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Treatment of Locally
Advanced RCC
Prepared by: Rojan Adhikari
FCPS II Urology Resident
References
Definition of radical nephrectomy
• Classically Robson describe Radical nephrectomy as
complete removal of the kidney outside the Gerota’s fascia
together with the ipsilateral adrenal gland and complete
regional lymphadenectomy from the crus of the diaphragm
to the aortic bifurcation. 1
• Nowadays the definition has changed , adrenalectomy and
lymphadenectomy is not performed until it is involved 2
1. Robson et al. (1969)
2. Shah et al., 2017b
Indication
• tumors in nonfunctional kidneys,
• large tumors replacing the majority of renal parenchyma,
• tumors associated with detectable regional lymphadenopathy,
• tumors associated with renal vein thrombus.
• Tumors invading collecting system
Campbell-Walsh- Wein Urology, 12th edi
Surgical Procedure
Position : modified lateral decubitus position
incisions : subcostal flank
Campbell-Walsh- Wein Urology, 12th edit
On right
• The posterior parietal peritoneum on the white line of Toldt is incised from
the pelvis (region of the iliac artery) to the right upper quadrant (region of
hepatic flexure).
• anterior pararenal space is developed by dissecting in the plane between
the anterior renal fascia and the mesentery of the ascending colon.
• After mobilizing the hepatic flexure of the colon using sharp and blunt
dissection, the second part of the duodenum is mobilized medially using
the Kocher maneuver .
• With medially located tumors, mobilization of the duodenum should be
performed with extreme care to avoid injury.
Campbell-Walsh- Wein Urology, 12th editi
Campbell-Walsh- Wein Urology, 12th ed
• After mobilization of the duodenum, the IVC is identified posteriorly.
• Dissection anterior to the IVC will enable identification of the renal
vein and gonadal vein. Placement of a vessel loop will enable gentle
traction of the renal vein
• The renal vein is palpated for any tumor thrombus.
Campbell-Walsh- Wein Urology, 12th edi
• Next the renal artery is
identified posterior to the
renal vein.
• If identification of the
renal artery is difficult,
attention is turned to the
lower pole of the kidney
to identify the ureter and
gonadal vein.
• If technically feasible, the gonadal vein is spared. However, often
because of the large size of the renal tumor, the gonadal vein cannot
be safely left intact without the risk for avulsion from the IVC
• With ligation of the ureter, the kidney is lifted from a posterior to an
anterior position to aid in identification of the renal artery posterior
to the kidney.
Campbell-Walsh- Wein Urology, 12th ed
• With the renal artery controlled, the right kidney and tumor will
decrease in size and engorgement, easing the dissection of the kidney
at the hilum and the remaining sites.
• The right renal vein, which should now be flaccid, is examined for any
tumor thrombus
Campbell-Walsh- Wein Urology, 12th ed
On left
• Incision of the white line of Toldt from the splenic flexure to the common
iliac artery, the descending colon is reflected medially.
• The renocolic ligament is divided, and extreme care is taken to avoid injury
to the tail of the pancreas.
• The left renal vein is identified using the anterior surface of the aorta as a
guide.
• The left renal artery is usually located cranial and posterior to the left renal
vein.
Campbell-Walsh- Wein Urology, 12th edit
• After further mobilization of the lower pole of the kidney, the left ureter
and the left gonadal vein are identified.
• The left gonadal vein can be traced to its insertion to help identify the left
renal vein.
• The ureter is divided, and the inferior and posterior surface of the kidney is
mobilized to identify the left renal artery.
• Once the renal artery and vein are identified, the renal artery is ligated and
divided first then follows the vein.
Campbell-Walsh- Wein Urology, 12th edit
• Sometimes renal artery and vein cannot be separated individually
because of significant hilar lymphadenopathy or adhesion.
• Then, a whole pedicle clamp technique may be utilized to control the
hilar vessels. Although the risk for arteriovenous fistula may be
associated with en bloc ligation of the whole renal pedicle.
Campbell-Walsh- Wein Urology, 12th edition
Complications
Intra-operative Bleeding
Trauma to adjacent organs
Tumor seeding
Pneumothorax
Post-operative Bleeding
Infection
AKI
late HTN
Tumor recurrance
Aneurysm, Pseudoaneurysm
AV fistula
Adrenalectomy
• overall incidence of adrenal metastasis is less than 5% 1
• Indications 2
diffuse involvement by tumor,
large tumor size of upper pole (>10 cm),
extrarenal tumor extension,
tumor thrombus,
lymphadenopathy and regional metastasis, or an adrenal mass on
imaging.
