In details about staging and treatment regarding renal cell carcinoma

2. Staging and Treatment of Renal Cell
Carcinoma
Dr. Bikash Chandra Sah.
JR General Surgery.

4. Screening
• RCC remains primarily a surgical disease
requiring early diagnosis to optimize the
opportunity for cure.
• Primary factor that limits the widespread
implementation of screening for RCC is the
relatively low incidence of RCC in the general
population

5. Risk factor for RCC
General
 Male gender,
 Increased age, and
 Heavy tobacco use.
 Generalized screening would be difficult to
justify because the increase in relative risk
associated with each of these factors is at best
twofold to threefold.

6. Targeted population risk factor
Patients with
 End-stage renal disease (5- to 20-fold higher than that in the general population)
 Acquired renal cystic disease,
 Tuberous sclerosis, and
 Familial RCC( Molecular screening, C-MET
protooncogene mutation like others)
 Renal transplant recipients remain at high risk for RCC
in the native kidneys, with detection in between 1.4% and 2.3% of
patients within 3 years of transplantation.
 Patients suspected of having von Hippel-Lindau disease,
or the appropriate relatives of those with documented
disease.

7. Investigators at the National Institutes
of Health have recommended that such
patients be evaluated with
(1) Annual physical examination and ophthalmologic
evaluation beginning in infancy;
(2) Estimation of urinary catecholamines at the age
of 2 years and every 1 to 2 years thereafter;
(3) MRI of the central nervous system biannually
beginning at the age of 11 years;
(4) Ultrasound examination of the abdomen and
pelvis annually beginning at the age of 11 years,
followed by CT every 6 months if cysts or tumors
develop; and
(5) Periodic auditory examination.

9. Staging

10. Staging.
• Until the 1990s the most commonly used staging
system for RCC was Robson’s modification of
the system of Flocks and Kadesky.
• Limitations of this classification scheme are
– Tumors with lymphatic metastases, a very poor
prognostic finding, were combined with those with
venous involvement, many of which can be treated and
potentially cured with an aggressive surgical approach.
– The extent of venous involvement was not delineated
in this system, and
– Tumor size, an important prognostic parameter, was
not incorporated.

11. • TNM staging classically is defined by the most
advanced feature demonstrated by the tumor,
yet important prognostic information can be lost
in the process
• Systemic symptoms such as
– Significant weight loss (>10% of body weight),
– Cachexia, or
– Poor performance status at presentation all suggest
advanced disease, as do physical examination
findings of a palpable mass or lymphadenopathy.
– A non reducing varicocele and lower extremity
edema suggest venous involvement.

12. Significant anemia, hypercalcemia, abnormal liver
function parameters or sedimentation rate, or elevated
serum alkaline phosphatase or lactate dehydrogenase
level all point to the probability of advanced disease.
Radiographic staging of RCC by high-quality
abdominal CT scan and a routine chest
radiograph:

13. CT Scan.
• Enlarged hilar or retroperitoneal lymph nodes
(2 cm or more in diameter),
• But, this should be confirmed by surgical
exploration or percutaneous biopsy if the
patient is not a surgical candidate.
• Many smaller nodes prove to be
inflammatory rather than neoplastic and
should not preclude surgical therapy.

14. • The sensitivities of CT for
detection of renal venous
tumor thrombus and IVC
involvement are 78% and 96%,
respectively .
• CT findings suggestive of
venous involvement include
– Venous enlargement,
– Abrupt change in the caliber
of the vein,
– Filling defects.

15. • patients with right-sided tumors produce Most
false-negative findings because of short
length of the vein and the mass effect from
the tumor combine to make detection of the
tumor thrombus difficult.
• Venacavography is now best reserved for
patients with equivocal MRI or CT findings or
for patients who cannot tolerate or have other
contraindications to cross-sectional imaging.

