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National Collaborating Centre for Cancer (UK). Diagnosis and Management of Metastatic Malignant Disease of Unknown Primary Origin. Cardiff (UK): National Collaborating Centre for Cancer (UK); 2010 Jul. (NICE Clinical Guidelines, No. 104.)

Cover of Diagnosis and Management of Metastatic Malignant Disease of Unknown Primary Origin

Diagnosis and Management of Metastatic Malignant Disease of Unknown Primary Origin.

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3Organisation of services and support

3.1. Introduction

Patients with malignancy of undefined primary origin (MUO) present in many different ways to different parts of the health service. There is a small proportion for whom treatment will make a significant difference and they need to be identified promptly and treatment commenced. But the experience of many is of going through a lengthy diagnostic process with little new information discovered. These patients voice disquiet at a string of investigations which seem to have no logic and which may cause discomfort, adding little to their care or subsequent treatment. They speak of confusion as to who is in charge of their care and who is directing progress. They are often in hospital for long periods of time with little perceived benefit. On being told that they have a cancer but that the primary source is unclear they feel further lack of fitting into a defined system. They meet other cancer patients with a named oncology consultant, named specialist nurses, MDT decision making, targets for time to treatment, organised support systems, major national charities, patient advocate groups and often feel added disenfranchisement. The absence of an organised research programme is a further disadvantage for this group of patients.

When I went from colorectal MDT to gynae MDT, there was a ten day gap until my appointment. I was then sent back, now having an ultrasound which confirmed a tumour taking up most of my upper abdomen. I had to wait a week for appointment, then another three weeks while MDTs quibbled about whose surgery time would be used for my op

Some patients present with advanced disease when further investigations and thoughts of systemic treatment are wholly inappropriate. Often there is a lack of an appropriately skilled clinician to explain the futility of invasive tests with no prospect of beneficial anti-cancer treatment. Involvement of specialist clinicians and palliative care is delayed while the primary is chased.

The whole time, my symptoms were getting increasingly worse and I did not have any symptom control. What will (would) also make a huge difference is early oncology and palliative care input

For those patients who are offered treatment it is not clear whether they are fully aware of the limitations and potential side effects of treatment, and whether they are able to make informed decisions.

3.2. Current deficiencies in the management of patients with carcinoma of unknown primary (CUP)

The process for investigating and subsequently managing patients with MUO or CUP is complex, variable and imperfect. The shortcomings in existing strategies for initial management of patients without a “site-specific” diagnosis can be attributed to the following:

  • Lack of agreed definitions of the clinical entity.
  • No referral guidelines for suspected cancer relevant to patients without an obvious or strongly suspected primary.
  • No system to rapidly identify patients and to ensure early specialist involvement.
  • Lack of efficient arrangements to manage the initial diagnostic phase.
  • Neglected status of the clinical entity.
  • Lack of a team structure to efficiently care for newly presenting patients.
  • Insufficient specialist oncology expertise.
  • Referral to inappropriate site-specific cancer teams.
  • Lack of support and information for the defined patient group.
  • Delays in involvement of specialist palliative care.
  • Lack of an overall organisational structure to ensure high-quality care.
  • Lack of adequate epidemiology data.
  • No research organisation.

Resolution of these problems has been approached by examining whether, for newly-presenting patients with MUO undergoing initial investigations to establish a primary site, there are organisational and support arrangements which can improve outcomes.

There is an important overlap between the developments necessary for optimum management of patients with MUO/CUP, and the acute oncology initiatives arising from the 2009 NCAG Report. This guideline has been devised to complement and support the relevant recommendations in the NCAG Report.

The guideline requires the development of a CUP specialist role for oncologists, MDT functioning, and site-specific group organisation in line with practice for cancers with identified primary sites. It is expected that consultant oncologists who develop a site-specialist interest in CUP will, in many cases, also be involved in the organisation and delivery of those aspects of the acute oncology service dealing with newly presenting patients with previously undiagnosed cancer.

