Renal Cell Carcinoma

Dr. Sunil Shroff

Prof. & HOD – Urology and Renal Transplantation
Sri Ramachandra Medical College & Research Institute,
www.srmcurology.com

• Introduction
• Incidence and Global Burden
• Types of Renal Tumors
• SCREENING FOR RCC: TARGET POPULATION
• PATHOLOGY
• CLINICAL FEATURES
• INVESTIGATIONS
• STAGING 
• TREATMENT

INVESTIGATIONS

Investigation include –

• Urine analysis,
• Complete blood count,
• Electrolytes,
• Renal profile,
• Liver function tests,
• Calcium,
• ESR,
• PT, PTT

Ultra sonogram - is usually the initial investigation, and CT scan with IV contrast is the investigation of choice. Picks up early RCC and these are called Incidentaloma.

An incidentaloma is a tumor (-oma) found by coincidence (incidental) without clinical symptoms and suspicion.



Ultrasound showing lower pole Tumor


CT scan has a sensitivity of 78% and 96% for renal vein and IVC involvement. 



CT scans showing the lower pole renal tumor

MRI has benefit in defining venous invasion.
Indications for MRI

• Locally advanced malignancy
• Venous involvement
• Renal insufficiency
• Contrast allergy
• To distinguish tumor thrombus from bland thrombus.

IVU, Arteriography, Venography are seldom performed now.

PET scan has a role to play in detecting metastasis than for detecting primary tumor.

Bone scan is indicated only if patients are symptomatic or has elevated alkaline phosphatase.

Role of FNAB in RCC

• Fine needle aspiration or biopsy (FNAB) of RCC not indicated as 83 - 90 % of renal masses prove to be RCC and 5 -15% of RCC are missed by FNAB.
• Indications of FNAB
  1. Metastatic RCC
  2. Renal abscess
  3. Lymphoma
  4. Metastasis to kidney
• Complication of Renal Biopsy –
  1. Bleeding
  2. Infection
  3. A-V Fistula
  4. Needle tract seedling
  5. Pneumothorax

STAGING

2002 AJCC cancer staging for RCC

TX : Primary tumor cannot be assessed T0 : No evidence of primary tumor T1a : Tumor ≤ 4.0 cm and confined to kidney T1b : Tumor > 4 cm and ≤ 7 cm and confined to kidney T2 : Tumor > 7 cm and confined to kidney T3a : Tumor invades adrenal gland or perinephric fat but not beyond Gerota’s fascia T3b : Tumor extends into the renal vein or vena cava below diaphragm T3c : Tumor extends into IVC above the diaphragm or invades wall of IVC T4 : Tumor invades beyond Gerota’s fascia Nx : Regional LN cannot be assessed N0 : No regional LN metastasis N1 : Metastasis in a single regional LN N2 : Metastasis in more than one regional LN Mx : Distant metastasis cannot be assessed M0 : No distant metastasis M1 : Distant metastasis present

Stage I	T1	N0	M0
Stage II	T2	N0	M0
Stage III	T1 or T2	N1	M0
	T3	N0 or N1	M0
Stage IV	T4	any N	M0
	Any T	N2	M0
	Any T	any N	M1

Simpler Staging based on modification of Robson staging
Stage I and II is considered early tumor that has a better cure rate. Stage III and IV is advanced disease with guarded prognosis In clinical practice a modification of Robson staging (Flocks and Kadesky system) is used. The Robson staging system is as follows: Stage I - Tumor confined within capsule of kidney Stage II - Tumor invading perinephric fat but still contained within the Gerota fascia Stage III - Tumor invading the renal vein or inferior vena cava (A), or regional lymph-node involvement (B), or both (C) Stage IV - Tumor invading adjacent viscera (excluding ipsilateral adrenal) or distant metastases

TREATMENT

Treatment of Localized RCC

Radical nephrectomy-

Objective of radical surgery is to excise the tumor with an adequate surgical margin. It is considered as Gold standard treatment for localized RCC with contralateral normal kidney.

PRINCIPLES OF SURGERY – Early ligation of renal artery and vein , removal of kidney including Gerota’s fascia, removal of ipsilateral adrenal gland, regional lymphadenectomy from crus of diaphragm to aortic bifurcation.