16. Metastatic evaluation in all cases should include
– Routine chest radiograph,
– Systematic review of the abdominal and pelvic CT or MRI, and
– Liver function tests.
– Bone scintiscan can be reserved for patients with elevated serum
alkaline phosphatase, bone pain, or poor performance status
– chest CT scan for patients with pulmonary symptoms or an
abnormal chest radiograph .
– Patients with locally advanced disease, enlarged retroperitoneal
lymph nodes, or significant comorbid disease may mandate more
thorough imaging to rule out metastatic disease and to aid in
treatment planning.
– Positron emission tomography (PET) has also been investigated for
patients with high risk of metastatic RCC.
• Biopsy of the primary tumor and/or potential metastatic sites is also
selectively required as part of the staging process.

18. • Five year survival rate of Renal Cell Cancer.

21. Other factor like
Patient-related factors such as:
• Age,
• CKD, and
• Other comorbidities have a significant impact
on overall survival and should be a primary
consideration during treatment planning for
patients with localized RCC
• Compromised prognosis in patients with
presumed localized RCC include systemic
symptomatic

22. Pathologic staging
Pathologic stage has proved to be the single
most important prognostic factor for RCC.
• Renal sinus involvement is classified along with
perinephric fat invasion as T3a are higher risk
of metastasis because of access to the venous
system.
• Collecting system invasion has also been
shown to confer poorer prognosis in otherwise
organ-confined RCC.

23. • Several studies demonstrate 5-year survival
rates of 70% to 90% for organ-confined disease
and document a 15% to 20% reduction in
survival associated with invasion of the
perinephric fat.
• Patients with direct or metastatic ipsilateral
adrenal involvement,
– Found in 1% to 2% of cases,
– Suggesting a hematogenous route of dissemination
or a highly invasive phenotype.
– Eventually succumb to systemic disease progression
with poor prognosis.

24. Venous involvement
• Once thought to be a very poor prognostic
finding for RCC,
• Several reports demonstrate that many patients
with tumor thrombi can be salvaged with an
aggressive surgical approach.
• These studies document 45% to 69% 5-year
survival rates for patients with venous tumor
thrombi as long as the tumor is otherwise
confined to the kidney.

25. • Patients with venous tumor thrombi and
concomitant lymph node or systemic
metastases have markedly decreased survival,
and those with tumor extending into the
perinephric fat have intermediate survival.
• Direct invasion of the wall of the vein appears
to be a more important prognostic factor than
level of tumor thrombus and is now classified
as pT3c independent of the level of tumor
thrombus

26. • The major drop in prognosis comes in patients
whose tumor extends beyond the Gerota fascia to
involve contiguous organs (stage T4) and in
patients with lymph node or systemic metastases
• Lymph node involvement has long been recognized
as a dire prognostic sign because it is associated
with 5- and 10-year survival rates of 5% to 30% and
0% to 5%,
• Systemic metastases also portend a particularly
poor prognosis for RCC, traditionally with 1-year
survival of less than 50%, 5-year survival of 5% to
30%, and 10-year survival of 0% to 5%.
• Patients presenting with synchronous metastases
fare worse.

27. Tumor size
• An independent prognostic factor for both
organ-confined and invasive RCC.
• Larger tumors are more likely to exhibit clear
cell histology and high nuclear grade, and both
of these factors correlate with a compromised
prognosis.

29. Nuclear grade and histologic subtype
• RCC have been proposed on the basis of nuclear
size and morphology and presence or absence of
nucleoli.
• Nuclear grade has proved in most cases to be an
independent prognostic factor
• Histologic subtype also carries prognostic
significance.
– The presence of sarcomatoid differentiation or
collecting duct, renal medullary, or unclassified
histologic subtype denotes a poor prognosis.

30. • The SSIGN score can be used to estimate
cancer-specific survival based on TNM stage,
tumor size, nuclear grade, and presence of tumor
necrosis (Frank et al, 2002).
• The SSIGN score has been validated in
multiple data sets,
• But the inclusion of histologic necrosis as a
predictor limits its clinical usefulness.