3.3. The CUP team and its functions

Traditional approaches in medicine are being revised, through the establishment of teams responsible for rapid assessment and diagnosis. Alert systems exist which notify clinical teams of new admissions, and real-time tracking of patients can be used to streamline care. Newly presenting patients are investigated in a timely fashion, with early assessment by senior clinicians to refine the diagnostic process. These innovations can deliver advantages both to patients and hospitals, in terms of more rapid treatment and more efficient resource use.

My late wife’s journey could have been so much better and handled much better

Some problems encountered in managing patients with MUO might be similarly improved by ensuring early expert assessment by senior oncology clinicians. Undertaking relevant investigations in a rational order, using specialised tests at an appropriate stage and implementing expert decision-making to inform treatment plans could all contribute to an improved outcome.

The provision of support from a specialist nurse is now an accepted intervention for patients with the major common cancers as there is evidence that this reduces patient concerns and suffering. Patients with CUP undergoing investigations are not currently provided with the support offered to the majority of other cancer patients. This, combined with the additional concerns and uncertainties associated with this particular diagnosis, may result in unmet needs, and avoidable psychological morbidity.

Very little information either written or verbal on the difficulties of this condition was available. Not many of the specialist nurses had much knowledge of this type of problem and dealt only on a day to day basis with the effects of the cancer rather than the huge crisis we were facing due to an unknown outcome

The optimum organisation of a system to rapidly identify and then manage newly presenting patients with MUO has been examined. Key considerations were:

  • development of mechanisms for early identification of patients and subsequent tracking
  • the role of a small specialist team (“CUP team”) responsible for guiding decision making and orchestrating care for problems related to a new diagnosis of cancer, particularly of an unidentified primary site.

Recommendations

  • 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, a palliative care physician and a CUP specialist nurse or key worker as a minimum

    have administrative support and sufficient designated time in their job plans for this specialist role and

    have a named lead clinician.

  • The CUP team’s named lead clinician should:

    take managerial responsibility for the CUP service within the cancer centre or unit

    ensure there is a clinical system for the appropriate care of MUO and CUP patients

    ensure that each patient has an identified CUP specialist nurse or key worker

    ensure there is cover for all members of the CUP team during periods of absence

    ensure that senior clinical input is available to inform decision making and treat patients as necessary

    ensure that there is a single point of contact for the patient to access the CUP team

    implement the care pathway and help to educate other healthcare professionals in diagnosing and managing MUO and CUP

    ensure timely and effective communication between all healthcare professionals involved in the care of patients with MUO or CUP, including primary and palliative care

    represent the cancer centre or unit at the CUP network site-specific group and CUP network MDT and

    contribute to regular local and network audits of the management of MUO or CUP.

Qualifying statement: There is evidence from retrospective comparative studies that specialist referral improves care for cancer patients. The GDG also considered recent reports and took evidence from experts, it reached unanimous consensus that patients with MUO would benefit from early intervention and active tracking to ensure timely care in line with standard practice for site specific cancers.

  • Every hospital with a cancer centre or unit should assign a CUP specialist nurse or key worker to patients diagnosed with MUO or CUP. The CUP specialist nurse or key worker should:

    take a major role in coordinating the patient’s care in line with this guideline

    liaise with the patient’s GP and other community support services

    ensure that the patient and their carers can get information, advice and support about diagnosis, treatment, palliative care, spiritual and psychosocial concerns

    meet with the patient in the early stages of the pathway and keep in close contact with the patient regularly by mutual agreement and

    be an advocate for the patient at CUP team meetings.

Qualifying statement: There is little evidence on the effect of key workers for people with cancer, however they have become standard practice for site-specific cancers and the GDG reached unanimous consensus that CUP patients should not be disadvantaged and should also have benefit of key worker input.

