1. Kidney Cancer – RCC & TCC
Julian Mander
RPH Urology

2. Upper Tract RCC vs TCC Both upper renal tract tumours
RCC = Renal cell carcinoma
Renal parenchymal cancer, arising from renal
tubular cells (proximal convoluted tubule).
Most common upper tract malignancy.
TCC = Transitional cell carcinoma
Arising from “urothelium” lining the urinary
collecting system, (which was original called transitional epithelium).
Relatively uncommon, usually in heavy smokers.

3. Renal Parenchyma and RCC Histology
Clear Cell Renal Cell Carcinoma

4. RCC Macroscopic

5. Transitional Epithelium and TCC Histology
Transitional Cell Carcinoma Low Grade
Transitional Epitheium

6. Papillary TCC Macroscopic

7. Epidemiology Renal Cell Carcinoma
2.4% of all cancers in Australia.
2,586 cases diagnosed in Australia in 2008 = 2.2% increase in diagnoses from 2003.
Diagnosis twice as common in men.
855 deaths in Australia in – 539 male 316 female (13% of these TCC).
Mortality fallen 2.1% from 2004 to 2007.
5 year survival has improved 47% 1982 – vs 76% – 2010
Source: AHIW Australian Cancer Database

8. Public Health - Screening
Formal screening for renal cell carcinoma is not advocated
In effect we now have “non systematic partial screening” of the population through
increased use of ultrasound and CT scanning for diagnostic imaging
“Partial screening” reflected in transient peak in incidence in 1994 in USA
“Partial screening” reflected in stage migration
Memorial Sloan Kettering 1989 – decrease mean tumour size 7.8cm to 5.3cm
increase organ confined tumours 47% to 78%
Pantuck et al The Changing Natural History of Renal Cell Carcinoma J Urology, 166, 1611, 2001

9. Increase in Diagnosis of Small Solid Renal Masses
Increased use of diagnostic imaging, both ultrasound and CT scanning, has resulted in
a significant increase in the diagnosis of small solid renal masses.
61% of renal masses incidental finding in (Chow et al JAMA 281:1628–1631, 1999)
13% of renal masses incidental finding in 1973
Stage migration is associated with the increase in incidentally detected RCCs, with
more small solid renal masses now being diagnosed at a lower stage.
Greatly increased scope for nephron sparing partial nephrectomy (or minimally invasive
ablative techniques – RFA and Cryotherapy) with stage migration.

10. Etiology Renal Cell Carcinoma
Smoking thought to account for around 50% of RCC
Genetic predisposition syndromes
1) Von Hippel-Lindau syndrome and HIF (Hypoxia Inducible Factor) pathways:
Associated with multiple bilateral clear cell RCC starting at a young age
Autosomal dominant
Results from a mutation in the Von Hippel-Lindau tumour suppressor gene on chromosome 3p25.3.
Incidence of one in 36,000 births. There is over 90% penetrance by the age of 65.
Associated with retinal angioma, haemangioblastoma, pheochromocytoma, pancreatic serous cystadenoma, endolymphatic sac tumour
and bilateral papillary cystadenomas of the epididymis in men or broad ligament of the uterus in women.
VHL gene has a mutation and produces a faulty VHL protein (pVHL).
VHL gene protein product binds 2 proteins, called Elongin C and B. These belong to family of proteins that are critical to transcriptional
regulation.
VHLprotein-Elongin C/B complex binds to Cul-2, a member of the multigene cullin family
VHLprotein-ElonginC/B-Cul-2 complex targets a protein called HIF1-alpha = hypoxia inducible factor leading to ubiquitin mediated
degradation of HIF1-alpha.
In kidney cancer, mutant VHL gene product does not degrade HIF1-alpha and HIF accumulates, stimulating VEGF, GLUT 1, PDGF,
TGF-alpha and erythropoietin
HIF1-alpha is a protein that accumulate under hypoxic stress and controls the transcription of a number of downstream genes:
VEGF – vascular endothelial growth factor, GLUT 1 – glucose transporter, PDGF - platelet derived growth factor,
TGF-alpha – transforming growth factor alpha and Erythropoietin i.e. genes theoretically important to tumourogenesis
Approximately 20% of cases of VHL disease are found in individuals without a family history, known as de novo mutations.
An inherited mutation of the VHL gene is responsible for the remaining 80 percent of cases.

