THIS DOCUMENT North of Scotland Cancer Network Carcinoma of the Uterine Cervix UNCONTROLLED WHEN PRINTED DOCUMENT CONTROL Prepared by A Kennedy/AG Macdonald/Others Approved by NOT APPROVED Issue date April 2016 Review date September 2016 Version Version 2.4 (20160628) Page 1 of 10
General Principles: Clinical judgement should ultimately determine which diagnostic tests require performed for each patient. However, as a general rule: Initial ALL PATIENTS investigations: THIS DOCUMENT Full Medical History Physical Examination (including examination of the pelvis) Routine Blood Screen: ie Full Blood Count (FBC), Biochemistry (U&E s) CEA, CAI25, Bone profile Further SUSPICION OF CANCER OF THE CERVIX investigations: Other considerations Examination Under Anaesthetic (EUA) Fertility expectations should be discussed Histology CT of Abdomen and Pelvis (and of chest if indicated) MRI pelvis ECG, echo, PFTs if surgery considered an option FDG PET may be considered [See separate MCN Guideline s for further advice on Imaging of Gynaecological Malignancy] Initial Diagnosis and Staging The following information should only be used to guide the management of adult patients with cancer of the cervix and who have not been entered into a clinical trial only All patients (including those who decline, or are considered clinically not suitable for active treatment) should be registered with the North of Scotland regional Gynaecological cancer MDT in order to ensure accurate data capture and an opportunity for peer review. In advance of any patient being discussed at the above specialist weekly MDT, it is important to have locally taken steps earliest to establish i) a definitive diagnosis, as well as ii) an indication of FIGO* clinical staging (available on page 8) Where available clinical trials should always be considered the preferred option for all eligible patients In addition to above, all patients should be referred or made aware earliest to the service identified Clinical Nurse Specialist for assessment and ongoing specialist advice education, support and co-ordination of care for both the patient and their relatives throughout the treatment pathway: this is in addition to any other specialist referrals that may also be clinically warranted depending on individual patient circumstances. Version 2.4 (201600628) Page 2 of 10
THIS DOCUMENT Staging and Primary Treatment (Stage I-IIA) Initial Evaluation Stage Primary Treatment Follow Up History and exam FBC, LFTs, U&Es, bone profile Histological confirmation Examination under anaesthesia MRI pelvis (in stage IAii IV) FDG PET scan in all patients not suitable for surgery Fertility expectations Physiological assessment where required (ECG, echo, PFTs, egfr) Stage IA1 Stage IA2 Stage IB1 Stage IB2 Stage IIA Notes: 1 PLND can be considered if LVSI +ve 2 if <2cm and no LVSI Surgical options: a) simple hysterectomy (see note 1) b) conisation/lletz if fertility preservation considered Non-surgical option in unfit: Intracavitary brachytherapy alone Surgical options: a) simple hysterectomy + PLND b) radical trachelectomy + PLND if fertility preservation considered (see note 2) Non-surgical option in unfit: EBRT 45Gy/25# (+/- SACT) see page 5 for details ICBT (For a small number of/some suitable selected patients) a) radical hysterectomy + PLND b) radical trachelectomy + PLND if fertility preservation considered (see note 2) (For a small number of/some suitable selected patients) EBRT 45-50.4Gy/25-28# (+ concurrent SACT if fit) see page 5 for details ICBT Note: PLND Pelvic Lymph Node Dissection EBRT External Beam Radiotherapy ICBT Intra-Cavitary Brachytherapy Version 2.4 (201600628) Page 3 of 10 SACT Systemic Anti-Cancer Therapy See follow up schedule on page 6
Staging and Primary Treatment (Stage IIB-IVB) THIS DOCUMENT Initial Evaluation Stage Primary Treatment Follow Up History and exam FBC, LFTs, U&Es, bone profile, CXR Histological confirmation Examination under anaesthesia +/- cystoscopy MRI pelvis (in stage IAii IV) FDG PET scan Fertility expectations Physiological assessment where required (ECG, echo, PFTs, egfr) Stage IIB-IVA extensive distant mets Stage IVB minimal distant mets Note: EBRT external beam radiotherapy ICBT intra-cavitary brachytherapy in presence of extensive retroperitoneal or pelvic lymphadenopathy, or in trial context EBRT (45-50.4Gy in 25-28#) (+ concurrent SACT if fit) see page 5 for details ICBT consider neoadjuvant chemotherapy (see p4) palliative chemotherapy (see p4) palliative radiotherapy EBRT (45-50.4Gy in 25-28#) (+ concurrent SACT if fit) see page 5 for details +/- ICBT palliative chemotherapy (see p4) See follow up schedule on page 7 Version 2.4 (201600628) Page 4 of 10
