Kidney tumors

Petr Klézl

Urologická klinika 3. LF UK a FNKV

Kidney tumors - incidence

Renal cell carcinoma – 2-3% of all cancersAnnual increase of incidence apx. 2% 2007 CZ 34.8: 100 000 men

19.7: 100 000 womenMen 1756, women 1039Peak incidence 60-75 years1.5:1 ratio men: womenAetiology - smoking, obesity, antihypertensive

treatment

Renal tumors - diagnosis

More than 50% tumors diagnosed incidentallyAsymptomatic tumors are generally smaller and of lower

stage classic triad (flank pain, gross hematuria, palpable mass) –

6-10%Paraneoplastic symptoms ( hypertension, weight loss,

pyrexia, neuromyopathy, anaemia, polycythaemia, amyloidosis, elevated erythrocytes sedimentation rate, abnormal liver function) – apx 20-30% patients

About 20-30% of patients with paraneoplastic symptoms present as a result of metastatic disease

Kidney tumours - TNM system

Tx - Primary tumour cannot be assessed T0 - No evidence of primary tumour T1 - tumour ≤ 7 cm in greatest dimension limited to the kidney T1a tumour < 4 cm in greatest dimension, limited to the kidney T1b tumour > 4 cm but < 7 cm in greatest dimension T2 - tumour > 7 cm in greatest dimension, limited to the kidney T2a tumour > 7 cm in greatest dimension but < 10 cm T2b tumours > 10 cm limited to the kidney T3 - tumour extends into major veins or perinephric tissues, but not into the ipsilateral adrenal gland and not beyond Gerota’s fascia T3a tumour grossly extends into the renal vein or its segmental (muscle-containing)

branches, or tumour invades perirenal and/or renal sinus (peripelvic) fat but not

beyond Gerota’s fascia T3b tumour grossly extends into the vena cava below diaphragm T3c tumour grossly extends into vena cava or its wall above the diaphragm or invades the wall of the vena cava T4 - tumour invades beyond Gerota’s fascia (including contiguous extension into the ipsilateral adrenal gland)

Kidney tumours – TNM system

N - Regional lymph nodes NX Regional lymph nodes cannot be assessed No regional lymph node metastasis N1Metastasis in a single regional lymph node N2Metastasis in more than one regional lymph nodeM - Distant metastasis M0 No distant metastasis M1 Distant metastasis

G - HISTOPATOLOGICAL GRADING GX differentiation cannot be assed G1 well differentiated G2 intermediate differentiation G3-4 poor differentiated

STAGE CLASSIFICATION Stage I T1 N0 M0 Stage II T2 N0 M0 Stage III T3 N0 M0 T1,T2,T3 N1 M0 Stage IV T4 N0, N1 M0 any T N2 M0 any T jakékoliv N M1

http://www.uicc.org/tnm

Kidney tumors – histopathological classification

Fuhrman nuclear gradingRenal cell carcinoma – subtypes - clear cell carcinoma (80-90%)

- papillary RCC ( 10-15%) - chromophobe RCC (4-5%) - collecting duct carcinoma (1%)

Other renal tumors

RCC types account for about 85-90% renal malignancies

10-15% variety of uncomon carcinomas, several benign kidney tumor masses

Angiomyolipomas AML– can be differentiated by radiological imaging from RCC

AML – surgery, thermal ablation, embolisationRenal cysts – Bosniak classificationOncocytomas – verified by biopsy, follow-up can be

considered

Kidney tumours - diagnosis

CT scan with intravenous contrast - enhancement

UltrasoundMRI – alternative to CT scanChest X-ray

Bone scanBrain CTRenal biopsy

US - abscessus

US – tumour of lower pole

Tumour on convexity of kidney

Kidney tumours - treatment

Nephron-sparing surgeryNephrectomyAblative therapiesMetastasectomyEmbolisationAdjuvant therapy ( only clinical trials)Systemic therapyRadiotherapy

Localized RCC - treatment

• nephron-sparing surgery - open partial resection - laparoscopic resection – centres - robotic resectionNephrectomy – when nephron-sparing

surgery not indicated - tumour size - unfavourable localization - general health status

Nephron – sparing surgery - indications

Absolute indications - anatomical or functional solitary kidney - bilateral kidney tumours

Relative indications - functioning opposite kidney affected by a condition

that may impair renal function - hereditary forms of RCC with high risk developing tumour in contralateral kidney - elective operation – healthy contralateral kidney

Kidney tumours – treatment

Radical nephrectomy Approach – laparoscopic nephrectomy T1bT2 - open surgery Adrenalectomy Lymphadenectomy

T2

T2

Xantogranulomatous pyelonephitis

Open resection of renal tumour

Specimen after tumour resection

T3b

Minimally invasive alternative treatment

RFA – radio-frequency ablationcryotherapyMicrowave terapieHIFU- Experimental methods- Low morbidity- Risk pacients not fit for surgery- Recurrence rate higher than nephron-

sparing surgery

Embolization

Embolization of primary tumour - gross hematuria - local symptoms – pain - patients unfit for surgical operation - no benefit before radical nephrectomy

• embolization of metastasis - before resection of major bone metastasis

Adjuvant treatment

Adjuvant tumour vaccination may improve duration of progression-free survival – high risk pt – T3

Cytokine therapy does not improve survival 3 phase III studies are ongoing – therapy

with targeting agents

Outside controlled trials no indication for adjuvant therapy

Metastasesectomy

Complete removal of metastases contributes to improved clinical prognosis

Patients with resectable mets and good performance status ( PS)

Radiotherapy for metastases

Non-resectabel brain metastasesBone metsSymptomatic therapy – pain relief

Surgical treatment of metastatic RCC ( mRCC)

Cytoreductive nephrectomy – only palliative Meta analysis comparing NE +

imunotherapy vs imunotherapy alone – increase of long term survival of patients who underwent nephrectomy

No data available for antiangiogenic therapy

Cytoreductive nephrectomy is recommended when possible

Systemic therapy for mRCC

Imunotherapy – IFN-α (patients with PS, preferably sole lung mets)

Targeting agents – sunitinib, bevacuzimab, temsirolimus

Prognostic criteria (MSCC) Motzer - Karnowsky performance status - Hemoglobin - lactate dehydrogenase - serum calcemia

Angiogenesis inhibitor drugs

Advances in molecular biology led to development of novel agents

Vascular endothelial growth factor (VEGF) and platelet –derived growth factor (PDGF) overexpression due to defective VHL protein

Tyrosin kinase inhibitors ( TKIs) – Sorafenib, Sunitib, Pazopanib

VEGF antibodies – BevacuzimabMammalian target of Rapamycin

(mTOR)inhibitors –Temsirolimus, Everolimus

Systemic therapy - RCC

Systemic therapy of mRCC

therapy risk and previous therapy recommended agent

First - line low and intermediate risk sunitinib bevacizumab + IFN-α high risk temsirolimus

Second line prior cytokine therapy sorafenib prior VEGFR therapy everolimus prior mTOR inhibitor therapy clinical trialsdie

Surveillance after treatment for RCC

Low risk - chest X-ray, US Intermediate risk - chest X-ray, US, CT every 2nd yearHigh risk - chest X-ray, US, CT every year