11. Etiology Renal Cell Carcinoma
Genetic predisposition syndromes
2) Papillary Type 1 RCC and c-MET Oncogene
Papillary RCC is associated with loss of Y chromosome, trisomies 7 and 17, and a specific translocation between chromosome X and
chromosome 1 t(X;1)(p11.2;q21.2)
Some Papillary RCC shown to be caused by activating mutations in the c-MET proto-oncogene in chromosome 7q
= Hereditary renal cell carcinoma
Hereditary papillary renal carcinoma type 1 (HPRC)
Autosomal dominant and highly penetrant
Gene responsible is located at chromosome 7q
Missense mutations found in the tyrosine kinase domain of the MET gene – product is cell surface receptor for ligand hepatocyte growth
factor HGF(A)
Three mutations in MET gene found located in codons homologous to those in the c-KIT and RET oncogenes
“These findings suggest that the missense mutations located in the MET proto-oncogene lead to constitutive activation of the MET protein in
papillary renal carcinomas.”
Mutations in MET gene also found in some sporadic noninherited type I papillary renal carcinomas

12. Etiology Renal Cell Carcinoma
Genetic predisposition syndromes
3) Papillary Type 2 RCC, HLRCC/MCL and FH Gene:
HLRCC Hereditary leiomatosis renal cell carcinoma / MCL Multiple cutaneous leiomyoma
HLRCC/MCL is a disease complex with multiple cutaneous leiomyomas, uterine leiomyoma, uterine leiomyosarcoma and papillary type 2
RCC
FH Fumarate hydratase gene for HLRCC/MCL is the gene that codes for Krebs cycle enzyme fumarate hydratase
Tumourogenesis mechanisms as yet undetermined
(Papillary Type 2 RCC is aggressive and treatment surgical)
Linehan et al The Genetic Basis of Cancer of the Kidney J Urology 170,

13. Etiology Renal Cell Carcinoma
Genetic predisposition syndromes
4) Hereditary Chromophobe RCC and BHD Gene
BHD Birt Hogg Dube syndrome described in 1977
Inherited autosomal dominant syndrome with cutaneous hair follicle tumours involving face and neck, and pulmonary cysts associated spont
pneumothorax 25%
Linked to chromophobe bilateral, multifocal chromophobe RCC by Roth in 1993
Genetic linkage analysis in 2002 found BHD gene at 4cM area on short arm of chromosome 17
Mutations of the BHD gene found in germline of those with BHD syndrome characteristics of tumour suppressor gene
Current work on BHD gene in sporadic chromophobe RCC and oncocytoma
Linehan et al The Genetic Basis of Cancer of the Kidney J Urology 170,

14. Staging of Renal Cell Carcinoma
Staging improvements evolved to reflect improvements in imaging and appreciation of natural history of the cancer, ultimately leading to UICC 1997 TNM staging and subsequent AJCC modification of 1997 UICC staging

15. Staging of Renal Cell Carcinoma and Prognosis
Staging is the most important prognostic indicator for renal cell carcinoma
Pantuck et al The Changing History of Renal Cell Carcinoma J Urology 166,1611, 2001

16. Grading of Clear Cell Renal Cell Carcinoma
Tumour grading is the second most important independent prognostic indicator
Fuhrman grading accepted in for clear cell carcinoma
incidence Grade %
Grade %
Grade %
Grade %
Fuhrman Grade Fuhrman Grade Fuhrman Grade 3

17. Grading of Clear Cell Renal Cell Carcinoma and Prognosis
Tsui et al Prognostic Indicators For Renal Cell Carcinoma: A Multivariate Analysis of 643 Patients Using The Revised 1997 TNM Staging
Criteria J Urology 163,