1. Siemer et al., 2004
2. Campbell-Walsh- Wein Urology, 12th ed
Regional lymphadenectomy
• incidence of lymph node disease is about 5% 1
• The role of regional lymphadenectomy on RCC has remained controversial 2
• Indications 3
enlarged lymph nodes on imaging,
cytoreductive surgery for metastatic disease,
tumor size greater than 10 cm, nuclear grade 3 or greater,
sarcomatoid histology,
presence of tumor necrosis on imaging,
extrarenal tumor extension, and
tumor thrombus 1. Capitanio et al., 2013;
2. Sun et al., 2014
3. Campbell-Walsh- Wein Urology, 12th edition
Sample size: 772
RCC with N0M0 and
resectable, patients were
randomly into two group
Conclusion: The incidence of
unsuspected lymph-node metastases
is 4.0% and no survival advantage of
a complete lymph-node dissection in
conjunction with a radical
nephrectomy alone .
Conclusion:
• The existing literature does not support a survival benefit with LND in either
M0 or M1 RCC
• A small subset of patients with isolated nodal metastases experience long-
term survival after surgical resection.
Inferior Vena Cava Involvement
• 4% to 10% of patients with RCC 1
• 45-70 % of patients with venous tumor thrombus can be cured with
nephrectomy and thrombectomy 1
• two components associated with IVC thrombi are tumor thrombus (tumor
cells contained within bland thrombus) and bland thrombus (blood
coagulum without tumor cells) 2
• In RCC with venous thrombus, 10% have associated positive regional lymph
nodes, 25% have associated metastases, and 50% have perirenal fat
invasion 2
1. Blute et al., 2004b;
2. Martinez-Salamanca et al., 2011
• MRI, CECT, and echocardiography are useful adjuncts in the pre- and
perioperative planning
• MRI is the preferred diagnostic study at many centers , however,
recent literature indicates that an appropriately performed CT can
provide essentially equivalent information
• venacavography, is rarely used and reserved for patients whom MRI
and CT are contraindicated
Pouliot et al., 2010
Campbell-Walsh- Wein Urology, 12th edition
Preoperative Considerations
• Anticoagulation with intravenous or low-molecular-weight heparin to
be started
• Temporary suprarenal IVC filters are also an option for patients with
level I, and II tumor thrombi but controversial as provoke
embolization to contralateral renal vein and hepatic vein
• Preoperative angioembolization can be considered because tumor
thrombi have an independent blood supply arising from the renal
artery and/or aorta in one-third of cases
Campbell-Walsh- Wein Urology, 12th edition
Mayo classification of macroscopic venous invasion
Patching, Replacing, and Interrupting the
Inferior Vena Cava
• If the IVC is expected to be less than 50%
of its original size, a patch cavoplasty is
necessary to prevent IVC stenosis and
thrombosis-related events.
• Autologous and bovine pericardium,
polytetrafluoroethylene (PTFE), collagen-
impregnated Dacron , or autologous
saphenous vein are materials that can be
used for patch cavoplasty.
Conclusion,
• In patients with non-metastatic RCC with thrombus, independent predictors of
recurrence include: BMI ≤20 kg/m2, preoperative haemoglobin , perinephric fat
invasion, IVC thrombus height, tumour diameter, nuclear grade and non-clear-cell
histology. Patients with >2 risk factors are at highest risk of recurrence and should
be considered for adjuvant therapy trials or increased surveillance.
• Conclusions
• Survival in patients with pT4 remains poor. pT4 is associated with a
locally and regionally invasive biology that requires specific attention
and warrants careful study
Complications
Intra-operative Air Embolism
Acute Pulmonary Embolism
Massive Hemorrhage
Hepatic dysfunction
Organ Ischemia
Trauma to adjacent organs
Post-op Hemorrhage
Infection
late Tumor recurrance
Aneurysm,
Pseudoaneurysm
AV fistula
Conclusions
The addition of adjuvant
therapy provided no survival
benefit but increased the rates
of adverse events for locally
advanced RCC patients.
