Enterprise Interest None

Enterprise Interest None

Cervical Cancer -Management of late stages ESP meeting Bilbao Spain 2018 Dr Mary McCormack PhD FRCR Consultant Clinical Oncologist University College Hospital London On behalf of the international development guidelines group

Locally advanced cervical cancer Heterogenous group: Stage IB2/IIB to IVA disease Surgery, chemotherapy, radiation therapy, brachytherapy: treatment based on data vs availability of resources vs tradition Challenges in staging and treatment Improvements in techniques and outcomes Treatment morbidity and quality of life

Guideline ratings- SIGN grading system

General recommendations Multidisciplinary approach based on knowledge of prognostic & predictive factors for outcome,morbidity,qol Patients counselled on treatment plan Treatment undertaken by a dedicated team of specialists

TNM classification & FIGO staging Recommended use of TNM classification & record FIGO stage TNM stage based on correlation of -physical exam/imaging/pathology Record the methods used to determine TNM status Clinical-c, Imaging i, Pathological p Lymph nodes - number involved/retrieved, +/- ECS, site should be recorded - anatomical sites should be labelled & submitted separately

Prognostic factors & importance of pathology

Local clinical and radiological diagnostic workup Pelvic examination & biopsy mandatory for diagnosis B Pelvic MRI mandatory to assess local extent & guide treatment Endovaginal/transrectal USS an option if performed by suitable skilled sonographer Cystoscopy/proctoscopy & biopsy may be considered for suspicious lesions identified on imaging

Nodal/distant diagnostic work-up PET-CT or CT for assessment of nodal and distant disease PET-CT preferred option for treatment planning before definitive CCRT Consider PA lymph node dissection (at least up to IMA ) when PALN negative on imaging Consider biopsy for equivocal extrauterine disease

T1b2/T2a2 & negative LN on imaging Treatment strategy to avoid combination of radical surgery & post operative radiotherapy Definitive platinum based chemo radiation (CRT)& Brachy is preferred treatment Consider PALN dissection at least up to IMA Radical surgery is an alternative in patients in absence of negative risk factors ( size/lvsi/depth of stromal invasion) If LN detected intraoperatively- abandon further pelvic LN dissection & hysterectomy and proceed to CRT PALN dissection may be considered Neoadjuvant chemotherapy followed by Rad surgery is a controversial alternative

T1b2/T2a2 & involved LN on imaging Definitive chemo-radiation & brachytherapy is recommended Additional radiation boost to involved nodes recommended Consider PA lymph node dissection in those with negative PALN on imaging Debulking of suspicious pelvic LN may be considered

T2b-T4 irrespective of nodal status Definitive CRT & brachytherapy recommended Additional radiation boost to involved nodes recommended Consider PALN dissection in patients with negative PALN on imaging Consider debulking suspicious pelvic lymph nodes Pelvic exenteration option in selected cases (T4N0M0) Management of cervical stump cancer follows same principles as for those with intact uterus

Radiotherapy general principles Definitive management combination of external beam RT & Brachytherapy Target volumeprimary cervical tumour /uterine corpus/parametria/draining nodes +/- para-aortic nodes Concomitant weekly platinum based chemo where appropriate Overall treatment time should not exceed 7-8 weeks Must avoid treatment interruptions & delays

External beam radiation Minimum- 3D conformal Ideal intensity modulated RT (IMRT)

Definitive Brachytherapy Image guided adaptive brachytherapy (IGABT) recommended MRI preferable (CT or USS) & Gyn examination (2D brachy acceptable) Target (CTV HR )- residual tumour & adjacent cervix /parametria Applicator uterine tandem/ vaginal component+/- interstitial needles Overall dose ( ExBRT + Brachy ) to target CTV HR >/=85-90Gy Brachy dose delivered in 3-4 fractions HDR / 1-2 PDR Treatment should be delivered towards end of EXBRT, -Remembering to keep total overall treatment time to <8 weeks

MRI & target definition for Brachytherapy

Distant metastatic disease at presentation Full diagnostic workup to assess suitability for active treatment / treatment modality or best supportive care Recommend combination platinum/ taxane chemotherapy +/- bevacizumab in medically fit patients with widespread metastatic disease Metastatic disease confined to PA lymph nodes - definitive extended field CRT & Brachytherapy with CURATIVE intent Treatment may include surgical debulking of nodes pre CRT Treatment may also include additional chemotherapy Supraclavicular LN as only site of distant disease should also be treated with curative intent

Recurrent disease-management principles Diagnostic workup to exclude distant mets & locoregional tumour extension beyond curative intent Recurrence confirmed on histology Treatment of recurrent disease with curative intent requires centralisation and involvement of a broad MDT Pelvic recurrence ONLY- CRT or Exenteration ( depending upon primary treatment ) Each centre treating cervical cancer should have an established network for discussion of difficult cases & willingness to refer to specialist centres Participation in clinical trials is encouraged

Nodal & oligometastatic recurrences Localised PA/mediastinal or periclavicular recurrences ABOVE previously irradiated fields may be treated by radical RT /CRT Therapeutic effect nodal resection / debulking unclear so should be followed by RT if possible Treatment of isolated organ metastasis ( lung/liver etc) should be discussed in a specialist MDT. -options include resection,radiofrequency ablation, stereotactic ablative radiotherapy or interventional brachytherapy

Recurrent disease- symptom control Radiation for analgesia/bleeding/spinal cord compression Chemotherapy (Platinum & Taxane +/-Bevacizumab) Surgery-diversion stoma/stenting Supportive care only

Summary Locally advanced disease heterogenous group T1b2/2a2 N0 T1b2/2a2 N1 CRT preferred CRT recommended T2b2 T4a N0,1 CRT recommended Radiotherapy- external beam + Brachy + concomitant chemo unless contraindicated Metastatic disease at presentation distinguish localised nodal v visceral Recurrent disease Pelvic only potentially salvageable ( CRT or surgery ) OR widespread palliative intent ( RT/Chemo/Supportive care )

Special thanks Alexandra Ospanova ESGO guidelines coordinator Institut National de Cancer (France )for major funding 159 international reviewers