18. Histological Subtyping – Vital to Understanding Molecular Biology and New Therapies
Clear cell carcinoma % (Von Hippel-Lindau syndrome and HIF pathways)
Papillary carcinoma % Type 1 and Type 2 – histological typing
Multifocal 41% important for consideration partial nephrectomy
Bilateral 8% “ “ “ “
Type 1 papillary RCC better prognosis than clear cell
Type 1: small basophilic cells lower grade and stage, better prognosis (c-Met oncogene association)
Type 2: large eosinophilic cells poorer prognosis 66% 5 year survival c/f 95% for type 1 (HLRCC/MCL FHgene)
Familial predisposition documented but rare 0.03%. Association bladder TCC standardised incidence ratio 23.88
Chromophobe carcinoma %
Similar appearance to benign oncocytoma Similar prognosis as clear cell RCC, stage for stage
(Birt Hogg Dube syndrome chromosome 17 (17p11))
Unclassified carcinoma %
Large aggressive tumours with early metastasis and poor prognosis 90% present with
metastases. Includes “sarcomatoid” tumours, with spindle cell appearance – median survival
3.8 to 6.8 months. Surgery alone does not improve survival. Surgery + immunotherapy (IL-2)
does improve survival. Immunotherapy alone (IL-2) does improve survival - but months only.
Collecting duct carcinoma %
Aggressive tumours, commonly present with symptoms. Currently not curable. Average survival 11.5 months.
Very rare subtypes:
Epithelioid angiomyolipoma
Clear cell variant of epithelioid angiomyolipoma

19. Histological Subtyping and Genetic Associations
Linehan et al The Genetic Basis of Cancer of the Kidney J Urology , 2163, 2003

20. Investigation of Renal Mass Lesion – Blood and Urine tests
Blood tests: U&E creatinine required for CT scan and decision making for treatment
Calcium – hypercalcemia as a paraneoplastic or metastatic phenomenon
LFTs occasionally abnormal as paraneoplastic phenomenon – Stauffer’s syndrome poorer prognosis
as liver metastases - relatively rare
FBP polycythemia as paraneoplastic syndrome
Coagulation profile required if pending biopsy or RFA in particular
Urine Tests: MSU occasionally diff diagnosis “nephronia” (focal pyelonephritis)
Cytology if differential diagnosis includes TCC
Paraneoplastic syndromes and RCC
Constitutional symptoms: PUO, cachexia and weight loss
Specific metabolic and biochemical abnormalities:
Hypercalcemia – 20% of cases (when not from bone metastases)
Hypertension double the hypertension rate of age matched controls – renin elevation in 37% RCC
Hepatic dysfunction – 20% of cases Stauffer’s syndrome (when not from liver metastases)
Polycythemia – 8% of cases thought due paraneoplastic EPO, though 66% have elevated EPO
Amyloidosis – 8% of cases (nonendocrine paraneoplastic syndrome)

21. Investigation of Renal Mass Lesion – Abdominal Imaging
Solid renal mass lesions
Renal cell carcinoma malignant with no specific identifying features on imaging
Oncocytoma benign “with theoretical malignant potential” with no specific identifying features on imaging
Angiomyolipoma benign and generally containing fat, heperechoic on U/S and fat density on non contrast CT
Complex cystic renal masses
Simple cysts containing dense or hyperechoic material – haemorrhagic cysts, proteinaceous cysts, infected cysts
Cystic renal cell carcinoma – generally contain contrast enhancing components
Bosniak Score Bosniak simple cyst, imperceptible wall, generally round 0% malignant
Bosniak minimally complex, a few thin (< 1mm) septa, thin Ca++; non-enhancing high-attenuation (due to to proteinaceous or haemorrhagic fluid) renal lesions of less than 3 cm are also included in this category; these lesions are generally well marginated.
Bosniak 2F minimally complex but requiring follow up. Increased number of septa, minimally thickened or enhancing septa or wall, thick Ca++, hyperdense cyst that is: > 3 cm diameter, mostly intrarenal (less than 25% of wall visible); no enhancement. Needs ultrasound / CT follow up
~ 25 % malignant
Bosniak indeterminate, thick or multiple septations, mural nodule, hyperdense on CT. Treatment is necessary - partial nephrectomy or RF ablation in elderly / poor surgical risk ~ 54% malignant
Bosniak clearly malignant, solid mass with large cystic or necrotic component . Treatment: partial / total nephrectomy or RFA
~100% malignant

