Carcinoma Unknown Primary by 56K74R

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									Carcinoma Unknown Primary


              Louise Medley
           Medical Oncologist
               Overview:
Malignancies of Undefined Primary Origin

 Overview
 Definitions
 Challenges faced
 Priorities
 Meaningful investigations
 Evidence based treatment?
 RUH experience and………….the future
      Carcinoma Unknown Primary
 3-5% all cancers (>10,000 cases per year)
 2% of all cancer patients in hospital
 72% admitted as an emergency
 Length of stay 8-10 days
 4th largest cause of cancer deaths
 Median survival 11weeks -11 months
 No change in survival over last 15 years

   Appropriate management depends on ability to recognise the
    subset of these patients whose tumours have a favourable
    prognosis and those which are highly responsive to therapy
     Terminology (as per draft NICE guidance)
Community referral
Malignancy of            Metastatic (or suspected) disease based on
undefined primary        minimal tests without obvious primary site
origin (MUPO)            Eg USS Liver/CXR/limited CT scan

Emergency presentation
Provisional CUP          Metastatic epithelial or NET identified on
                         basic histology, prior to specialist review
                         Eg Liver biopsy/FNA lymph node mass

Specialist referral
Confirmed CUP            ONCOLOGICAL DIAGNOSIS
                         Metastatic epithelial or NET identified on
                         final histology with no obvious primary
                         following specialist guided
                         investigations and specialist review
 Since the tests that have been run fail to turn up a location, and
  since I haven‟t presented any symptoms that would indicate the
  presence of cancer elsewhere, they have just chalked it up to a
  mystery. For me that is probably the scariest part. The image that
  often comes to mind is a time bomb ticking away somewhere. You
  know that a bomb may exist but you don‟t know if it really does nor
  do you know where it is and when it will go off

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

 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
Clinically meaningful and Cost-effective
   Investigations (Initial assessment)
•History and physical      Inc breasts, nodes, genital, rectal and pelvic examination
examination
•FBC, U+E, LFT, Ca,
LDH, urinalysis
•CXR
•CT chest, abdo, pelvis
•Symtom directed           No evidence for routine use to diagnose primary
endoscopy
•Mammography               Only if clinical or pathological features are consistent with
                           breast primary
                           (‘routine’ use has pick up of only 6-14%)
•PET                       directed by the CUP MDM
                           Evidence for whether PET can improve diagnosis AND
                           prognosis not clear
                           Evidence needed on impact of early use reducing
                           investigations

    Diagnostic Yield:
    Basic tests = 60% (restricted panel of tests can identify most primaries)
    Additional tests = 30%
    Exhaustive tests = high rate of false +ve results may delay diagnosis
Clinically meaningful and Cost-effective
    Investigations (Tumour Markers)
 Occasionally early use of these tests can facilitate speedy diagnosis and
  prompt treatment with significant clinical gain
 In general inappropriate ordering of these markers leads to:
    Unnecessary and costly investigations
    Incorrect management
    Needless distress and worry for patients

AFP and HCG      Presentations consistent with germ cell tumours
                 (esp midline nodal / retroperitoneal disease)

AFP              HCC

PSA              Men with presentations compatible with prostate cancer

Ca125            Women with presentations compatible with ovarian cancer
                 (inc inguinal nodes, chest, pleural, peritoneal and retroperitoneal presentations)
CEA and CA19.9   low specificity for primary site in patients presenting with provisional CUP and are unlikely
                 to be helpful when diagnosing a primary site
                 (DUKES D: 65% elevation of CEA)
    Carcinoma Unknown Primary 2010
     ….the role of molecular profiling
 Molecular profiling (mRNA PCR) on paraffin-
  embedded tissue (sensitivities 85-90%, specificities 99%)

 GRECO: 84 patients known primary + 38
  patients unknown primary: 75% predictions
  correct*

 Patients with MUPO who subsequently are
  given a ‘defined’ primary often present with
  atypical patterns of spread

                 NOT SUPPORTED IN NICE GUIDANCE
* Horlings et al J Clin Oncol 2008;26;4435-4441
              Management decisions
 Do not investigate further to identify primary site if patient unfit for
  treatment

 Perform investigations ONLY if:

     Results are likely to affect treatment decisions
     Patients understand why investigations are necessary
     Patient understands the risks/benefits of investigations and
      treatment AND is prepared to accept treatment

 Provide information about CUP to patients and carers

 Always consider early referral to Palliative care team/clear
  communication with GP to reduce emergency re-admission
                  Systemic therapy

 Unclear as to the benefit of chemotherapy in confirmed CUP
  presentations

  Data from 29 phase II trials of 39 regimens [Adenis et al 2009]:
      -objective RR of 10-30%
      -median survival 5-7 months, 2 year survival rare
       [prognosis = advanced NSCLC/pancreatic cancer]

 On the assumption that the commonest primaries identified in
  CUP patients are Lung, Pancreas and UGI….and palliative
  chemotherapy in these situations prolongs survival by 3-6
  months over BSC alone ? = benefit of chemotherapy in
  confirmed CUP
Favourable Prognostic Subsets
(clinical or pathological features)

