update on cancer of unknown primary oct 2019... · 87% 1 month survival tww 38% 1 month survival ed...
TRANSCRIPT
The Royal Marsden
Update on Cancer of Unknown
Primary
Oct 2019
Dr Charlotte Fribbens
Consultant Medical Oncologist
AOS/GI Cancer
1. Definitions
2. Referral and Diagnosis
3. Cases
4. Future
5. Questions
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Patient presents with weight loss and generally feeling unwell but no site specific symptoms, you wish to refer with a ‘suspicion of cancer’. Which route would you currently use?
1. Two week wait
2. A and E
3. Multidisciplinary diagnostic clinic
4. Other
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The following definitions are used
Malignancy of unknown origin (MUO) Metastatic malignancy identified on the
basis of a limited number of tests
without an obvious primary site
before comprehensive investigation or
histology
Carcinoma of unknown primary (CUP) Metastatic epithelial or neuro-
endocrine malignancy
identified on the basis of final histology
with no primary site detected despite a
selected initial screen of investigations
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Apply caution in using MUO, never assume a patient with suspected cancer has cancer ….
73 year old presents with weight loss and cough
CT – mediastinal lymphadenopathy and pulmonary nodules likely to represent metastases
PET - Intense activity in enlarged nodes in the thorax and upper abdomen
Likely diagnosis?
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Mediastinoscopy – Sarcoidosis
Sarcoid is a well recognised mimic of malignancy
Nodal and lung disease most common but can affect many organs
PET positive
May need biopsy to confirm diagnosis
Others to be cautious of include TB and pancreatitis
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Cancer unknown primary
Group of metastatic tumours where standard diagnostic workup fails to identify a site of origin Account for 3-5% of all malignancies 4th most common cause of cancer related death Median survival 6-16 months – early palliative care
involvement important At autopsy, pancreas, HBP, large bowel and lung are most common sites identified (Eur J Cancer 2007 Sep;43(14):2026-36)
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Routes to diagnosis
59% diagnosed
following GP
referral
21% via ED – 77%
late stage
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Routes to diagnosis study
National Cancer Registration and Analysis Service
All Px diagnosed 2006-2010 with CUP 3% of all tumours 44,100 cases M:F 1:1.2 5% under 50, 40% over 80 years
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57% of patients diagnosed with CUP presented as an emergency Reflects in part the non specific nature of symptoms experienced making site specific referral difficult Overall 1 year survival is 16% but…. For managed routes is 24% For those presenting as an emergency is 5%
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Percentage of patients by route and age group for
Cancer of Unknown Primary
www.ncin.org.uk/publications/routes_to_diagnosis
www.ncin.org.uk/publications/routes_to_diagnosis
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Relative survival estimates by presentation route and survival
time, Cancer of Unknown Primary, 2006-2010
www.ncin.org.uk/publications/routes_to_diagnosis
87% 1 month survival TWW
38% 1 month survival ED
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Assessing a suspected cancer patient
Important to include non-cancer differentials
Try to avoid the term MUO – unless bx has confirmed malignancy
Review history
– Symptoms - cough, ENT symptoms, dysphagia, pain, bloating, early satiety, change in bowel habit, bone pain, PV discharge/bleeding, rectal discharge/bleeding, haematuria, headaches, B symptoms.
– Prior malignancy
– Smoker, alcohol, work,
- Family history
– Performance status, co-morbidities - are they suitable and do they want Ix and Rx
– Examination to include all nodes, mouth, skin, breasts, limbs, testes, PR, PV – as indicated
–CXR, blds - Hb, WCC, Total protein, Ca, LDH
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Assessed a patient and have suspicion of malignancy but not clearly site specific
Options -
TWW
Multidisciplinary/Rapid diagnostics centres
A and E
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Pan London suspected upper GI cancer referral form
Referral is due to CLINICAL CONCERNS that do not meet NICE/pan-London
referral criteria (the GP MUST give full clinical details in the ‘additional clinical
information’ box at time of referral)
Referral is due to GP not having direct access to relevant investigations (the GP MUST
give full clinical details in the ‘additional clinical information’ box at time of referral)
MANDATORY BOX FOR ALL PATIENTS - WHO PERFORMANCE SCORE
Enter score to establish if patient is suitable for straight to test CT scan, endoscopy or
ultrasound prior to first outpatient appointment
0 Fully active, able to carry on all pre-disease performance without restriction.
1 Restricted in physically strenuous activity but ambulatory and able to carry out work
of a light or sedentary nature, e.g. light housework, office work.
