North of Scotland Cancer Network Clinical Management Guideline for Metastatic Malignancy of Undefined Primary Origin (MUO)

Transcription

1 North of Scotland Cancer Network Clinical Management Guideline for Metastatic Malignancy of Undefined Primary Origin (MUO) UNCONTROLLED WHEN PRINTED DOCUMENT CONTROL Original Prepared by NMcL April 2016 Approved by NOT APPROVED Issue date Review date September 2016 Version 1.2 ( ) NMcL Page 1 of 10

2 Background Clinical Management Guideline for Introduction For the purposes of this guideline, the wider title and definition of Metastatic Malignancy of undefined Origin (or MUO) has been adopted. This is because the more established term of Metastatic Cancer of Unknown Primary (or mcup) is often too imprecise a clinical term (since it is sometimes used to refer to patients who have had only limited investigations, but subsequent tests later reveal the primary source), as opposed to a metastatic malignancy identified on the basis of a limited number of tests, without an obvious primary site, before comprehensive investigation.* Many patients first presenting with MUO will undergo further tests which either a. Result in the revelation or identification of the primary carcinoma b. Demonstrate a non-epithelial malignancy c. Result (despite extensive investigation) in a true metastatic carcinoma of unknown primary (or mcup) Whilst both a) and b) can be managed according to specific NOSCAN (or other nationally agreed) Clinical Management Guidelines (CMGs), this guideline will focus on managing patients presenting with i) MUO and ii) those found to have mcup Patients presenting with mcup are perceived as a disadvantaged group who fall outside of the recognised and established cancer pathways: as a group they constitute around 3-5% of all cancers, have a poor prognosis and (due to the limited treatment options available) tend to have very limited life expectancy when compared to many other cancers. Furthermore, (due to the limited evidence base and/or other uncertainties), they are frequently subject to significant delays and inefficiencies in their clinical management which can result in additional psych-social burden and sensitive communication difficulties. * NICE (2010) Metastatic malignant disease of unknown primary origin CG104 [online]. Available from: Version 1.2 ( ) Page 2 of 10

3 General Guidance Notes Clinical Management Guideline for Principles of Care Diagnostic investigation in this group of patients should primarily aim to define the extent of tumour dissemination help identify patients who may benefit from treatment (ie neuroendocrine tumours, breast, colorectal and prostate cancer) It is of primary importance to identify potentially curable types of MUO earliest and ensure their prompt and appropriate treatment Further Investigation to identify the primary origin of the malignancy is often not appropriate for patients who are unfit for treatment (ECOG Performance Status 3 and 4). Though some patients will not be appropriate for clinical intervention (due to poor condition at time of first presentation), nonetheless in line with best principles, all patients should be discussed at one of the cancer specialist Multidisciplinary Team Meetings (or MDTs) to ensure optimal clinical management and audit capture. Patients with suspected lymphoma/germ cell/small cell cancers and recent rapid cancer growth, should be investigated and discussed promptly as these patients generally respond well to chemotherapy even in the setting of poor performance status. Patients should only be referred to one of the North of Scotland Oncology services once a tissue diagnosis has been obtained: failure to do so, or making an earlier referral risks delaying the patient pathway The first point of contact for oncological emergencies (eg neutropaenic sepsis, spinal cord compression, hypercalcaemia of malignancy, superior vena cava obstruction) should be according to the agreed local Board departmental guidelines/arrangements. Where available, clinical trials should always be considered the preferred option for eligible patients Version 1.2 ( ) Page 3 of 10