Surgical approach to RCC

1. Extraperitoneal flank incision- Used for small tumors, elderly people
2. Thoracoabdominal incision- Large tumor involving upper pole of kidney
3. Transperitoneal incision - Helps in abdominal exploration and early access to vessels
4. Extended subcostal incision
5. Laparoscopy - Tumor size less than 8 cms, no local or renal vein invasion.

Nephron Sparing Surgery

Indications-

1. Bilateral RCC
2. RCC in a solitary functioning kidney
3. Unilateral RCC with contralateral kidney under threat of its future function (Renal artery stenosis, Chronic pyelonephritis , Hydronephrosis, Ureteral reflux, Calculus disease, Systemic disease such as diabetes )
4. Tumor less than 4cms with normal opposite kidney.

• Cancer free survival rates are 78% to 100%
• Local tumor recurrence of 10% is reported.

Renal cryosurgery

• Aim - To ablate the same amount of tissue as excised in open procedure.
• Prerequisites- Rapid freezing and gradual thawing, with repetition of freeze thaw cycle.
• The devitalized tissue sloughs over time with healing by secondary intention.
• Temperature range from ( -19.4c to 0c)
• Performed by Open, Percutaneous or Laparoscopic technique.

Treatment of Metastatic RCC

33% patients of RCC present with metastatic disease at presentation

Palliative Nephrectomy –

Indicated in patients with –

• Severe hemorrhage,
• Severe pain,
• Paraneoplastic syndrome
• or compression of adjacent viscera
• Solitary metastasis can be resected and may show some survival advantage.

Chemotherapy

• RCC is a chemo resistant tumor. Phenomenon due to presence of multi drug resistant glycoprotein (MDR) in tumor cell - causes extrusion of the drug
• 5-FU alone has a response rate of 10%,
• 5- FU but when used in combination with interferon - 19% response rate
• Phase 2 trial of weekly intravenous gemcitabine (600 mg/m2 on days 1, 8, and 15) with continuous infusion fluorouracil (150 mg/m2/d for 21 d in 28-d cycle) in patients with metastatic renal cell cancer produced
• Partial response rate of 17%, Floxuridine (5-fluoro 2'-deoxyuridine [FUDR]), 5-fluorouracil (5-FU), Vinblastine, Paclitaxel (Taxol), Carboplatin, Ifosfamide, Gemcitabine.

Recent Treatment options for Metastatic RCC –

1. Sunitinib for first-line treatment of patients with favorable or intermediate outlooks
2. Temsirolimus for first-line treatment of patients with a poor outlook
3. Sorafenib (Nexavar®) – approved by the FDA in 2005 – for second-line treatment of patients previously treated with biological therapy.

Vaccines

Vaccines for RCC includes autologous tumor cells, autologous dendritic cells and heat shock protein. The use of vaccines in patients with advanced RCC remains investigational.

Immunotherapy

RCC evokes an immune response, which has occasionally resulted in spontaneous and dramatic remissions. In an attempt to reproduce or accentuate this response, various immunotherapeutic strategies have been used, including nonspecific stimulators of the immune system, specific antitumour immunotherapy, adoptive immunotherapy, the induction of a graft-vs-tumor response via allogeneic haematopoietic stem cell transplantation, and the administration of partially purified or recombinant cytokines.

The nonspecific cytokines IL-2 and IFNα have shown promising results with improvement in median survival.

Clinical response to immunotherapy seen in patients with -

1. Good performance status
2. Had a prior nephrectomy
3. Non bulky pulmonary or soft tissue metastasis
4. Asymptomatic patient

PROGNOSIS

Depends on

Pathological stage
Tumor size
Nuclear grade
Histological subtype prove to be important prognostic factors

Prognosis – RCC / Radical Nephrectomy

A tumor confined to the kidney is associated with a better prognosis.
Stage I - 5-year survival rate is approximately 94%,
Stage II - Survival rate of 79%.
Stage III - IIIB renal cell carcinoma is 18%.
Stage IV 0 - 20%
Surgical removal of renal vein or IVC thrombus – 5-yr survival 25 -50%.
15-20% reduction in survival over 5 year with invasion of perinephric fat.
Systemic metastasis 1 year survival rate less than 50%

References

1. This figure is based on the male population only. American Cancer Society website, Statistics for 2005. (http://www.cancer.org)
2. Jemal A, et al. CA Cancer J Clin. 2006;56:106-130.
3. Ries LAG, et al. SEER Cancer Statistics Review, 1975-20