Cancer f Unknwn Primary (CUP) Pathways and Guidelines (v 2) Lndn Cancer April 2017 The fllwing pathways and guidelines dcument has been cmpiled by the Lndn Cancer CUP technical subgrup and agreed by the Acute Onclgy ERG chair fr use in all Trusts acrss Lndn Cancer. Agreed at the Cancer f Unknwn Primary Expert Reference Grup Meeting Date: Tuesday 16 th May 2017 1
1. Intrductin Cancer f Unknwn Primary (CUP) sits within the remit f the Acute Onclgy Service (AOS) Expert Reference Grup. This dcument utlines the specific agreed patient pathways and the expectatins fr investigatin and management f this subgrup f patients. This plicy has been develped using the NICE Guidance CG104: Diagnsis and management f metastatic malignancy disease f unknwn primary rigin, July 2010 http://www.nice.rg.uk/cg104 and the ESMO clinical practice guidelines fr CUP 2015. Agreed services are in place t ensure that unnecessary investigatin is avided, and management is apprpriate, with ptimal patient experience 2. Definitins Patients cvered by these guidelines fall int 3 main grups: 3. Pathways between teams and services Preliminary investigatins may have been carried ut in A&E, by the patient s GP, by the AOS team r by anther specialist team which raise the suspicin f MUO. Clse wrking relatinships with A&E are required since ~57% f all MUO/CUP patients present via this rute. Hspital inpatients shuld be referred t the CUP r Acute Onclgy teams if there is any suspicin f a new cancer diagnsis based n imaging suggestive f metastatic malignancy in the absence f an identifiable primary tumur. Patients shuld be referred t the CUP MDT n the basis f limited imaging which is suggestive f metastatic disease (eg chest X ray with lung metastases, ultrasund abdmen suggesting liver metastases) withut an bvius primary site. Smetimes this referral will be via the AOS team, and in ther cases this will be frm anther team in primary r secndary care. 2
The CUP team will review all patients with metastatic disease frm suspected r diagnsed cancer f unknwn primary (MUO), including peple wh have been treated fr cancer befre. The CUP team will aim t see and assess a newly diagnsed MUO patient by the end f the next wrking day if an inpatient r within 2 weeks if referred as an utpatient (Appendix 1 fr pathways between teams). Fllwing initial assessment, any further investigatins shuld be decided by the CUP MDT in cnjunctin with the infrmed patient. The CUP/MUO teams will als assess the hlistic needs f the patient and make early referral t palliative care if apprpriate. The team will cnsider the patients wishes and the suitability fr further investigatins. All cases f MUO/CUP shuld be discussed at the weekly lcal CUP MDT but management decisins shuld nt be delayed fr thse patients presenting between the MDTs. The case may als be discussed at a lcal site-specific MDT as apprpriate depending n the clinical features. The CUP team shuld ensure that fr each referral a management plan exists which includes: a) Apprpriate investigatins (see belw) b) Symptm cntrl (early palliative care referral is advised) c) Access t psychlgical supprt and d) Access t infrmatin The CUP team shuld cntinue t be invlved in the patient s care until the patient is either: a) Referred t a site-specialist cnsultant r b) Referred fr palliative care alne r c) Diagnsed with a nn-malignant cnditin. The CUP team will cntinue t manage the patient s care if cnfirmed CUP (ccup) is diagnsed. 4. Patient Investigatins The investigatin f all patients presenting as MUO is utlined belw: The CUP team agrees that fr each patient a) Further investigatins t identify the primary site f rigin f the malignancy shuld nt be ffered t patients wh are t unfit fr treatment b) Investigatins t find the primary shuld nly be carried ut if a. The results are likely t affect a treatment decisin b. The patient understands why the investigatins are being carried ut c. The patient understands the ptential risks and benefits f investigatins and treatment and d. The patient is prepared t accept the eventual treatment 3