4 Clinical Management Guideline for Initial diagnosis and Assessment It is important to establish a cancer diagnosis and an indication of clinical staging earliest and in advance of patient being referred and discussed at the most appropriate weekly specialist cancer MDTs (further details on page 5) Confirm Diagnosis Full medical history and comprehensive Physical examination - including of skin, testes, breasts and lymphatic systems + Digital Rectal Examination (DRE) and Vaginal Examination (VE) in females. Assess recent and current rate of change of symptoms and ECOG (East Coast Oncology Group) Performance Status and co-morbidities Urinalysis for blood Laboratory Investigations (ie FBC, U&E, LFTs, Calcium, LDH & CRP) (Consider HPV & HIV) Serum αfp and βhcg (young patients with metastatic disease) Ca125 (women with pelvic or peritoneal disease) PSA (men with bone metastases and/or lymphadenopathy) αfp (patients with liver only disease) Imaging: CT thorax, abdomen and pelvis with contrast is the staging investigation of choice in most circumstances. Other imaging as clinically indicated: PET as per current national guidelines Note: Consider myeloma screen (eg where isolated or multiple lytic bone lesion visble on scan with no obvious primary ) Other tumour markers are generally not useful in diagnosis Other investigations (including endoscopies) should be done ONLY as indicated by signs and symptoms Establish patients expectations and wishes Due to the nature of their presenting disease, likely treatment, and poor prognosis, all patients should be referred earliest to the most appropriate Clinical Nurse Specialist (CNS) for assessment and ongoing specialist advice, education, support and co-ordination of care for patient and their relatives throughout the treatment pathway (Note: other specialist referrals may also be clinically required depending on individual patient circumstances) In line with best principles, at all stages throughout the treatment pathway: Any treatment plans should be discussed with patient and relatives during their preparation Patients and their relatives should be provided with written information Primary Care should be notified of patients pathway progress If available, clinical trials should always be considered the preferred option for eligible patients Version 1.2 ( ) Page 4 of 10

5 Clinical Management Guideline for Disease Presentations & Referral General Guidance: The most common sites of metastatic spread include liver, lymph node, lung, brain and peritoneum. The majority of patients presenting with MUO or mcup will have more than 1 site of metastases. In a third of patients, 2 or more organs are involved at time of diagnosis Patterns of disease and Management: Spinal cord compression (MCC) Suspected germ cell tumour Men with bone only metastases and PSA > 20 Women with axillary nodes Women with disease limited to peritoneum: a) Histology suggestive of gynae origin b) Histology not suggestive of gynae origin Solitary or multiple liver lesions with: a) no previous cancer history b) Previous known cancer histology Neck Nodes Brain metastases a) Isolated with no previous cancer history nor other mets on CT b) Previous known cancer histology Suspected lymphoma, myeloma, plasmacytoma Lung metastases (no previous cancer history) Isolated inguinal nodes a) Males b) Females This warrants urgent discussion with oncology: contact On-Call as per local established arrangement urgent referral to oncology: contact On-Call as per local established arrangement referral to Urology Team/Service as ( Urgent Suspected Cancer ) or identified local MDT referral to Breast Team/Service (as Urgent Suspected Cancer ) or identified local MDT a) referral to Gynaecology Team/Service (as Urgent Suspected cancer ) or regional MDT b) referral to?? a) referral to Hepatobiliarypancreatic ( HPB) (as Urgent Suspected cancer ) b) referral back to appropriate prior tumour specific team referral to Head & Neck Team/Service (as Urgent Suspected cancer ) or regional MDT a) refer to Neurology Team/Service as Urgent Suspected cancer or relevant MDT b) referral back to appropriate prior tumour specific team refer to Haematology Team/Service (as Urgent Suspected cancer ) or regional MDT refer to Lung Team/Service as Urgent Suspected cancer or relevant MDT a) Seek advice from Gynaecology Team/Service b) Seek advice from Colorectal Team/Service If available clinical trials should always be considered the preferred option for eligible patients Version 1.2 ( ) Page 5 of 10

