MANAGEMENT OF RENAL TUMORS

By Dr Anil Gupta Moderator Dr Renu Madan

Classification of renal tumors

Renal parenchymal tumorsAdult renal tumors- Benign renal tumors- angiomyolipoma, oncocytoma, adenoma, cysts- Malignant renal tumors- Renal cell carcinoma(mc), sarcoma, lymphoma

Paediatric renal tumors- wilm's tumor, rhabdoid tumor

Renal Pelvis and Ureter- urothelial carcinoma

Renal Pelvis and Ureter

> 90% urothelial carcinoma

Accounts for 7% of all kidney tumors and 5% of all urothelial malignancies

Staging similar to bladder cancer

Treated in the line of bladder cancer

Renal parenchymal tumors

WHO classification of renal tumors(2016)

RENAL CELL CARCINOMA

Introduction

Malignant tumors of the kidney and renal pelvis account for nearly 4% of cancer cases and over 2% of cancer deaths in the United States

RCC represents over 90% of all malignancies of the kidney in adults

Male:Female ratio is 2:1

It predominantly in the sixth to eighth decade of life with median age at diagnosis around 64 years of age

Highly vascular

Not grossly infiltrative, except some collecting duct RCC and some sarcomatoid variants

No reliable histologic or ultrastructural criteria to differentiate benign from malignant renal cell epithelial tumors, except oncocytoma which is always benign

Epidemiology

Increases were seen mainly for localized cancers
- heightened clinical surveillance
- improved diagnostic capabilities

EstablishedTobacco exposure- Increases risk by about 50% in men and 20% in women

Obesity- Increases 24% for men and 34% for women for every 5 kg/m2 increase in BMI

Hypertension

Genetic factors- Von Hippel-Lindau (VHL) syndrome- heriditary papillary RCC- heriditary leiomyoma RCC- Birt-Hogg-Dube syndrome(BHD)- TS-ADPKD

Risk Factors

Putative (generally considered to be)Lead compoundsVarious chemicals (e.g., aromatic hydrocarbons)Trichloroethylene exposureOccupational exposure (metal, chemical, rubber, and printing industries)Asbestos or cadmium exposureCRF on dialysis and antihypertensiveRadiation therapyDietary (high fat/protein and low fruits/vegetables)

Genetic factors

Clinical Presentation

Called the great mimicker or the internists tumor

Many remain asymptomatic until the late disease stages

Classic triad - unilateral flank pain, hematuria, and palpable mass in 6-10%

Propensity to present with manifold clinical signs, symptoms, and paraneoplastic syndromes on the basis of local tumor extent, distant spread, biological activity

Can be true incidental tumors, classic triad symptoms, and constitutional symptoms (weight loss, fever, night sweats, anorexia, cough, malaise, etc.)

Anemia (21-41%)

Elevated sedimentation rate (50-60%)

Reversible hepatic dysfunction (10-15%)

Fever (7-17%)

Amyloidosis (3-5%)

Neuromyopathy (3%)

Hypercalcemia (3-6%)

Paraneoplastic syndromes

Erythrocytosis (3-4%)

Hypertension (22-38%)

Elevated human chorionic gonadotropin levels

Cushing syndrome

Hyperprolactinemia

Ectopic insulin and glucagon production

Raised alkaline phosphatase levels (10%)

Cachexia, weight loss (35%

Stauffer syndrome- liver dysfunction secondary to RCC- due to production of hepatotoxins or IL-6, IL-8

Grading

Fuhrman grading

A simplified, nuclear grading system, based only on size and shape of nucleoli, will replace present system (ISUP conference 2015)

Prognostic factors

Overall, tumor related factors such as pathologic stage, tumor size, nuclear grade, and histologic subtype= independent

Patient related factors such as CKD and co-morbidity have a significant impact on overall survival

Clinical findings s/o compromised prognosis in presumed localized RCC- Symptomatic presentation- Weight loss of more than 10% of body weight- Poor performance status

Other molecular prognostic factors,

Normogram

Karakiewicz PI et al

Diagnostic evaluation

Baseline workup - LFT, KFT, Creatinine clearance, CBC, ESR, coagulation study, urinalysis , Renal scintigraphy

Essential workupCT Scan

Complimentary workupUltrasound, MRI, PET, renal tumor biopsy

Emits sounds ( 3 to 7 Mhz) and receives echo

Strength of the echo determines the brightness setting for that cell

white for a strong echo, black for a weak echo, and varying shades of grey for everything in between

.

Ultrasonography

Normal KidneyMeasures 9-11 cm's

Has the same extent of echoes as liver

Cortex measures about 2.5 cm's

Central echoes are from fat surrounding renal pelvis.

Renal pelvis is filled with urine and is echo free. Note the posterior enhancement behind renal pelvis

Major criteria for a single simple cyst are:the mass is round and sharply demarcated with smooth walls

no echoes (anechoic) within mass

strong posterior wall echo indicating good sound transmission through the cyst

If US equivocal (complex cyst), or suggestive of malignancysolid or complex

with internal echoes

and irregular walls

if calcifications or septae are seen

if multiple cysts are clustered so that they may be masking underlying carcinoma

PROCEED TO CT....

