Renal Tumors

Part II
Scott Wilkinson, DO, MS

Treatment Pearls

Obstacles Towards
Treatment

RCC is historically resistant to many

types of treatment

Chemotherapy (MDR-1)
Radiation

Very aggressive in nature (TGF alpha

and EGFR)
Highly vascular (VEGF secondary to
loss of vHL)
Expresses tumor-associated antigens
(PRAME, RAGE-1, gp75, and MN-9)
which contributes to its
immunogenicity

Tx of Localized RCC
Radical nephrectomy
Nephron-sparing surgery (NSS)
NSS with normal opposite kidney
NSS with vHL disease
Thermal ablative therapies
Observation

Radical nephrectomy
Robson and colleagues gold
standard 1969
Prototype A then B, Gerotas
intact, ipsi adrenal, LND (crus to
aortic bifurcation)
Now no adrenal if: no rad
evidence unless extensive renal
involvement, locally advanced,
located upper pole, immediately
adjacent to adrenal

Today LND = controversial

Heme & Lymph spread
Lymphatic drainage variable

<2-3%

benefit

However, more accurate staging

Risk factors indicating LND

High tumor grade
Sarcomatoid component
Histologic tumor necrosis
Large size (> 10 cm)
pT3 or pT4

*incidence 10% with 2 or >, 0.6% if <

Surgical approach determined by

size, location of tumor and body
habitus
Transperitoneal

Subcostal
thoracoabdominal

Extraperitoneal

Flank

Laparoscopic (trans, retro, handassist)

Laparoscopic
Cancer specific survival comparable
to open
Usually < 8-10cm; localized with no
local invasion, renal vein
involvement, or lymphadenopathy

RN Surveillance
Stage

H/E/labs CXR CTa/p

T1NOMO

yearly

----

T2NOMO

yearly

T3a-cNOMO
1yr then q 2 yr

Bone scans, plain xr, and head CT if clinically

indicated

yearly

q 6m x 3 yr - yr

---q 2 yrs
same

Nephron-Sparing Surgery
Czerny 1890
Vermooten 1950 NSS
Indications include situations
where pt would be anephric or
high risk of needing HD

Solitary kidney RCC

Bilateral RCC
Contralateral dz (RAS, Hydro,
chronic pyelo, reflux, stones, DM,
nephrosclerosis)

A functional remnant of at least 20%

of one normal kidney is necessary to
avoid end-stage renal failure
IF solitary kidney, > 50% reduction
in renal mass = incr risk of
hyperfiltration renal injury
(proteinuria, focal segmental
glomerulosclerosis, progressive renal
failure)

Prevention: Protein restriction & ACEI

Preoperative testing
r/o local extension, mets,
vascular/collecting system relationship
Renal angio, veno, 3DCT or MRI

Cancer-specific survival rates 78100%

Recurrence undetected dz in
remnant
Complications majority
hemorrhagic

NSS Surveillance
Stage

H/E/labs

CXR
----

T1NOMO

yearly

T2NOMO
yrs

yearly

T3NOMO q 6m x 3 yr - yr
x3y q2yr

CTa/p
----

yearly

q2

same

q6m

NSS with normal opposite kidney

CSS 5yr 100% with small unilat T1-2

CSS 5 yr central vs peripheral (100

vs 97%), tumor recurrance (5.7 vs
4.5%), renal fxn equivocal

Licht et al 1994 (< 4 cm)

Hafez et al 1999

Adv: 17-28% excised = benign

(MSK)

NSS in vHL disease

Differs via young age @ dx,
usually multiple bilateral tumors
Solid and cystic (lining of
hyperplastic clear cells)
Intraop US may help to get all
Options B/l RN, PN & RN, B/l PN

High incidence of recurrence in

remnant 27.4%

Duffey and colleuges 2004 3 cm

threshold

Thermal ablative
Both

perc or lap approach

Lack of histo/path staging
? High recurrence rate
Ideal advanced age, comorbidities, local
recurrance, hereditary renal cancer

Cryosurgery
Repetition of freeze-thaw cycle (-20C)
Immediate cellular cryodestruction
and delayed microcirculatory failure.