22. Diagnosis of Renal Mass Lesion – Abdominal Imaging
Generally U/S followed by 3 phase contrast CT scan non contrast, arterial and portal venous phase, with pyelographic
phase added if concerns about transitional cell carcinoma (= 4 phase CT scan)
Very limited place for MRI, mainly in assessing renal vein involvement (4 – 9% of cases)
Very limited place for PET scan – sensitivity 75% with PPV 92.3% - not useful if negative
Large left RCC U/S Complex right renal cyst right kidney U/S Renal Angiomyolipoma U/S
Large right RCC CT
Small right RCC non con CT
Small right RCC arterial phase CT
Small right RCC portal venous phase CT
Left RCC with IVC involved CT

23. Diagnosis of Renal Mass Lesion – Chest Imaging
CT scan chest problematic
Invariably one or two small peripheral lung lesions ?tumour ?benign granuloma with respiratory referral and long term F/U with 6 monthly CT chest, most commonly do not turn out to be metastases.
CXR preferred option
Will demonstrate cannonball metastases, which are obviously important from a management perspective.
(Lung metastases are relatively rare, more common in large poorly differentiated RCC).

24. Investigation Core Needle Biopsy for Histopathological Diagnosis
6% - 20% of solid renal masses benign (more commonly benign if < 4cm diameter)
Angiomyolipomas usually but not always identifiable from RCC radiologically with U/S + CT
Oncocytomas not radiologically identifiable as different from RCC
Complex cystic masses problematic with imaging and biopsy – Bosniak classification
Fine needle biopsy abandoned as largely considered inaccurate
Core biopsy developed as spring loaded 18G “Biopty” guns became available
histopathology more accurate than FNA cytology
Advances in CT scanning – more accurate needle placement in select cases
U/S guided core biopsy still used in many cases, but targeting remains a
theoretical concern – negative biopsy becomes a problem

25. Core Needle Biopsy for Histopathological Diagnosis
Neuzillet Accuracy and Clinical Role of Fine Needle Percutaneous Biopsy with Computerized Tomography Guidance of Small (Less Than
4.0cm) Renal Masses J Urology 171,

26. Solid Renal Mass Biopsy
Mean tumour size 3.3 cm % benign % inconclusive
Percutaneous Core Biopsy for Renal Masses Lebret et al J Urology 178,1184 October 2007

27. Solid Renal Mass Biopsy
Median tumour size 2.9 cm, average less than 5 cm % benign 18% non diagnostic
The Value of Preoperative Needle Core Biopsy for Diagnosing Benign Lesions Among Small, Incidentally Detected Renal Masses Shannon et al J Urology 180,

28. Treatment of Renal Cell Carcinoma
Curative RCC does not respond to standard chemotherapy and radiotherapy regimes
Surgery Radical nephrectomy - open
Radical nephrectomy - laparoscopic
Partial nephrecomy open
Partial nephrectomy laparoscopic
Minimally invasive ablative techniques RFA Radiofrequency Ablation
Cryotherapy – percutaneous and laparoscopic
HIFU
Cyberknife radiotherapy

29. Radical Nephrectomy - Open
First description by Mortenson in 1948 via thoracoabdominal incision
Popularised by Robson 1960’s
“The results of radical nephrectomy for renal cell carcinoma.” Robson et al J Urol 1969 Mar;101(3):
Substantial improvements in cancer survival once radical nephrectomy was widely adopted
Various open surgical approaches: loin incision – 12th , 11th , 10th rib incisions and thoracoabdominal

30. Radical Nephrectomy - Laparoscopic
First laparoscopic radical nephrectomy performed in 1990 at Washington University, St Louis, Missouri by Clayman
in an 85 year old woman with 3cm solid renal mass. The operation took 6 hours 45 minutes and the kidney was
removed by morcellation with port site extraction extraction. Turned out to be a benign oncocytoma (luckily).
Became standard of care after 2000 and the specimen is now removed intact (seeding occurred with morcellation).
Now 3 – 4 hours surgical time, using 3 ports on the left and 4 ports on the right, with 3” incision for extraction site
Transperitoneal and retroperitoneal approaches, with patient positioning same as open (open conversion 2%)
Oncological outcome are now the same as open surgery
Slightly higher complication rate than with open surgery

31. Partial Nephrectomy
Developed in USA through the 1990’s at Cleveland Clinic, Mao Clinic and Memorial
Sloan Kettering as curative therapy for renal cell carcinoma while preserving renal fn.
Open partial nephrectomy initially, now extended to laparoscopic partial nephrectomy.
Can be technically demanding, with slow uptake by the urologists outside these centres.
Ultimately, cancer outcomes the same for T1 tumours whilst preserving renal function.
Should now be standard therapy for T1A RCC.
Recent evidence for lower cardiovascular death risk with nephron sparing surgery.