31. Nutshell
• RCC prognosis depends on clinical presentation,
TNM staging, Histologic grading and other factor
like age, stages of CKD, other comorbidities.
• Pathologic stage has proved to be the single
most important prognostic factor for RCC
• organ confined RCC have better prognosis in
comparison to involvement to adrenal gland,
perinephric fat and collecting system
involvement .
• If Venous thrombus or IVC involved thrombus
level and invasion of wall determine prognosis

32. • Lymph node invasion, systemic metastasis ,
synchronous metastasis have worst long term
prognosis.
• Tumor size show independent prognostic
factor.
• Nuclear grading in multivariate studies have
proved to be independent of prognostic value
nevertheless, Histologic sub variants have
prognostic role.

33. Treatment.

34. TREATMENT OF LOCALIZED RENAL
CELL CARCINOMA
• After recognizing great heterogeneity in the
tumor biology of these lesions, and multiple
management strategies are now available,
including
1. Radical Nephrectomy (RN),
2. partial nephrectomy (PN),
3. Thermal ablation (TA),
4. Active surveillance (AS)

35. Renal Function after Surgery for Localized Renal
Cell
• Surgery remains the mainstay for curative
treatment of this disease.
• The objective of surgical therapy is to excise
all tumor with an adequate surgical margin.
• RN when Robson and colleagues (1969)
established this procedure as the gold
standard curative operation for localized
RCC.

36. • RN is still a preferred option for
– Many patients with localized RCC, such as those with
very large tumors (most clinical T2 tumors).
– The relatively limited subgroup of patients with
clinical T1 tumors that are not amenable to
nephron-sparing approaches.
• The main concern with RN is that it predisposes
to CKD, which is potentially associated with
morbid cardiovascular events and increased
mortality rates.

37. Though Partial Nephrectomy (PN) is not a stronger
oncologic intervention than RN, and the only reasonable
way to explain an advantage for PN .
Significant results in favor of PN in mangment for T1
mass :
(1) A 61% risk reduction for the development of severe
CKD,
(2) A 19% risk reduction in overall mortality, and
(3) A 29% risk reduction in cancer-specific mortality.

38. Radical Nephrectomy

39. Radical Nephrectomy:
The prototypical concept of RN encompasses
the basic principles of
• Early ligation of the renal artery and vein,
• Removal of the kidney with primary dissection
external to the Gerota fascia,
• Excision of the ipsilateral adrenal gland, and
• Performance of an extended lymphadenectomy from
the crus of the diaphragm to the aortic bifurcation.

40. • Performance of a perifascial nephrectomy is of
during RN to prevent postoperative local tumor
recurrence as approx 25% of clinical T1b/T2
RCCs manifest perinephric fat involvement.
• Tumor located in the upper portion of the kidney
immediately adjacent to the adrenal gland is
another relative indication for adrenalectomy

41. • RCC metastasizes through the bloodstream
independent of the lymphatic system in many
patients, involved lymph nodes in many of
these patients would be removed by
conventional RN, which incorporates the
renal hilar and immediately adjacent
paracaval or paraaortic lymph nodes.

42. Approach
The operation is usually performed through
– Transperitoneal incision to allow abdominal exploration for
metastatic disease and early access to the renal vessels.
– Extended subcostal incision for most patients undergoing
open RN.
– Midline incision is a reasonable alternative, and the
– Thoracoabdominal approach can be useful for
• very large and potentially invasive tumors involving the
upper portion of the kidney.
– Extraperitoneal flank incision may be appropriate in
• Elderly patients or patients of poor surgical risk, but
• Limited exposure, particularly for large tumors or those
with contentious hilar anatomy.

43. • Laparoscopic RN is now established as a less
morbid alternative to open surgery in the
management of
1. Low - to moderate volume (10 to 12 cm or
smaller),
2. Localized RCCs with no local invasion,
3. Limited or no venous involvement, and
4. Manageable lymphadenopathy.
• Robotic assisted surgery.

45. Follow up protocol

46. Partial Nephrectomy Nephron-sparing
surgery

47. PN for the treatment of a renal tumor
• First described by Czerny in 1890
• Nephron-sparing surgery entails complete local resection of
the tumor while leaving the largest possible amount of
normal functioning parenchyma in the involved kidney.
• Margin width appears to be immaterial as long as the final
margins are negative;
– This is particularly relevant when the tumor is located within the
hilum and preservation of renal function is at a premium.
• Gold standard management of small renal masses (clinical
T1a) in the presence of a normal contralateral kidney,
presuming that the mass is amenable to this approach.

