Cancer of Unknown Primary FRCR

Question 1

What is cancer of unknown primary origin?

Answer 1

Cancer of unknown primary origin is a condition in which a patient has metastatic tumour without an identified primary source.

(NICE, 2010)

Question 2

What terms are used in NICE clinical guideline CG104 for cancer of unknown primary?

Answer 2

The terms used are: metastatic malignancy of uncertain origin (MUO), provisional carcinoma of unknown primary (provisional CUP), and confirmed carcinoma of unknown primary (confirmed CUP).

(NICE, 2010)

Question 3

What should be done if a primary tumour is identified?

Answer 3

If a primary tumour is identified, treatment should continue as for that individual tumour site.

Question 4

What is the treatment approach if a primary tumour is not identified?

Answer 4

If a primary tumour is not identified, treatment has to be empirical and based on research in patients whose primary tumour is known.

Question 5

What percentage of all invasive malignancies does cancer of unknown primary account for?

Answer 5

Cancer of unknown primary accounts for 3–5% of all invasive malignancies in the western world.

Question 6

How many new cases of cancer of unknown primary were diagnosed in the UK in 2011?

Answer 6

In 2011, there were 9762 new cases of cancer of unknown primary diagnosed in the United Kingdom.

Question 7

What is the age-standardised rate of cancer of unknown primary in the UK?

Answer 7

The age-standardised rate in the UK is 10.2 per 100,000 population.

Question 8

What is the median age at diagnosis for cancer of unknown primary?

Answer 8

The median age at diagnosis is 65–70 years.

Question 9

What are the commonest primary sites identified in patients with cancer of unknown primary?

Answer 9

The commonest primary sites are pancreas (20–26%), lung (17–23%), liver (3–11%), large bowel (4–10%), stomach (3–8%), kidney (4–6%), ovary (3–4%), prostate (3–4%), and breast (2%).

Question 10

What is the importance of investigating patients with cancer of unknown primary?

Answer 10

It is important to consider potentially curable malignancies, such as germ cell tumours or lymphoma.

Question 11

What is the definition of malignancy of undefined primary origin (MUO)?

Answer 11

Metastatic malignancy identified on the basis of a limited number of tests, without an obvious primary site, before comprehensive investigation.

Question 12

What is the definition of provisional carcinoma of unknown primary origin (provisional CUP)?

Answer 12

Metastatic epithelial or neuroendocrine malignancy identified on the basis of histology/cytology, with no primary site detected despite a selected initial screen of investigations.

Question 13

What is the definition of confirmed carcinoma of unknown primary origin (confirmed CUP)?

Answer 13

Metastatic epithelial or neuroendocrine malignancy identified on the basis of final histology, with no primary site detected despite a selected initial screen of investigations.

Question 14

What are some risk factors and aetiology associated with CUP?

Answer 14

Several genetic mutations have been implicated including MYC, RAS, EGFR, PDGFR, MET, KIT, and p53.

Question 15

What percentage of cancer patients present with symptoms from metastases from an unknown primary site?

Answer 15

15% of cancer patients present with symptoms from metastases from an unknown primary site.

Question 16

What are the most frequent presenting features of malignancy of undefined primary origin (MUO)?

Answer 16

The most frequent presenting features are pain (60%), liver mass or abdominal symptoms (40%), palpable nodal disease (20%), bone pain or fracture (15%), chest symptoms (15%), and central nervous system abnormality (5%).

Question 17

What is the recommended approach for the investigation of MUO?

Answer 17

There should be a CUP team in every cancer centre, and a two-phase diagnostic approach should be carried out guided by the patient’s clinical condition.

Question 18

What initial assessments are required for patients with MUO?

Answer 18

Patients require a thorough comprehensive history and physical examination, along with laboratory tests including full blood count and serum LDH.

Question 19

What imaging tests are recommended for patients with MUO?

Answer 19

CXR and CT scanning of the thorax, abdomen, and pelvis are recommended.

Question 20

What are the common histopathological findings in patients with MUO?

Answer 20

The most common findings are adenocarcinoma, squamous carcinoma, and poorly differentiated types.

Question 21

What immunohistochemical biomarkers help in tumour diagnosis?

Answer 21

Some biomarkers include CK for carcinoma, PSA for prostate, and ER for breast.

Question 22

What is the significance of t(11;22) in cancer?

Answer 22

It is associated with Ewing sarcoma and peripheral neuroendocrine tumours (PNET).

Question 23

What specialized tests may be indicated for patients with MUO?

Answer 23

Further investigations may be indicated, particularly if patients have symptoms or signs suggesting a primary site.

Question 24

What blood tests are performed for suspected germ cell tumours or hepatocellular carcinoma?

Answer 24

Serum αFP and βhCG are carried out.

Question 25

What blood test is done if prostate cancer is suspected?

Answer 25

PSA is done if the presentation is compatible with prostate cancer.

Question 26

What blood test is done if ovarian cancer is suspected?

Answer 26

CA125 is done if the presentation is compatible with ovarian cancer.

Question 27

What is the purpose of endoscopy in cancer diagnosis?

Answer 27

Endoscopy is performed if clinically indicated and not already carried out.