6 Clinical Management Guideline for Management General Guidance: Where a patient s pattern of disease fits with a specific disease presentation, or if investigations suggest a specific cancer primary, they should be referred to the relevant service/clinical team or MDT and treated as per existing NOSCAN Clinical Management Guideline (CMG) for that disease. Otherwise: mcup patients are generally divided into favourable and unfavourable subsets. Unfavourable: approximately 80% with a median overall survival of around 4 months Favourable: remainder with a more favourable median survival of around 12 months Patients with more treatable subtypes of mcup should be managed as per the relevant NOSCAN or national CMG (see page? for more details). As well as referral to the local/board identified tumour-specific or mcup Clinical Nurse Specialist where this is provided, early referral to Specialist Palliative Care should be considered for all/the majority of patients. Choice of oncological treatment will be decided by the patient s performance status, extent of disease, co morbidities, organ function and the patient s wishes. If available, clinical trials should always be considered the preferred option for eligible patients Version 1.2 ( ) Page 6 of 10

7 General principles Clinical Management Guideline for Systemic Anti-Cancer Therapy Systemic Anti-Cancer Therapy (SACT) or chemotherapy for patients with cancer of unknown primary is aimed at prolonging survival and relieving any related symptoms. For patients who are either a) symptomatic or b) asymptomatic but with an aggressive cancer, it may offer therapeutic benefits and should be considered an appropriate option for all such patients Whilst there is little evidence regarding which chemotherapy offers best outcome in patients who have CUP, empirical chemotherapy regimens are often used, with patient choice and characteristics determining which is most appropriate for any individual. The following regimens (together with the maximum starting doses and treatment duration indicated) have been identified appropriate for routine use in the NoS as follows: Epirubicin + Cisplatin + Capecitabine or Epirubicin 50mg/m² IV infusion (15 minute duration) on Day 1 Cisplatin 60 mg/m² IV infusion (60 minute duration) on Day 1 Capecitabine 625mg/m² Administered Orally (2 x daily) on Days 1-14 only Repeat every 3 weeks/21 days Continue therapy for up to 6 cycles or until unacceptable toxicity Carboplatin + Paclitaxel Carboplatin [AUC*2/3] IV infusion on Day 1 Paclitaxel?? mg/m² IV infusion on Day 1 Repeat every week/7days Continue therapy for up to? weeks (or as long as patient tolerates/fit enough) *AUC Area Under Curve (as per Cockcroft-Gault) equation) Note: In cases where patients cannot tolerate oral capecitabine therapy, 5FU may be given with starting doses and dose modifications according to peri-operative gastric ECF protocol UGWOS004. There is increasing evidence for deciding medical therapy according to immunohistochemistry (e.g. tumours which are CK20 +ve, CDX2 +ve and CK7 -ve should be treated like colon cancer) see page? for details. If available, clinical trials should always be considered the preferred option for eligible patients Version 1.2 ( ) Page 7 of 10

8 Clinical Management Guideline for Sub-types and Treatment Strategies Subtype of mcup Treatment Strategies Extragonadal germ cell syndrome eg midline/retroperitoneal disease distribution/raised αfp and βhcg Poorly differentiated neuroendocrine carcinoma of unknown primary Node predominately poorly differentiated Axillary node in female Neck node squamous Inguinal node - squamous Bone metastases and high PSA in males Peritoneal papillary or serous histology in female Single potentially resectable metastatic site (eg liver, lung, node, brain) Predominantly abdomen/liver metastases with CK20+, CDX2 and CK7-ve on immunohistochemistry Combination chemotherapy: platinum based as if germ cell cancer Combination chemotherapy: platinum/etoposide or platinum /taxane combination Combination chemotherapy: platinum based Treat with surgery/hormones/chemotherapy as if breast cancer Radiotherapy+/- platinum based chemotherapy as if head & neck cancer, or surgical resection (if appropriate) Lymph node dissection or radiotherapy +/- chemotherapy as if anal/cervical/penile/vulval cancer Hormonal therapy as if prostate cancer Surgical debulking then chemotherapy (platinum +/- paclitaxel) as if in gynaecological cancer Surgical resection (without biopsy first) or radiotherapy followed by chemotherapy or radiotherapy as appropriate Chemotherapy as if in colon cancer If available clinical trials should always be considered the preferred option for eligible patients Version 1.2 ( ) Page 8 of 10