32. Partial Nephrectomy and Cancer Outcomes
70 patients with median follow up 10 years – 1997
98.5% no local recurrence 97% no metastases
Mean tumour size 3 cm
Partial Nephrectomy for Unilateral Renal Cell Carcinoma and a Normal Contralateral Kidney: 10 Year Followup Herr J Urology 161, 33 January 1999
107 patients before with ~ 10 year follow up
Mean tumour size 4.7 cm
40% T1a % 10 year CSS
20% T1b % “
4% T % “
20% T3a % “
16% T3b % “
Long Term Results of Nephron Sparing Surgery For Localised Renal Cell Carcinoma: A Ten Year Review Novick et al J Urology 163, 442 Feb 2000

33. Partial Nephrectomy and Cancer Outcomes
Nephron Sparing Surgery for Renal Tumours: Indications, Techniques and Outcomes Novick et al J Urology 166,
Safety and Efficacy of Partial Nephrectomy for all T1 Tumours Based on an International Multicenter Experience Patard et al J Urology 171,

34. Partial Nephrectomy for Renal Tumours 4 - 7 cm Diameter
Expansion of partial nephrectomy into larger RCCs - study on 1,159 patients with sporadic RCC at 2 centres Mayo Clinic and Sloan Kettering between 1986 and 2006.
10% solitary kidney and 15% chronic kidney disease in partial nephrectomy group.
Partial nephrectomy
Radical nephrectomy
Cancer specific survival in 704 patients treated with RN ….… and 239 treated with PN _____(p ), tumour size 4 – 7 cm.
Partial Versus Radical Nephrectomy for 4 to 7 cm Renal Cortical Tumors Russo, Blute et al J Urology 182, 2601 Dec 2009

35. Slow Urologist Upskilling in Partial Nephrectomy
SEER Data patients > 66 years old cases where tumour ≤ 4 cm diameter (up to 2002)
Diffusion of Surgical Innovation Among Patients With Kidney Cancer Miller et al Cancer 112, April 2008

36. Partial Nephrectomy - Open
Larger tumours and centrally located tumours require vascular control with renal arterial and venous cross clamping.
Acceptable warm ischaemic time has traditionally been 30 minutes, so “clamp and cool” necessary in many circumstances.
Small arteries and veins underrun.
Collecting system closure is important.
“Bolsters” commonly used to fill defect.

37. Partial Nephrectomy - Laparoscopic
Specific laparoscopic skill set required, generally in the bigger centres in USA – Cleveland Clinic, Mayo and MSK. Robotic surgery probably advantageous here. “Clamp and cool” problematic still. Floseal haemostatic agent appears to be important.

38. Minimally Invasive Ablative Techniques

39. Radiofrequency Ablation of Renal Cell Carcinoma
Using techniques developed for management liver metastases
Early experience with those unsuitable or refusing surgery
Recent sloughed upper ureter in Brisbane
McDougal et al Long Term Follow Up of Renal Cell Carcinoma After Radiofrequency Ablation J Urology 174,
16 patients, minimum 4 year followup - No patient died of metastatic disease patients died of other causes
Imaging showed 64% reduction in average mass size - One mass incresed in size considered failure
But no followup histopathology

40. Cryoablation of Renal Cell Carcinoma
Early experience – percutaneous vs laparoscopic
Potential vascular complications with splitting ice ball and torrential haemorrhage
Gill et al Renal Cryoablation: Outcome at 3 Years J Urology 173,
Laparoscopic approach – visual and laparoscopic U/S observation of ice ball patients
37.8% cryolesions completely disappeared on MRI at 5 years
2/39 biopsied lesions showed RCC 6 months after cryo

41. High Intensity Focussed Ultrasound HIFU
Experimental
Kohrmann et al High Intensity Focussed Ultrasound as Nononvasive Therapy for Multifocal Renal Cell Carcinoma: Case Study and Review of The
Literature J Urology

