Renal Cell Carcinoma

Question 1

What is the most common kidney cancer in adults?

Answer 1

Renal cell carcinoma is the most common kidney cancer in adults.

Question 2

Renal cell carcinoma is the most common kidney cancer in adults it accounts for … % of kidney cancers

Answer 2

It accounts for around 80-85% of kidney cancers. They may be found incidentally on abdominal imaging, present symptomatically (e.g. haematuria, loin pain, loin mass, fever) or with features of paraneoplastic syndromes.

Question 3

In 2017, kidney cancers (overall) were the …. most common cancer in the UK.

Answer 3

In 2017, kidney cancers (overall) were the 7th most common cancer in the UK.

Question 4

There are three main types of renal cell carcinoma: …. Cell, p… and chromophobe

Answer 4

There are three main types of renal cell carcinoma: clear cell, papillary and chromophobe.

Question 5

What is the most common type of renal cell carcinoma?

Answer 5

Clear cell is the most common type of renal cell carcinoma. It tends to have a worse prognosis than the papillary and chromophobe subtypes. Mutations to the von Hippel-Lindau gene are commonly seen.

Question 6

What is the next most common type of renal cell carcinoma after clear cell?

Answer 6

Papillary is the next most common and is split into type 1 (associated with mutation to MET) and type 2.

Question 7

Where does renal cell carcinoma typically spread to?

Answer 7

Spread may be local to surrounding structures (e.g. adrenals, spleen or colon) including the renal vein and IVC. The lungs are the most common site of distant spread. Here the characteristic appearance is that of ‘cannon balls’ (large circular white opacifications). Spread to lymph nodes, liver, bones and brain may also occur.

Question 8

Risk factors for renal cell carcinoma: (5)

Answer 8

Advancing age
Smoking
Obesity
Family history
Hypertension

Question 9

Renal cell carcinoma may also be associated with a number of hereditary syndromes: (4)

Answer 9

Von Hippel-Lindau syndrome
Tuberous sclerosis
Birt–Hogg–Dubé syndrome
Hereditary papillary renal carcinoma

Question 10

Renal cell carcinoma may be asymptomatic for much of its development, the ‘classic’ triad of …, … pain and … mass is uncommon in practice.

Answer 10

Renal cell carcinoma may be asymptomatic for much of its development, the ‘classic’ triad of haematuria, flank pain and flank mass is uncommon in practice.

Question 11

Many renal cell carcinomas are found …

Answer 11

Many renal cell carcinomas are found incidentally on abdominal imaging obtained for other indications. Others may present with symptoms of haematuria, tumour mass effect, tumour burden or paraneoplastic syndromes.

Question 12

Clinical features of renal cell carcinoma: (11)

Answer 12

Haematuria
Flank pain
Flank mass
Fever
Night sweats
Malaise
Weight loss
Varicocele (classically left-sided)
Hypertension
Hypercalcaemia
Bone pain

Question 13

What may be a sign of renal cancer?

Answer 13

Varicoceles may be a sign of renal cancer. The majority of all varicoceles occur on the left side as the left gonadal vein tends to drain at a sharp angle into the left renal vein and is longer than the right draining into the IVC. The vast majority of varicoceles will not indicate cancer, however, tumours that compress venous return (classically left-sided, but the right side may also be affected) can be a cause. As such conduct a close examination and routine investigations and consider referral, particularly in older patients with unexplained new varicocele. Additionally NICE advise urgent referral in those with varicocele which appear suddenly and are painful, do not drain when lying down or a solitary right-sided varicocele.

Question 14

A significant number of patients exhibit features of …. syndromes at diagnosis of renal cell carcinoma

Answer 14

A significant number of patients exhibit features of paraneoplastic syndromes at diagnosis of renal cell carcinoma

Question 15

Paraneoplastic syndromes are relatively … disorders occurring in patients with cancer typically said to be triggered by an immune response to the malignancy.

Answer 15

Paraneoplastic syndromes are relatively rare disorders occurring in patients with cancer typically said to be triggered by an immune response to the malignancy.

Question 16

According to figures from the European Association of Urology (EAU), up to 30% of patients with symptomatic renal cell carcinoma have … syndromes.

Answer 16

According to figures from the European Association of Urology (EAU), up to 30% of patients with symptomatic renal cell carcinoma have paraneoplastic syndromes.

Question 17

In renal cell carcinoma paraneoplastic syndromes may result in (amongst many others): (6)

Answer 17

Fever
Hypercalcaemia
Hypertension
Neuromyopathies
Polycythaemia
Cushing’s syndrome

Question 18

NICE guidance NG12, Suspected cancer: recognition and referral advise urgent referral on the suspected cancer pathway if aged … and over and have:

Unexplained visible haematuria without urinary tract infection or
Visible haematuria that persists or recurs after successful treatment of urinary tract infection

Answer 18

NICE guidance NG12, Suspected cancer: recognition and referral advise urgent referral on the suspected cancer pathway if aged 45 and over and have:

Unexplained visible haematuria without urinary tract infection or
Visible haematuria that persists or recurs after successful treatment of urinary tract infection

Question 19

CT, USS and MRI may be used to make a diagnosis of … cancer.