c) CUP team will ffer explanatin t patients and carers when further investigatins will nt alter treatment ptins d) Prvide emtinal and psychlgical supprt, infrmatin abut treatment ptins and palliative care Cnfirmed CUP patients wh are being cnsidered fr chemtherapy shuld a) Have the balance between ptential risks and benefits discussed with them b) If it is decided t prceed with chemtherapy, be ffered entry int a clinical trial if available 5. CUP / MUO Investigatin prtcls If the patient is fit and agrees t further investigatin the fllwing are suggested based n the NICE guidance (CG104) Initial diagnstic phase fllwing review by MUO/CUP MDT member and guided by the patient s symptms and perfrmance status: Cmprehensive Histry and examinatin (including breast / ndal regins / skin/genital/rectal and pelvic examinatin) Blds full bld cunt, urea and electrlytes, bne prfile, liver functin tests and cltting CT chest / abdmen and pelvis Rutine measurement f tumur markers is nt recmmended except in certain patterns f disease Myelma screen (fr islated r multiple lytic bne lesins) PSA in men AFP and hcg especially in midline ndal distributed disease (mediastinal masses and / r retrperitneal masses) AFP t aid diagnsis f hepatcellular cancer Ca125 in wmen with peritneal and r ascites Bipsy with standard histlgical examinatin, with immunhistchemical examinatin accrding t RCPath guidelines and lcal departmental plicy in rder t distinguish carcinma frm ther malignant prcesses Slitary metastases: In cases where there is evidence f an islated lesin and slitary site f disease, further discussin at a site-specific MDT is encuraged BEFORE any bipsy which culd cmprmise the chance f ptentially curative treatment eg liver / brain / bne / skin and lung. Secnd diagnstic phase: Careful cnsideratin f further investigatins shuld be made by the CUP MDT taking int cnsideratin the fllwing: 4
Upper and Lwer GI endscpy Only in patients with MUO if the symptms, histlgy r radilgy suggest a GI primary and its determinatin changes future management Mammgraphy D nt ffer mammgraphy rutinely t wmen presenting with MUO unless clinical r pathlgical features are cmpatible with breast cancer Breast magnetic resnance imaging (MRI) Patients with adencarcinma invlving the axillary lymph ndes shuld be referred t the breast MDT fr further evaluatin and treatment. If n breast primary tumur is identified after standard breast investigatins the breast MDT may recmmend dynamic cntrast-enhanced breast MRI t identify lesins suitable fr targeted bipsy Psitrn emissin tmgraphy-cmputed tmgraphy (PET) Offer 18F-FDG PET t patients with prvisinal CUP presenting with cervical lymphadenpathy with n primary detected n ear, nse and thrat panendscpy if radical treatment is cnsidered an ptin. Cnsider PET in patients with prvisinal CUP with extra-cervical presentatins after discussin with the CUP team Testicular ultrasund Only use testicular ultrasund in men with presentatins cmpatible with germ cell tumurs eg CT demnstrating enlarged para-artic lymph ndes Investigatin f specific clinical presentatins (as per CG104) Intrapulmnary ndules withut evidence f end-brnchial disease r ther site specific disease These patients shuld be referred t a specialist chest team fr nging management and investigatin Investigatin f malignant peritneal disease Obtain a tissue sample fr histlgical examinatin in patients with MUO presenting as ascites, if technically pssible Histpathlgy Pathlgical wrk up f a suspected CUP shuld be undertaken in accrdance with the NICE and ESMO guidance Immunhistchemistry Use a panel f antibdies cmprising cytkeratin 7 (CK7), CK20, thyrid transcriptin factr- 1 (TTF-1), placental alkaline phsphatase (PLAP), estrgen receptr (ER; wmen nly) and PSA (men nly) in all patients with adencarcinma f unknwn rigin. Use additinal immunhistchemistry (see ESMO guidelines) t refine the differential diagnsis, guided by the results f the panel f antibdies abve and the clinical picture. ROUTINE GENE-EXPRESSION-BASED PROFILING TO IDENTIFY PRIMARY IN PATIENTS WITH pcup IS NOT RECOMMENDED 6. Patient Management pathway 5