CT Imaging

Radiologist's tumor

Most reliable method for detecting and staging renal cancers

Ideal CT examination for renal masses

- precontrast

- arterial phase (~25 seconds post injection)---> useful for identifying the renal arteries and for hypervascular masses

The nephrographic phase is generally the most useful for detecting renal lesions because the normal renal parenchyma is uniformly enhanced, yet there is still no excretion within the collecting system to interfere with the image. As a consequence, tumors generally appear low in density compared to the normal parenchyma. Highly vascular tumors, however, may be masked by the relatively high-density normal parenchyma. This phase also offers uniform enhancement of the veins making it the best time point for assessing renal vein and inferior vena cava thrombus arising from a tumor (Fig. 42.5). This phase has the highest sensitivity and specificity for renal masses (Fig. 42.6). Direct coronal and sagittal reconstructions have been particularly useful in identifying vessels, thrombi, and anatomic relationships between the renal cancer and adjacent structures.

- nephrographic (~90 seconds post injection)---> has the highest sensitivity and specificity for renal masses - excretory phase (~57 minutes post injection---> assessment of collecting system and renal pelvic involvement by a tumo

A change of 15 or more HUs demonstrates enhancement

CT provides information on- Function and morphology of the contralateral kidney

- Primary tumour extension; - Venous involvement; - Enlargement of locoregional LNs; - Condition of the adrenal glands and other solid organsA typical finding of RCC- heterogeneous pattern of enhancement-enhancement of iv contrast material by more than 15 HU should be considered an RCC until proved otherwise

MRI

MRI is used to evaluate solid tumors seen on CT if a patient is unable to receive IV contrast.

Vascular invasion, IVC thrombi are better demonstrated than CT

Using bight blood technique running blood shows bright signals except thrombus which shows as defects within the lumen

PET Scan

For patients with high risk of metastatic RCC

Good specificity but suboptimal senstivity

At present its best role is for patients with equivocal findings in conventional imaging

Radiolabelled monoclonal antibody to CA-IX is virtually present in all ccRCC

Monoclonal antibody G250 labelled PET is explored

Intravenous pyelographyPros- provide valuable information pertaining to the pyelocalyceal system- less resources required Cons- limited sensitivity for renal parenchymal pathologies and small renal masses- time consuming-Contrast toxicity

Renal angiogram- now limited role- guiding the operative

approach when attempting to perform a partial nephrectomy

Renal tumor biopsy

Can be performed under LA, with core needle or fine needle

At least two good quality cores should be obtained

Peripheral biopsies are preferable for larger tumours, to avoid areas of central necrosis

A coaxial technique allows multiple biopsies

Sensitivity- 99.1 %

Specificity 99.7%

Diagnosis of tumour histotype is good

Complications - bleeding, infection, arteriovenous fistula, needle track seeding, pneumothoraxMoreover........ - sampling error, -difficulty interpreting limited tissue - now we have improved diagnostic accuracy of imaging modalities

90% of solid renal masses thought to be suspicious for RCC on imaging prove to be RCC on final pathologic analysis

Present day indications- radiologically indeterminate renal masses- select patient kept on active surveillance with small renal mass- obtain histology before ablative treatments- select the most suitable form of medical and surgical treatment strategy in the setting of metastatic disease

STAGING

- Renal hilar
- Caval (paracaval, precaval, and retrocaval) -Interaortocaval
- Aortic (paraaortic, preaortic, retroaortic)

Clinical Staging

Survival by stage

Management of Localized RCC(Stage I)

Radical nephrectomy

Earlier gold standard( Robson et al, 1969)PrototypeEn bloc removal of the kidney and its perirenal fat, enveloping Gerota's fascia with I/L adrenal, proximal one-half of the ureter, and lymph nodes dissection from crus till the area of transection of the renal vessels( or aortic bifurcation)

Much has changed now

Only 7% of patients with RCC tumors larger than 4 cm have micrometastatic adrenal involvement

Adrenalectomy only if - extensive renal involvement- locally advanced- upper pole tumor- SRM adjacent to adrenals

LN dissection still contoversial

Recent studies failed to show survival benefit

More accurate pathological stagingpresent day indications of LN dissection- high grade tumor- sarcomatoid component- histologic tumor necrosis- large size of tumor (>10cm)- pT3 or pT4

Changes in radical nephrectomy

Open

Laparoscopic- Decreased need for postoperative analgesic drugs(24 mg vs 40 mg morphine- Shorter hospital stay(1.5 day vs 5 day- Shorter recovery period (4 wk vs 8 wk)Laparoscopy have similar DFS at 5 years and 10 years.as open surgery

Limitations of Laparoscopic procedure -two-dimensional imaging-restricted range of motion of the instruments-poor ergonomic positioning of the surgeon

Advantage over laproscopic- improved visualization- more degree of movements

Limited evidence currently available for radical nephrectomy

Robot assisted Radical nephrectomy

Complications of Radical Nephrectomy

Intraoperative complication- injury to any GIT organs or to any major blood vessels, pleural injuries can result in pneumothorax.

Postop complications- secondary hemorrhage, atelectasis, ileus, superficial and deep wound infections,renal failure, and incisional hernia.

Other well-recognized systemic complications include MI, CHF, pulmonary embolism, CVA, pneumonia, and thrombophlebitis

Results in CKD

Nephron sparing surgery(NSS)

Partial nephrectomy (PN)

Standard of care

Surgical removal of a kidney tumor along with a thin rim of normal kidney

Preserves renal functioning

Indications of NSS

Imperative- solitary kidney- B/L RCC

Relative- opposite kidney dysfunctioning

Elective(ideal) - easily resectable, small ( 3cm- resection>2cm with symptomatic peritumoral edema- resection>2 asymptomatic- gamma knife sx