Radiofrequency ablation
45C irreversible cell damage
55-60C immediate cell death

Thermal Ablative Pearls

In general, enhancement within the

tumor bed on extended follow-up
has been considered diagnostic of
local recurrence, and the clinical
experience thus far has supported
this

Observation
Median growth rate 0.36 cm/yr
Alternative for asymptomatic elderly
and poor surgical risk, consider with
solid/small/enhancing/wellmarginated/homogeneous

Serial imaging 6mo or 1yr intervals

Not appropriate: >3cm, poor

margins, nonhomogeneous, young
healthy with abn imaging

Tx of Locally Advanced
RCC
IVC involvement
Locally invasive RCC
Local recurrence after RN or NSS
Adjuvant therapy for RCC

IVC Involvement
Unique feature of RCC
45-70% of RCC with IVC
thrombus cured

Local extension/invasion much

higher risk of recurrence

Occurs 4-10% of patients

Suspect with : LE edema, R
varicocele, distended abd veins,
proteinuria, PE, R atrial mass,
nonfxn kidney

IVC Thrombus staging

I adjacent to ostium of renal vein
II extends up to liver
III intrahepatic portion of IVC below
diaphragm
IV above the diaphragm

Imaging
? CT & AUS
Occasional TEE and TA doppler
Contrast inferior venacavography if
prob with MRI
MRI study of choice
? Renal arteriography

Locally Invasive RCC

Present with pain from invasion of
posterior abd wall, nerve roots or
paraspinous muscles
Duodenal & pancreas uncommon
En bloc may be beneficial
Partial / debulking only 12% alive
in 1 yr
Preoperative rad not beneficial
(van der Werf-Messing 1973)
Residual tumor, rad may retard
growth (Kao et al 1994)

Local Recurrence after RN or NSS

LR in RN 2-4%
Risk factors T stage, local adv,
node + disease
LR in NSS 1.4-10%
Risk factors T stage
Most LR occur distant to tumor bed

*pts with isolated recurrence after PN can ?

Repeat PN

Adjuvant Therapy for RCC

Include hormonal manipulation,
radiotherapy, vaccines, cytokines,
etc
Most studies to date not
significant
Vaccine irradiated tumor
cells/BCG, heat shock proteins
(HSPPC) = no proven benefit
Interferon alfa modest survival
benefit
IL-2 no benefit

Tx of Metastatic RCC
Nephrectomy
Hormonal therapy
Chemotherapy
Radiation therapy
Cytokines and Immunologic
therapy
Multimodal therapy

Nephrectomy
1/3rd of RCC have mets
40-50% will develop mets after
initial dx
Regression of mets after RN 1-2%
(lung)
Benefit for synchronous mets with
interferon alfa after RN

Individuals with: adv dz (PS > 2), mets

(CNS, SC compression), MOD,
significant comorbidities not
candidate

Hormone Therapy
Minimal value

Progesterone inhibit growth of

DES-induced renal tumors in Syrian
hamsters
No

correlation with human RCC

Progestational agents = useful

for symptom palliation

Chemotherapy
1980s chemo-resistant tumor
Variety of agents RR 6%
Yagoda and assoc 1995
In past, fluoropyrimidines & vinblastine
RR 2.5% (better with Vin and I-alfa)
Uniformly discouraging
MDR-1 (P-glycoprotein) = efflux pump
reducing intracellular [] of agents
? Role of Ca channel blockers,
cyclosporine

Metastatic Non-clear cell or sarcomatoid diff (doxorubicin &

gemcitabine) RR 39%
Anecdotal responses with collecting duct cancers with cisplatin
& gemcitabine

Radiation Therapy
Considered as the primary therapy
for palliation
Dose of 4500 centigray (cGy) is
delivered, with consideration of a
boost up to 5500 cGy
Preoperative radiation therapy
yields no survival advantage
Palliative radiation therapy often is
used for local or symptomatic
metastatic disease

Cytokines and Immunologic Therapy

Interferon alfa protein with antiviral,
immunomodulatory and
antiproliferative activity
IL-2 stimulates cell mediated
immunity (cytotoxic T cells)

Single agent ORR 13-15%

Combination > 20%, no change OS
Most effective regimen for IL-2 =
high dose

SE vascular leak (HypoTN, oliguria,

organ failure = tx IVF)

*Improved OS with combo (vin, 5-FU, IL-2)

Treatment
Multi-kinase inhibitors (VEGF and PDGF)
Sorafenib (Nexavar) OS 3 months

Sunitinib (Sutent)