  • Refer outpatients with MUO to the CUP team immediately using the rapid referral pathway for cancer, so that all patients are assessed within 2 weeks of referral. A member of the CUP team should assess inpatients with MUO by the end of the next working day after referral. The CUP team should take responsibility for ensuring that a management plan exists which includes:

    appropriate investigations

    symptom control

    access to psychological support and

    providing information

  • The CUP team should actively review the outcome of all investigations with a nominated pathologist and radiologist as appropriate.
  • A CUP network MDT should be set up to review the treatment and care of patients with confirmed CUP, or with MUO or provisional CUP and complex diagnostic or treatment issues. This team should carry out established specialist MDT responsibilities.
  • The CUP team should be involved in the patient’s care until the patient is:

    referred to a site-specialist consultant or

    referred for palliative care alone or

    diagnosed with a non-malignant condition

    If CUP is confirmed, the CUP team should continue managing the patient’s care.

  • Every hospital with a cancer centre or unit should ensure that patients are upgraded to the existing cancer waiting times pathway when MUO is suspected or first diagnosed.
  • Every hosptital with a cancer centre or unit undertaking diagnostic investigations of patients with MUO should ensure that services are set up for rapid and appropriate investigation of patients according to this guideline, and staff are appropriately trained.

Qualifying statement: There is evidence from retrospective comparative studies that specialist referral improves care for cancer patients. The GDG also considered recent reports and took evidence from experts. It reached a unanimous consensus that patients with MUO would benefit from early intervention and active tracking to ensure timely care in line with standard practice for site specific cancers.

The GDG was intent on ensuring that rapid expert assessment was available to both inpatients and outpatients with MUO. Applying Fast Track referral principles to patients with metastatic cancer without an obvious primary is the best way to achieve this for outpatients.

There is evidence from systematic reviews that site specific MDTs improve out-comes and cancer patient satisfaction with their care. The GDG also took evidence from experts who demonstrated reduced length of stay in hospital for patients with MUO whose care was influenced by a CUP team.

Clinical evidence

There was no direct evidence about the early referral of people with MUO to specialist oncologists. Evidence supports specialist cancer care in general, (Grilli et al, 1998; Gruen et al, 2009) and it is reasonable to assume that early referral to a specialist could mean earlier initiation of therapy and the avoidance of inappropriate tests or treatment.

A report published in 2008 by the National Confidential Enquiry into Patient Outcome and Death (NCEPOD, 2008), examined the process of care of patients who died within 30 days of receiving systemic anti-cancer therapy in June or July 2006. The report highlighted deficiencies in the initial assessment of patients, treatment decisions and in the management of complications and oncological emergencies. The report's advisors recommended the establishment of an acute oncology service (with access to specialist oncologist advice) in all hospitals with emergency departments.

The NHS Institute for Innovation and Improvement (NHSIII, 2009) published a report about improving the care pathway for people diagnosed with cancer after emergency admission to hospital. The report's authors examined hospital episode data from 20 acute trusts. They also studied care pathways for this patient group in three cancer centres and three cancer units. They observed that "[in cases where cancer is possible] it is vital that the cancer team is notified early on. This can prevent often unnecessary admission, speed up the diagnosis and improve the patients overall experience."

The NICE Improving Outcomes series of cancer service guidance1 consistently recommends that people with cancer should have a named key worker. There is relatively little evidence from randomised trials, however, about their effectiveness.

Two randomised trials investigated nurses who coordinated care or provided support for women undergoing radical therapy for breast cancer. McArdle et al (1996) reported that psychological and physical symptoms were less severe when women received support from a specialist breast cancer nurse. Goodwin et al (2003) found that when care was coordinated by a nurse case manager, women were more likely to receive breast conserving surgery and have better post operative arm function. A randomised trial of palliative care coordinators found they had little effect on the severity of symptoms of terminally ill patients with cancer when compared with usual care (Addington-Hall et al, 1992).

There was no evidence, however, about the effect of key workers on the diagnostic process in those with suspected cancer.

Health economic evaluation

The GDG did not consider this topic suitable for health economic evaluation because it would have been difficult to identify discrete pathways and consequences/outcomes of each strategy or service configuration in a manner that would lend itself to economic evaluation or decision analytic techniques (see the Economic Plan in Appendix B of the Evidence Review), therefore no further economic analysis was undertaken.