2 Ambulatory and capable of all self-care but unable to carry out any work activities.
The patient is up and about more than 50% of waking hours.
3 Capable of only limited self-care; confined to bed or chair more than 50% of waking
hours.
4 Completely disabled; cannot carry out any self-care. The patient is totally confined to
bed or chair.
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Multidisciplinary diagnostic centres
CRUK – 5 MDC pilots
Aim was to improve access to diagnostics, patient survival, experience and costs associated with cancer presenting with non-specific but concerning symptoms
Cancer conversion rate of 8%
Top 5 were –
Upper Gi 22%
Lung 22%
Lower GI 13%
Urological 13%
Haematlogical 13%
More than 1/3 diagnosed with non cancer condition
Interval times across the pathway –
median time (range) in days
GP referral to first seen: 8 (0-84)
N:2744
GP referral to cancer diagnosis
(clinical): 19 (0-199) N:217
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Other examples – Acute diagnostic oncology clinic
The purpose is to provide a better patient and GP experience with faster access to relevant diagnostic tests to diagnose or exclude cancer
High clinical or radiological suspicion of cancer
Do not meet a clear alternative pathway or too unwell to wait for a ‘two-week wait’ appointment
GPs email or speak directly to team and aim to see and access investigations within 5 days but often sooner
Run by CNS, Oncologist and GP with specialist interest
Cancer conversion rates of 20-25% (5% on TWW) and patients start treatment on average by day 11
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Once referred to clinic/seen by AOS CT imaging – check for patterns - lung/brain, lung/adrenal, pancreas/liver,
colon/liver, prostate/bone, breast/bone/liver.
• Specific bloods
– AFP and Beta-HCG - germ cell tumour suspected: young men with midline lymph node metastases
– AFP - hepatocellular carcinoma suspected (Etoh history)
– PSA - men with bone metastases
– CA125 - women with peritoneal or pelvic metastases, ascites, pleural effusions
– CA19-9, CEA – hepatobiliary
- CA15-3 - breast
– Myeloma screen – isolated or lytic bony metastases
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• Is further specialist assessment required
– Gynae (cervical, endometrial), ENT (H&N nodes), MSCC
– MRI imaging – pelvis, liver, brain, spine, US testis
- Symptom directed endoscopy
If no primary identified on imaging /biopsy and patient suitable for Rx
– PET-CT – may assist in identifying a primary site (~30-50%
reported).
Could this be lymphoma, germ cell, potentially treatable or non cancer?
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NICE
The CUP team Every hospital with a cancer centre or unit should
establish a CUP team, and ensure that patients have access to the team when MUO is diagnosed.
The team should consist of an - Oncologist Palliative care physician CUP specialist nurse or key worker as a minimum CUP MDTs
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Prognosis for the majority of patients with CUP is poor but there are certain presentations where treatment can be curative or have good outcome
Squamous carcinoma involving upper- or mid-neck nodes - refer to head and
neck MDT
Adenocarcinoma involving the axillary nodes - refer to breast cancer MDT
Squamous carcinoma involving the inguinal nodes - refer patients with squamous carcinoma confined to the inguinal nodes to a specialist surgeon in an
appropriate MDT to consider treatment with curative intent
Solitary metastases - Refer patients with a solitary tumour in the liver, brain,
bone, skin or lung to the appropriate MDT to consider radical local treatment
Women with predominantly peritoneal adenocarcinoma
Neuroendocrine carcinomas
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Subsequent Management of presentations with a poor prognosis
Early palliative care input
If performance status 0-1 assess if suitable for clinical trial or consider doublet platinum based palliative chemotherapy – response rates of 25-40% and median survival around 9 months
Performance status 2 or more consider best supportive care
Prognosis is much poorer than the favourable subtypes and with no treatment can be as little as weeks to short months
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77 year old male • 6 month history feeling generally unwell with abdominal pain, 16kg
weight loss, change in bowel habit, night sweats.
