STEP 2: Presentation, initial investigations and referral
This step outlines the process for establishing a diagnosis and appropriate referral. The types of investigation undertaken by the general practitioner (GP) depend on many factors, including access to diagnostic tests and medical specialists and patient preferences.
It is important for patients with CUP to be recognised as early as possible so that specialist assessment and management is not delayed and futile investigations are avoided.
In order to achieve this, a clear definition of CUP is required so that patients can be directed along a specialised pathway analogous to the pathways for existing tumour streams where possible.
Patients often present to their general or primary medical practitioner with heterogeneous, non- specific symptoms and abnormal test results that demonstrate very likely metastatic malignancy but without a clear primary site on history or initial investigations.
While some people may have no symptoms, common symptoms may include (Cancer Council Australia 2017, Vajdic & Goldstein 2015):
- loss of appetite
- fatigue
- weight loss
- breathlessness or discomfort in the chest
- cough
- persistent pain (for example, bone, back, abdomen)
- swelling of the abdomen
- jaundice
- swollen lymph glands
- headaches.
GP assessments will include routine tests for a patient with apparent or suspected metastatic disease, guided by the symptoms of the individual patient.
Assessments that should be undertaken by the GP for a patient with apparent or suspected metastatic disease include:
- a thorough medical history and physical examination, including systematic review to identify signs and symptoms that might suggest a possible primary site
- routine blood tests
- contrast-enhanced computed tomography (CT) of the chest/abdomen and pelvis
- arrangement of a biopsy in patients with readily accessible disease to allow early diagnosis of those with specific CUP subsets and established treatment pathways (Note: Consideration should be given as to whether this is best done by the GP or the specialist team, depending on the jurisdiction. In general, a core biopsy rather than a fine needle aspiration (FNA) is preferred to increase the chances of collecting sufficient material for a specific diagnosis (Berner et al. 2003))
- additional investigations as indicated based on the specific presentation, clinical symptoms and signs of the patient. (These are discussed in section 3.1). In some situations, if they can be easily obtained, it may be appropriate for the GP to organise some of these tests in parallel with specialist referral to expedite the work-up of the patient.)
Further important considerations
- Patients with CUP may present as clinically unwell with poorly controlled symptoms. Symptomatic care must be provided in parallel with the investigation process.
- Patients with suspected CUP and poor performance status are at risk of over-investigation, and results from exhaustive tests commonly will not result in useful action. Early specialist input should be sought to limit the extent of futile investigation.
- Early specialist input will also assist in dealing with the uncertainty that patients and their carers experience during the confusing period when clear answers to their diagnosis and prognosis are not apparent.
Patients with a disease pattern suggesting a specific CUP subset should be referred to a relevant disease-specific oncology team. These include patients with lymphadenopathy restricted to the neck, and a biopsy showing squamous cell carcinoma should be referred to a specialist on a head and neck cancer MDT. Women with isolated axillary nodal metastases should be referred to a specialist on a breast cancer MDT.
When apparent metastatic disease without a clear primary site is recognised as CUP, patients should be referred to an oncologist with adequate experience in managing acute patients with CUP. Oncology services should identify oncologists with an interest in CUP within their services where available, and should provide clear routes of rapid access to specialist evaluation.
Patients who appear to fall into a non-specific CUP subset may be referred to the general medical oncology service, which can then triage the patient to be seen in the most appropriate clinic depending on the jurisdiction. Since most centres do not have a specific CUP clinic, this may include the patient being seen in a general oncology clinic or a disease-specific clinic depending on the presentation and suspected diagnosis.
Referral for suspected CUP should incorporate appropriate documentation sent with the patient including:
- the patient’s name, date of birth, contact details and next of kin
- details of the patient’s guardian, advance care plan or enduring power of attorney if relevant
- a letter that includes important psychosocial history and relevant past history, family history, current symptoms, medications and allergies
- results of current clinical investigations (imaging and pathology reports)
- results of all prior relevant investigations
- any prior imaging, particularly a hard copy or CD of previous chest x-rays and CT scans where online access is not available (lack of a hard copy should not delay referral)
- notification if an interpreter service is required.
Although referral to specialist oncology services is essential, it is important that regular communication between the oncology specialists and the referring GP occurs to ensure timely, coordinated care and support for the patient and their family.
Timeframe for referral to a specialist
Timeframes for specialist referral should be informed by evidence-based guidelines (where they exist) while recognising that shorter timelines for appropriate consultations and treatment can reduce patient distress.
Patients with CUP should be referred to a specialist for further investigation. The specialist appointment should take place within two weeks of the initial GP referral. A patient with uncontrolled symptoms or who is deteriorating may require urgent assessment, and the GP should call the medical oncology unit to expedite a review.
An individualised clinical assessment is required to meet the identified needs of a patient, their carer(s) and family. Referral should be as required; however, given the generally poor prognosis of this malignancy, early supportive care is strongly encouraged.
In addition to common issues identified in the Appendix, specific needs that may arise at this time include:
- communication to ensure the patient understands that they are being investigated for a possible cancer diagnosis, even prior to a tissue diagnosis being obtained
- support and information to assist with any distress while patients are undergoing these tests – patients with CUP will most likely undergo extensive testing (Wagland et al. 2017)
- psychosocial support and specific interventions – depressive symptoms are higher in people with CUP when compared with people with cancer of a known origin (Hyphantis et al. 2013)
- good communication from experts – CUP patients are more likely to want written information about their type of cancer and tests received but less likely to understand explanations of their condition (Wagland et al. 2017)
- coordination of care – GPs play an important role in coordinating care for patients, including assisting with side effects and offering support when questions or worries arise
- treatment for physical symptoms such as pain and fatigue
- guidance about financial and employment issues (such as loss of income, travel and accommodation requirements for rural patients and caring arrangements for other family members)
- appropriate information for people from culturally and linguistically diverse backgrounds.
Effective communication is essential at every step of the care pathway. Effective communication with the patient and carer is particularly important given the prevalence of low health literacy in Australia, which is estimated at 60 per cent of Australian adults (ACSQHC 2013).
The general or primary medical practitioner who made the referral is responsible for the person until care is passed to another practitioner.
The general or primary medical practitioner may play a number of roles in all stages of the cancer pathway including diagnosis, referral, treatment, coordination and continuity of care as well as providing information and support to the person and their family.
The GP should:
- provide the patient with information that clearly describes who they are being referred to, the reason for referral and the expected timeframe for appointments
- support the patient while waiting for the specialist appointment.