Dec 2005 FDA - 769 patients randomized

median PFS was 6 mo sorafenib vs. 3 mo placebo
7 (2%) sorafenib patients and 0 (0%) placebo
patients had confirmed partial responses.
FDA in January 2006
(40% partial responses) and a median time to
progression of 8.7 months and an overall survival of
16.4 months

Bevacizumab (IgG1 monoclonal ab

Time to progression 4.8 mo vs placebo 2.5 mo

Combo with erlotinib ORR 26% with PFS 11 mo

Multimodal Therapy
Synchronous mets = RN then
systemic therapy (IL-2, I-a, kinase
inhibitors)
Most = RN first
Alternative delayed RN and only
patients showing regression or
stability of mets get surgery
Solitary mets = metatectomy
(pulm have more favorable
prognosis, > 12mo)

Other Malignant Renal

Tumors
Sarcomas of the kidney
Renal lymphoma and leukemia
Metastatic tumors
Other malignant tumors of the
kidney

Sarcomas of the kidney

1-2% of adult malignant tumors
5th decade
Rapid growth +/- lymphadenopathy
Derived mesenchymal components
(free of barriers)
Pseudocapsule
Tx RN with enbloc
Chemo (doxycycline and ifosfamide)
have shown some activity
Combo rad / chemo not well
defined for renal

Leiomyosarcoma most common

50-60%
Origin smooth muscle
Female / 4th to 6th decade
Liposarcoma confused with AML
+/- response to rad/cisplatin
Osteogenic sarcoma Calcium /rock
hard
*Less common rhadomyosarcoma,
fibrosarcoma, carcinosarcoma,
angiosarcoma, malignant
hemangiopericytoma (very vascular)

Renal Lymphoma and Leukemia

Found in autopsy of 34% pts with L
or L
Renal involvement more common
with Non-Hodgins

B symptoms fever, wt loss, fatigue

Heme dissem 90%

Suspect with mass RPLA,
splenomegaly, LA elsewhere
Renal leukemia more common in
children (ALL > AML)

Perc bx, chemo +/- rad (CHOP)

Metastatic tumors
Most common malignant tumor
of the kidney
Sources lung, breast, GI,
malignant melanoma
Suspect with multiple renal
lesions and widespread mets or a
h/o nonrenal primary ca = Bx

Other Malignant Tumors of the Kidney

Carcinoid (neuroedocrine cells) rare
Correlation with horseshoe kidney
Check urine or plasma serotonin
Minority carcinoid syndrome (episodic
flushing, wheezing, diarrhea)
Surgical exision is mainstay of tx

NSS

preferred
Colon/EGD r/o multifocal

Wilms
3% seen in adults
Triphasic
Staging and tx same as for children
Multimodal therapy (surg, chemo,
+/- rad)
Prognosis worse in adults

PNET (primitive neuroectodermal

tumor)
Related to Ewings sarcoma
Derived from neural crest cells
Hist small round cells (Homer
Wright rosettes)
Difficult to differentiate from RCC
Multimodal tx (RN or debulk,
chemo, rad)

Small cell carcinoma

Locally advanced or metastatic
at presentation
Multimodal tx (RN or debulk with
platinum based chemo)

Paraneoplastic
Syndromes

Up to 30% of RCC patients

Reversible with tumor resection
If persist after resection, r/o mets
Syndromes

Elevated ESR
Wt loss, cachexia
Fever
Anemia
HTN (increased renin)
Hypercalcemia (PTH like substance
Stauffers syndrome
Elevated Alk phos
Polycythemia (incr erythropoietin)

Management of Para-neoplastic
Problems

Hypercalcemia

Pamidronate or zolendronate
These

may also alter the bone

microenvironment in a way that
interrupts tumor growth
Inhibits osteoclastic activity

Hydration
Diuretics
Steroids
Calcitonin

Resolve with nephrectomy

Palliative / supportive care

Pain, bleeding

Analgesic medications
XRT to sites of painful mets (esp bone mets)
XRT for cord compression
Arterial embolization

No survival benefit but can relieve Sx

Clot colic

Ureteral stents
hydration

References

Wein, Alan J.; et al; Campbell-Walsh

Urology, Saunders publishing, 9th edition,
chapter 47, pages 1608-37.
Hanno, Philip M.; et al; Clinical Manual of
Urology, McGraw-Hill Publishing, 3rd
edition, pages 487-502.
Wieder, Jeff A.; Pocket Guide To Urology,
Griffith Publishing, 3rd edition, pages 1-20.

Questions