Answer 19

CT, USS and MRI may be used to make a diagnosis of renal cancer.

Question 20

Urine investigations for suspected renal cancer: (2)

Answer 20

Urine dip and MSU

Urine cytology

Question 21

Blood investigations for suspected renal cancer: (5)

Answer 21

FBC
U&Es
LFTs
ESR
Bone profile

Question 22

In renal cell carcinoma what may be seen in the blood results?

Answer 22

A rise in the WCC and ESR is often seen. Hypercalcaemia may be present (and cause clinical presentation).

Question 23

Imaging for suspected renal cancer:

Answer 23

CT: generally the modality of choice. Though different set-ups and phases may be used to identify primary lesions and metastasis, a triple-phase (renal mass) CT is typically ordered. The thorax should be included if a suspicious renal lesion is identified in the abdomen. CT venogram may be used if renal vein/IVC involvement is suspected.
MRI: offers excellent diagnostic capabilities and may help identify the likely histology. MRI is often preferred in young patients, pregnant women or those with a contrast allergy. Also used where the diagnosis is unclear.
USS: renal cell carcinomas are often picked up ‘incidentally’ on abdominal USS. However not as sensitive as CT or MRI so typically not the investigation of choice.
Bone scan: may be used if bony metastasis is suspected.

Question 24

What is generally the modality of choice for imaging in suspected renal cancer?

Answer 24

CT: generally the modality of choice. Though different set-ups and phases may be used to identify primary lesions and metastasis, a triple-phase (renal mass) CT is typically ordered. The thorax should be included if a suspicious renal lesion is identified in the abdomen. CT venogram may be used if renal vein/IVC involvement is suspected.

Question 25

Renal cell carcinomas are often picked up ‘incidentally’ on abdominal ….

Answer 25

USS: renal cell carcinomas are often picked up ‘incidentally’ on abdominal USS. However not as sensitive as CT or MRI so typically not the investigation of choice.

Question 26

Is a biopsy required in suspected renal cancer?

Answer 26

A biopsy is not normally required and the decision to undertake one should be made by an appropriate MDT.

Reasons for biopsy include diagnostic uncertainty (e.g possibility lesion is lymphoma or metastasis) or prior to ablative or systemic therapy or lesion surveillance.

Question 27

The … classification may be used to describe renal cysts.

Answer 27

The Bosniak classification may be used to describe renal cysts.

Question 28

The Bosniak classification is a 5-point system based on findings from CT.
Label them

Answer 28

It is a 5-point system based on findings from CT. Bosniak I are never malignant, and malignancy in Bosniak II is very rare.

Bosniak IIF have approximately 5% risk of cancer, III are 31-100% malignant and IV are almost always malignant. All Bosniak IIF, III, and IV are typically discussed at specialist MDT.

Normally Bosniak IIF will be monitored with further imaging. If interested see this paper from Harvard Medical School.

Question 29

Renal cell carcinomas are staged using the … classification system.

Answer 29

Renal cell carcinomas are staged using the TNM classification system.

Question 30

Staging of renal cell carcinoma - T1 vs T2 cm?

Answer 30

A key distinction is made between localised disease as to whether or not the tumour is < 7cm. T1 lesions are less than 7cm whilst T2 are > 7cm - this is one factor that guides the decision to opt for radical or partial nephrectomy. T3/4 involve local spread of disease.

Question 31

In renal cell carcinomas, a key distinction is made between localised disease as to whether or not the tumour is < ….cm. T1 lesions are less than …cm whilst T2 are > …cm - this is one factor that guides the decision to opt for radical or partial nephrectomy. T3/4 involve local spread of disease.

Answer 31

A key distinction is made between localised disease as to whether or not the tumour is < 7cm. T1 lesions are less than 7cm whilst T2 are > 7cm - this is one factor that guides the decision to opt for radical or partial nephrectomy. T3/4 involve local spread of disease.

Question 32

Management of renal cell carcinoma - general principles

Answer 32

Management is guided by patient wishes, staging and patient-based factors.

Question 33

Localised disease - renal cell carcinoma management

Answer 33

As discussed above management is guided by staging. Currently for those with lesions < 7cm (i.e. T1a and T1b) - partial nephrectomy is preferred where possible.

Some with T1a lesions may opt for surveillance and ablation therapy may be used - typically in those who are not good surgical candidates.

In those with T2 tumours radical nephrectomy is typically preferred. However, in certain circumstances, partial nephrectomy may be considered including:

Solitary kidney or diseased contralateral kidney
Those with congenital disease at risk of further tumours
When possible laparoscopic +/- robotic assistance is preferred.

Question 34

Renal cell carcinoma - for those with lesions < 7cm (i.e. T1a and T1b) - … … is preferred where possible.

Answer 34

For those with lesions < 7cm (i.e. T1a and T1b) - partial nephrectomy is preferred where possible.