3.4. Organisation of CUP services at network and national level

The management of the major common cancers has been revolutionised and improved by the introduction of the multidisciplinary team (MDT) approach. Designated specialist teams comprising all relevant disciplines provide better treatment and the organisational arrangements in which such teams function can deliver improvements in the speed of investigation and diagnosis. Supportive care from a designated disease site-specific specialist nurse is an additional benefit provided by the MDT approach to patients.

During my investigations (before I was diagnosed with cancer following an exploratory laparotomy), I became aware that some MDTs are very dependent on their meetings, with not a lot of communication happening in between meetings and limited or no cross-talk between MDTs when the picture was confusing

Patients with MUO and confirmed CUP are not currently “owned” by a specific MDT, and hence their management and support is fragmented and poorly coordinated. Organisation of data collection, trial entry, patient experience data and assessment of outcomes are similarly lacking. Some patients are discussed at varying points in their diagnostic course at disease specific MDTs, but the lack of defined policies and pathways result in poor outcomes

Formal application of an MDT approach to patients with MUO early in their clinical course may be advantageous, but needs to take into account the very different clinical scenarios faced by patients and clinicians in the rapidly moving early diagnostic phase. Formal multidisciplinary review of individual cases should not delay this phase, nor should there be a requirement for too frequent re-discussion in MDT meetings. Development of a structure incorporating the best features of conventional MDT working at critical points in the management of a patient with CUP, offers the best way to provide the maximum benefit and efficiency.

High-level organisation of services, in the form of guidelines for the referral of suspected cancer (NICE 2005), Network site-specific groups, peer review processes, and national research programmes have all contributed to increased quality of care and clinical outcomes for patients with cancer from a recognised primary site. Extension of these administrative structures and resources to patients with MUO or CUP is a logical extension of existing policies.

Recommendation

  • Every cancer network should establish a network site-specific group to define and oversee policies for managing CUP. The group should:

    ensure that every CUP team in the network is properly set up (see recommendation on page 15)

    ensure that the local care pathway for diagnosing and managing CUP is in line with this guideline

    be aware of the variety of routes by which newly diagnosed patients present

    advise the cancer network on all matters related to CUP, recognising that many healthcare professionals have limited experience of CUP

    maintain a network-wide audit of the incidence of CUP, its timely management and patient outcomes

    arrange and hold regular meetings for the group to report patient outcomes and review the local care pathway.

Qualifying statement: The GDG considered expert advice and reached unanimous consensus that services for CUP patients should b e organised along similar lines to those for site-specific cancers with cancer network site specific groups. Significant deficiencies in epidemiological data, and the almost complete absence of organised research for CUP patients were noted.

Clinical evidence

The NICE Improving Outcomes series of cancer service guidance recommended that people with cancer should have their treatment managed by multidisciplinary teams (MDTs). Although largely lacking at the time, evidence about the clinical effectiveness of MDTs has since emerged.

There is evidence from observational studies (Coory et al, 2008; Stephens et al, 2005, 2006 and Morris et al 2006, 2008) that management by MDT is associated with improved overall survival in people with cancer. Some small studies (Stephens et al, 2005, 2006) observed large improvements in overall survival associated with MDT management, but the weight of evidence suggests a more modest beneficial effect (Coory et al, 2008; Morris et al, 2006, 2008).

Evidence from two patient questionnaire studies suggests that patients managed by MDT report greater satisfaction than those managed elsewhere (Coory et al, 2008; Gabel et al, 1997)

There was some evidence that the time from diagnosis to treatment was shorter (of the order of a couple of weeks) when patients were managed by an MDT (Coory et al, 2008; Gabel et al, 1997) although none of the studies directly addressed the diagnostic process.

Health economic evaluation

The GDG did not consider this topic suitable for health economic evaluation because it would have been difficult to identify discrete pathways and consequences/outcomes of each strategy or service configuration in a manner that would lend itself to economic evaluation or decision analytic techniques (see the Economic plan in Appendix B of the Evidence Review), therefore no further economic analysis was undertaken.

Research recommendation

  • A clinical studies group should be established at National Cancer Research Network (NCRN) level for CUP, to coordinate and direct a broad portfolio of research examining basic science, clinical studies, organisational processes and patient-centred topics.

