RENAL CELL CARCINOMA

                 
                     

                       

RENAL CELL CARCINOMA

(Blog by Dr.S.UMA DEVI)

Renal cell carcinoma (RCC)

Introduction

Synonyms Renal adenocarcinoma,Hyper nephroma

A relatively rare and serious disease

The cancerous process starts in certain areas of the kidney.

Early stage renal cancers grow and spread slowly -have a better prognosis, advanced/metastatic cancers rapidly progress and have a worse prognosis.

Facts and Figures about Renal Cell Carcinoma

•   Approximately 210,000 new cases were diagnosed worldwide.

•   ,20-30 percent of RCC patients present with advanced (metastatic) disease. at diagnosis

•   Five-year survival rates

If the tumor is confined to the kidney as high as 80-95 percent. If  with metastatic disease much lower- 20 percent.

•   Until 2005, only limited treatment options were available

•   Interleukin-2 or interferon alfa was widely used as first-line treatment of metastatic disease.

Overall survival rates in  these patients was approximately 12 months.

Risk Factors

Smoking:

smoking doubles the risk of developing RCC.

Obesity:

obese people have a higher risk of developing many types of cancer, including RCC.

In 20 percent of RCC- obesity is a factor.

Age group

50-70yrs

Rare in young age.s

Gender:

Men: women ratio3;1

Family history and genetics:

a strong family history has a higher chance of developing RCC.

Certain genetic conditions including von Hippel-Lindau disease, a rare inherited disorder in which there is abnormal growth of blood vessels in certain parts of the body, increase the risk of developing RCC.

Other risk factors Long term dialysis Tuberous sclerosis

Histological sub types of RCC

Clear cell renal carcinoma most common,less favorable prognosis

Papillary -15% Chromophobe4% Collecting duct carcinoma

And Medullary are aggressive and carry poor prognosis

Other types

Sarcomatoid(high grade end of all subtypes) Heriditory cancer syndrome

Multilocular

Mucinous,tubular and spindle cell carcinoma

Neuroblastoma associated RCC Unclassified

Different subtypes have distinct genetic abnormalities

Genetic testing helps accurate diagnosis and detects recurrence

Biology of Renal Cell Carcinoma

•   Two Proteins found at high levels in RCC

1. Vascular endothelial growth factor (VEGF)

2. Platelet-derived growth factor (PDGF)

•   .Overproduction of these proteins is caused by a genetic mutation,

•   Most common of mutation is the inactivation of the von Hippel-Landau gene.

•   VEGF and PDGF are important to the growth and survival of tumors.

High VEGF levels lead to angiogenesis –that feed the tumor.

High PDGF levels lead to the maturation and survival of newly formed and existing blood vessels and supporting tissue.and thus to tumor progression

.This knowledge is utilized for new therapeutic ventures

Clinical features

Symptoms of RCC

Hematuria – may be painless/blood clots can cause uretric colic lump or a mass in the lumbar region with dull pain

Back pain /flank pain

Tiredness,

Loss of appetite, Weight loss, anemia, Recurrent fever

Hypertension in advanced cases

May be asymptomatic at times.

Signs

1.Abdominal mass 25%

2.Varicocele on left side 2%

(Tumor invasion of left renal vein leads to blocking of left testicular vein) Rt gonodal vein drains directly into IVC

3.Hypertension(secretion of rennin by the tumor)

4.Hirsutism(in females)

5.Stauffers syndrome-Paraneoplastic non metastatic liver disease

Stages of renal cell carcinoma

Stage I Tumor confined to kidney;measures about7cm

StageII spread to fat tissue around kidney measures above 7cm

StageIII has 3 possible situations

INVESTIGATIONS CT scan abdomen MRI

Ultra sound KUSB area Intravenous pyelography Biopsy

Ultraound image of Renal cell carcinoma

Treatment

Cure is related to degree of dissemination and stage of tumor

Early-stage tmt-survival .prolonged (even when regional lymphatics involved)