All patients with MUO / prvisinal CUP shuld be discussed at the next CUP MDT fr a) Discussin f further investigatins b) Discussin f suitability fr active treatment c) Any ther relevant treatment planning decisins including early referral t palliative care if apprpriate Patients will be re-discussed fllwing any further investigatins t agree a diagnsis f cnfirmed CUP (ccup). Patients may be re-discussed at any time as required fr their nging management. Where patients have been referred t a site-specific team (see sectin 7) then nging MDTdiscussin and decisin making is expected t be at the site-specific MDT meeting. They shuld be identified in thse discussins as an MUO/CUP patient but d nt need t be rediscussed at the CUP MDT as well. 7. Specific Presentatins that may benefit frm radical treatment and r nging referral t specialist MDT input Sme presentatins f MUO have ptentially mre favurable utcme if managed apprpriately. These presentatins need t be identified at the CUP MDT and managed and referred n accrdingly. Squamus carcinma invlving upper- r mid-neck ndes If the bipsy shws squamus cell carcinma invlving nly upper r mid-neck ndes, and the CT scan excludes metastatic disease, the patient shuld be referred t the head and neck MDT fr evaluatin and treatment. Offer PET-CT t patients with prvisinal CUP presenting with cervical lymphadenpathy with n primary tumur identified n ear, nse and thrat pan-endscpy if radical treatment is cnsidered t be an ptin. Adencarcinma invlving the axillary ndes in females Refer female patients with adencarcinma invlving the axillary ndes t a breast cancer MDT fr evaluatin and treatment. Squamus carcinma invlving the inguinal ndes Refer patients with squamus carcinma cnfined t the inguinal ndes t the specialist anal MDT fr review by a specialist surgen t cnsider treatment with curative intent. Slitary metastases In cases where there is evidence f an islated lesin and slitary site f disease, further discussin at a site-specific MDT is encuraged BEFORE any bipsy which culd cmprmise the chance f ptentially curative treatment. Cnsider that an apparent metastasis culd be an unusual primary tumur. Other presentatins that require specialist input are Prly differentiated carcinma with a midline distributin Fr cases with features f extra-gnadal germ cell tumurs, refer urgently t specialist germ cell tumur team fr evaluatin and nging management. 6
Prly differentiated neurendcrine carcinma Refer patients t the specialist neurendcrine MDT fr nging evaluatin and treatment Wmen with predminantly peritneal adencarcinma Refer patients t the specialist gynaeclgy MDT fr nging evaluatin and treatment. 8. Specific presentatins with a pr prgnsis Brain metastases A significant prprtin f patients presenting with brain metastases f unknwn primary are likely t present as inpatients and the AOS/CUP team shuld be cntacted fr advice and t review the patient within ne wrking day f admissin. Patient shuld have initial investigatins, including histry and clinical examinatin, bld tests and a CT scan f the chest, abdmen and pelvis as detailed previusly. Refer patients presenting with apparent brain metastases as the nly sign f malignant disease after initial investigatins t the specialist neur-nclgy MDT fr further management advice. If there is systemic disease, a bipsy f ne f the ther sites f metastasis may be apprpriate. Early referral t palliative care shuld be cnsidered. Multiple Metastases Including Brain Patients diagnsed with cnfirmed CUP invlving the brain and multiple ther sites are knwn t have a pr prgnsis. The care f these patients shuld be fcused n ptimal symptm management and palliative care supprt, with palliative cranial irradiatin ffered t sme patients. Early referral t palliative care shuld be encuraged. It remains imprtant t cnsider mre treatable primaries with a high respnse rate t systemic therapies and if apprpriate refer t a site-specific MDT. Hwever extensive investigatins t seek a primary shuld nt be undertaken due t evidence shwing that these are unlikely t field useful results and may impair quality f life. Patients with brain metastases f unknwn primary rigin and their carers shuld be infrmed that there is currently n evidence that any treatment ffers imprved survival and that there is limited evidence f imprvement in neurlgical symptms with surgery and/r whle brain raditherapy. 