42. High Intensity Focussed Ultrasound HIFU

43. Results of Percutaneous Ablative therapy
Problem with histopathology on both initial diagnosis and proof of cure
with cryo and RFA – few biopsies done on these patients.
“Incomplete treatment” defined as contrast enhancement of lesion on CT scan.
Local recurrence rates
Partial nephrectomy 2.6% of 5,037 cases
Cryotherapy % of 496 cases
RFA % of 607 cases

44. AUA Guidelines for Management of T1a RCC
For Index Patient No. 1: A healthy patient with a clinical T1a (≤4.0 cm) enhancing renal mass
Standard: Complete surgical excision by partial nephrectomy is a standard of care and should be strongly considered.
[Based on review of the data and Panel consensus.]
Both open and laparoscopic approaches to PN can be considered, dependent on tumor size, location and the surgeon's expertise. LPN can provide more rapid recovery, although this approach has been associated with increased warm ischemic times and an increased risk of urological complications including postoperative hemorrhage and urinary fistula. Most patients with a solitary kidney, preexisting renal dysfunction, hilar tumor, multiple tumors or predominantly cystic tumor are best managed with an open surgical technique. With improved laparoscopic instrumentation and greater dissemination of expertise, improved outcomes and more widespread application of LPN is anticipated in the future.
Standard: Radical nephrectomy should be discussed as an alternate standard of care which can be performed if a partial nephrectomy is not technically feasible as determined by the urologic surgeon.
Radical nephrectomy can lead to an increased risk of CKD, which is associated with increased risks of morbid cardiac events and death according to population-based studies. Management should focus on optimizing renal function rather than merely precluding the need for dialysis. PN is a greatly underutilized procedure that is often feasible even for central or hilar tumors, given adequate surgeon expertise. Nevertheless, occasional localized renal tumors in this size range are not amenable to PN, and RN should be considered an alternative standard of care. A laparoscopic approach can provide reduced blood loss and more rapid recovery and should be considered, presuming adequate surgeon expertise.
Option: Thermal ablation, such as cryoablation or radio frequency ablation, should be discussed as a less-invasive treatment option, but local tumor recurrence is more likely than with surgical excision, measures of success are not well defined, and surgical salvage may be difficult.
Thermal ablation is associated with a substantially increased risk of local recurrence, the majority of which can be managed with a second attempt at thermal ablation. However, some local recurrences are not amenable to this approach and require surgical salvage. In this setting laparoscopic surgery and PN are often not possible due to extensive reactive fibrosis within the perinephric space. In addition, measures of success for thermal ablation have come into question with some studies demonstrating apparently viable cancer cells despite loss of contrast enhancement. It is possible that outcomes associated with ablative modalities will improve with further advances in technology and application; however, judicious patient selection and counseling remain of paramount importance for these less-invasive technologies.
Option: Active surveillance with delayed intervention should be discussed as an option for patients wishing to avoid treatment and willing to assume oncologic risk.
Approximately 80% of all clinical T1a renal masses are malignant, and of these, about 20% to 30% demonstrate potentially aggressive histologic features. The risk of tumor progression that could preclude NSS or lead to unsalvageable systemic metastases is not well defined in the current literature. Enhanced renal mass biopsy (incorporating molecular analyses) holds promise for assessing aggressive potential; however, further research will be required to define the utility and limitations of this approach. Healthy patients considering AS must be willing to assume a calculated risk of tumor progression.
Guideline for Management of the Clinical T1 Renal Mass Campbell et al J Urology 182: October 2009

45. AUA Guidelines Meta-analysis – Local Recurrence-Free Survival Results of Percutaneous Ablation vs Partial vs Radical Nephrectomy
Local Recurrence-Free Survival
Study Type
# of Studies
Survival Rate (%)1
95% Confidence Interval2
Mean/Median Patient Age (yrs)3
Mean/Median Tumor Size (cm)3
Mean/Median Follow-Up (mos)3
Lower Limit (%)
Upper Limit (%)
Cryo 10
90.6
83.8
94.7
67.0/67.0
2.5/2.6
19.5/18.2
RFA
87.0
83.2
90.0
67.6/70.0
2.8/2.7
22.9/19.4
LPN 17
98.4
97.1
99.1
61.2/61.0
2.6/2.6
20.8/15.0
OPN 21
98.0
97.4
98.5
60.5/60.0
3.3/3.1
55.5/46.9
LRN 8
99.2
98.2
99.7
60.7/61.0
4.6/4.6
30.2/17.7
ORN
98.1
97.3
98.6
62.6/63.0
4.6/4.8
59.3/58.3
Cryo = cryotherapy RFA = radiofrequency ablation LPN = laparoscopic partial nephrectomy OPN = open partial nephrectomy
LRN = laparoscopic radical nephrectomy ORN = open radical nephrectomy