 Poorly differentiated carcinoma with a midline distribution
    Suspicion of germ cell tumours
    25% Complete remission, long term survival possible
 Women with predominately peritoneal adenocarcinoma
    Median survival up to 24 months
    Long term survival 5-25%

 Women with adenocarcinoma of axillary nodes
  Outcome = Stage II breast cancer
 Squamous cell carcinoma of cervical neck nodes
  5 year OS 75-80% if treated radically (chemo-rad + surgery)
 Poorly differentiated neuroendocrine carcino   ma
  Doubling of median survival to apporx 14 months
                Challenges…..
 Lack of agreed definitions of the clinical entity and
  lack of an overall organisational structure to ensure
  high-quality care NICE Guidance August 2010
 No referral guidelines for suspected cancer relevant
  to patients without an obvious or strongly suspected
  primary Local guidelines in development August 2010
 Lack of a team structure to efficiently care for and
  manage initial diagnostic phase of newly presenting
  patients Lead Clinician, key worker, MDM, SSG
 Lack of support and information for the defined
  patient group.
 No research organisation
                  MUPO flow chart
  Symptoms or radiological                  Patient pre se ntsto GP and
    evidence of cance r,                    found to have symptoms
           s
   me dical/ urgical take or                         o
                                            or radiol gical evidence of
                 tie
        ward pa nt                          cance r




Initial tests have be e nunde rta  ken with results available whe re
possible
     Full examination (including neurological, lymph nodes, external
        genitalia, rectal examination)
     Full blood count, urea and electrolytes, liver function tests, CRP,
        LDH, calcium (serum and urine electrophoresis in case of isolated
        lytic bone lesions)
     CT chest/abdomen/pelvis (skeletal survey in isolated lytic bone
        lesions)
     Biopsy




Fill in Ņp
         rovisional carcinoma of unknown primary MDT referral formÓand
fax urgently to 2 week wait office (outpatient referrals) or CUP
administrator (inpatient)




                           What to expe ct                                  Non-Malignant
                           from CUP te am

                                                                            Primary identified

   Outpatient re fe rrals          Inpatie nt re fe rrals
   Outpatient appointment with CUP Review of patient by end of next         Confirmed CUP        BSC
   team within 2 weeks of referral working day (this will usually be
                                   in person, but due to clinical                                Consideration of
                                   commitments may be over the
                                   phone and advice given on how                                 therapy
                                   best to proceed
                                                                                                 CUP-One Trial
MUPO: RUH Experience

      January-September 2010
36 referrals (average 1 per week)
Mean age = 70.8 years (range 37-90)
Mean survival = 56 days (range 3*-151)
           MUPO Referral Source (Jan-Sept 2010)

                 10
                  9
                  8                                                       4 referred between 18th
                  7                                                       June - 12th July 2010
                  6
      Number of
                  5
       Referrals
                  4
                  3
                  2
                  1
                  0
                        A




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                                          Referral Source
Diagnosis and Staging Investigations

                                         Investigations for MUPO

                           100%
                           90%
Undergoing Investigation




                           80%
 Percentage of Patients




                           70%                                       Image
                           60%
                                                                     guided        Series4
                                                                     Biopsy        Series3
                           50%
                                                                                   Series2
                           40%                                                     Series1
                           30%
                           20%
                                                                   Not Indicated
                           10%
                                                                   ? Not Done
                            0%
                                  C T Scan                             Biopsy
                                                 Investigation
No single point of discussion

               MDM where Case Discussed

          18
          16
          14
          12
Number of 10
 Patients  8
          6
          4                                      Series1
          2
          0



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                                MDM Speciality
                        Diagnosis Following Specialist Review

                     100%                         1
                     90%                          1
                                                  1
                     80%                                 Gynae
                                                  1
Number of Patients




                                                         Renal
                     70%
                                                  2      Neuroendocrine
                     60%                                 Gastric
                                                  2
                     50%         20                      Lymphoma
                     40%                          2      Colorectal
                                                         Cholangiocarcinoma
                     30%
                                                  2      Pancreas
                     20%
                                                         Lung
                     10%                          3
                      0%
                            Confirmed CUP    Suspected
                                             Diagnosis
                                      Diagnosis
       Management Decision following Specialist Review

100%
                           1
90%

80%
                           4
70%

60%
                                                                Surgery
50%         15                              8                   Radiotherapy
                                                                C hemotherapy
40%

30%                        8

20%

10%

 0%
           BSC       Active Treatment   Unknown

                                        Response to Active Treatment

                                                3
                                                                       1
                                                2
                                   Number                                             3
                                                1                      2                           2
                                                         1
                                                0
                                                     Response
                                                     Complete


                                                                   Response




                                                                                Progressive


                                                                                              Treatment
                                                                    Partial


                                                                                  Disease




                                                                                                 On
                                                    Lym phoma          Neuroendocrine
Questions ?

								
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