• Twelve studies (5,936
patients)
• compared to placebo or
observation
• targeted therapy, and
immune therapy
Double-blind, phase 3
trial, randomization with
1:1 ratio, patients after
nephrectomy, with or
without metastasectomy,
to receive either adjuvant
pembrolizumab
total of 496 patients
were randomly
assigned to receive
pembrolizumab, and
498 to receive placebo
Conclusion:
Pembrolizumab treatment
led to a significant
improvement in disease-
free survival as compared
with placebo after surgery
among patients with
kidney cancer
THANK YOU

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Locally advanced renal cell carcinoma RCC

  • 1. Treatment of Locally Advanced RCC Prepared by: Rojan Adhikari FCPS II Urology Resident
  • 3.
  • 4. Definition of radical nephrectomy • Classically Robson describe Radical nephrectomy as complete removal of the kidney outside the Gerota’s fascia together with the ipsilateral adrenal gland and complete regional lymphadenectomy from the crus of the diaphragm to the aortic bifurcation. 1 • Nowadays the definition has changed , adrenalectomy and lymphadenectomy is not performed until it is involved 2 1. Robson et al. (1969) 2. Shah et al., 2017b
  • 5. Indication • tumors in nonfunctional kidneys, • large tumors replacing the majority of renal parenchyma, • tumors associated with detectable regional lymphadenopathy, • tumors associated with renal vein thrombus. • Tumors invading collecting system Campbell-Walsh- Wein Urology, 12th edi
  • 6. Surgical Procedure Position : modified lateral decubitus position incisions : subcostal flank Campbell-Walsh- Wein Urology, 12th edit
  • 7. On right • The posterior parietal peritoneum on the white line of Toldt is incised from the pelvis (region of the iliac artery) to the right upper quadrant (region of hepatic flexure). • anterior pararenal space is developed by dissecting in the plane between the anterior renal fascia and the mesentery of the ascending colon. • After mobilizing the hepatic flexure of the colon using sharp and blunt dissection, the second part of the duodenum is mobilized medially using the Kocher maneuver . • With medially located tumors, mobilization of the duodenum should be performed with extreme care to avoid injury. Campbell-Walsh- Wein Urology, 12th editi
  • 9. • After mobilization of the duodenum, the IVC is identified posteriorly. • Dissection anterior to the IVC will enable identification of the renal vein and gonadal vein. Placement of a vessel loop will enable gentle traction of the renal vein • The renal vein is palpated for any tumor thrombus. Campbell-Walsh- Wein Urology, 12th edi
  • 10. • Next the renal artery is identified posterior to the renal vein. • If identification of the renal artery is difficult, attention is turned to the lower pole of the kidney to identify the ureter and gonadal vein.
  • 11. • If technically feasible, the gonadal vein is spared. However, often because of the large size of the renal tumor, the gonadal vein cannot be safely left intact without the risk for avulsion from the IVC • With ligation of the ureter, the kidney is lifted from a posterior to an anterior position to aid in identification of the renal artery posterior to the kidney. Campbell-Walsh- Wein Urology, 12th ed
  • 12. • With the renal artery controlled, the right kidney and tumor will decrease in size and engorgement, easing the dissection of the kidney at the hilum and the remaining sites. • The right renal vein, which should now be flaccid, is examined for any tumor thrombus Campbell-Walsh- Wein Urology, 12th ed
  • 13. On left • Incision of the white line of Toldt from the splenic flexure to the common iliac artery, the descending colon is reflected medially. • The renocolic ligament is divided, and extreme care is taken to avoid injury to the tail of the pancreas. • The left renal vein is identified using the anterior surface of the aorta as a guide. • The left renal artery is usually located cranial and posterior to the left renal vein. Campbell-Walsh- Wein Urology, 12th edit
  • 14. • After further mobilization of the lower pole of the kidney, the left ureter and the left gonadal vein are identified. • The left gonadal vein can be traced to its insertion to help identify the left renal vein. • The ureter is divided, and the inferior and posterior surface of the kidney is mobilized to identify the left renal artery. • Once the renal artery and vein are identified, the renal artery is ligated and divided first then follows the vein. Campbell-Walsh- Wein Urology, 12th edit
  • 15. • Sometimes renal artery and vein cannot be separated individually because of significant hilar lymphadenopathy or adhesion. • Then, a whole pedicle clamp technique may be utilized to control the hilar vessels. Although the risk for arteriovenous fistula may be associated with en bloc ligation of the whole renal pedicle. Campbell-Walsh- Wein Urology, 12th edition
  • 16. Complications Intra-operative Bleeding Trauma to adjacent organs Tumor seeding Pneumothorax Post-operative Bleeding Infection AKI late HTN Tumor recurrance Aneurysm, Pseudoaneurysm AV fistula
  • 17. Adrenalectomy • overall incidence of adrenal metastasis is less than 5% 1 • Indications 2 diffuse involvement by tumor, large tumor size of upper pole (>10 cm), extrarenal tumor extension, tumor thrombus, lymphadenopathy and regional metastasis, or an adrenal mass on imaging. 1. Siemer et al., 2004 2. Campbell-Walsh- Wein Urology, 12th ed
  • 18. Regional lymphadenectomy • incidence of lymph node disease is about 5% 1 • The role of regional lymphadenectomy on RCC has remained controversial 2 • Indications 3 enlarged lymph nodes on imaging, cytoreductive surgery for metastatic disease, tumor size greater than 10 cm, nuclear grade 3 or greater, sarcomatoid histology, presence of tumor necrosis on imaging, extrarenal tumor extension, and tumor thrombus 1. Capitanio et al., 2013; 2. Sun et al., 2014 3. Campbell-Walsh- Wein Urology, 12th edition
  • 19.