46. AUA Guidelines Meta-analysis – Complication Rates Percutaneous Ablation vs Partial vs Radical Nephrectomy
Major Urological Complications
Study Type
# of Studies
Complication Rate (%)1
95% Confidence Interval2
Mean/Median Patient Age (yrs)3
Mean/Median Tumor Size (cm)3
Lower Limit (%)
Upper Limit (%)
Cryo 15
4.9
3.3
7.4
67.0/66.7
2.6/2.6
RFA 20
6.0
4.4
8.2
68.5/70.0
2.7/2.7
LPN 22
9.0
7.7
10.6
60.4/59.9
OPN
6.3
4.5
8.7
59.5/59.0
3.2/3.0
LRN 13
3.4
2.0
5.5
60.7/61.0
4.8/5.1
ORN 6
1.3
0.6
2.8
62.7/62.3
4.9/5.2
Cryo = cryotherapy RFA = radiofrequency ablation LPN = laparoscopic partial nephrectomy OPN = open partial nephrectomy
LRN = laparoascopic radical nephrectomy ORN = open radical nephrectomy

47. Worse Survival For Radical Nephrectomy vs Partial Nephrectomy
“Compared with partial nephrectomy, radical nephrectomy increases the risk of chronic kidney disease, which is a significant risk factor for cardiovascular events and death. Given equivalent oncological efficacy in patients with
small renal tumors, radical nephrectomy may result in overtreatment.”
A total of 2,547 patients (81%) underwent radical nephrectomy and 556 (19%) underwent partial nephrectomy. During a median followup of 4 years 609 patients experienced a cardiovascular event and 892 died. When adjusting for
preoperative demographic and comorbid variables, radical nephrectomy was associated with an increased risk of overall mortality (HR 1.38, p 0.01) and a 1.4 times greater number of cardiovascular events after surgery (p 0.05). However,
radical nephrectomy was not significantly associated with time to first cardiovascular event (HR 1.21, p 0.10) or with cardiovascular death (HR 0.95, p 0.84).
SEER data used, 2991 patients, all > 66 years old
Renal tumours ≤ 4 cm diameter
Surgery between 1995 and 2002
Partial Nephrectomy Versus Radical Nephrectomy in Patients With Small Renal Tumors—Is There a Difference in Mortality and Cardiovascular Outcomes?
Russo et al J Urology 181, 55 January 2009

48. Worse Survival For Radical Nephrectomy vs Partial Nephrectomy
From 1999 to 2006, 1,004 patients with renal masses between 4 and 7 cm underwent extirpative surgery, partial nephrectomy (524) or radical nephrectomy (480) = T2 b tumours.
On multivariate analysis cancer specific survival was equivalent for patients treated with partial nephrectomy or radical nephrectomy.
Those patients undergoing radical nephrectomy lost significantly more renal function than those undergoing partial nephrectomy.
The average excess loss of renal function observed with radical nephrectomy was associated with a 25% (95% CI 3–73) increased risk of cardiac death and 17% (95% CI 12–27) increased risk of death from any cause on multivariate analysis.
OS = Overall Survival
Nephrectomy Induced Chronic Renal Insufficiency is Associated With Increased Risk of Cardiovascular Death and Death From AnyCause in Patients With Localized cT1b Renal Masses Novick et al J Urology 183, April 2010

49. Worse Survival For Radical Nephrectomy vs Partial Nephrectomy
Renal function vs survival in entire surgical group of 1004 patients
Nephrectomy Induced Chronic Renal Insufficiency is Associated With Increased Risk of Cardiovascular Death and Death From AnyCause in Patients With Localized cT1b Renal Masses Novick et al J Urology 183, April 2010