9. Active treatment f CUP patients In rder t select the ptimal treatment fr patients with pcup and ccup certain prgnstic factrs need t be taken int accunt including Perfrmance status f the patient Patient preference Patient cmrbidities Presence f liver metastases Presence f brain metastases (see abve) The results f investigatins shuld be reviewed by the lcal CUP team. If a primary is fund, the patient shuld be referred t the site-specific MDT. If a nn-epithelial malignancy such as lymphma, melanma, sarcma and germ cell tumur is diagnsed the patient shuld be referred t the apprpriate specialist MDT. Patients wh fit the criteria within 7
sectin 7 shuld be referred t the apprpriate MDT as utlined abve and managed in line with thse prtcls and algrithms. Otherwise cnfirmed CUP patients wh are being cnsidered fr chemtherapy shuld a) Have the balance between ptential risks and benefits discussed with them b) If it is decided t prceed with chemtherapy, be ffered entry int a clinical trial if available Systemic chemtherapy in patients with cnfirmed ccup If chemtherapy is being cnsidered fr patients with CUP, with n clinical features suggesting a specific treatable syndrme, the case shuld be discussed at the lcal CUP MDT. The clinical and pathlgical characteristics f the tumur and the txicity prfile f the drugs shuld be cnsidered in treatment recmmendatins, alng with the likely respnse rate. Patients shuld nly be ffered chemtherapy if f adequate perfrmance status. Pssible regimes include: ECF ECX EOX Oxaliplatin and MDG/ capecitabine Irintecan and MDG Single agent Capecitabine Cisplatin and Gemcitabine Carbplatin and Gemcitabine Cisplatin / Etpside Carbplatin / Etpside Carbplatin and Paclitaxel Single agent Paclitaxel 10. Data Cllectin Frm January 2013, the Cancer Outcmes and Service Dataset (COSD) replaced the previus Natinal Cancer Dataset as the new natinal standard fr reprting cancer in the NHS in England. It incrprates a revised generic Cancer Registratin Dataset, and additinal clinical and pathlgy site specific data items relevant t different tumur types. The CUP Subgrup agrees with the Natinal plicy fr the cllectin f COSD, which specifies: when each data items shuld be captured n the patient pathway; hw the data will be stred and managed within lcal data systems; that in additin t the abve, each MDT shuld recrd the number f patients referred t them and each f the MDT's assciated MUO/CUP assessment services shuld register all referrals f patients with MUO. 8
Appendix 1. Pathways between teams and services A+E X ray Care f the elderly Primary care Other AOS pathways AOS r CUP cre team Malignancy f undefined primary rigin (MUO) Metastatic malignancy identified n the basis f a limited number f tests, withut an bvius primary site befre cmprehensive investigatins Sitespecific cancer team Carcinma Unknwn Primary MDT Face t face inpatient review by end f next wrking day Outpatient review within 2 weeks Decisin regarding further diagnstics based n patient chice, perfrmance status and ptential management plan Initial diagnstic Phase Cmprehensive histry and examinatin, Blds, CT chest, abdmen and pelvis Myelma screen (fr islated r multiple bne mets), PSA in men. Bipsy and standard histlgical examinatin with immunhistchemistry (CK7, CK20, TTF1 and CDX2) CUP MDM discussin Secnd diagnstic Phase Further directed investigatins if indicated by initial investigatins (see guidelines) CUP MDM discussin If further investigatins negative diagnse ccup Nn-malignant Management by CUP team Palliative care alne Site-specific 9 cancer team