  • 20. Sample size: 772 RCC with N0M0 and resectable, patients were randomly into two group Conclusion: The incidence of unsuspected lymph-node metastases is 4.0% and no survival advantage of a complete lymph-node dissection in conjunction with a radical nephrectomy alone .
  • 21. Conclusion: • The existing literature does not support a survival benefit with LND in either M0 or M1 RCC • A small subset of patients with isolated nodal metastases experience long- term survival after surgical resection.
  • 22. Inferior Vena Cava Involvement • 4% to 10% of patients with RCC 1 • 45-70 % of patients with venous tumor thrombus can be cured with nephrectomy and thrombectomy 1 • two components associated with IVC thrombi are tumor thrombus (tumor cells contained within bland thrombus) and bland thrombus (blood coagulum without tumor cells) 2 • In RCC with venous thrombus, 10% have associated positive regional lymph nodes, 25% have associated metastases, and 50% have perirenal fat invasion 2 1. Blute et al., 2004b; 2. Martinez-Salamanca et al., 2011
  • 23. • MRI, CECT, and echocardiography are useful adjuncts in the pre- and perioperative planning • MRI is the preferred diagnostic study at many centers , however, recent literature indicates that an appropriately performed CT can provide essentially equivalent information • venacavography, is rarely used and reserved for patients whom MRI and CT are contraindicated Pouliot et al., 2010 Campbell-Walsh- Wein Urology, 12th edition
  • 24. Preoperative Considerations • Anticoagulation with intravenous or low-molecular-weight heparin to be started • Temporary suprarenal IVC filters are also an option for patients with level I, and II tumor thrombi but controversial as provoke embolization to contralateral renal vein and hepatic vein • Preoperative angioembolization can be considered because tumor thrombi have an independent blood supply arising from the renal artery and/or aorta in one-third of cases Campbell-Walsh- Wein Urology, 12th edition
  • 25. Mayo classification of macroscopic venous invasion
  • 26.
  • 27.
  • 28.
  • 29. Patching, Replacing, and Interrupting the Inferior Vena Cava • If the IVC is expected to be less than 50% of its original size, a patch cavoplasty is necessary to prevent IVC stenosis and thrombosis-related events. • Autologous and bovine pericardium, polytetrafluoroethylene (PTFE), collagen- impregnated Dacron , or autologous saphenous vein are materials that can be used for patch cavoplasty.
  • 30. Conclusion, • In patients with non-metastatic RCC with thrombus, independent predictors of recurrence include: BMI ≤20 kg/m2, preoperative haemoglobin , perinephric fat invasion, IVC thrombus height, tumour diameter, nuclear grade and non-clear-cell histology. Patients with >2 risk factors are at highest risk of recurrence and should be considered for adjuvant therapy trials or increased surveillance.
  • 31. • Conclusions • Survival in patients with pT4 remains poor. pT4 is associated with a locally and regionally invasive biology that requires specific attention and warrants careful study
  • 32. Complications Intra-operative Air Embolism Acute Pulmonary Embolism Massive Hemorrhage Hepatic dysfunction Organ Ischemia Trauma to adjacent organs Post-op Hemorrhage Infection late Tumor recurrance Aneurysm, Pseudoaneurysm AV fistula
  • 33.