3.5. Definitions and data collection for MUO and CUP

The review of the epidemiology of CUP (see Epidemiology section) has shown it to be a “common cancer”. Accurate epidemiology and measurement of the burden of disease remains difficult to assess due to the lack of a common data definition of what constitutes CUP; the fact that there is no uniform point in the patient’s pathway at which the definition is applied and an inability to look at the pathway for people who later are shown to have a site specific or non-cancer diagnosis.

Recommendations

  • Data and coding definitions for MUO and CUP should be developed and routine statistics should use these definitions.
  • A minimum data set for MUO and CUP should be agreed nationally. The data set should be collected by clinicians seeing MUO and CUP patients and reviewed at network level.
  • A national audit should be established for MUO and CUP patients based on the agreed minimum data set.
  • The National Cancer Intelligence Network should analyse current data on the epidemiology of MUO and CUP and use of the NHS by MUO and CUP patients.

Qualifying statement: There was unanimous consensus among the GDG that these recommendations were needed to provide important information about this heterogeneous group of patients.

References

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  • Coory M, Gkolia P, Yang IA, Bowman RV, Fong KM. Systematic review of multidisciplinary teams in the management of lung cancer. Lung Cancer. 2008;60(1):14–21. [PubMed: 18304687]
  • Gabel M, Hilton NE, Nathanson SD. Multidisciplinary breast cancer clinics. Do they work? Cancer. 1997;79(12):2380–4. [PubMed: 9191526]
  • Goodwin JS, Satish S, Anderson ET, Nattinger AB, Freeman JL. Effect of nurse case management on the treatment of older women with breast cancer. J Am Geriatr Soc. 2003;51(9):1252–9. [PubMed: 12919237]
  • Grilli R, Minozzi S, Tinazzi A, Labianca R, Sheldon TA, Liberati A. Do specialists do it better? The impact of specialization on the process and outcomes of care for cancer patients. Annals of Oncology. 1998;9:365–374. [PubMed: 9636826]
  • Gruen RL, Pitt V, Green S, Parkhill A, Campbell D, Jolley D. The effect of provider case volume on cancer mortality. CA: A Cancer Journal for Clinicians. 2009;59:192–211. [PubMed: 19414631]
  • McArdle JM, George WD, McArdle CS, Smith DC, Moodie AR, Hughson AV, et al. Psychological support for patients undergoing breast cancer surgery: a randomised study. BMJ. 1996;312(7034):813–6. [PMC free article: PMC2350687] [PubMed: 8608288]
  • National Confidential Enquiry into Patient Outcome and Death. Systemic Anti-Cancer Therapy: For better, for worse? 2008.
  • National Institute for Health and Clinical Excellence. Referral guidelines for suspected Cancer (Clinical guideline 27). National Institute for Health and Clinical Excellence; London: 2005.
  • NHS Institute for Innovation and Improvement. Focus on: Cancer. Jun 1, 2009.
  • Morris E, Haward RA, Gilthorpe MS, Craigs C, Forman D. The impact of the Calman-Hine report on the processes and outcomes of care for Yorkshire's breast cancer patients. Annals of Oncology. 2008;19(2):284–91. [PubMed: 17785759]
  • Morris E, Haward RA, Gilthorpe MS, Craigs C, Forman D. The impact of the Calman-Hine report on the processes and outcomes of care for Yorkshire's colorectal cancer patients. British Journal of Cancer. 2006;95(8):979–85. [PMC free article: PMC2360721] [PubMed: 17047646]
  • Stephens MR, Hopper AN, Blackshaw G, Barry JD, Edwards P, Hodzovic I, et al. Multidisciplinary team management is associated with improved outcomes after surgery for gastric cancer. Gut. 2005;54:A111.
  • Stephens MR, Lewis WG, Brewster AE, Lord I, Blackshaw GR, Hodzovic I, et al. Multidisciplinary team management is associated with improved outcomes after surgery for esophageal cancer. Diseases of the Esophagus. 2006;19(3):164–71. [see comment] [PubMed: 16722993]
Copyright © 2010, National Collaborating Centre for Cancer.

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Bookshelf ID: NBK82152

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