• PMH – MI, T2DM, Diverticulitis. Father had colon cancer
• June 2019 2 attendances to A and E with abdominal pain - given antibiotics for diverticulitis
• June 2019 CT as part of investigations for diverticulitis – diverticular changes with possible inflammatory mass in sigmoid colon
• July 2019 CA19-9 17437, CEA normal.
• CT - thickened and inflamed sigmoid colon. There were some peritoneal abnormalities noted and a atrophic pancreas, but a non-dilated pancreatic duct and pulmonary nodules
• What would you do next?
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Omental biopsy – metastatic adenocarcinoma, CK7 positive, CK20 negative. Immuno profile favours pancreatic cancer
PET - widespread disease with lung, liver, peritoneal involvement with a likely nodal mass at the porta hepatis and again the sigmoid appears abnormal.
Of note, there is no pancreatic lesion evident on either scan.
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Aug 2019 seen in CUP clinic – PS 1, arranged colonoscopy and to start chemotherapy for presumed colon cancer
CUP MDT - Diagnostic uncertainty ? sigmoid ? pancreatic primary
Path - not typical for sigmoid malignancy
MRI - within an area of diverticular change, consistent with a sigmoid tumour, liver metastases
MDT - treat as metastatic colon cancer
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Sept 2019 Admission for symptom control – abdominal pain and nausea, referred to palliative care and discharged with syringe driver. Chemotherapy held with plan to review in OP
October 2019 Admission to local hospital with sepsis, E Coli in blood cultures. Plan for best supportive care
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62 year old female
Attended A and E with back pain and leg weakness and reduced mobility
MRI spine – widespread marrow infiltration, multiple liver lesions, pathological # T12, L1, L3, non compressive retropulsed bone fragments at multiple levels
Seen as inpatient by Acute Oncology
CT CAP – multiple bony metastases, lung mass, multiple liver lesions
Tumour markers not raised, high LDH
Differential diagnosis?
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Lung MDT - ?lung primary, for biopsy of lung lesion
Biopsy of lung mass – High grade and shows numerous nuclear inclusions. Tumour is focally positive for S100 and melan-A. The ki67 proliferation index is high. The tumour is negative for HMB45, CD117, CK7, CK20, TTF-1, ER, CAM5.2, synaptophysin and chromogranin. The findings suggest metastatic malignant melanoma
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Discussed with melanoma team
Felt as she had been bed bound for several weeks, PS 4, very borderline for treatment
But after discussion with patient and family - given ipilimumab and nivolumab
Has had 3 cycles, LDH falling, mobilising well and discharged to rehab with a plan for home
Recent study – 52% 5 year survival with ipi/nivo in advanced melanoma
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Future
• Improved pathways for diagnosis
Suspected cancer and rapid diagnostic clinics –in 2019/2020 all cancer alliances expected to set up at least one rapid diagnostic centre for patients with non specific symptoms which could indicate cancer
• Trials – historically underresearched, understanding the biology has potential to improve treatment and identify biomarkers to select treatment and monitor response
RMH currently have the CUPem trial of immunotherapy – but need PS 0/1
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Take home messages
Much better outcomes in this group with a managed referral route
Very poor prognosis for most patients, early palliative care referral vital
However – certain patients picked up via this route can have curable disease so
important to identify this group early
If available use ‘suspected cancer clinics’ if too unwell for TWW
If no site specific symptoms use ‘clinical concerns that do not meet NICE/pan-
London referral criteria’ on TWW
Every hospital with a cancer centre or unit/emergency admissions will have a
CUP or AOS team