Question 35

In those with T2 tumours … … is typically preferred. However, in certain circumstances, … … may be considered including:
Solitary kidney or diseased contralateral kidney
Those with congenital disease at risk of further tumours
When possible laparoscopic +/- robotic assistance is preferred.

Answer 35

In those with T2 tumours radical nephrectomy is typically preferred. However, in certain circumstances, partial nephrectomy may be considered including:

Solitary kidney or diseased contralateral kidney
Those with congenital disease at risk of further tumours
When possible laparoscopic +/- robotic assistance is preferred.

Question 36

In those with T2 tumours radical nephrectomy is typically preferred. However, in certain circumstances, partial nephrectomy may be considered including:

….. kidney or … kidney
Those with …. disease at risk of further tumours

Answer 36

In those with T2 tumours radical nephrectomy is typically preferred. However, in certain circumstances, partial nephrectomy may be considered including:

Solitary kidney or diseased contralateral kidney
Those with congenital disease at risk of further tumours

Question 37

Advanced disease - renal cell carcinoma management

Answer 37

In appropriate patients, nephrectomy may be considered, even in the presence of metastatic spread - and may offer a survival benefit. Selective metastasectomy (surgical removal of metastasis) can also be considered.

There are a number of systemic therapies are available:

Sunitinib: inhibitor of tyrosine kinase receptors
Pazopanib: inhibitor of tyrosine kinase receptors
Temsirolimus: inhibitor of the mammalian target of rapamycin (mTOR)
Everolimus: inhibitor of the mammalian target of rapamycin (mTOR)
Radiotherapy may be used - typically for symptomatic relief (e.g. brain metastasis).

Care involves specialist urology, radiology, specialist nurses and palliative care.

Question 38

There are a number of systemic therapies are available for advanced disease (renal cell carcinoma)

Answer 38

Sunitinib: inhibitor of tyrosine kinase receptors
Pazopanib: inhibitor of tyrosine kinase receptors
Temsirolimus: inhibitor of the mammalian target of rapamycin (mTOR)
Everolimus: inhibitor of the mammalian target of rapamycin (mTOR)

Question 39

… is dependent on staging and histological grade of the renal cell carcinoma.

Answer 39

Prognosis is dependent on staging and histological grade of the renal cell carcinoma.

Question 40

According to the European Association of Urology, the overall 5-year survival is …% in renal cell carcinoma

Answer 40

According to the European Association of Urology, the overall 5-year survival is 49%.

Question 41

Figures from Cancer Research UK (accessed Nov 2021) indicate a 1-year survival of …% in stage 1 disease which falls to …% in stage 4 disease in renal cell carcinoma

Answer 41

Figures from Cancer Research UK (accessed Nov 2021) indicate a 1-year survival of 96% in stage 1 disease which falls to 39% in stage 4 disease.

Question 42

A rare cause of varicocele is…

Answer 42

A rare cause of varicocele is a compressive mass, such as a renal cell carcinoma, which leads to back pressure in the venous system and dilatation of the pampiniform plexus.

Question 43

The classic triad of renal cell carcinoma is …

Answer 43

The classic triad of renal cell carcinoma is haematuria, flank pain and a palpable mass. However, this combination of clinical features is uncommon. In this case, the presence of haematuria, abdominal pain and a new varicocele on examination is highly suspicion for a renal cell carcinoma, particularly with a strong smoking history and constitutional symptoms (e.g. weight loss).

Question 44

Visible haematuria, in the absence of infection, is a red flag symptom and warrants further investigation. … (3) can all lead to haematuria.

Answer 44

Visible haematuria, in the absence of infection, is a red flag symptom and warrants further investigation. Bladder, prostate and renal cancer can all lead to haematuria.

Question 45

In the presence of unexplained visible haematuria in the absence of a urinary tract infection, or persistent following treatment, NICE recommend urgent referral for suspected bladder and renal cancer in patients >… years old.

Answer 45

In the presence of unexplained visible haematuria in the absence of a urinary tract infection, or persistent following treatment, NICE recommend urgent referral for suspected bladder and renal cancer in patients >45 years old. They also recommend checking a prostate specific antigen (PSA). In addition, NICE advise urgent referral in those with a varicocele which appears suddenly and is painful, a varicocele that does not drain when lying down or a solitary right-sided varicocele.

Question 46

NICE advise urgent referral in those with a varicocele which appears suddenly and is …, a varicocele that does not drain when … or a solitary …-sided varicocele.

Answer 46

NICE advise urgent referral in those with a varicocele which appears suddenly and is painful, a varicocele that does not drain when lying down or a solitary right-sided varicocele.

Question 47

NICE guidance makes no recommendation about the referral of patients with visible haematuria who are <45 years old. These patients may still need urgent referral for assessment, but other causes should be considered (e.g. …). These patients, depending on investigations and the clinical history, may need referral to urology or nephrology.

Answer 47

NICE guidance makes no recommendation about the referral of patients with visible haematuria who are <45 years old. These patients may still need urgent referral for assessment, but other causes should be considered (e.g. glomerulonephritis). These patients, depending on investigations and the clinical history, may need referral to urology or nephrology.