Rare Variations in course

1.Sometimes locally advanced /metastatic cases show indolent course lasting several years

2.Late recurrence many years after treatment posible

3.Well documented case of spontaneous regression exists but may not survive long

Mainstay of therapy

Surgical removal

In disseminated cases-local regional therapy –is palliative

Systemic therapy-only limited effectiveness

Summary of treatment

Surgery -most common modality

o Partial nephrectomy is as beneficial as total nephrectomy

o Partial nephrectomy reduces chance of kidney failure

Radiation not very effective Chemotherapy not very effective Biological therapy Immunotherapy

Biotherapy

Biological response modifier therapy

Biological therapy uses body’s immune system directly or indirectly Can be complementary to surgery,radiation and chemotherapy Hormone therapy

DETAILS OF TREATMENT

Treatment varies from patient to patient

Treatment approach takes 5 factors into cosideration

1.RCCtype

2.Tumorsize and location

3.Stage of cancer

4.General condition of the patient

5.Patients age Treatment option Surgery Radiotherapy Chemotherapy Hormone therapy

Arterial embolisation Target therapy Biological therapy

SURGERY

2 types

1.Nephrectomy

2.Metastatic removal

Types of Nephrectomy

1.Partial nephrectomy-only part of kidney i.e.site of tumor

Indications:

Patients with only one kidney

BilateralRCC Small tumor

2.Radical nephrectomy

Entire kidney,

adrenal gland,

tissues around the kidney

and regional lymph nodes-removed

3.Simple nephrectomy

Removal of just kidney ;no other additional tissues

Nephrectomy can be

I.         Open nephrectomy

II.       Laproscopic nephrectomy

Common side effects of nephrectomy

Bleeding

Wound infections

Pneumothorax

Damage to nearby organs-

(Spleen,pancreas, aorta,venacava,smalllarge bowel bowel) Kidney failure

Laproscopic nephrectomy –I when tomr is small,confined

ARTERIAL EMBOLISATION

Embolisation of renal artery-

Using small pieces of gelatin sponge,orplasticmicrospheresor ethanolor chemotherapy- injected into renal artery

approach via femoral artery

this procedure shrinks the tumor before surgery used for cases unfit for surgery.

Side effects; back pain ,fever,nausea,vomitting

CHEMO THERAPY

Single drug /combination of several drugs

Administered in cycles(treatment period followed by recovery period) Route of administration  Oral or/Im or IV

But chemotherapy is not very effective

Drus used-Vinblastin,Gemcitabin,5-flurouracil

RADIOTHERAPY

Usually in the form of external beam therapy

1.Before surgery-to reduce size of tumor

2.After surgery-as adjuvant to destroyany remaining cancer cells

3. as palliative therapy

Radiation therapy is not very effective for RCC

HORMONE THERAPY used in advanced stages e.g.Medroxyprogesterone

BIOLOGICAL THERAPY or IMMUNOTHERAPY

Systemic therapy

Acts by improving body’s immune system Used in cases of metastatic cancer Interleukin2

Interferonalfa2a

Bevaci zumab

Side effects-Flu like symptom,kidney damage,breathing difficulty,intestinal bleed

Not very effective TARGETED THERAPY New approach

Targets only the tumor

Mechanism of action:

stop the new blood vessels from growing by blocking vascular endothelial growth factor and platelet derived growth factorVEGF /PDGF

And targets certain factors which cause the cancerous cells to grow

Only 2 drugs have been approved by FDA.

SORAFENIB orally effective/in advanced stagesss

Side effects; rashes,diahrroea,high BP,erythema/blistering of skin over palms and soles

SUNITINIB orally effective

S.E;Diahhroea,high BP,altered taste,bleeding,hypotyroidsm,skin colour change

ANNEXURE

.VEGF as a molecular targeting factor in the treatment of RCC

BEYOND VEGFr INHIBITION

OPTIONS :

INHIBITION OF OTHER MAJOR PATHWAYS

mTOR as a molecular target

mTOR stands for Mammalian Target of Rapamycin

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