50. Palliative Treatment for Renal Cell Carcinoma
Targeted therapy:
medication that blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumour growth.
Following on from the identification of HIF pathways in Von Hippel-Lindau syndrome, “pathways” identified that are open to manipulation by various molecules.
Currently in Australia two targeted therapies are available on PBS: Sunitinib and Pazaponib, both tyrosine kinase inhibitors.
Bevacizumab (VEG-F monoclonal antibody) has been used and does work in some cases, but not on PBS.
Thalidomide is being trialled for treatment of RCC.
Immunotherapy
originally great hope because of anecdotes of resolution of metastatic RCC after tumour nephrectomy
Interfereron initially used but subsequently proven not to be effective.
Interleukin 2 (IL2) used in the 1990’s but proven ineffective.
IL2 – LAK therapy (lymphokine activated killer cells) with exposure to tumour used NCI shown possible cure in a few
cases.

51. Clear Cell Renal Cancer and Molecular Therapies
Lam et al
Renal Cell Carcinoma 2005:
New Frontiers in Staging, Prognostication
and Targeted Molecular Therapy.
J Urology 173,

52. Targeted Therapy for Metastatic Renal cell Carcinoma
At present, in Europe and/or the USA, six targeted agents are approved for first and
second-line treatment of clear cell metastatic RCC:
sunitinib
sorafenib
temsirolimus
everolimus
bevacizumab (in combination with interferon)
pazopanib
In addition, several new targeted agents, are also currently in development for the treatment of metastatic RCC:
axitinib
tivozanib

53. Targeted Therapy for Metastatic Renal cell Carcinoma
Therapy % Prior nephrectomy Median survival (months) Overall survival (months)
Sunitinib %
Pazopanib (overall survival similar to sutent with ~ 50% less foot-mouth (NEJM )
Bevacizimab %
Sorafanib %
Recent Advances in the Treatment of Advanced Renal Cell Carcinoma: Toward Multidisciplinary Personal Care Bex et al BJUI ;
Sunitinib listed on PBS for Stage IV Renal Cell Carcinoma (RCC), patient must meet the Memorial Sloan Kettering Cancer Centre (MSKCC) low to intermediate risk group criteria, patient must have a WHO performance status of 2 or less, the treatment must be the sole PBS-subsidised tyrosine kinase inhibitor therapy for this condition. Patients who have developed progressive disease on pazopanib are not eligible to receive PBS-subsidised sunitinib
Pazopanib listed on PBS for Stage IV clear cell variant renal cell carcinoma (RCC) Treatment Phase: Initial treatment, Patient must meet the Memorial Sloan Kettering Cancer Centre (MSKCC) low to intermediate risk group criteria, patient must have a WHO performance status of 2 or less, the treatment must be the sole PBS-subsidised tyrosine kinase inhibitor therapy for this condition. Patients who have progressive disease on sunitinib are not eligible to receive PBS-subsidised pazopanib.
Bevacizimab listed on PBS for treatment in combination with first-line chemotherapy, of a patient with previously untreated metastatic colorectal cancer with a WHO performance status of 0 or 1.
Sorafenib listed on PBS for Stage C hepatocellular carcinoma

54. Upper Tract TCC Clinical Management
Relatively uncommon, more common in smokers and in the old days in those exposed to APC analgesics.
3% of patients with bladder TCC get upper tract TCC – more common in high grade bladder TCC.
Lynch syndrome – colorectal cancer and TCC, more commonly ureteric.
Macroscopic haematuria with loin pain and no stone.
CT pyelogram +/- urine cytology useful in diagnostic workup.
Modern diagnosis with flexible ureteroscopy and biopsy.
Traditional management with nephroureterectomy including a 1 cm cuff of bladder adjacent to ureteric orifice.
Laparoscopic radical nephrectomy with open approach to lower ureter and UO with 1 cm bladder cuff now common.
Ureteroscopy and diathermy of small renal pelvic TCC now possible +/- intrarenal Mitomicin to reduce recurrence.
Segmental distal ureteric resection with renal preservation for distal ureteric tumour best option.
Endoscopic resection of UO with “pluck” of ureter (after Semple) for large renal pelvic TCC removed with
laparoscopic nephrectomy is appropriate management.