STEP 3: Diagnosis, staging, and treatment planning

Step 3 outlines the process for confirming the diagnosis and stage of cancer and for planning subsequent treatment. The guiding principle is that interaction between appropriate multidisciplinary team members should determine the treatment plan.

Once full blood count and immunophenotyping are complete and diagnosis is confirmed, additional assessments are recommended to help inform prognosis and to develop a treatment plan.

The treatment team, after taking a thorough medical history and making a thorough medical examination of the patient, should undertake the following investigations under the guidance of a specialist.

These include:

  • careful palpation of all lymph node areas, spleen and liver
  • serum chemistry (creatinine, uric acid, bilirubin, lactate dehydrogenase, haptoglobin, transaminases, alkaline phosphatase, ß2-microglobulin), serum immunoglobulin levels, direct antiglobulin test and serum protein electrophoresis to look for the presence of any paraprotein
  • chest radiograph (unless computed tomography [CT] has been performed for other reasons)
  • viral serology (hepatitis B, hepatitis C, HIV, Epstein-Barr virus and cytomegalovirus) (Hallek et 2018). The following investigations are only recommended under certain circumstances:
  • Marrow aspirate and biopsy – This is only recommended when the cause of any cytopenias (neutropenia, anaemia, thrombocytopenia) is unclear (Hallek et al. 2018), disease phenotype is inconclusive (Eichhorst et 2021) or the exact diagnosis is uncertain.
  • CT scans and other imaging – CT scans are not recommended for asymptomatic patients or during routine evaluation. A meta-analysis (Eichhorst et al. 2011) reported that most instances of relapse and disease progression are found during physical exam and by checking blood counts, and that imaging studies only affect relapse treatment decisions in 1 per cent of The International Working Group guidelines for CLL do not recommend routine use of CT scan,

PET scan, MRI or ultrasound for patients with CLL outside of clinical trials. Exceptions include PET scans for patients with confirmed or suspected Richter’s transformation (Hallek et al. 2018).

  • Situations where imaging is appropriate can include bulky or painful lymphadenopathy or significant symptoms or physical findings that suggest a local compressive complication.
  • For patients who do have symptoms, or where treatment will be initiated, CT scans are necessary to assess the tumour burden and risk of tumour lysis They can also be used in clinical trials to form a baseline and assess treatment response (Eichhorst et al. 2021).

Molecular genetics tests

The following tests aren’t recommended at diagnosis but should be done before initiating treatment or when there are signs of disease progression that may soon lead to treatment initiation:

  • interphase fluorescence-in situ hybridisation (FISH) for del(13q), del(11q), del(17p), +12 and DNA sequencing for the presence of a TP53 mutation
  • IGHV mutational

IGVH mutational status is invariant and unchanging through an individual patient’s disease course and need only be performed once.

These molecular genetic tests inform the most appropriate therapy (Eichhorst et al. 2021) and are useful to predict prognosis (Hallek et al. 2018).

Five to 10 per cent of patients with CLL will develop a more aggressive form of lymphoma (diffuse large B-cell lymphoma or Hodgkin lymphoma) at some point during their disease course. This

is termed Richter’s transformation. The managing team need to consider this possibility at every instance of disease evaluation and weigh up the potential need for a tissue biopsy to investigate. For more information see the optimal care pathway for people with Hodgkin and diffuse large B-cell lymphomas 

Features that can suggest the presence of Richter’s transformation and prompt tissue biopsy of the most suspicious site include (Petrackova et al. 2021):

  • new-onset B symptoms (fevers, sweats, weight loss)
  • rapidly growing, or a specific site of dominant or bulky, lymphadenopathy
  • markedly elevated serum LDH level or new onset of hypercalcemia
  • atypical extranodal site of disease involvement such as central nervous system, kidney, lytic bone lesions etc. or significantly elevated avidity (SUVmax above 5 – 10) on FDG-PET scanning (Wang et al. 2020).