Question 28

What procedure is used for patients with intrapulmonary nodules unsuitable for percutaneous biopsy?

Answer 28

Flexible bronchoscopy with biopsy, brushings, and washings is used.

Question 29

What is VATs exploration used for?

Answer 29

It is used in patients with a negative bronchoscopy where percutaneous biopsy is not appropriate.

Question 30

What should be combined with panendoscopy in patients with malignant neck lymph nodes?

Answer 30

Directed biopsies of the nasopharynx, tongue base, hypopharynx, and if negative, bilateral tonsillectomy.

Question 31

When should 18F-FDG PET-CT be offered?

Answer 31

It should be offered to patients with cervical lymphadenopathy and no primary tumour identified.

Question 32

What is the role of mammography in cancer diagnosis?

Answer 32

Mammography is undertaken if the presentation is compatible with breast cancer.

Question 33

When is breast MRI carried out?

Answer 33

Breast MRI is carried out for patients with adenocarcinoma of the axillary nodes.

Question 34

What is the TNM classification used for?

Answer 34

It is used to stage patients with cancer of unknown primary according to the most likely primary site.

Question 35

What should be done when a probable primary site is found in patients with MUO?

Answer 35

Standard treatment for that site should be given.

Question 36

What percentage of patients with CUP are in the unfavourable group?

Answer 36

80% of patients will be in the unfavourable group.

Question 37

What role does surgery play in managing patients with CUP?

Answer 37

Surgery may be useful, particularly for those in one of the more favourable subgroups.

Question 38

What was investigated in a phase II prospective trial regarding cancer classification?

Answer 38

The effectiveness of a 92-gene reverse transcriptase polymerase chain reaction cancer classification assay to predict tumour origin.

Question 39

What was the median survival for patients receiving assay-directed site-specific treatment?

Answer 39

The median survival was 12.5 months compared to 8.9 months historically.

Question 41

What is the management approach for isolated brain metastases?

Answer 41

Management includes palliation of specific problems and referral to an MDT for local treatments ## Footnote MDT refers to multidisciplinary team, which may consider other factors like unusual primary tumors.

Question 42

In which scenarios may radiotherapy be indicated?

Answer 42

Radiotherapy may be indicated for: * Standard treatment for probable primary cancer in CUP * Treatment of squamous cell cancer of cervical lymph nodes * Palliative treatment for bone pain, epidural spinal cord compression, SVCO

Question 43

What is the overall response rate of chemotherapy regimens for CUP based on phase II studies?

Answer 43

The overall response rate is less than 20% ## Footnote This indicates limited effectiveness of chemotherapy regimens in CUP.

Question 44

Which chemotherapy regimens appear to have a higher response rate for CUP?

Answer 44

Platinum-based chemotherapy regimens appear to give a higher response rate ## Footnote Examples include cisplatin and gemcitabine.

Question 45

What percentage of patients with CUP are in the unfavourable subgroup?

Answer 45

80% of patients with CUP are in the unfavourable subgroup

Question 46

What are commonly used chemotherapy regimens for patients with CUP?

Answer 46

Commonly used regimens include: * Epirubicin * Cisplatin * 5-FU * Capecitabine * Gemcitabine * Taxanes

Question 47

What is the prognosis for one-year and five-year survival in CUP?

Answer 47

One-year survival is 16% and five-year survival is 8%

Question 48

What are poor prognostic factors for CUP?

Answer 48

Poor prognostic factors include: * More than three metastatic sites * Performance Status (PS) 2 or more * Male gender * Non-lymph node metastases * Raised LDH, lymphopaenia, low serum albumin * Unfavourable CUP subgroup

Question 49

What is the median survival for patients with CUP who undergo chemotherapy?

Answer 49

The median survival is 11.0 months with only 1.5% alive at 5 years

Question 50

True or False: Patients treated with radiotherapy have a significantly better survival compared to those who had no radiotherapy.

Answer 50

False

Question 51

What is the CUP-One trial focused on?

Answer 51

The CUP-One trial focuses on: * New diagnostic tools like molecular profiling * Effectiveness of ECX chemotherapy

Question 52

Fill in the blank: The treatment for patients with cancer of unknown primary is likely to move towards treatment based on _______ predicting treatment response.

Answer 52

molecular profiling

Question 53

What is the recommendation for patients with unfavourable CUP and poor performance status?

Answer 53

Best treated with supportive care alone, with palliative radiotherapy for local symptom control

Question 54

What should be considered for patients with predominant liver metastases?

Answer 54

Consider a 5-FU-based regimen, e.g. epirubicin, oxaliplatin, and capecitabine

Question 55

What is the recommended treatment for patients with predominant lung metastases if breast or thyroid cancer is thought unlikely?

Answer 55

Consider a platinum-based treatment regimen

Question 56

What is the suggested approach for patients with bone metastases?

Answer 56

Consider radiotherapy for painful sites and a trial of hormone treatment or possible combination chemotherapy

Question 57

What is the significance of obtaining a tissue diagnosis in CUP cases?

Answer 57

It is valuable if epithelial markers are positive with radiological evidence of malignancy, PS > 2, and more than three metastatic sites