  • 34.
  • 35.
  • 36. Conclusions The addition of adjuvant therapy provided no survival benefit but increased the rates of adverse events for locally advanced RCC patients. • Twelve studies (5,936 patients) • compared to placebo or observation • targeted therapy, and immune therapy
  • 37. Double-blind, phase 3 trial, randomization with 1:1 ratio, patients after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo Conclusion: Pembrolizumab treatment led to a significant improvement in disease- free survival as compared with placebo after surgery among patients with kidney cancer

Notes de l'éditeur

  1. Hyperfiltration injury is most common when the total nephron mass of both kidneys is reduced by more than 80%
  2. Multiple retrospective studies have suggested a possible benefit to regional lymphadenectomy for carefully selected patients Regional lymphadenectomy extending from the crus of the diaphragm to the aortic bifurcation is employed in select cases of advanced local disease and when technically feasible.
  3. Regional lymphadenectomy extending from the crus of the diaphragm to the aortic bifurcation is employed in select cases of advanced local disease and when technically feasible.
  4. One of the unique features of RCC is its frequent pattern of growth intraluminally into the renal venous circulation, also known as venous tumor thrombus. This growth may extend into the IVC with cephalad migration as far as the right atrium or beyond. The absence of metastases in many patients with vena cava extension is an intriguing aspect of this cancer’s behavior In children, Wilms tumor, clear cell sarcoma of the kidney, adrenocortical carcinoma, and neuroblastoma can all be associated with IVC thrombi. In adults, urothelial carcinoma of the renal pelvis, lymphoma, retroperitoneal sarcoma, adrenocortical carcinoma, pheochromocytoma, and angiomyolipoma are all potential sources of an IVC thrombus Usually, IVC thrombectomy is accompanied by radical nephrectomy and regional lymph node dissection.
  5. Patients with renal tumors are at increased risk for pulmonary embolism as a result of malignancy-associated hypercoagulability and venous thrombus embolization. Angiographic infarction of the blood supply to the tumor thrombus can help shrink a large thrombus to a more manageable size, potentially avoiding the need for bypass or extensive mobilization of the liver. Angioembolization can be considered when caval thrombi appear to invade the IVC, when the thrombus invades the intrahepatic or suprahepatic veins and cannot be excised,
  6.  Level I: The tumor thrombus is either at the entry of the renal vein or within the IVC < 2 cm from the confluence of the renal vein and the IVC. Level I IVC thrombus managed with a Satinsky clamp to achieve vascular isolation.
  7. Level II: The thrombus extends within the IVC > 2 cm above the confluence of the renal vein and the IVC but still remains below the hepatic veins. Level II IVC thrombus managed by sequential clamping of the For right side lower IVC, contralateral renal vein, and cephalad IVC, along with mobilization of the IVC and occlusion of lumbar veins, allowing for vascular isolation For left side Vascular control is obtained sequentially in the following order: (1) the ipsilateral (left) renal artery is ligated, (2) the infrarenal IVC is clamped, (3) the contralateral (right) renal vein is clamped, (4) the suprarenal IVC is clamped,
  8. Level III: The thrombus involves the intrahepatic IVC. The size of the thrombus ranges from a narrow tail that extends into the IVC to one that fills the lumen and enlarges the IVC. Level III IVC thrombus managed by mobilization of the liver, providing exposure of the intrahepatic IVC and retraction of the thrombus to facilitate placement of the upper IVC clamp just below the level of the hepatic veins. Through this approach vascular isolation is achieved in a manner similar to that in B. If the cephalad clamp must be placed above the level of the hepatic veins, a Pringle maneuver should be performed to temporarily occlude the hepatic blood flow
  9. Level IV: The thrombus extends above the diaphragm or into the right atrium  Clamping the suprahepatic IVC results in a 60% reduction in cardiac preload, an 80% increase in peripheral vascular resistance, a 50% increase in heart rate, a 40% drop in cardiac output, and a 10% to 20% drop in mean arterial blood pressure. If the cardiac output drops more than 50% or the mean arterial blood pressure drops more than 30%, the patient will not tolerate suprahepatic IVC clamping. Options for managing this situation include bypass and clamping of the supraceliac aorta.
  10. Sequencial clamping
  11. Hyperfiltration injury is most common when the total nephron mass of both kidneys is reduced by more than 80%