48. Indication PN
1. Pt. with bilateral RCC or RCC involving a solitary
functioning kidney.
– A solitary functioning kidney may be the result of unilateral
renal agenesis, prior removal of the contralateral kidney, or
irreversible impairment of contralateral renal function by a
benign disorder.
2. Relative indication for PN was represented by patients
with unilateral RCC and a functioning opposite kidney
affected by a condition that might threaten its future
function,
– Such as renal artery stenosis, hydronephrosis, chronic
pyelonephritis, ureteral reflux, calculus disease, or systemic
diseases such as diabetes and nephrosclerosis.

49. • A functioning renal remnant of at least 20% to
30% of one kidney is necessary to avoid end-
stage renal failure, although this presumes good
functional status of the remaining parenchyma.
• So, pt must be advised about the potential
need for temporary or permanent dialysis
postoperatively.
• Local recurrence after PN for imperative
indications traditionally ranged from 3% to 5%,
mainly when tumor is located in hilar region.

50. • The RENAL scoring
– Radius,
– Endophytic vs. exophytic,
– Nearness to collecting system,
– Anterior/posterior,
– Location relative to polar lines
• Other nephrometry scoring systems allow for
assessment of the complexity of the tumor and
have facilitated comparison of evolving surgical
techniques for PN in this era.

52. Follow up protocol.

54. Long term complication
• Pt. increased risk for development of
proteinuria, focal segmental
glomerulosclerosis, and progressive renal
failure due to
– Patients who undergo nephron-sparing surgery for
RCC may be left with a relatively small amount of
renal tissue and are at risk for development of
long-term renal functional impairment from
hyperfiltration renal injury.

55. Patients with bilateral RCC and von
Hippel-Lindau disease require
• Surgery is the mainstay of treatment.
– Bilateral nephrectomy and renal replacement therapy
or
– Nephron-sparing approaches such as PN
• For PN, an enucleative approach is often preferred rather
than wide resection or TA to avoid end-stage renal disease.
• Local recurrence rates for patients treated with
PN were 100% and 81%, respectively.
• Survival free of local recurrence after PN was
71% at 5 years but only 15% at 10 years.

56. • LLocal recurrence, which was defined as any
persistent or recurrent disease present in the
treated kidney or ipsilateral renal fossa after
initial treatment

57. Thermal Ablative Therapies
Includes
1. Renal cryosurgery and
2. Radiofrequency ablation (RFA).
3. High Intensity Focused Ultrasound ( HIFU)
• Both can be administered percutaneously or
through laparoscopic .

58. Ideal candidates for TA procedures
1. patients with advanced age or
2. Significant comorbidities who prefer a proactive approach
but are not optimal candidates for conventional surgery,
3. patients with local recurrence after previous
nephronsparing surgery.
4. patients with hereditary renal cancer who present with
multifocal lesions for which multiple PNs might be
cumbersome.
5. Patient preference must also be considered, and some
patients not fitting these criteria may also select TA, a
decision that can be supported as long as balanced
counseling about the current status of these modalities has
been provided
6. Tumor size <4 cm.

59. Renal cryosurgery
• Prerequisites for successful cryosurgery include rapid
freezing, gradual thawing, and a repetition of the freeze-
thaw cycle.
• The mechanism underlying tissue cryodestruction is
– Involve immediate membrane and cellular damage followed by
microcirculatory failure .
– Intracellular ice irreversibly disrupts cell organelles and the cell
membrane, a lethal event.
– Delayed microcirculatory failure occurs during the slow thaw
phase of the freeze-thaw cycle, leading to circulation arrest and
cellular anoxia.
– Cells that survive the initial cryogenic assault are destroyed by
this secondary insult of ischemia.
– Repetition of the rapid freeze–slow thaw cycle potentiates the
damage.