Most baseline evaluation studies should be performed in the two to four weeks before initiating treatment. However, CT scans can be done up to two months prior. Molecular cytogenetics (FISH) and marrow aspirate and biopsy can be performed up to 12 months before starting treatment, provided there have been no intervening therapies and the general disease course is unchanged.

Staging is a critical element in treatment planning and should be clearly documented in the patient’s medical record.

Staging for CLL involves a physical exam and complete blood count.

In Australia, the Rai staging system is most often used to determine the stage of CLL (the Binet staging system is more commonly used in some other regions). For the purposes of this OCP, we will use the Rai staging system.

Rai system

Low risk:

  • Rai 0 – an isolated peripheral blood lymphocytosis > 5 × 109/L Intermediate risk:
  • Rai I – lymphocytosis and lymphadenopathy on clinical examination
  • Rai II – lymphocytosis and hepatomegaly and/or splenomegaly with/without lymphadenopathy High risk:
  • Rai III – lymphocytosis and haemoglobin < 110 g/L (6.83 mmol/L) with/without lymphadenopathy/ organomegaly
  • Rai IV – lymphocytosis and platelets < 100 × 109/L with/without lymphadenopathy/organomegaly

The ESMO guidelines define Rai 0 as low risk, Rai I and II as intermediate risk, and Rai III/IV as high risk. But it may be more useful to consider CLL in terms of early-stage disease: Rai 0 to I, and late-stage disease, Rai II to IV (Eichhorst et al. 2021).

Newer prognostic models such as the CLL International Prognostic Index  can identify patients with high-risk disease who may benefit from investigational therapy, as well as those who have a good prognosis despite advanced stage (Hallek et al. 2018).

Prognostic markers include:

  • IGHV mutational status
  • serum beta-2 microglobulin
  • presence of del(17p) and/or TP53 mutations – these are strong determinants of high-risk

Patient performance status is a central factor in cancer care and should be clearly documented in the patient’s medical record.

Performance status should be measured and recorded using an established scale such as the Karnofsky scale or the Eastern Cooperative Oncology Group (ECOG) scale.

A number of factors should be considered at this stage:

  • the patient’s overall condition, life expectancy, personal preferences and decision-making capacity
  • discussing the multidisciplinary team approach to care with the patient
  • appropriate and timely referral to an MDM
  • pregnancy and fertility (if applicable)
  • support with travel and accommodation
  • teleconferencing or videoconferencing as

The multidisciplinary team should meet to discuss patients before initiating treatment so a treatment plan can be recommended and there can be early preparation for the post-treatment phase. The level of discussion may vary, depending on the patient’s clinical and supportive care factors. Some patients with non-complex cancers may not be discussed by a multidisciplinary team; instead the team may have treatment plan protocols that will be applied if the patient’s case (cancer) meets the criteria. If patients are not discussed at an MDM, they should at least be named on the agenda for noting. The proposed treatment must be recorded in the patient’s medical record and should be recorded in an MDM database where one exists.

Teams may agree on standard treatment protocols for non-complex care, facilitating patient review (by exception) and associated data capture.

Results of all relevant tests and access to images should be available for the MDM. Information about the patient’s concerns, preferences and social and cultural circumstances should also be available.

The multidisciplinary team requires administrative support in developing the agenda for the meeting, for collating patient information and to ensure appropriate expertise around the table to create an effective treatment plan for the patient. The MDM has a chair and multiple lead clinicians. Each patient case will be presented by a lead clinician (usually someone who has seen the patient before the MDM). In public hospital settings, the registrar or clinical fellow may take this role. A member of the team records the outcomes of the discussion and treatment plan in the patient history and ensures these details are communicated to the patient’s general practitioner. The team should consider the patient’s values, beliefs and cultural needs as appropriate to ensure the treatment plan is in line with these.

The multidisciplinary team should be composed of the core disciplines that are integral to providing good care. Team membership should reflect both clinical and supportive care aspects of care.