THIS DOCUMENT Adjuvant therapy Pathology Adjuvant Treatment Follow Up any one of: positive nodes positive surgical margins parametrial extension or any two of: greater than 50% stromal invasion (of hysterectomy specimen) lymphovascular space invasion tumour diameter of >4 cm EBRT 45Gy/ 25# (+ concurrent SACT if fit) see page 5 for details vault brachytherapy if close vaginal margin See follow up schedule on page 7 Note: EBRT external beam radiotherapy Version 2.4 (201600628) Page 5 of 10
Neoadjuvant Treatment THIS DOCUMENT Systemic Anti-Cancer Therapy (SACT) - Curative Therapy NOSCAN Gynaecology Cancer MCN has identified the following chemotherapy regimens (including the maximum commencing doses and treatment durations indicated) suitable for systemic management with curative intent of adult patients with carcinoma of the cervix only: any patients who have been entered in a clinical trial should be managed according to the appropriate trial protocols Final choice of chemotherapy regimen is individually patient dependent on (ECOG) Performance Status, pre-existing health conditions or co-morbidities, age/ life expectancy as well as any lifestyle preferences they might have indicated: scoring systems may aid decision making Carboplatin + Paclitaxel Clinical indications: Carboplatin [AUC2] IV infusion on Day 1 Paclitaxel 80mg/m 2 IV infusion on Day 1 Repeat every week/7 days Continue for up to 6 weeks Concurrent Treatment Carboplatin + Etoposide Clinical indications: Small Cell cancers only Carboplatin [AUC 5] IV infusion on Day 1 Etoposide IV 100mg/m 2 IV infusion on Day 1, Etoposide 200mg/m 2 administered Orally on Days 2 & 3 Repeat every 3 weeks/21 days. Continue for up to maximum of 6 cycles Weekly Cisplatin (assuming GFR>50ml/min) Clinical indications: Cisplatin* 40mg/m 2 (to a maximum dose of 70mg) IV infusion on Day 1 Repeat every week/7 days Continue for duration of EBRT *Note: Carboplatin [AUC3] may be substituted in event of patient identified clinically unsuitable to receive Cisplatin Note: EBRT External Beam RadioTherapy AUC Area Under the Curve (as per Cockcroft-Gault equation) GFR Glomular Filtration Rate Version 2.4 (201600628) Page 6 of 10
THIS DOCUMENT Systemic UNDER Anti-Cancer REVIEW Therapy (SACT) Palliative Therapy NOSCAN Gynaecology Cancer MCN has identified the following chemotherapy regimens (including the maximum commencing doses and treatment durations indicated) suitable for systemic management with palliative intent of adult patients with carcinoma of the cervix only: any patients who have been entered in a clinical trial should be managed according to the appropriate trial protocols Final choice of chemotherapy regimen is individually patient dependent on (ECOG) Performance Status, pre-existing health conditions or co-morbidities, age/ life expectancy as well as any lifestyle preferences they might have indicated: scoring systems may aid decision making Cisplatin + Paclitaxel Clinical indications:????? Cisplatin * 70mg/m 2 IV infusion on Day 1 Paclitaxel 175mg/m 2 IV infusion on Day 1 Repeat every 3-weeks/21 days Continue for up to 6 Cycles or as long as acceptable toxicities * Note: in event of Cisplatin contra-indicated, Carboplatin [AUC 5] may be substituted Bevacizumab + Cisplatin + Paclitaxel Clinical indications:????? Bevacizumab 15mg/kg IV infusion on Day 1 Cisplatin* 50mg/m 2 IV infusion on Day 1 Paclitaxel 175mg/m 2 IV infusion on Day 1 Repeat every 3 weeks/21 days Continue therapy for up to? Cycles or as long as acceptable toxicities * Note: in event of Cisplatin contra-indicated, Topotecan may be substituted Bevacizumab + Paclitaxel + Topotecan Clinical indications:????? Bevacizumab 15mg/kg IV infusion on Day 1 Paclitaxel 175mg/m 2 IV infusion on Day 1 Topotecan 0.75mg/m 2 IV infusion on Day 1 First Cycle only then Topotecan 0.75mg/m 2 on Days 1-3 thereafter Repeat every 3 weeks/21 days Continue therapy for up to? Cycles or as long as acceptable toxicities Carboplatin + Etoposide Clinical indications: Small Cell cancers only Carboplatin [AUC5] IV infusion (? hr duration) on Day 1 Etoposide IV 100mg/m 2 IV infusion (? hr duration) on Day 1 only Etoposide 200mg/m 2 administered Orally on Days 2 & 3 Repeat every 3-weeks/21 days Continue therapy for up to 6 Cycles or as long as acceptable toxicities Note; EBRT external beam radiotherapy AUC Area under the Curve (as per Cockcroft-Gault equation) Version 2.4 (201600628) Page 7 of 10