62. • Campbell and coworkers (1998) confirmed that
the target lethal temperature of −20°C was
achieved at a distance of 3.1 mm inside the
leading edge of the iceball as visualized by real-
time ultrasonography.
• In practice, we routinely extend the iceball
approximately 1 cm beyond the edge of the
tumor
• Encouraging outcomes for smaller tumors,
particularly those less than 3.0 cm in
diameter.

63. Complications associated with cryoablation
Include
– Renal fracture,
– Hemorrhage,
– Adjacent organ injury,
– Ileus, and
– Wound infection,
– Incidence of treatment.
– Local recurrences (may require repetitive ablation
or conventional surgery)

64. Radio Frequency Ablation
• Application of high-frequency electrical current by
RFA induces excitation of ions, frictional forces, and
heat, which in turn cause denaturation of intracellular
proteins and melting of cellular membranes, a lethal
sequence of events.
• These effects are observed at tissue temperatures above
41°C but increase directly with increasing temperature
and duration of treatment.
• Temperatures in excess of 100°C are typically obtained
at the tips of the probes, and thermosensors can be used
to monitor progress during active treatment.

66. Complications from RFA
• Are uncommon but have included
– Acute renal failure,
– Stricture of the ureteropelvic junction,
– Necrotizing pancreatitis, and
– Lumbar radiculopathy.
– Relatively low rates of local recurrence, although
some patients require repeat treatments to achieve
local control, which is an infrequent event with
cryoablation.

68. Other exciting new technologies
Such as
– High-Intensity focused Ultrasound (HIFU) and
– Frameless, image-guided radiosurgical treatments
(CyberKnife),
– These are also under development and may allow
extracorporeal treatment of small renal tumors in
the future .
• However, at present cell kill with these
modalities is not sufficiently reliable and
they are best considered developmental.

69. Active Surveillance
• Indication : The incidental discovery of many
small RCCs in
– Small, solid, enhancing, well-marginated, homogeneous
renal lesions ; Tumor <3.5cm.
– Asymptomatic elderly patients orThose of poor surgical
risk
– Patients who are unable or unwilling to undergo
surgery.
– Those tumors grew at slow and variable rates of up to
1.1 cm per year, with a median growth rate of 0.36
cm per year.
• It can safely be managed with observation and serial
renal imaging at 6-month or 1-year intervals.

70. AS is not appropriate for patients with
– Larger (>3 to 4 cm), poorly marginated, or
nonhomogeneous solid renal lesions,
– when biopsy indicates a potentially aggressive
RCC,
– Exception in patients with limited life
expectancy .

74. TREATMENT OF LOCALLY
ADVANCED RENAL CELL
CARCINOMA

75. Inferior Vena Caval Involvement
• RCC has frequent pattern of growth intra-
luminally into the renal venous circulation,
also known as venous tumor thrombus.
• 4-10% of RCC involves IVC
• 45% to 70 % of patients with RCC and IVC
thrombus can be cured with an aggressive
surgical approach including RN and IVC
thrombectomy.

76. IVC tumor thrombus
It should be suspected in patients with a renal
tumor who also have
– Lower extremity edema,
– Isolated right-sided varicocele or one that does not
collapse with recumbency,
– Dilated superficial abdominal veins,
– Proteinuria,
– Pulmonary embolism,
– Right atrial mass, or nonfunction of the involved
kidney.

77. Imaging
• MRI:
– Noninvasive and accurate modality
– Demonstrates both the presence and the cephalad extent of
vena caval involvement and
– The preferred diagnostic .
– Gadolinium contrast MRI: Enhance the tumor thrombus
which differentiate from bland thrombus as it does not
enhances

78. Renal vein thromus level
Staging of the level of IVC thrombus is as follows:
 Level I: Adjacent to the ostium of the renal
vein;
 Level II: extending up to the lower aspect of the
liver;
 Level III :involving the intrahepatic portion of
the IVC but below the diaphragm; and
 Level IV: extending above the diaphragm.

81. Transesophageal echocardiography
• Is an invasive study
• Unnecessary before surgery,
• Important intraoperative diagnostic modality for
evaluation of
– Thrombus extension,
– Monitoring for embolic phenomena,
– Recognition of residual tumor during and after
resection, and
– Assessment of preload/cardiac function during IVC
clamping.

