and renal function tests.
• Stage T2 or T3 - more frequent follow-up of at least 3-month or 6-month intervals in the early postoperative period.
• Repeat CT scans of the abdomen should also be obtained,especially in those who have undergone partial nephrectomy, to rule
out local recurrence.