Haemato-pathology and radiology expertise are essential.

See Appendix E for a list of team members who may be included in the multidisciplinary team for CLL.

Core members of the multidisciplinary team are expected to attend most MDMs either in person or remotely via virtual mechanisms. Additional expertise or specialist services may be required for some patients. An Aboriginal and Torres Strait Islander cultural expert should be considered for all patients who identify as Aboriginal or Torres Strait Islander.

The general practitioner who made the referral is responsible for the patient until care is passed to another practitioner who is directly involved in planning the patient’s care.

The general practitioner may play a number of roles in all stages of the cancer pathway including diagnosis, referral, treatment, shared follow-up care, post-treatment surveillance, coordination and continuity of care, as well as managing existing health issues and providing information and support to the patient, their family and carer.

A nominated contact person from the multidisciplinary team may be assigned responsibility for coordinating care in this phase. Care coordinators are responsible for ensuring there is continuity throughout the care process and coordination of all necessary care for a particular phase (COSA 2015). The care coordinator may change over the course of the pathway.

The lead clinician is responsible for overseeing the activity of the team and for implementing treatment within the multidisciplinary setting.

Participation in clinical trials, patient registries and tissue banking, where available, is encouraged for patients with CLL. Cross-referral between clinical trials centres should be encouraged to facilitate participation.

For more information visit:

Cancer prehabilitation uses a multidisciplinary approach combining exercise, nutrition and psychological strategies to prepare patients for the challenges of cancer treatment such as systemic therapy and radiation therapy. Team members may include anaesthetists, oncologists, surgeons, haematologists, clinical psychologists, exercise physiologists, physiotherapists and dietitians, among others.

Patient performance status is a central factor in cancer care and should be frequently assessed. All patients should be screened for malnutrition using a validated tool, such as the Malnutrition Screening Tool (MST). The lead clinician may refer obese or malnourished patients to a dietitian preoperatively or before other treatments begin.

Patients who currently smoke should be encouraged to stop smoking before receiving treatment. This should include an offer of referral to Quitline in addition to smoking cessation pharmacotherapy if clinically appropriate.

Evidence indicates that patients who respond well to prehabilitation may have fewer complications after treatment. For example, those who were exercising before diagnosis and patients who use prehabilitation before starting treatment may improve their physical or psychological outcomes, or both, and this helps patients to function at a higher level throughout their cancer treatment (Cormie et al. 2017; Silver 2015).

For patients with CLL, the multidisciplinary team should consider these specific prehabilitation assessments and interventions for treatment-related complications or major side effects:

  • conducting a physical and psychological assessment to establish a baseline function level
  • identifying impairments and providing targeted interventions to improve the patient’s function level (Silver & Baima 2013)
  • reviewing the patient’s medication to ensure optimisation and to improve adherence to medicine used for comorbid conditions.

Following completion of primary cancer treatment, rehabilitation programs have considerable potential to enhance physical function.

Cancer and cancer treatment may cause fertility problems. This will depend on the age of the patient, the type of cancer and the treatment received. Infertility can range from difficulty having a child to the inability to have a child. Infertility after treatment may be temporary, lasting months to years, or permanent (AYA Cancer Fertility Preservation Guidance Working Group 2014).

Patients need to be advised about and potentially referred for discussion about fertility preservation before starting treatment and need advice about contraception before, during and after treatment. Patients and their family should be aware of the ongoing costs involved in optimising fertility. Fertility management may apply in both men and women. Fertility preservation options are different for men and women and the need for ongoing contraception applies to both men and women.

The potential for impaired fertility should be discussed and reinforced at different time points as appropriate throughout the diagnosis, treatment, surveillance and survivorship phases of care. These ongoing discussions will enable the patient and, if applicable, the family to make informed decisions. All discussions should be documented in the patient’s medical record.

More information

See the Cancer Council website  for more information.