82. Treatment
• The surgical approach is tailored to the level of IVC
thrombus,
• In general it uniformly begins with careful
mobilization of the kidney and early ligation of
the arterial blood supply .
• level I thrombi are isolated by a Satinsky clamp and
are thus readily addressed.
• Level II thrombi require sequential clamping of the
caudal IVC, contralateral renal vasculature, and
cephalad IVC along with mobilization of the relevant
segment of the IVC and occlusion of lumbar veins.
The renal ostium is then opened and the thrombus is
removed, all in a bloodless field.

83. • Vascular control for level III and level IV
IVC thrombi requires more extensive
dissection, venovenous bypass, or
cardiopulmonary bypass and hypothermic
circulatory arrest.
• For level III thrombi, mobilization of the liver
and exposure of the intrahepatic IVC will often
allow the thrombus to be mobilized caudad to
the hepatic veins, and venous isolation can then
proceed as for a level II thrombus.

85. Locally Invasive Renal Cell Carcinoma
• Patients with pathologic stage T4 disease have
represented less than 2% of surgical series.
• Patients with locally advanced RCC usually
present with pain, generally from invasion of
the posterior abdominal wall, nerve roots, or
paraspinous muscles.
• Large tumors may indent and compress
adjacent liver parenchyma.

86. • Surgical therapy :
– The only potentially curative management for RCC.
– Extended operations with en bloc resection of
adjacent organs are occasionally indicated.
• The aim of therapy is
– Complete excision of the tumor, including resection
of the involved bowel, spleen, or abdominal wall
muscles.
• Incomplete excision of a large primary
tumor, or debulking, is rarely indicated as
survival estimates are only 10% to 20% at 12
months.

87. Lymph Node Dissection for Renal Cell
Carcinoma
• The need for extensive lymphadenectomy in
patients undergoing RN remains
controversial, as a randomized trial of
lymphadenectomy at nephrectomy failed to
show a distinct advantage.

88. Adjuvant Therapy for Renal Cell
Carcinoma
• Unfortunately, recurrence develops in a
significant proportion of patients thought to be
rendered disease free after surgical resection,
primarily due to occult micrometastatic
disease.
• Distant metastases develop in 20% to 35% and
• Local recurrence in 2% to 5% of patients .

89. • A strong rationale for systemic adjuvant
therapy exists in high-risk patients.
• However, none of the adjuvant studies in this
field have been convincingly positive thus far,
and the standard of care remains observation
if the patient will not consider an adjuvant
trial.

91. Metastatic Tumors
• Metastatic tumors are the most common malignant
neoplasms in the kidney, outnumbering primary renal
tumors by a wide margin.
• The profuse vascularity of the kidney makes it a fertile soil
for the deposition and growth of cancer cells.
• Autopsy studies have shown that 12% of patients dying of
cancer have renal metastases.
• The most frequent sources of renal metastases include
– Lung,
– Breast, and
– Gastrointestinal cancers,
– Malignant melanoma, and
– Hematologic malignant neoplasms .

92. • Most renal metastases are
– Multifocal, and
– Almost all are associated with widespread nonrenal
metastases
• The typical pattern of renal metastases consists of
– Multiple small nodules that are often clinically
silent,
– Although they can lead to hematuria or flank pain in
exceptional circumstances .
– CT typically demonstrates isodense masses that
enhance only moderately (5 to 30 HU) after
administration of intravenous contrast material .

93. • Renal metastases should be suspected in any
patient with
– Multiple renal lesions and widespread systemic
metastases or
– History of nonrenal primary cancer.
• If there is any uncertainty about the diagnosis,
percutaneous renal biopsy usually provides
pathologic confirmation

94. Management
• Most patients with renal metastases are
managed with
– Systemic therapy or
– Placed on a palliative care pathway,
– Depending on the clinical circumstances.
– Nephrectomy is almost never required except in
extenuating circumstances, such as renal
hemorrhage that is refractory to embolization.

96. Be the ray of hope when there is no hope
- Oncosurgeon