Follow up schedule following radical therapy THIS DOCUMENT NB. PATIENTS ON CLINICAL TRIALS FOLLOW UP SHOULD BE ACCORDING TO THE TRIAL PROTOCOL STRATEGY Year 1 Year 2 Year 3 Year 4 Year 5 3-monthly clinic visit* 3-monthly clinic visit* 4-monthly clinic visit* 6-monthly clinic visit* 6-monthly clinic visit* Surveillance Asymptomatic: 9-month PET scan should be considered in patients who have undergone nonsurgical treatment and in whom salvage exenterative/pelvic sidewall surgery or stereotactic body RT for isolated recurrence would be appropriate Symptomatic: evaluate with MRI or CT and consider EUA Cervical cytology or vault smears are not indicated to detect asymptomatic recurrence of cervical cancer in patients who have not undergone fertility conserving surgery Consider hormone replacement therapy (HRT) in those <50 who have lost ovarian function as a result of therapy If uterus in situ, recommend combined continuous HRT preparation until age 50, if no contra-indications Recommend use of vaginal dilators to women who have received non-surgical treatment for cervical cancer Version 2.4 (201600628) Page 8 of 10
Staging THIS DOCUMENT Management of relapsed disease Salvage Treatment Pelvic relapse only following EBRT/ICBT Consider pelvic exenteration or pelvic side wall surgery depending on fitness and location of recurrence Consider SABR for isolated pelvic nodal relapse if unresectable MRI or CT scan and following surgery Pelvic (chemo)radiotherapy (see page 5/6 for details) +/- vaginal brachytherapy PET scan Retroperitoneal nodal relapse +/- pelvic relapse only following surgery following EBRT/ICBT Extended field (chemo)radiotherapy +/- vaginal brachytherapy Distant relapse Note: EBRT External Beam Radiotherapy ICBT Intra-Cavitary Brachytherapy SABR Stereotactic Ablative Body Radiotherapy Palliative chemotherapy (see page 6 for details) Palliative radiotherapy Version 2.4 (201600628) Page 9 of 10
FIGO*/ AJCC** (7 th Edition) TNM Staging Primary Tumour (T) AJCC TNM FIGO Staging TX - Primary tumour cannot be assessed T0 - No evidence of primary tumour Tis - Carcinoma in situ (pre-invasive carcinoma) T1 I Cervical carcinoma confined to the cervix (disregard extension to the corpus) T1a IA Invasive carcinoma diagnosed only by microscopy; stromal invasion with a maximum depth of 5.0 mm measured from the base of the epithelium and a horizontal spread of 7.0 mm or less; vascular space involvement, venous or lymphatic, does not affect classification T1a1 IA1 Measured stromal invasion 3.0 mm in depth and 7.0 mm in horizontal spread T1a2 IA2 Measured stromal invasion > 3.0 mm and 5.0 mm with a horizontal spread 7.0 mm T1b IB Clinically visible lesion confined to the cervix or microscopic lesion greater than T1a/IA2 T1b1 IB1 Clinically visible lesion 4.0 cm in greatest dimension T1b2 IB2 Clinically visible lesion > 4.0 cm in greatest dimension T2 II Cervical carcinoma invades beyond uterus but not to pelvic wall or to lower third of vagina T2a IIA Tumour without parametrial invasion T2a1 IIA1 Clinically visible lesion 4.0 cm in greatest dimension T2a2 IIA2 Clinically visible lesion > 4.0 cm in greatest dimension T2b IIB Tumour with parametrial invasion T3 III Tumour extends to pelvic wall and/or involves lower third of vagina and/or causes hydronephrosis or nonfunctional kidney T3a IIIA Tumour involves lower third of vagina, no extension to pelvic wall T3b IIIB Tumour extends to pelvic wall and/or causes hydronephrosis or nonfunctional kidney T4 IV Tumour invades mucosa of bladder or rectum and/or extends beyond true pelvis (bullous edema is not sufficient to classify a tumor as T4) T4a IVA Tumour invades mucosa of bladder or rectum (bullous edema is not sufficient to classify a tumour as T4) T4b IVB Tumour extends beyond true pelvis Regional lymph nodes (N) NX - Regional lymph nodes cannot be assessed N0 - No regional lymph node metastasis N1 - Regional lymph node metastasis Distant Metastases (M) M0 - No distant metastasis M1 - Distant metastasis (including peritoneal spread; involvement of supraclavicular, mediastinal, or para-aortic lymph nodes; and lung, liver, or bone) *FIGO The International Federation of Gynecology and Obstetrics **AJCC American Joint Committee on Cancer Version 2.4 (201600628) Page 10 of 10