Consultant Medical Oncologist Cancer of Unknown Primary: Progress in the search for improved Diagnosis and and Treatment David Farrugia Consultant Medical Oncologist GP Masterclass 10 Feb 2016

The Challenges: CUP makes up 5% of all metastatic malignancies. Heterogenous group of conditions: different clinical syndromes, different histology. Often affects older patients with comorbidity. Apart from a few “favourable subgroups”, prognosis generally poor.

Modes of presentation Likely to present to different medical & surgical specialties. Pathway: GP to hospital specialist Acute medical or surgical admission Hospital specialist to oncologist Oncologist to oncologist

Modes of presentation Symptoms: Fatigue, weight loss, anorexia, night sweats, “aches and pains”, lumps. Signs: Wt loss, anaemia, lymphadenopathy, cutaneous lesions, effusions, organomegaly, VTE. Organ specific complaints should be investigated: e.g change in bowel habit, dysphagia, dyspnoea.

What needed changing... Poor communication. Unclear investigation pathway. Bottlenecks in investigation. When to stop investigating. Lack of ownership of disease entity. Late or no palliative care input. “MDT tennis”

NICE development of national guidelines Guideline development group set up consisting of oncologists, pall care workers, pathologist, radiologist, biochemist, patient and carer reps, NICE. Scope & review questions identified Member opinions & literature searches. Elicitation of external expert opinions Debate and formulation of recommendations. Meetings 2007-2009.

Key priorities Local level Every hospital cancer centre or unit should: − set up a CUP team. − ensure patients have access to the CUP team when MUO is diagnosed − assign a specialist nurse or key worker to patients with MUO or CUP (box 2) − upgrade patients to the cancer waiting times pathway when MUO is suspected or first diagnosed − ensure services are set up for rapid and appropriate investigation in line with this guideline − ensure staff are appropriately trained.

Management pathway

Terminology

Terminology: MUO MUO: needs malignancy to be confirmed. Often imaging is not enough. Biopsy required. Should be referred under 2WW rule using existing pathways for suspected cancer. Will often have a primary site discovered or be a type of cancer already covered by and MDT e.g. melanoma, lymphoma, NET. Site specific symptoms should be investigated. If after triage: carcinoma with no obvious primary-provisional CUP

Terminology: pCUP Metastatic carcinoma confirmed histologically and radiologically. CUP MDT involved at this point. Immunohistochemistry Cautious interpretation of serum tumour markers Additional imaging .e.g PET Investigation of “loose ends” If after above: carcinoma with no obvious primary- confirmed CUP

Terminology: cCUP Metastatic carcinoma of unknown primary confirmed histologically and radiologically. Assignment of key worker to assist with info, counseling, treatment pathway, coordinating assessment of needs. Does patient belong to a favourable subset? Is patient suitable for SACT? Additional sets to look for targetable genetic mutations in tumour-use of biological therapies. Palliative care needs. Avoidance of over-investigation, reduce acute hospital stay, rapid access to care at home or hospice.

F a v o u r a b l e S u b s e t s (20%) 1. Poorly differentiated carcinoma with midline distribution (extragonadal germ cell syndrome). 2. Women with papillary adenocarcinoma of peritoneal cavity. 3. Women with adenocarcinoma involving only axillary lymph nodes. 4. Squamous cell carcinoma involving cervical lymph nodes 5. Poorly differentiated neuroendocrine carcinomas. 6. Men with blastic bone metastases and elevated PSA (adenocarcinoma). 7. Isolated inguinal adenopathy (squamous carcinoma).

U N F A V O U R A B L E S U B S E T S (80%) Adenocarcinoma metastatic to the liver or other organs. 2. Non-papillary malignant ascites (adenocarcinoma) 3. Multiple cerebral metastases (adeno or squamous Ca) 4. Multiple lung/pleural metastases (adenocarcinoma) 5. Multiple metastatic bone disease (adenocarcinoma) 6. Squamous cell carcinoma of the abdominal cavity

This is a service development..... Needs investment: Staff: n/p, oncology, pall.care, rad, path, mdt coor., data collection. Time: mdt meetings, clinic slots, ward rounds. Inv. Capacity: imaging, biopsy, path review. Audit. Research

Investment needed (OECD, EU Health at a Glance 2010)

CUP