See validated screening tools mentioned in Principle 4 ‘Supportive care’.

A number of specific challenges and needs may arise for patients at this time:

  • assistance for dealing with psychological and emotional distress while adjusting to the diagnosis and any initial period of observation; treatment phobias; existential concerns; stress; difficulties making treatment decisions; anxiety or depression or both; psychosexual issues such as potential loss of fertility and premature menopause; history of sexual abuse; and interpersonal problems
  • management of physical symptoms such as pain and fatigue (Australian Adult Cancer Pain Management Guideline Working Party 2019)
  • malnutrition or undernutrition, identified using a validated nutrition screening tool such as the MST (note that many patients with a high BMI [obese patients] may also be malnourished [WHO 2018])
  • support for families or carers who are distressed with the patient’s cancer diagnosis
  • specific spiritual needs that may benefit from the involvement of pastoral/spiritual care. Additionally, palliative care may be required at this

A number of specific challenges and needs may arise for patients at this time. Consider:

  • optimising dental hygiene and ensuring restorative dental work is up to date
  • support to cease smoking
  • discussing fertility issues if relevant (see section 6.2)
  • vaccinations for seasonal influenza, pneumococcal disease and COVID-19, ideally before starting any immunosuppressive therapy because subsequent responses are greatly impaired (Herishanu et al. 2021)
  • correcting vitamin D deficiency (Molica et 2012; Shanafelt et al. 2011)
  • immunoglobulin replacement therapy for patients with hypogammaglobulinemia and frequent infections. The National Blood Authority has information on the eligibility criteria for immunoglobulins

For more information on supportive care and needs that may arise for different population groups, see Appendices A, B and C.

In discussion with the patient, the lead clinician should undertake the following:

  • establish if the patient has a regular or preferred general practitioner and if the patient does not have one, then encourage them to find one
  • provide written information appropriate to the health literacy of the patient about the diagnosis and treatment to the patient and carer and refer the patient to the Guide to best cancer care

(consumer optimal care pathway) for CLL, as well as to relevant websites and support groups such as Cancer Council  and Lymphoma Australia 

  • provide a treatment care plan including contact details for the treating team and information on when to call the hospital
  • discuss a timeframe for diagnosis and treatment with the patient and carer
  • discuss the benefits of multidisciplinary care and gain the patient’s consent before presenting their case at an MDM
  • provide brief advice and refer to Quitline (13 7848) for behavioural intervention if the patient currently smokes (or has recently quit), and prescribe smoking cessation pharmacotherapy, if clinically appropriate
  • recommend an ‘integrated approach’ throughout treatment regarding nutrition, exercise and minimal or no alcohol consumption among other considerations
  • communicate the benefits of continued engagement with primary care during treatment for managing comorbid disease, health promotion, care coordination and holistic care
  • where appropriate, review fertility needs with the patient and refer for specialist fertility management (including fertility preservation, contraception, management during pregnancy and of future pregnancies)
  • be open to and encourage discussion about the diagnosis, prognosis (if the patient wishes to know) and survivorship and palliative care while clarifying the patient’s preferences and needs, personal and cultural beliefs and expectations, and their ability to comprehend the communication
  • encourage the patient to participate in advance care planning including considering appointing one or more substitute decision-makers and completing an advance care directive to clearly document their treatment Each state and territory has different terminology and legislation surrounding advance care directives and substitute decision-makers.

The lead clinician has these communication responsibilities:

  • involving the general practitioner from the point of diagnosis
  • ensuring regular and timely communication with the general practitioner about the diagnosis, treatment plan, any specific preventative measures and recommendations from MDMs and inviting them to participate in MDMs (consider using virtual mechanisms)
  • supporting the role of general practice both during and after treatment
  • discussing shared or team care arrangements with general practitioners or regional cancer specialists, or both, together with the patient.

More information

Refer to Principle 6 ‘Communication’ for communication skills training programs and resources.